journal of surgical radiology

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193Contents

210 Original Article18F-FDG Diagnosis of SCCEvaluation of metastatic disease using PET.

Yumi moChizuki et al.

216 Original ArticleGastrinoma LocalizationAnatomic variation and successful localiza-tion of an occult gastrinoma.

irwin Best

220 Original ArticleCrossing High BifurcationsTechnique to cross high aortic bifurcations.

irwin Best

224 Original ArticleContrast MR for Budd-ChiariNodular regenerative hyperplasia in Budd-Chiari syndrome diagnosed with contrast MR.

Drew Davis et al.

198 Feature ArticlePolydimethylsiloxaneAn innovation in radioguided surgery.

GeralDo vitral et al.

204 Original ArticleMDCT & Coronary AngioDiagnosis of coronary artery stenosis.

nariman nezami et al.

1 OCTOBER 2012J

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194 eDitors | oCtoBer 2012

Journal of Surgical Radiology

Executive EditorSapan Desai

Surgisphere Corporation

Science EditorThomas KoenigsbergerSurgisphere Corporation

Senior Staff EditorCarol Fisher

Surgisphere Corporation

Editor-in-ChiefCynthia Shortell

Duke University Medical Center, Durham, North Carolina

Managing EditorMark Shapiro Duke University Medical Center, Durham, North Carolina

Journal EditorsHasan Alam Massachusetts General Hospital, Boston, MassachusettsAli Azizzadeh University of Texas at Houston, Houston, TexasStanley Ashley Brigham and Women’s Hospital, Boston, MassachusettsAnthony Atala Wake Forest Baptist Health, Winston-Salem, North CarolinaDavid Bentrem Northwestern University, Chicago, IllinoisGavin Britz Duke University Medical Center, Durham, North CarolinaAlasdair Conn Massachusetts General Hospital, Boston, MassachusettsJames Cusack Jr. Massachusetts General Hospital, Boston, MassachusettsDaniel Dent University of Texas Health Sciences Center, San Antonio, TexasCelia Divino Mount Sinai School of Medicine, New York, New YorkN. Joseph Espat Roger Williams Medical Center, Providence, Rhode IslandSteven Evans Georgetown University Medical Center, Washington, DCThomas Fahey III Weill Cornell Medical College, New York City, New YorkKevin Foster Arizona Burn Center, Phoenix, ArizonaAllan Friedman Duke University Medical Center, Durham, North CarolinaRichard Gray Mayo Clinic, Phoenix, ArizonaRalph Greco Stanford University, Stanford, CaliforniaRajan Gupta Duke University Medical Center, Durham, North CarolinaTimothy Hall Stamford Hospital, Stamford, ConnecticutW. Scott Helton Hospital of Saint Raphael, New Haven, ConnecticutG. Chad Hughes Duke University Medical Center, Durham, North CarolinaRonald C. Jones Baylor University Medical Center, Dallas, TexasCharles Kim Duke University Medical Center, Durham, North CarolinaDavid King Massachusetts General Hospital, Boston, MassachusettsChristopher J. Kwolek Massachusetts General Hospital, Boston, MassachusettsMichael Leitman Beth Israel Medical Center, New York City, New YorkMatthew Menard Brigham and Women’s Hospital, Boston, MassachusettsMichael Miller Duke University Medical Center, Durham, North CarolinaStephen Milner Johns Hopkins University, Baltimore, MarylandEugene Moretti Duke University Medical Center, Durham, North CarolinaTheodore Pappas Duke University Medical Center, Durham, North CarolinaJeff Pruitt UT Southwestern Medical Center, Dallas, TexasScott Pruitt Duke University Medical Center, Durham, North CarolinaHazim Safi University of Texas at Houston, Houston, TexasRanjan Sudan Duke University Medical Center, Durham, North CarolinaGilbert Upchurch, Jr University of Virginia, Charlottesville, Virginia

Advisor to the JournalDanny O. Jacobs Duke University Medical Center, Durham, North Carolina

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Citation Vitral et al. Polydimethylsiloxane: an innovation in radioguided surgery. J Surg Radiol. 2012 Oct 1;3(4).

CorrespondenCe Geraldo S.F. Vitral, MD E-mail [email protected].

reCeived April 3, 2012. aCCepted October 1, 2012. epub October 11, 2012.

Polydimethylsiloxane: An Innovation in Radioguided Surgery Geraldo S. F. Vitral MD, PhD1, Ronaldo R. Bastos PhD2, Nádia R. B . Raposo PhD3

1. Research Center for Innovative Health Sciences (NUPICS), School of Pharmacy, Federal University of Juiz de Fora, Brazil.2. Department of Statistics, Federal University of Juiz de Fora, Brazil.3. Department and Institute of Psychiatry, Neuroscience Laboratory (LIM 27), School of Medicine, University of São Paulo, Brazil.

AbstractintroduCtion The certification of correct positioning of radiotracers in relationship to suspected lesions of the breast in radioguided occult lesion localization (ROLL), is a well-known problem. The objective of this study was the clinical evaluation of an innovative technical step in ROLL, utilizing a high viscosity polymer as a radiological contrast and tissue marker.Methods Thirty patients bearing impalpable mammary lesions were submitted to the ROLL technique by injection of high viscosity polydimethylsiloxane (PDMS), after introducing the radio-isotope 99mTc- MAA. Statistical analyses were completed using SPSS version 13.0.results We obtained 100% radiological free margins in the specimens radiographed after surgical excision. ConClusion An increase in surgical precision was achieved using ROLL technique, by the use of high viscosity PDMS. Negative interference was not identified in any of the other stages of ROLL technique, and there were no adverse reactions to the PDMS used.

Keywords surgery, breast, cancer, ROLL, PDMS, radioguided

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Vitral et al. PDMS in Radioguided Surgery original artiCle

IntroductionWhen planning a surgical procedure for eradication of a suspected sub-clinical mammary lesion, it should be kept in mind the necessity to remove it in the most centralized meth-od possible in the surgical specimen. Thus, obtaining a greater probability of obtaining surgical margins free from neoplasy.1

Developed at the European Institute of Oncology in Milan, Italy (1996), the radioisotopic marking technique using intra-operative orientation by a radiation detecting probe (ROLL - Radioguided Occult Lesion Localization) is a high efficiency procedure in lesion removal.2 Quite superior to the hook-wire technique, ROLL gives advantages such as decreased amounts of eradicated mammary tissue, greater lesion centralization in the surgical specimen, reduced compromised margins and better aesthetic results.3

The determining factor for the surgical diagnostic modality, success and therapeutics is the absolute correct radioisotope positioning (technetium pertechnetate bonded with human albumin - 99mTc-MAA) in the suspicious tissue.4 For this, the use of small amounts of radiological iodinated contrast in-

jected immediately after the radioisotope is recommended, followed by mammography control within a short period (no more than five minutes), as a way to verify this position.5 Prob-lems arising, beyond the inherent risks in this contrast medi-um (allergic reactions in varying degrees of severity and local reactions), include production of a dispersal image where it is difficult to verify the exact injection point in the mammogra-phy control. This is due to the rapid tissue absorption of this contrast medium which can discredit the analysis.6,7

The use of high viscosity polydimethylsiloxane (PDMS) in substitution of the iodinated contrast could correct this prob-lem, with substantial image improvement of the radiological contrast, without interference in the nuclear medicine tech-niques and histological preparation employed in ROLL.8,9 A more regular and permanent injection point marking was obtained, also allowing its identification in the surgical speci-men’s radiograph, without toxicity signs, justifying clinical evaluation of this use; the objective of this study.

Materials and MethodsParticipantsThis study was approved by the Federal University of Juiz de Fora, Human Research Ethics Committee (protocol no 237/2009) and was in compliance with the Helsinki conven-tion. Thirty patients were selected between the ages of 43 and 87, all had impalpable mammary lesions (BI-RADS™ 4 and 5), which were referred for histological investigation through the ROLL technique. The patients were informed about all stages of the study, their potential risks and data of literature.

Table 1 – Radiological, surgical and pathological param-eters of the investigated lesions.

Parameters Frequency Percentile

Radiological status margins

Free

Compromised

30

0

100.0

0.0

Classification BI-RADS™ of the lesions

4

5

20

10

66.3

33.3

Radiological description of the lesion

Nodule

Microcalcifications

Focal asymmetry

12

16

2

40.0

53.3

6.7

Marking method

Mammography

Ultrasound

23

7

76.7

23.5

Mammography Density

N1

P1

P2

Dy

7

9

12

2

23.3

30.0

40.0

6.7

Adjustments in the surgical approach

Yes

No

16

14

53.3

46.7

Nature of the lesion

Benign

Malignant

15

15

50.0

50.0

Figure 1. Mammograph of surgical specimen showing the lesion suspects centralized and radiotracer (PDMS + 99mTc-MAA) probe detection intentionally peripherally positioned. Images were taken before fixation in buffered formalin, using a mammography Contour Plus / Bennett-Hologic and measurements performed utilizing digital cali-per Tresna EC16.


original artiCle Vitral et al. PDMS in Radioguided SurgeryThe material was fixed in buffered for-malin at 10% for a minimum period of 24 hours. During the macroscopic study measurement of the piece’s three dimen-sions (height, width and depth) was accomplished. After, the paraffin em-bedded material was cut in microtome Leica RM 2025 (Germany), resulting in sections 4 µm thick and slides were pre-pared in a classical way. Following, they were stained with hematoxylin and eo-sin, examined by an optical microscope

(Nikon Ellipse E400, Japan) and photographed (Nikon Cool-pix 5000, Japan).

Statistical AnalysisThrough the use of Statistical Package for the Social Sciences (SPSS) software version 13.0, descriptive statistics were made from the following variables: radiological margins, classifica-tion BI-RADS™ of the lesion, radiological lesion description, mammographic density (Wolfe), marking method, the larger radiological lesion diameter, the larger PDMS radiological marking, the greater distance between the center of the lesion and the center of the marking with PDMS, making adjust-ments in the surgical approach orientation by PDMS mark-ing, the average diameter of the surgical specimen (average of three dimensions) and nature of the lesion. These results were compared with the literature data.

ResultsTable 1 shows the frequency and percentile values of the pa-rameters: radiological status margins, classification of the le-sions according to BI-RADS™ criteria, radiological descrip-tion of the lesion, method used in the pre-surgical marking, classification of the mammography density by Wolfe’s criteria, implementation of adjustments in the surgical approach and histological nature of the lesion.

Figure 1 shows the x-ray of a surgical specimen, in which the lesion is observed occupying the center of the piece, as well as the presence of PDMS in the periphery of the same. This im-age exemplifies the necessity of surgical adjustments accord-ing to preoperative data obtained with the use of PDMS (and mammographic post-marking controls) that shows the real positioning of the radiotracer in relationship with the lesion.

In this case, the centralized excision of the lesion into the sur-gical specimen was obtained only with the surgical adjust-ments performed. The hot spot gamma-probe detection was located in the peripheral area of the specimen, and not in the center, as is the classical approach.

Table 2 describes the findings related to the larger diameter of the radiological lesion, the larger the radiological marking with PDMS, the greater distance between the center of the le-sion and the center of the marking with PDMS and the average

Following, those that agreed to participate in the study signed a term of free and clear consent.

The classic stages of ROLL were performed, except for the use of PDMS in substitution of iodinated contrast.

PolydimethylsiloxaneBLD Marker® containing 30,000 centistokes (cs) viscosity PDMS, medical degree of purity, in volume of 0.2 ml, in the form of a single use sterile kit, was used (Saldanha Rodrigues Ltda. - Manaus / São Paulo - Brazil).

Radiological Control and Surgical Specimen Post-Marking After marking, by stereotactic or ultrasound, the patient was positioned in a mammography Contour Plus / Bennett-Ho-logic (USA) and imaged in craniocaudal and side views. With the aid of a digital caliper, Tresna EC16 (USA) measurements of the greater diameter of the radiological lesion, greater ra-diological marking with PDMS and greater distance between the center of the lesion and the center of the marking with PDMS were performed. Immediately after the excision, the surgical specimen was positioned in a mammography and submitted to complementary radiographs (anteroposterior and side views, after 90 degree rotation). Thus, all margins could be radiologically evaluated.

Nuclear MedicineNuclear medicine analyses were performed at the Nuclemi-nas / Nuclear Med-Center (Juiz de Fora - Brazil). We utilized the 99mTc-MAA (CNEN - IPEN - Brazil), as isotopic marker, in volume of 0.2 ml, corresponding to the approximate dose of 80 megabecquerel (MBq). The reading was done, after the marking, in gamma - camera Elscint Apex SP6 (Israel). The in-tra-operative detection was performed using a gamma-probe NEO Neoprobe 2000 (USA).

Radiological Margins Status EvaluationIn this study, we considered the free radiological margins when the suspicious lesion did not touch the margin in the surgical specimen radiographed in two complementary views.

Histological Processing

Table 2. Linear measurements related to the lesion, pre-surgical marking and sur-gical specimen.

Measurements Average Standard deviation

Larger radiological diameter of the lesion (millimeters) 8.3 3.7

Larger radiological diameter marking with PDMS (millimeters) 7.3 2.1

Greater distance from the marking / profile (millimeters) 5.8 6.4

Greater distance from the marking / craniocaudal (millimeters) 5.4 6.5

Average diameter of the surgical specimen (centimeters) 4.4 1.0

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glandular and adipose tissue variations can also influence the specimen weight.

Our results showed an average surgical specimen diameter of 4.4 cm and an average radiological lesion diameter of 8.3 mm (Table 1), very close to those reported by Caughran et al.18

Another important discovery observed in this study was the high number of non -coincidental markings with the suspi-cious lesion. In all of the cases (n = 30), the demarcations were accomplished by one experienced radiologist and with radio-graphical documentation (mammography in two comple-mentary incidences – craniocaudal profile – before the radio-isotope and PDMS injection) and photographic (ultrasound marking) certifying the correct positioning of the needle in the center of the suspect lesion. It probably occurred due to the peculiar characteristics of the breast tissue concerning its elasticity, producing the so-called “sponge effect” (compres-sion and decompression in the mammograph or under ultra-sound). The obtaining of free radiological margins in all of the analyzed cases was only possible with the performed adjust-ments (Table 2) according the post-marking control informa-tion provided by the use of PDMS.

It was demonstrated the applicability of high viscosity PDMS in place of iodinated contrast in ROLL, increasing the accu-racy of this surgical technique and providing key information for individualized approaches. The x-ray specimen in two complementary incidences adopted in this study, constituted another innovative approach previously not described in the literature. No adverse effects in patients or negative interfer-ences in radiological, nuclear and histological techniques were observed.

DisclosuresThe Federal University of Juiz de Fora (Brazil) provided this study’s costs.

References1. Pleijhuis RG, Graafland M, Vries J, Bart J, Jong JS, Dam GMV: Ob-

taining adequate surgical margins in breast-conserving therapy for patients with early-stage breast cancer: current modalities and future directions. Ann Surg Oncol 2009;16:2717-2730.

2. Paganelli G, Luini A, Veronesi U: Radioguided occult lesion localiza-tion (ROLL) in breast cancer: maximizing efficacy, minimizing mutila-tion. Ann Oncol 2002;13:1839-1840.

3. Van der Ploeg IM, Hobbelink M, Van den Bosch MA, Mali WP, Borel Hinkes IH, Van Hillegersberg R: Radioguided occult lesion localisa-tion (ROLL) for non-palpable breast lesions: A review of the relevant literature. EJSO 2008;34: 1-5.

4. Galimberti V, Zurrida S, Luini A, Paganelli G, Cassiano E, Veronesi P, Pizzamiglio M, Fiorenza M: Use of Tc-99 labelled colloidal albumin for preoperative and intraoperative localization of non-palpable breast lesions. Eur J Cancer 1997;33(8):79.

5. De Cicco C, Pizzamiglio M, Trifirò G, Viale G, Sachini V, Mazzarol G, Bonanni B, Farante G, Andreoni G, Ballardini B: Radioguided occult lesion localisation (ROLL) and surgical biopsy in breast cancer. Tech-nical aspects. Q J Nucl Med 2002;46(2):145-151.

diameter of the surgical specimen.

Additionally, we observed that no adverse reactions attribut-able to the PDMS were identified, as well as any complications of injecting the product.

DiscussionSeveral studies correlate the incidence of local recurrence af-ter conservative breast cancer treatment with the presence of compromised resection margins by tumor or, in other words, inaccuracy in the surgical approach.10-13

ROLL, as a diagnostic technique and conservative treatment of impalpable and suspicious malignant breast lesions, has been increasingly used worldwide, mainly due to their greater ability to remove the suspicious lesion with tumor-free mar-gins in the surgical specimen.14 In order to obtain this result, precise presurgical marking is fundamental as well as its con-firmation. This is eventually accomplished with the iodinated radiological contrast injection, immediately after the radio-isotope injection. This iodinated contrast, having inadequate characteristics for this use, is seldom used with credit for the marking given exclusively to the expertise of the radiologist.7,15 This way leads to highly variable success rates in ROLL (69% to 99%), often linked to the volume of eradicated breast tis-sue.3,14,16

As shown, the use of PDMS, substituting iodinated contrast for verification of the correct positioning of 99mTc-MAA in the breast tissue, allowed 100% removal of suspicious lesions in the first intervention, with tumor-free radiological margins (Table 1). Luini et al. reported the intraoperative confirma-tion of the suspicious lesions removal by radiography on the surgical specimen positioned in an anteroposterior view, which allowed the top, bottom, lateral and medial analyses.17 In our study, the radiological control during the surgery was performed in two mammographic views of specimens, rotat-ed 90 degrees (an innovative approach). This procedure also minimizes the distortions produced by the compression in the mammograph, suggested to cause interpretational errors.18,19 In cases where the preoperative marking did not occur at the center of the lesion, identification of this position has enabled us to make modifications in the surgical approach with milli-metric adjustments in the resection lines in order to centralize the lesion as much as possible in the specimen.

We opted to measure the average diameter (simple average of the specimen’s three dimensions) as a way of estimating the amount of excised tissue (Table 2). The measurements of volume and weight are, in our opinion, more susceptible to misinterpretation. In the study of Tengher-Barna et al., the vol-ume of lumpectomy ranged from 10 to 217 cubic centimeters.20 Rizzo et al. used different scales for measuring the tumor (lin-ear, in centimeters) and surgical specimen (volume, in cubic centimeters), making result interpretations more difficult.21 Moreover, the fragility of the mammary adipose tissue often disrupts the uniform surgical removal of the specimen, which affects the volume calculation.22 Additionally, the proportional


original artiCle Vitral et al. PDMS in Radioguided Surgery6. Machado RH, Oliveira AC, Rocha AC, Landesmann MC, Martins

FP, Lopes SA, Gutfilen B, da Fonseca LM: Radioguided occult lesion localization (ROLL) and excision of breast lesions using technetium-99m macroaggregate albumin and air injection control. J Exp Clin Cancer Res 2007;26(3):323-327.

7. Sarlos D, Frey LD, Haueisen H, Landmann G, Kots LA, Schaer G: Ra-dioguided occult lesion localization (ROLL) for treatment and diagno-sis of malignant and premalignant breast lesions combined with sen-tinel node biopsy. A prospective clinical trial with 100 patients. EJSO 2009;35:403-408.

8. Vitral GSF, Raposo, NRB: Polydimethylsiloxane: a new contrast material for localization of occult breast lesions. Radiol Oncol 2011;45(3):166-173.

9. Vitral GSF, Raposo NRB, Barroso AA, Laporte BEP: Avaliação e con-firmação do acerto da marcação radioguiada. In: Chagas CR, Menke CH, Vieira R, Boff RA. Tratado de Mastologia da SBM. 1st ed. Rio de Janeiro: Revinter 2011;1:400-404.

10. Barros A, Pinotti M, Ricci MD, Nisida AC, Pinotti JA: Immediate ef-fects of intraoperative evaluation of surgical margins over the treat-ment of early infiltrating breast carcinoma. Tumori 2003;89(1):42-45.

11. Goldstein NS, Kestin L, Vicini F: Factors associated with ipsilateral breast failure and distant metastases in patients with invasive breast carcinoma treated with breast-conserving therapy. A clinicopatho-logic study of 607 neoplasms from 583 patients. Am J Clin Pathol 2003;120(4):500-527.

12. Law TT, Kwong A: Surgical margins in breast conservation therapy: how much should we excise? Southern Med J 2009;102(12):1234-1237.

13. Vicini FA, Goldstein NS, Pass H, Kestin LL: Use of pathologic factors to assist in establishing adequacy of excision before radiotherapy in patients treated with breast-conserving therapy. Int J Radiat Oncol Biol Phys 2004;60(1):86-94.

14. Rovera F, Frattini F, Marelli M, Corben AD, Vanoli C, Dionigi G, Boni L, Dionigi R: Radio-guided occult lesion localization versus wire-guided localization in non-palpable breast lesions. Int J Surg 2008;6(1):101-103.

15. Paredes P, Vidal-Sicart S, Zanón G, Roé N, Rubí S, Lafuente S, Paví AJ, Pons F: Radioguided occult lesion localisation in breast cancer using an intraoperative portable gamma camera: first results. Eur J Nucl Med Mol Imaging 2008;35:230-235.

16. Gennari R, Galimberti V, De Cicco C, Zurrida S, Zerwes F, Pigatto F, Luini A, Paganelli G, Veronesi U: Use of the technetium-99m-labeled colloid albumin for preoperative and intraoperative localization of nonpalpable breast lesions. J Am Col Surg 2000;90(6):692-698.

17. Luini A, Zurrida S, Paganelli G, Galimberti V, Sachini V, Monti S, Vero-nesi P, Viale G, Veronesi U: Comparison of radioguided excision with wire localization of occult breast lesions. Br J Surg 1999;86(4):522-525.

18. Caughran JL, Vicini FA, Kestin LL, Dekhne NS, Benitez PR, Goldstein NS: Optimal use of re-excision in patients diagnosed with early-stage breast cancer by excisional biopsy treated with breast-conserving ther-apy. Ann Surg Oncol 2009;16:3020-3027.

19. Lovrics PJ, Cornacchi SD, Farrokhyar F, Garnett A, Chen V, Franic S, Simunovic M: The relationship between surgical factors and margin status after breast-conservation surgery for early stage breast cancer. Am J Surg 2009;197:740-746.

20. Tengher-Barna I, Hequet D, Reboul-Marty J, Frassati-Biaggi A, Seince N, Rodrigues-Faure A, Uzan M, Ziol M: Prevalence and predictive fac-tors for the detection of carcinoma in cavity margin performed at the time of breast lumpectomy. Modern Pathol 2009;22:299-305.

21. Rizzo M, Iyengar R, Gabram SGA, Park J, Birdsong G, Chandler KL, Mosunjac MB: The effects of additional tumor cavity sampling at the time of breast-conserving surgery on final margin status, volume of resection, and pathologist workload. Ann Surg Oncol 2010;17:228-234.

22. Skripenova S, Layfield LJ: Initial margin status for invasive ductal car-cinoma of the breast and subsequent identification of carcinoma in reexcision specimens. Arch Pathol Lab Med 2010;134:109-113.

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64-Slice Multidetector Computed Tomographic Angiography and Invasive Coronary Angiography in Diagnosis of Significant Coronary Artery StenosisMohammad Hossein Daghighi1, MD, Reza Javadrashid1, MD, Samad Ghaffari2, MD, Alireza Sadighi3, MD, Masoud PourIssa1, MD, Mohammad Hossein Abdkarimi4, MD,

Sona Ghorashi5, MD, Nariman Nezami6, MD

1. Department of Radiology, Tabriz University (Medical Sciences), Tabriz, Iran.2. Department of Cardiology, Tabriz University (Medical Sciences), Tabriz, Iran.3. Neuroscience Research Center, Tabriz University (Medical Sciences), Tabriz, Iran.4. Iran Diagnostic Imaging Center, Tabriz, Eastern Azerbaijan, Iran.5. Young Researchers Club, Tabriz Branch, Islamic Azad University, Tabriz, Iran.6. Drug Applied Research Center, Tabriz University (Medical Sciences), Tabriz, Iran.

AbstractintroduCtion Introduction of 64-slice multidetector computed tomography (MDCT) has resulted in a great improvement of the non-invasive coronary artery imaging. The present study aimed to evaluate the diagnostic accuracy of 64-Slice MDCT among patients with coronary artery disease (CAD) candidates for invasive coronary angiography (ICA) study. Methods During the present retrospective study, from March 2009 to March 2010, the diag-nostic accuracy of 64-Slice MDCT were evaluated versus ICA in patients with suspected coronary artery disease. MDCT and ICA findings of each coronary segment were compared to determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of MDCT in the detection of significant lesions (≥50% stenosis).results A total of 125 patients were evaluated with both methods. In per patient assessment, the sensitivity, specificity, PPV and NPV of MDCT were 97.6%, 85.2%, 95.2% and 92%, respectively. These values in per vessel evaluation were 86.3%, 92.2%, 86.8%, and 92.2%, and also corresponding values in per segment evaluation were 69.8%, 94.8%, 69%, and 95%, respectively. ConClusion The coronary angiography with 64-Slice MDCT has high diagnostic performance for evaluation of significant CAD in patients with suspected CAD, but still cannot replace conven-tional coronary angiography at present time.

Keywords coronary artery disease, invasive coronary angiography, multidetector computed to-mography, accuracy

Citation Daghighi et al. 64-Slice Multidetector Comput-ed Tomographic Angiography and Invasive Coronary Angiography in Diagnosis of Significant Coronary Ar-tery Stenosis. J Surg Radiol. 2012 Oct 1;3(4).

CorrespondenCe Nariman Nezami, MD E-mail [email protected]

reCeived February 7, 2012. aCCepted October 1, 2012. epub October 1, 2012.

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Daghighi et al. 64-Slice MDCT vs. Invasive Angiography original artiCle

IntroductionNowadays, coronary artery disease is the leading cause of adult mortality and morbidity, although the combination of life style change, drug therapy, angioplasty, stenting and coro-nary artery bypass have provided excellent long-life therapeu-tic outcomes.1,2

In the half of patients with coronary artery disease, myocardi-al Infarction (MI) or sudden death are the first manifestations, so waiting for development of clinical symptoms and signs of disease for starting therapeutic intervention may be too late.3

Although, invasive coronary angiography (ICA) is the stan-dard method for evaluation of the coronary artery stenosis, it is an invasive method and results of cardiac catheterization reported normal or nonsignificant in 20-27% of all catheter-ized patients in spite of true coronary artery disease (CAD).4,5

During the recent years, multidetector computed tomography (MDCT) has become a more popular method for noninvasive evaluation of coronary arteries, because of its safety, rapidity and patients’ acceptance.5-8

The purpose of the present study was to evaluate the diagnos-tic accuracy of 64- Slice MDCT among relatively large number of patients with CAD symptoms and signs who were candi-dates of evaluation with ICA. Patients with acute coronary syndrome were excluded from the study.

Materials and MethodsDesignBetween March 2009 and March 2010, a total of 125 suspected CAD patients who underwent both coronary artery MDCT evaluation at Iran Diagnostic Imaging Center (a private cen-ter), and afterward ICA at Shahid Madani Hospital of Tabriz

University of Medical Sciences, were enrolled into the present retrospective study.

The study protocol, which was in compliance with Helsinki declaration, was approved by the Ethics Committee of Tabriz University of Medical Sciences.

Study PopulationOf patients that had abnormal MDCT angiography find-ings, those underwent ICA in next two months included in this study. All of enrolled patients had CAD symptoms and signs. Patients with acute coronary syndrome (ACS) were not included in to the study, but those with more than two month after initial event were included.

Exclusion criteria were: patients with ACS in first two months, previous coronary by-pass graft surgery or stenting, history of previous adverse reaction to contrast substance, renal func-tional disease (serum creatinine> 1.5 mg/dl), atrial fibrillation or frequent (>15 extrasystoles/min) extrasystoles, interval be-tween two diagnostic methods more than 2 months, and calci-um score more than 600 Agatston units. Patients with a heart rate > 70 beats/min received an oral dose of a beta blocker [propranolol (40-120 mg), metoprolol (100-150 mg), or ateno-lol 50- 100mg)] and alprazolam (0.5-1 mg) about one hour be-fore scanning. Patients who did not respond to B-blockers or had been scanned in spite of higher heart rates were excluded from the study, too.

64-Slice Multidetector Computed TomographyScanning was performed using a 64-Slice MDCT scanner (So-matom Sensation 64, Siemens Medical Solutions, Forch heim, Germany) associated with synchronous electrocardiographic tracing of patients.

First, non-contrast electrocardiogram (ECG) gated scanning was carried out for calcium score determination, and then, in the coro-nary computed tomographic angi-ography phase, nonionic contrast substance (Ultravist, 300 mg I/ml, Schering AG, Germany) was used.

The transit time of contrast sub-stance for every patient was deter-mined by using a bolus (10-15 cc) injection of nonionic contrast sub-stance. After that, approximately 55 to 85 ml of the same nonionic con-trast substance, according to the ex-pected duration of scanning, was in-jected through an 18-G intravenous line into the antecubital vein at a rate of 5 ml/s, followed by injection of 40 ml of saline solution through a dual-head injector.

Figure 1. (A) Left anterior descending has a significant lesion in mid part with good distal run off in 64-slice multidetector computed tomography study. (B) Left anterior descending in invasive coronary angiography.


original artiCle Daghighi et al. 64-Slice MDCT vs. Invasive Angiography

Computed tomographic angiography parameters were colli-mation width 640.6 mm, tube potential 120 kv, tube effective current 650 to 850 mA, tube rotation time 330 ms, table feed 3.8 mm/rotation, temporal resolution 83 to 165 ms (based on whether adaptive cadiovolume mode was active, this system allows selection of a bisector or monosector reconstruction algorithm according to changes in heart rate), scanning time 8 to 13 seconds in an inspiratory breath hold, and scan field from tracheal carina to the diaphragm.

Source image data sets were loaded to reconstruct axial, coro-nal, sagittal and oblique multiplanar reconstruction, thin-slab maximum intensity projection (MIP); or curved reconstruc-tions and volume-rendered images on an on-line work station (Wizard, Siemens Medical Solutions, Erlangen, Germany).

Selected thickness of multiplanar reconstructed views was 0.6 mm with 0.4 mm intervals and MIP image thickness was 5 mm. Retrospective electrocardiography gated reconstruction temporal window settings at 28 to 73% of the electrocardiog-raphy peak of consecutive R waves (PR interval) were used in our study.

The position of the reconstruction temporal window within the cardiac cycle was individually optimized to diminish mo-tion artifacts.

Coronary calcium score was calculated for territory of main coronary arteries and expressed as Agatston equivalent units using dedicated calcium score module of Syngo software (Sie-mens Medical Solutions, Erlangen, Germany).

MDCT angiography images were reconstructed by a radiolo-gist and interpretation of images was done by cooperation of

one radiologist and a cardiologist.

Invasive Coronary AngiographyICA in all patients was performed by a cardiologist using a transfemoral approach. ICA results were reported in 3 grades: normal (No stenosis), nonsignificant stenosis (<50% diam-eter decrease stenosis), significant stenosis (maximal luminal diameter decrease stenosis ≥50% including total occlusion with no luminal flow shown).

Cardiologist was not informed of the MDCT result. Standard projections of ICA were obtained, and the mean diameter decrease caused by coronary lesions was determined in ≥2 orthogonal projections in a quantitative manner. The same 17-segment American Heart Association nomenclature was applied here. Coronary segments distal to complete occlusion were non assessable and so were not analyzed.

Patients who had no significant stenosis in any coronary seg-ment but had ≥1 no assessable segments according to either MDCT angiography or ICA were excluded from per-patient analysis.

Protocol for Classification of StenosisOn the basis of American Heart Association classification, major coronary arteries including the left main coronary, left anterior descending (LAD), left circumflex (LCX), and right coronary arteries (RCA) and their branches were divided into 17 segments (9). Vessel diameter of 1.5 mm was considered as a minimum size for assessment.

Table 1. Patients’ demographic characteristics (n=125). Age (year) 56±10

Male (%) 79(63%)

Stable angina pectoris (%) 63(50%)

Atypical chest pain (%) 19(15%)

Dyspnea on exertion (%) 13(10%)

Previous Myocardial infarction (%) 23(18.4%)

Hypertension (%) 56(44.8%)

Diabetes mellitus (%) 34(27%)

Smoking (%) 21(16.8%)

Hypercholesterolemia (%) (total Cholesterol>200mg/dl) 40(32%)

Positive family history of Myocardial infarction 12(10.4%)

Dyslipidemia 2(1.6%)

Invasive coronary angiography findings

Normal 29(23%)

1 vessel disease 32(25.6%)

2 vessel disease 35(28%)

3 vessel disease 24(19%)

One of the above +left main artery disease 5(4%)

Calcium score (Agatston units)

0-100 75(60%)

101-400 36(28%)

401-600 14(12%)

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As a first step, it was determined whether segments were as-sessable or not. Evaluating reconstructed images of assessable segments, along longitudinal and transverse axis of coronary arteries, the severity of coronary artery stenosis was classified normal (no stenosis), nonsignificant stenosis (<50% diameter decrease stenosis), significant stensosis (maximal luminal di-ameter decrease stenosis ≥50% including total occlusion with no luminal flow shown).

In per-vessel evaluation, each of the RCA, LAD, LCX and the left main coronary artery were assessed as an independent vessel.

The criteria used for determination of the severity of stenosis were similar to each other in both MDCT and ICA. The worst stenosis was considered to classify that segment if there were multiple lesions in a given segment. In per-vessel evaluation, the narrowest segment was selected when there was multiple segment involvement in one artery.

On a per-patient evaluation, one or more than one stenosis ≥50% was defined as positive coronary artery disease.

Statistical AnalysisStatistical analysis was performed by SPSS software package for windows version 13.0 (SPSS Ins., Chicago, USA). Quantita-tive variables were expressed as mean +/- standard deviation (SD), and discrete variables were presented as counts and per-centages. ICA considered the gold standard of reference, and descriptive statistics including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MDCT in determining the presence or exclusion of significant coronary artery stenosis were calculated using chi-square tests of contingency. Calculations were determined in per-segment, per-artery, and per patient bases. The results were considered significance when the p value was less than 0.05.

ResultsCollectively, data of 125 patients were analyzed who under-went both ICA and MDCT, with the interval of less than 2 months (27.0±9.5 days). Seventy nine patients were male and 46 were female; the mean age of patients was 56.5±10.8 years.

A total of 103 patients received B-blockers to decrease their heart rate from 81.7±9.3 beats/min to a lower rate. During scanning, the median heart rate was 66 beats/min. The mean spent time for reconstruction and analysis of images was 39.8±7.7 minutes per-patient.

In a per-segment analysis of patients, of 2125 segments of coro-nary arteries were evaluated of which 5 segments were related to ramus intermedius branch as a variant. Ninety one (4.3%) segments of all studied segments were no assessable although 2034 (95.7%) segments were analyzed, completely.

Of 91 no assessable segments, 31 were because of calcium in-duced artifact, 24 segments due to their position after com-plete occlusion, 5 because of accompanying arterial anomaly

(absence of artery also), 27 because of their small sizes and 4 secondary to low quality images were not assessable and were excluded from analysis.

In 95 (76%) patients coronary artery evaluation was complete and in 30 (24%) patients this evaluation was incomplete. Of 1657 negative segments, 1574 (95%) were reported true nega-tive, whereas 83 (5%) were reported false negative. Of 377 pos-itive segments 260 (69%) were reported true positive, whereas 117 (31%) were reported as false positive.

On a per-segment basis, MDCT had 91.3% accuracy in the de-tection of the presence or absence of significant CAD. Associa-tion between MDCT and ICA was 78%.

On the basis of ICA results, the most frequent involved seg-ment was proximal segment of LAD, whereas the least fre-quently involved segment was the posterior left ventricular artery (Figure 1).

On a per-vessel basis, of 505 evaluated vessels (5 vessels relat-ing to the ramus intermedius as a variant), 486 (96.2%) were assessable and 19 (3.8%) because of having one or more than one no assessable segments were excluded from the study. Of 311 vessels reported negative, 287 (92.3%) were true negative and 24 (7.7%) were false negative. Of 175 vessels reported posi-tive, 152 (86.8%) were true positive and 23 (13.2%) were false positive. The diagnostic accuracy of MDCT in the evaluation of the presence or absence of significant CAD was 90.3%. On a pervessel basis, association between MDCT and ICA for RCA, LM, LAD and LCX were 86%, 77%, 74% and 78%, re-spectively.

On a per-patient basis, the results were as follow: among total of 125 patients, 109 (87.2%) were assessable and 16 (12.8%) be-cause of having one or more than one no assessable segments were excluded from the study. Of 25 patients reported negative in MDCT evaluation, 23 (92%) were true negative and 2 (8%) were false negative. Of 84 patients reported positive for hav-ing CAD, 80 (95.2%) were reported true positive and 4 (4.8%) were reported false positive.

The accuracy of MDCT in the evaluation of the presence or absence of significant CAD was 94.5%. On a per-patient basis, association between MDCT and ICA was 93.0%.

Table 2 lists diagnostic sensitivity, specificity, PPV and NPV of 64-Slice MDCT in per-patient, per-vessele and per-segment analysis with their confidence intervals of 95.0%.

Table 2. Diagnostic accuracy of 64-slice MDCT angiogra-phy compared with ICA for detection of lesions with ≥50% diameter decrease stenosis in assessed patients.

Sensitivity Specificity PPV NPV

Patient (n=109) 97.6% 85.2% 95.2% 92%

Vessels (n=486) 86.3% 92.2% 86.8% 92.2%

Segments (n=1789) 69.8% 94.8% 69% 95%

MDCT: multidetector computed tomography; ICA: invasive coronary angiography; PPV: positive predictive value; NPV: negative predictive value.


original artiCle Daghighi et al. 64-Slice MDCT vs. Invasive Angiographybecause of the likelihood of the requirement to apply differ-ent phases of the cardiac cycle for image reconstructions, this method was not used in our patients.

Estimation of the stenosis severity was semi quantitative us-ing MDCT in our study that it was a limitation of this study; however Raff et al. showed that 17% of lesions could not be quantitatively analyzed.11

Another difference between our study and previous studies was in usage sublingual nitroglycerin. We did not administer nitroglycerin to our patients before CT Angiography; whereas in most other studies all patients received 0.8 mg sublingual nitroglycerin just before beginning of the scan. Receiving sub-lingual nitroglycerin dilates and straights coronary arteries during scan, and helps for better interpretation of images, but it can increase patient’s heart rate.

Our results showed that 64-slice MDCT angiography has powerful discriminative ability to identify, among symptom-atic patients who have coronary calcium scores of 600 or less and those with and those without coronary obstruction. However, given the positive predictive value of 69% and the negative predictive value of 95%, MDCT angiography cannot replace ICA in this population of patients at present time, al-though 64 slice MDCT is an acceptable method to rule out patients with significant CAD who have CAD symptoms and signs, however in the majority of patients with positive 64 slice MDCT findings, the severity of vessel stenosis is overestimat-ed. These findings will result in using ICA as the next diagnos-tic approach for management of patients. Further studies are needed to define the method’s precise role in the diagnostic algorithm for the evaluation of patients with suspected coro-nary artery disease.

The results of the present study showed, in patients with the signs and symptoms which suspected coronary artery disease, 64-slice MDCT may be used to differentiate coronary sources from other causes resulting in symptoms similar to the coro-nary artery involvement.

Recent studies focused on evaluating 256- and 320-slice MDCT angiographic systems accuracy in evaluation of CAD. Although diagnostic accuracy of 256- and 320-slice MDCT may be comparable to the performance of 64-slice scanners, technological advancements in new MDCT devices provide improved image acquisition as well as reduced radiation dose compared with retrospectively gated 64-slice MDCT. For the first time, since the introduction of MDCT technology, 16 cm volumetric data acquisition within a single gantry rotation has become possible, allowing full cardiac imaging within a single gantry rotation, even in patients with an enlarged heart. Accordingly, single heart beat image acquisition allows for a significant reduction of contrast material and breath-hold time (with a total breath hold time of 5 s) when compared with MDCT systems requiring multiple heart beats to im-age the entire heart. Furthermore, 256- and 320-slice systems have increased temporal resolution (350 ms per gantry rota-tion) which reduces cardiac motion artifacts. Although certain models of 64-slice systems have a slightly higher temporal res-

DiscussionThe results of the present study indicated the sensitivity, speci-ficity, PPV and NPV of MDCT were 97.6%, 85.2%, 95.2% and 92%, respectively In per patient assessment. These values in per vessel evaluation were 86.3%, 92.2%, 86.8%, and 92.2%, and also corresponding values in per segment evaluation were 69.8%, 94.8%, 69%, and 95%, respectively.

Previous studies comparing MDCT angiography and ICA have yielded variable results. The first report about the diagnostic accuracy of 64-Slice MDCT on 67 suspects of CAD showed sensitivity, specificity, PPV, and NPV of 94%, 97%, 87%, and 99%, respectively.10 These findings were obtained using a tube rotation time of 370 ms. These values were respectively varying 86 to 100%, 92 to 97%, 56 to 97%, and 98 to 100% respectively, in different reports using 64-Slice MDCT.11-14 In a similar study in Iran (Tehran), reported by Shabestari et al., per-segment analysis revealed the results 92%, 97%, 77% and 99% for sen-sitivity, specificity, PPV and NPV of MDCT.15 Comparison of our study’s results with the results of former studies reveals relatively similarity and the protocol of the present study was also similar to the other studies done around the world.

The percentage of no assessable segments in the formerly published reports were 4 to 12%, and in our study was 4.3% and is similar to that of Ropers et al., calculated to be 4% of their 84 patients had no assessable coronary artery segments.14 Although in the more experienced MDCT centers lower per-centages has been reported. However, Leschka et al. and Leber et al. had no inaccessible segments in their MDCT coronary assessment.10,12 Although there was a limitation of assessed artery caliber down to 1.5 mm in the study of Leschka et al., no artery was excluded because of its small diameter in the investigation of Leber et al.10,12

Application of 0.4 and 0.6 mm thickness slices in the present study with improving spatial resolution provided decreased partial volume artifacts. It has been well established that MDCT angiography in highly calcified vessels has historically been difficult because of artifacts caused by high-density cal-cified lesions; however patients with calcium scores of more than 600 were excluded from primary analysis because we hy-pothesized a prior that in these patients MDCT angiography would have limited diagnostic utility. Also in the present study patients were evaluated whom presenting with a clinical indi-cation for conventional coronary angiography, and therefore our study population had a higher prevalence of disease than is seen in the general outpatient population. Exposure to radi-ation is a major concern in methods involving radiography or nuclear isotopes. It has been estimated that the individual risk of radiation can be clinically significant and depends on the patient’s age, sex, and expected life span, with younger female patients at increased risk for radiation-induced complica-tion.16-18 Thus, 64-slice MDCT angiography, like radioisotope tests and ICA, should be used with caution in patients with suspected CAD. Some methods are used to decrease the pa-tient radiation dose, including use of an electrocardiography pulsing (tube current modulation) technique. Nevertheless,

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in the Diagnosis of Coronary Artery Disease: Interobserver Agree-ment Among Radiologists With Varied Levels of Experience on a Per-patient and Per-segment Basis. J Thorac Imaging.

9. Austen, W. G., J. E. Edwards, R. L. Frye, G. G. Gensini, V. L. Gott, L. S. Griffith, D. C. McGoon, M. L. Murphy, and B. B. Roe. 1975. A reporting system on patients evaluated for coronary artery disease. Report of the Ad Hoc Committee for Grading of Coronary Artery Disease, Council on Cardiovascular Surgery, American Heart Association. Circulation 51: 5-40.

10. Leschka, S., H. Alkadhi, A. Plass, L. Desbiolles, J. Grunenfelder, B. Marincek, and S. Wildermuth. 2005. Accuracy of MSCT coronary an-giography with 64-slice technology: first experience. Eur Heart J 26: 1482-1487.

11. Raff, G. L., M. J. Gallagher, W. W. O’Neill, and J. A. Goldstein. 2005. Di-agnostic accuracy of noninvasive coronary angiography using 64-slice spiral computed tomography. J Am Coll Cardiol 46: 552-557.

12. Leber, A. W., A. Knez, F. von Ziegler, A. Becker, K. Nikolaou, S. Paul, B. Wintersperger, M. Reiser, C. R. Becker, G. Steinbeck, and P. Boekste-gers. 2005. Quantification of obstructive and nonobstructive coronary lesions by 64-slice computed tomography: a comparative study with quantitative coronary angiography and intravascular ultrasound. J Am Coll Cardiol 46: 147-154.

13. Mollet, N. R., F. Cademartiri, C. A. van Mieghem, G. Runza, E. P. Mc-Fadden, T. Baks, P. W. Serruys, G. P. Krestin, and P. J. de Feyter. 2005. High-resolution spiral computed tomography coronary angiography in patients referred for diagnostic conventional coronary angiography. Circulation 112: 2318-2323.

14. Ropers, D., J. Rixe, K. Anders, A. Kuttner, U. Baum, W. Bautz, W. G. Daniel, and S. Achenbach. 2006. Usefulness of multidetector row spi-ral computed tomography with 64- x 0.6-mm collimation and 330-ms rotation for the noninvasive detection of significant coronary artery stenoses. Am J Cardiol 97: 343-348.

15. Shabestari, A. A., S. Abdi, S. Akhlaghpoor, M. Azadi, H. Baharjoo, M. D. Pajouh, Z. Emami, F. Esfahani, I. Firouzi, M. Hashemian, M. Kouhi, M. Mozafari, I. Nazeri, M. Roshani, B. Salevatipour, H. Tavalla, M. Tehrai, and A. Zarrabi. 2007. Diagnostic performance of 64-channel multislice computed tomography in assessment of significant coronary artery disease in symptomatic subjects. Am J Cardiol 99: 1656-1661.

16. Einstein, A. J., M. J. Henzlova, and S. Rajagopalan. 2007. Estimating risk of cancer associated with radiation exposure from 64-slice com-puted tomography coronary angiography. JAMA 298: 317-323.

17. Budoff, M. J., S. Achenbach, R. S. Blumenthal, J. J. Carr, J. G. Goldin, P. Greenland, A. D. Guerci, J. A. Lima, D. J. Rader, G. D. Rubin, L. J. Shaw, and S. E. Wiegers. 2006. Assessment of coronary artery disease by car-diac computed tomography: a scientific statement from the American Heart Association Committee on Cardiovascular Imaging and Inter-vention, Council on Cardiovascular Radiology and Intervention, and Committee on Cardiac Imaging, Council on Clinical Cardiology. Cir-culation 114: 1761-1791.

18. Jacobs, J. E., L. M. Boxt, B. Desjardins, E. K. Fishman, P. A. Larson, and J. Schoepf. 2006. ACR practice guideline for the performance and in-terpretation of cardiac computed tomography (CT). J Am Coll Radiol 3: 677-685.

19. Francone, M., A. Napoli, I. Carbone, M. Cavacece, P. G. Nardis, K. Lan-ciotti, S. Visconti, L. Bertoletti, E. Di Castro, C. Catalano, and R. Pas-sariello. 2007. Noninvasive imaging of the coronary arteries using a 64-row multidetector CT scanner: initial clinical experience and radia-tion dose concerns. Radiol Med 112: 31-46.

20. Achenbach, S., D. Ropers, A. Kuettner, T. Flohr, B. Ohnesorge, H. Brud-er, H. Theessen, M. Karakaya, W. G. Daniel, W. Bautz, W. A. Kalender, and K. Anders. 2006. Contrast-enhanced coronary artery visualization by dual-source computed tomography--initial experience. Eur J Ra-diol 57: 331-335.

olution (330 ms per gantry rotation), these systems just cover a small volume (3.2 cm) in a single heart beat.19 Similarly, dual-source systems, with even superior temporal resolution (83 ms), allow limited craniocaudal coverage per rotation.20 In contrast, 256- and 320-slice MDCT systems eliminate stair-step artifacts associated with helical and step-and-shoot scan-ning techniques and provide volumetric data acquisition with full cardiac coverage in a single rotation.

To the best of our knowledge, major advantages for this study could be increased external validity by enrolling a relatively large number of samples. Also, the results of the present study revealed that the reduction of tube rotation time to 330 ms and improving temporal resolution could result in 95% NPV.

However, as major limitations, the present study’s exclusion criteria were relatively limited and only patients were enrolled who had CAD symptoms and signs, and ICA indication. Pa-tients with acute coronary syndrome were excluded from the study.

In conclusion, the coronary angiography with 64-Slice MDCT has high diagnostic performance for evaluation of significant CAD in patients with the suspected coronary artery disease but still cannot replace conventional coronary angiography at the present time.

AcknowledgementWe offer our thanks to Dr. Ghalichi, the chairman of Iran Di-agnostic Imaging Center, and the staff of this center.

References1. Negi, S., and A. Anand. 2010. Atherosclerotic coronary heart disease-

epidemiology, classification and management. Cardiovasc Hematol Disord Drug Targets 10: 257-261.

2. Oppenheimer, G. M. 2006. Profiling risk: the emergence of coronary heart disease epidemiology in the United States (1947-70). Int J Epide-miol 35: 720-730.

3. Mehta, D., J. Curwin, J. A. Gomes, and V. Fuster. 1997. Sudden death in coronary artery disease: acute ischemia versus myocardial substrate. Circulation 96: 3215-3223.

4. Arbab-Zadeh, A., J. Texter, K. M. Ostbye, K. Kitagawa, J. Brinker, R. T. George, J. M. Miller, J. C. Trost, R. A. Lange, J. A. Lima, and A. C. Lardo. 2010. Quantification of lumen stenoses with known dimensions by conventional angiography and computed tomography: implications of using conventional angiography as gold standard. Heart 96: 1358-1363.

5. Arbab-Zadeh, A., and J. Hoe. 2011. Quantification of coronary arte-rial stenoses by multidetector CT angiography in comparison with conventional angiography methods, caveats, and implications. JACC Cardiovasc Imaging 4: 191-202.

6. Sun, Z. 2011. Multislice computed tomography angiography in the diagnosis of cardiovascular disease: 3D visualizations. Front Med 5: 254-270.

7. Pugliese, F., and R. Barbagallo. 2011. Multislice computed tomography in the diagnosis of coronary anomalies with superimposed coronary artery disease. J Cardiovasc Med (Hagerstown) 12: 351-352.

8. Kerl, J. M., U. J. Schoepf, R. W. Bauer, T. Tekin, P. Costello, T. J. Vogl, and C. Herzog. 2010. 64-Slice Multidetector-row Computed Tomography


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Citation Mochizuki et al. Evaluation of Metastatic Cervi-cal Lymph Nodes in Patients with Oral Squamous Cell Carcinoma Using 18F-FDG PET-CT Scans and Histo-pathologic Correlation. J Surg Radiol. 2012 Oct 1;3(4).

CorrespondenCe Yumi Mochizuki, DDS, PhD E-mail [email protected].

reCeived June 6, 2012. aCCepted October 1, 2012. epub October 1, 2012.

Evaluation of Metastatic Cervical Lymph Nodes in Patients with Oral Squamous Cell Carcinoma Using 18F-FDG PET-CT Scans and Histopatho-logic CorrelationYumi Mochizuki1, DDS, PhD, Ken Omura1, DDS, PhD, Shin Nakamura2, DDS, PhD, Kou

Kayamori3, DDS, PhD, Hiroyuki Harada1, DDS, PhD, Hitoshi Shibuya4, MD, PhD

1. Departments of Oral and Maxillofacial Surgery, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.2. Departments of Oral and Maxillofacial Radiology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.3. Departments of Oral Pathology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.4. Departments of Diagnostic Radiology and Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan

AbstractintroduCtion We studied the characteristics of each metastatic cervical lymph node in histological specimens detected on fluorine-18 fluorodeoxyglucose positron-emission tomography/computer-ized tomography (18F-FDG PET/CT) in patients with oral squamous cell carcinoma (OSCC).Methods Thirty-two patients who had undergone preoperative 18F-FDG PET/CT scan and had histopathologically proven cervical lymph nodes metastasis in surgical specimens were enrolled. Retrospectively, we compared spatial correlation between PET/CT and the anatomical sites based on surgical specimens, and threshold standardized uptake value (SUVmax) values were recorded. For metastatic lymph nodes, size of metastatic foci in each lymph node and Yamamoto–Kohama (YK) mode of invasion for primary tumor were recorded.results Larger lymph nodes and intranodal tumor foci increased 18F-FDG uptake in OSCC. The average values of early- and delayed-phase SUVmax and SUV increasing rate of YK-2 cases were 3.2, 3.5, and 0.043, while the corresponding values for YK-4D cases were 5.1, 6.1, and 0.14. The pattern of invasion of the primary tumor became more diffuse as tumor classification progressed from YK-2 to -4D, and SUVmax values were also higher. All the undetected lymph nodes were <6 mm, which contained metastatic foci >2 mm. However, some lymph nodes (<6 mm) or micrometastasis nodes were detected on 18F-FDG PET/CT.ConClusion 18F-FDG uptake in metastatic cervical lymph nodes varies with respect to lymph node size and tumor characteristics. Further study is needed to characterize inflammatory processes in metastatic lymph nodes.

Keywords 18F-FDG PET/CT, Yamamoto–Kohama (YK) mode of invasion, metastatic cervical lymph nodes, oral or oropharyngeal squamous cell carcinoma

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Mochizuki et al. PET/CT and Metastatic Cancer original artiCle

IntroductionFluorine-18 fluorodeoxyglucose positron-emission tomog-raphy/computerized tomography (18F-FDG PET/CT) is an imaging tool that provides biochemical and physiologic information.1The measure of energy metabolism by 18F-FDG accumulation by PET/CT has been recently used for the diag-nosis of metastatic cervical lymph nodes in patients with oral or oropharyngeal squamous cell carcinoma (OSCC).

Few studies have analyzed the size of metastatic lymph nodes and intranodal foci or determined the biological characteris-tics of tumor cells by pathological examination, which would affect the diagnostic utility of 18F-FDG-PET.2-4 Here we stud-ied whether 18F-FDG accumulation in metastatic lymph nodes has different tendencies based on the size of tumor foci in each metastatic lymph node and the pathological characteristics of invasion of the primary site.

Material and Methods SubjectsThe study was conducted with 665 consecutive patients seen at the Department of Oral and Maxillofacial Surgery, Tokyo Medical and Dental University Hospital for squamous cell carcinoma (SCC) of the oral cavity between November 2005 and February 2011. The inclusion criteria were as follows: (i) primary oral SCC, (ii) had undergone 18F-FDG PET/CT scan-ning, (iii) had received no preoperative chemo/radiotherapy, (iv) had undergone neck dissection, and (v) had pathologi-cally diagnosed metastatic cervical lymph nodes in surgical specimens. Of these 663 patients, 634 were excluded for the following reasons: 102 had undergone preoperative chemo-therapy, 40 had received preoperative radiotherapy, 45 had received preoperative chemoradiotherapy after 18F-FDG PET/CT scanning, 1 patient did not undergo surgery because of poor general condition, and 396 underwent only tumor re-section with no scanning or preoperative treatment. Although 47 patients with no other preoperative treatment underwent 18F-FDG PET/CT scanning before neck dissection, they were excluded from our analyses because they were confirmed to have no lymph node metastasis on pathological examination of the surgical specimens. Thus, in total 32 patients (17 men, 15 women; mean age 63.7 years, age range 33–83 years) were enrolled for further analysis. Patient characteristics are shown in Table 1. The disease was controlled in 27 patients, 2 patients had local failure, 2 patients died from uncontrolled disease be-cause of a primary recurrence, and one patient died of another disease, despite locoregional control of the cancer during the follow-up period, which was ranged from 219 to 2000 days after surgery (median:889 days).

The institutional review board of Tokyo Medical and Dental University approved this retrospective study. We obtained in-formed consent from all patients to performing 18F-FDG PET/CT examinations and to use the obtained data for research

purposes.

PET/CT examinationThe protocol for PET/CT examina-tion in our hospital has been described previously.5-8 Pa-tients received an intravenous injec-tion of 3.7 MBq/kg of 18F-FDG after fasting for 4 hours. Images were ob-tained using a PET/CT system (Aqui-duo, Toshiba Medi-cal Systems, Tokyo, Japan), which com-bines a full-ring PET scanner with lutetium oxyortho-silicate crystals and a 16-row helical CT scanner. CT images were acquired from the head to the up-per thigh and then 18F-FDG PET scan-ning of the same region was per-formed.

Attenuation cor-rection of 18F-FDG PET images was performed using CT data. 18F-FDG PET/CT scanning was acquired twice. After intravenous injection of 18F-FDG PET, the early phase was scanned at a mean time of 61.0 min (SEM ± 0.96 min) and the delayed phase at a mean time of 133.7 min (± 1.96 min).

Surgical Treatment and Pathological AssessmentPatients were surgically treated a median of 13 days (range, 1–33 days) after the PET/CT scan. All 32 patients were oper-ated on by two surgeons. We performed 3 suprahyoid neck dissections (SHND, cervical lymph node levels I, II), 9 suprao-mohyoid neck dissections (SOHND, levels I–III), 5 anterolat-eral neck dissections (ALND, levels I– IV), and 15 modified radical neck dissections (mRND, levels I–V). One contralat-eral neck dissection (ipsilateral mRND, contralateral SHND) was performed.

Table 1. Patient characteristics Characteristic Case No.

Localization Tongue 16

Lower gingiva 7

Buccal mucosa 5

Floor of mouth 2

Mandible 1

Upper gingiva 1

T T1 11

T2 14

T3 4

T4 3

N N0 0

N1 21

N2a 0

N2b 7

N2c 4

N3 0

Stage I 0

II 9

III 11

IV 12

YK mode of invasion 1 0

2 3

3 13

4C 13

4D 3


original artiCle Mochizuki et al. PET/CT and Metastatic Cancersurrounding normal tissue in both early- and delayed-phase PET/CT images,2,10 and which were correlated with the ana-tomical locations of lymph nodes in sur-gical specimens and level classification using a widely accepted scheme. 5,7 SUV-

max in each of the identified lymph nodes was evaluated as a spherical volume and recorded.

SUVmax increasing rate (SUV-IR) was generated using the following formula: SUV increasing rate = [delayed phase SUVmax – early phase SUVmax] / [time be-tween early and delayed phases (min)].

Lymph nodes that could not be spatial-ly correlated between PET/CT and the

anatomic location based on histopathological examination of surgical specimens were excluded from further statistical analysis.

Statistical AnalysisDifferences in the average size of nodes between the metastat-ic and non-metastatic node groups were compared using Stu-dent’s t test. Differences in the average size of the metastatic nodes and intranodal tumor foci according to the YK mode of invasion and differences in SUVmax among the different YK modes of invasion, size of the metastatic nodes, and internodal tumor foci were analyzed by Kruskal-Wallis testand post hoc comparisons (Scheffe F test;95% significance) was performed to determineintergroup differences.

Statistical analyses were carried out with statistical PASW Sta-tistics 18 software for Windows (SPSS Japan Inc, Tokyo, Japan). P<0.05 was considered statistically significant.

ResultsSize of Metastatic Lymph NodesThe average size of the metastatic nodes and intranodal tu-mor foci according to the YK mode of invasion are shown in Table 2.

All excised neck specimens were dissected and documented according to size, anatomical location, and level. A total of 1,596 lymph nodes from 32 cases (34 dissected neck-side spec-imens) were reviewed. Sixty-nine nodes were histopathologi-cally diagnosed as metastasis. Of the 69 metastatic nodes, 2 were level IA, 23 were level IB, 26 were level II, 4 were level III, one was level IV. Three were retropharyngeal nodes of the ipsilateral neck. On opposite site, 3 were in level IB, 5 were in level II, and one each was in level III and level IV.

Nodal specimens were totally embedded in paraffin blocks and stained with hematoxylin and eosin according to stan-dard histologic procedures. A pathologist microscopically re-viewed all slides from 2-mm-thick sections taken through the maximum cross-sectional area. Measurements of the patho-logically positive lymph nodes were: (1) lymph node size (long and short axis) and (2) actual size of intranodal tumor foci (maximum diameter of metastatic foci in each lymph node). When a lymph node had the extracapsular spread, the size of intranodal tumor foci was defined as the long axis of the node. Size of the metastatic lymph nodes and of the intranodal tu-mor foci were classified into five groups, ≤5 mm, 5–15 mm, 15–25 mm, 25–35 mm, and ≥35 mm.

For histologic features concerning the invasiveness of primary tumor, we recorded the Yamamoto–Kohama (YK) mode of in-vasion.9 The histological criteria of the YK mode of invasion are defined as follows: grade 1, well defined border; 2, cords, less marked border;3, groups of cells, no distinct border; 4C, cord-like, diffuse invasion type; and 4D, diffuse invasion. 9

Analysis and Comparison of 18F-FDG PET/CT Images with Pathological FindingsA retrospective comparison between the PET/CT imaging and pathological find-ings of excised lymph nodes was per-formed. One experienced radiologist and one oral surgeon visually identified lymph nodes that had a definite, local-ized area with higher uptake than the

Table 2. Average size of nodes with metastasis and intranodal tumor foci accord-ing to the Yamamoto-Kohama (YK) mode of invasion

YK mode of invasion, mean±SEM (range)

P value

2

(n=4)

3

(n=27)

4C

(n=25)

4D

(n=4)

Long axis (mm)15.0±2.3

(10.0-19.0)

12.2±1.3

(3.0-32.0)

18.0±2.1

(5.0-44.0)

13.5±3.2

(8.0-19.0)0.527

Short axis (mm)8.2±2.1

(4.4-8.9)

6.4±1.1

(1.0-10.0)

8.6±3.3

(2.0-15.6)

7.1±2.3

(2.2-14.4)0.558

Intranodal tumor foci (mm)13.0±3.7

(4.0-19.0)

8.7±1.3

(0.26-25.0)

14.2±2.1

(0.5-38.0)

8.1±3.8

(2.0-19.0)0.604

SEM; Standard error of the mean

Table 3. Average size of nodes with metastasis and intranodal tumor foci accord-ing to detected lymph node group and undetected lymph node group

Detection by spatial correlation between PET/CT images and anatomical location [mean±SEM (range)] P value

Undetected(n=9) Detected(n=60)

Large axis (mm) 4.3±0.41 (3.0-6.0) 15.6±1.5 (4.0-44.0) 0.027*

Short axis (mm) 1.4±0.56 (1.0-5.5) 4.6±2.1 (3.3-15.6) 0.061

Size of intranodal tumor foci (mm) 3.5±0.44 (2.0-6.0) 10.2±1.64 (2.6-38.0) 0.004*

SEM: Standard error of the mean, *p<0.05 (Student’s t test)

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the following groups: 5-15mm and 15-25mm (Scheffe F test:p = 0.043); 5-15mm and 25-35mm (Scheffe F test: p = 0.037). In delayed-phase SUVmax, post hoc analysis showed signifi-cant differences between the following groups: 15-25mm and 5-15mm (Scheffe F test:p = 0.033); 15-25mm and 25-35mm (Scheffe F test: p = 0.025).

In intranodal tumor foci, early-phase SUVmax (F=36.03; p<0.001), delayed-phase SUVmax (F=28.26; p<0.001) and SUV-IR (F=2.71; p=0.039) were statistically different. In early-phase SUVmax, post hoc analysis showed significant differences be-tween the following groups: 5-15mm and 15-25mm (Scheffe F test:p = 0.032); 5-15mm and 25-35mm (Scheffe F test: p = 0.025). In delayed-phase SUVmax, post hoc analysis showed significant differences between the following groups: 15-25mm and 5-15mm (Scheffe F test:p = 0.023); 15-25mm and 25-35mm (Scheffe F test: p = 0.035).

In terms of the differences in YK modes of invasion, signifi-cant differences were found in delayed-phase SUVmax (F=3.33; p=0.026) and in SUV-IR (F=3.07; p=0.035). In delayed-phase

Undetected Lymph Node GroupNine metastatic nodes could not be spatially correlated be-tween PET/CT images and the anatomical location based on surgical specimens. The YK modes of invasion of the primary tumor of these were YK3 and YK4C. The average size of the metastatic nodes and intranodal tumor foci in the detected and undetected lymph node groups are shown in Table 3. The intranodal tumor foci of each undetected lymph node were >2 mm. All the undetected lymph nodes were <6 mm.

Detected Lymph Node GroupIn terms of differences in size, the mean and standard devia-tion of SUVmax according to the long axis of metastatic lymph nodes and intranodal tumor foci are shown in Table 4. Sig-nificant differences in the long axis of metastatic lymph nodes were found in early-phase SUVmax (F=21.84; p<0.001) and delayed-phase SUVmax (F=14.99; p<0.001). In early-phase SU-Vmax, post hoc analysis showed significant differences between

Table 4. Threshold standard uptake value (SUVmax) for size of lymph nodes with metastasis , intranodal tumor foci and Yamamoto–Kohama mode of invasion.

SUVmax value [Mean±SEM (Range)]

early phased SUVmax delayed phased SUVmax SUV IR

Classification of the long axis of metastasis lymph nodes Number

<=5mm 3 2.1±0.24 (1.8-2.5) 2.3±0.21 (1.9-2.6) 0.0032±0.0040 (0.0014-0.0066)

5-15mm 28 2.9±0.15 (1.8-4.9) 3.3±0.18 (2.1-5.8) 0.0048±0.0034 (-0.00029-0.013)

15-25mm 21 4.5±0.36 (1.8-8.2) 5.6±0.48 (2.2-9.6) 0.0093±0.0042 (-0.024-0.030)

25-35mm 7 6.9±0.32 (5.5-7.9) 7.4±0.42 (5.1-8.2) 0.0056±0.0012 (-0.0039-0.011)

<=35mm 1 7.9 (7.9-7.9) 8.5 (8.5-8.5) 0.0075 (0.0075-0.0075)

21.84 <0.001* 14.99 <0.001* 1.32 0.274

Classification of intranodal tumor foci Number

<=5mm 22 2.4±0.12 (1.8-4.1) 2.8±0.16 (1.9-5.1) 0.0049±0.00070 (0.00047-0.014)

5-15mm 16 3.5±0.19 (2.6-4.9) 3.8±0.25 (2.7-5.8) 0.0034±0.0022 (-0.024-0.013)

15-25mm 18 5.6±0.36 (3.2-8.2) 6.3±0.44 (3.4-9.6) 0.011±0.0021 (-0.0039-0.030)

25-35mm 3 7.0±0.29 (6.5-7.5) 7.6±0.37 (6.9-8.1) 0.0075±0.0020 (0.044-0.011)

<=35mm 1 7.9 (7.9-7.9) 8.5 (8.5-8.5) 0.0075 (0.0075-0.0075)

36.03 <0.001* 28.26 <0.001* 2.71 0.102

Yamamoto–Kohama mode of invasion Number

2 4 3.2±0.51 (1.8-4.0) 3.5±0.97 (2.3-4.3) 0.043±0.012 (0.013-0.067)

3 27 3.4±0.30 (1.8-7.9) 3.7±0.35 (1.9-8.2) 0.041±0.017 (-0.024-0.030)

4C 25 4.5±0.4 (1.9-7.9) 5.1±0.4 (2.5-8.5) 0.081±0.011 (0.00029-0.025)

4D 4 5.1±1.1 (1.8-7.9) 6.1±1.2 (3.9-9.6) 0.14±0.0010 (0.0094-0.020)

2.33 0.085 3.33 0.026* 3.07 0.035*EM: Standard error of the mean, *p<0.05 (Kruskal-Wallis test)

SUV-IR: SUVmax increasing rate

F: F values corresponding to F statistics are reported for between-sample variation.

p values: corresponding to between-sample F statistics.


original artiCle Mochizuki et al. PET/CT and Metastatic CancerWe also considered the effects of inflammatory processes on 18F-FDG accumulation in micrometastasic lymph nodes, which would have been stimulated by cancer antigens. It is considered that follicular dendritic cells (FDCs) play an im-portant role when organs react to local antigenic stimuli in concert with the lymphoid cells.11 Nakagawa et al.11 reported that FDCs expressed GLUT1 in reactive lymphadenopathy and they might be avid for 18F-FDG..

In our study, no statistically significant differences were found between size of the metastatic lymph nodes and SUV IR and between YK mode of invasion and early-phase SUVmax were found. Although it is still unclear why inflammatory and ma-lignant lesions exhibit a different 18F-FDG uptake pattern over time, cellular factors such as hexokinase and glucose-6-phos-phatase have been suggested to contribute to this phenom-enon.17 We considered 18F-FDG uptake pattern over time of metastatic lymph nodes was affected by both inflammatory process and tumor proliferation. As far as we know, there are few reports of molecular and cellular biological mechanisms in metastatic lymph nodes stimulated by a carcinogenic anti-gen.18,19 Further research of molecular and cellular biological mechanisms in metastatic lymph nodes and consideration of relation between 18F-FDG PET/CT findings and those mecha-nisms are needed.

Conclusion 18F-FDG uptake in metastatic cervical lymph nodes has differ-ent characteristics with respect to size of the lymph nodes, size of the intranodal tumor foci, and the YK mode of invasion of the primary tumor. Our study provides some information on 18F-FDG PET/CT findings that are important in clarifying the biological tumor characteristics and inflammatory processes in metastatic lymph nodes.

Disclosures This study was provided no funding.

References1. Rohren EM, Turkington TG, and Coleman R. Clinical applications of

PET in oncology. Radiology 2004; 231 : 305–32.

2. Ng SH, Yen TC, Liao CT, Chang JTC, Chan SC, Ko SF,et al. F-18-FDG PET and CT/MRI in oral cavity squamous cell carcinoma: A prospec-tive study of 124 patients with histologic correlation. J Nucl Med 2005; 46 : 1136–43.

3. Yamazaki Y, Saitoh M, Notani K, Tei K, Totsuka Y, Takinami S,et al. Assessment of cervical lymph node metastases using FDG-PET in pa-tients with head and neck cancer. Ann Nucl Med 2008; 22 : 177–84.

4. Stuckensen T, Kovács AF, Adams S, and Baum RP. Staging of the neck in patients with oral cavity squamous cell carcinomas; a prospective comparison of PET, ultrasound, CT and MRI. J Craniomaxillofac Surg 2000; 28 : 319–24.

5. Nakamura S, Okochi K, and Kurabayashi T. Dual-time-point fluoro-deoxyglucose positron emission tomography for diagnosis of cervical lymph node metastases in patients with head and neck squamous cell

SUVmax, post hoc analysis showed significant differences be-tween the following groups: YK 4D and YK 2 (Scheffe F test:p = 0.012); YK 4D and YK 3 (Scheffe F test: p = 0.022); YK 4C and YK 2 (Scheffe F test:p = 0.025); YK 4C and YK 3 (Scheffe F test: p = 0.032). In SUV IR, post hoc analysis showed signifi-cant differences between the following groups: YK 4D and YK 2 (Scheffe F test:p = 0.012); YK 4D and YK 3 (Scheffe F test: p = 0.022).The summary of SUVmax values according to YK mode of invasion are shown in Table 4.

DiscussionIn this study we found that larger lymph nodes and intranodal tumor foci had higher SUVmax. Our results showed that more diffuse invasiveness of the primary tumor from YK-2 towards -4D contributed to higher SUVmax values.

We considered several factors including high proliferative ac-tivity and high tumor cellularity together have some relation-ships to FDG uptake.3 Compared with whole-body imaging, dedicated head and neck scanning showed an increase in SU-Vmax for most lymph nodes, due to constant stimuli by car-cinogenic and extrinsic antigens.11 We considered two factors related to FDG uptake in metastatic lymph nodes. One fac-tor was biological tumor characteristics such as proliferative activity and aggressiveness of tumor cells, and the other was inflammatory processes in the lymph node.

Biologically, increases in glucose consumption help supply the energy that is necessary for tumor cell proliferation and adap-tation of the normal tissues to the tumoral environment.10,12 Although the metabolic consequences of increased glucose transport are not understood, the ubiquitous type 1 glucose transporter (GULT-1) is highly expressed in head and neck squamous cell carcinomas (HNSCCs) [12], and 18F-FDG is transported into cells by GLUT-1 in HNSCCs.13,14 GLUT-1 ex-pression in all OSCC patients was found to be correlated with tumor invasiveness. 7,8

The YK mode of invasion criteria is correlated with progno-sis, particularly with lymph node metastasis 9,15,16 in OSCC patients. It has been reported that sprouting of the cancer cells and the subsequent desmoplastic reaction at the invasive front in YK-4C and -4D contribute to more frequent lymph node metastasis.15 It may be that tumor cells in the metastatic lymph nodes which originate from more diffusely invasive primary tumors could be more aggressive. However, we could not find any previous reports on differences in the GLUT-1 expression of tumor cells among the different YK modes of invasion. Further study is therefore needed.

Stuckensen et al. 4 reported that nodal metastases <6 mm were not detected by PET/CT scan in half of patients with head and neck cancer. Kitagawa et al.3 indicated that nodes or intrano-dal tumor foci <5 mm were not detected.

In the present study, all the undetected lymph nodes were <6 mm, but contained metastatic foci of >2 mm. On the other hand, some micrometastatic lymph nodes <6 mm were de-tected on PET/CT.

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carcinoma. J Comput Assist Tomogr 2011; 35 : 303–7.

6. Murata Y, Watanabe H, Kubota K, Toda K, Nakamura S, Okouchib K,et al. PET/CT evaluation of the physiologic accumulation of F-18-FDG within the gallbladder vesicle. Nuclear Medicine and Biology 2004; 34 : 961–6.

7. Ohba S, Fujii H, Ito S, Fujimaki M, Matsumoto F, Furukawa M,et al. Overexpression of GLUT-1 in the invasion front is associated with depth of oral squamous cell carcinoma and prognosis. J Oral Pathol Med 2010; 39 : 74–8.

8. Suzuki H, Fukuyama R, Hasegawa Y, Tamaki T, Nishio M, Nakashima T,et al. Tumor thickness, depth of invasion, and Bcl-2 expression are correlated with FDG-uptake in oral squamous cell carcinomas. Oral Oncol 2009; 45 : 891–7.

9. Yamamoto E, Kohama G, Sunakawa H, Iwai M, and Hiratsuka H. Mode of invasion, bleomycin sensitivity, and clinical course in squa-mous cell carcinoma of the oral cavity. Cancer 1983; 51 : 2175–80.

10. Oliver RJ, Woodwards RT, Sloan P, Thakker NS, Stratford IJ, and Air-ley RE. Prognostic value of facilitative glucose transporter Glut-1 in oral squamous cell carcinomas treated by surgical resection; results of EORTC Translational Research Fund studies. Eur J Cancer 2004; 40 : 503–7.

11. Nakagawa T, Yamada M, and Suzuki Y. 18F-FDG uptake in reactive neck lymph nodes of oral cancer: relationship to lymphoid follicles. J Nucl Med 2008; 49 : 1053–9.

12. Carvalho KC, Cunha IW, Rocha RM, Ayala FR, Cajaíba MM, Begnami MD,et al. GLUT1 expression in malignant tumors and its use as an im-munodiagnostic marker. Clinics (Sao Paulo) 2011; 66 : 965–72.

13. Mueckler M. Facilitative glucose transporters. Eur J Biochem 1994; 219:713-25.

14. Smith TA. Facilitative glucose transporter expression in human cancer tissue. Br J Biomed Sci 1999; 56 : 285–92.

15. Kaihara T, Kusaka T, Kawamata H, Oda Y, Fujii S, Morita K,et al. De-creased expression of E-cadherin and Yamamoto-Kohama’s mode of invasion highly correlates with lymph node metastasis in esophageal squamous cell carcinoma. Pathobiology 2001; 69 : 172-8.

16. Nakayama A, Ogawa A, Fukuta Y, and Kudo K. Relation between lym-phatic vessel diameter and clinicopathologic parameters in squamous cell carcinomas of the oral region. Cancer 1999; 86 : 200–6.

17. Zhuang H, Pourdehnad M, Lambright ES, Yamamoto AJ, Lanuti M, Li P, et al. Dual time point 18F-FDG PET imaging for differentiating malignant from inflammatory processes. J Nucl Med 2001; 42 :1412-17.

18. Sakakura K, Chikamatsu K, Sakurai T, Takahashi K, Murata T, Oriuchi N,et al. Infiltration of dendritic cells and NK cells into the sentinel lymph node in oral cavity cancer. Oral Oncol 2005; 41: 89-96.

19. Li X, Takahashi Y, Sakamoto K, and Nakashima T. Expression of den-dritic cell phenotypic antigens in cervical lymph nodes of patients with hypopharyngeal and laryngeal carcinoma. J Laryngol Otol 2009; 123 Suppl 31: 5-10.


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IntroductionIn addition to cross sectional imaging, selective mesen-teric arterial catheterization, and calcium stimulation is a standard method of localization tumors and plotting op-erative strategy. As this case illustrates, considerable vari-ability in the gastrointestinal blood supply might present challenges to accurate tumor localization. Defining the arterial anatomy is critical to successful arterial calcium stimulation and venous sampling.

Materials and MethodA 52 year old patient presented to the oncology service with a history of abdominal pain, nausea, vomiting and dyspepsia. Her gastrin level was 9020 units. Medical his-tory was significant for hemodialysis, hypertension, par-tial nephrectomy, parathyroidectomy, and appendectomy. Computed tomography of the abdomen showed a three centimeter mass at the head of the pancreas. Octreotide scan localized uptake at the pancreatic head. Serum calci-um levels were normal but PTH level was elevated at 384 units. Endoscopy with duodenal biopsy revealed chronic duodenitis. Patient was sent for surgical evaluation. Cal-cium stimulation testing with hepatic venous sampling was requested.

ResultsSelective visceral angiography and calcium infusion into the superior mesenteric, right hepatic, pancreatic, left gas-tric and splenic arteries were performed. Venous blood samples were obtained from the hepatic vein at intervals 0, 30, 60, 90, and 120 seconds. Hepatic venogram in fig. 1, demonstrated the hepatic location of the sampling cath-eter and the arterial catheter. Early phase of celiac angio-gram in fig. 2 shows an absent GDA. The left gastric and left hepatic arise as a common trunk off the celiac artery. A large dorsal pancreatic branch arose from the celiac trunk. Delayed venous imaging in fig. 3, showed a tumor blush at head of pancreas. The splenic and portal veins are clearly visualized. In figure 4, SMA angiogram, the superior and inferior pancreatico-duodenal arcades are noted as well as a large mid colic branch that ran well beyond the mid transverse colon to reach below the left splenic flexure of the colon. The summary image, fig. 5, displayed the various gastrin levels from 0, 30, 60, 90, and 120 sec. after calcium injection into the various arteries with sampling from the left hepatic vein. Note that when calcium gluconate was injected into the large dorsal pan-creatic artery branch, gastrin levels rose from 23800 to 44000 units. This confirmed location to head of pancreas as illustrated in fig. 5.

DiscussionPatients with renal failure develop elevated gastrin lev-els. Westdrop et al noted high levels of both gastrin and gastric acid secretions in patients without kidneys and in more than 50% of those with chronic or acute renal failure. They also noted that when the renal function re-turned to normal the gastrin levels also declined. It was

Citation Best IM. Gastrinoma Localization in a Patient with Variations in the Celiomesenteric Axis. J Surg Ra-diol. 2012 Oct 1;3(4).

CorrespondenCe Irwin M Best, M.D., MBA E-mail [email protected].

reCeived January 30, 2012. aCCepted October 1, 2012. epub October 1, 2012.

Gastrinoma Localization in a Patient with Variations in the Celiomesenteric AxisIrwin M Best, M.D., MBA

Department of Radiology, Emory University School of Medicine, Atlanta, GA.

Abstractoverview Patients with endocrine tumors can pose diagnostic and clinical challenges. In pa-tients with suspected multiple endocrine neoplasms, tumor localization can help to guide the surgi-cal therapy and limit the extent of resection particularly in medically complex patients. As this case illustrates, the clinician should be aware of the often varied anatomy of the celiomesenteric axis and consider this information when considering the sampling data for surgical planning.

Keywords Anatomical variations; tumor localization and arterial variations

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Best. Gastrinoma Localization original artiCle

believed that poor renal inactivation of gastrin led to these in-creased levels and clinical symptoms of increased acid secre-tion1.

However, when PTH levels are also elevated the MEN-1 must be considered in the differential diagnosis. Marx et al noted that in both the familial as well as the sporadic form the tu-

mor suppressor gene is implicated2. Some of these tumors might produce hormones of which gastrin is the most com-mon and is produced in greater than 50 % of patients with islet cell tumors of the pancreas. In this patient with a prior history of parathyroid surgery and elevated serum gastrin levels, a strong case can be made for considering MEN-1 in the differential diagnosis since parathyroid tumors usually precede pancreatic tumors by several years3, 4. Therefore, lo-calization of the secreting G-cell mass to the pancreatic head was a useful preoperative strategy.

Wada et al have demonstrated the efficacy of Calcium stimulation studies in the preoperative localization of gas-trinomas5. In this case surgical resection was limited to a duodeneotomy and the retroperitoneal mass at the head of pancreas. Even with Octreotide scanning, calcium stimula-tion still plays an important role in the preoperative local-ization of these lesions which are often less than 2 cm and multicentric6.

Norton noted that all tumors greater than 2 cm should be excised. Although Whipple procedure offers the best chanc-es for cure the operative mortality is higher and patient with localized tumors have had good results without the morbid-ity of the Whipple procedure7. Marx et al noted that a fun-damental problem in MEN-1 syndrome is that these patients develop tumors two decades earlier than patients the spo-radic variety of tumors because of the inherited autosomal dominant disease with a high degree of pentetrance. All cell lines have the genetic defect multiple lesions and recurrences is the rule8.

Therefore, it is important to localize the tumors preopera-tively as wells as intraoperativey to better match the patient’s disease with the extent of operation thereby ameliorating symptoms and limiting morbidity of an extensive operation.

Variations in the celiomesenteric arterial supply pose further challenges to accurate tumor localization since many patients do not have “Normal” mesenteric circulation as described by Gray and others9. Bergman et al noted in their atlas of hu-man anatomical variation that this three vessel celiac axis was present in 86% of the 756 cadavers studied. They also noted


original artiCle Best. Gastrinoma Localization4. Brandi ML, Gagel RF, Angeli A, et al. Guide-lines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001Dec;86(12):5658-71.

5. Wada M, Komoto I, Doi R, et al. Intravenous calcium injection test is a novel complementary proce-dure in differential diagnosis for gastrinoma. World J Surg. 2002 Oct;26(10):1291-6.

6. Honda M, Ishibashi M. [The diagnosis and treatment of insulinoma and gastrinoma]. Gan To Kagaku Ryoho. 2004 Mar;31(3):337-41.

7. Norton JA. Surgical treatment and progno-sis of gastrinoma. Best Pract Res Clin Gastroenterol. 2005 Oct;19(5):799-805.

8. Marx S, Spiegel AM, Skarulis MC, et sl. Mul-tiple endocrine neoplasia type 1: clinical and genetic topics. Ann Intern Med. 1998 Sep 15;129(6):484-94.

9. Gray, Henry. Anatomy of the Human Body. Philadelphia: Lea & Febiger, 1918; Bartleby.com, 2000. www.bartleby.com/107/. [Date of Printout].

10. Bergman, RA., Thompson, SA, Afifi, AK et al. (1988) Compendium of Human Anatomic Varia-tion: Catalog, Atlas and World Literature. Urban & Schwarzenberg, Baltimore and Munich.

11. Kitamura S, Nishiguchi T, Sakai A, Kuma-moto K. Rare case of the inferior mesenteric artery arising from the superior mesenteric artery. Anat Rec.

1987 Jan;217(1):99-102.that the celiac trunk is incomplete in 11.8%; joined to the SMA trunk in 1.4% and absent in 0.4% of cases. They also noted that the celiac trunk might have more than 3 branches.

The additional branch might be an inferior phrenic, a dor-sal pancreatic branch - as in this case, a supreme pancreatic branch or even a middle colic branch10. Kitamura et al. noted that there are considerable variations in the SMA trunk in-cluding fusion with the celiac trunk as previously mentioned and a fusion of the SMA and IMA trunks as well. They ex-plained this variation on the basis of a primitive dorsal aorta with many ventral splanchnic arteries interconnected by lon-gitudinal arteries. The regression or persistence of various connections determines the final pattern of the arterial distri-bution from the aorta11.

ConclusionConsiderable variation exists in the celiomesenteric vascula-ture. Therefore, the clinician must have a considerable appre-ciation for these anatomical variants not only during surgery but also during the calcium stimulation studies so that the data can be presented in a format that accurately reflects the vascular distribution and positively influences surgical resec-tion and operative outcomes.

References1. Wesdorp RI, Falcao HA, Banks PB, Martino J, Fischer JE. Gastrin and

gastric acid secretion in renal failure. Am J Surg. 1981 Mar;141(3):334-8.

2. Marx SJ, Agarwal SK, Kester MB, et al. Multiple endocrine neoplasia type 1: clinical and genetic features of the hereditary endocrine neo-plasias. Recent Prog Horm Res. 1999;54:397-438.

3. Piecha G, Chudek J, Więcek A. Primary hyperparathyroidism in pa-tients with multiple endocrine neoplasia type 1. Int J Endocrinol. 2010;2010:928383.

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IntroductionShort aortic trunks and endografts complicate contralat-eral lower extremity access for both diagnostic and thera-peutic interventions. We demonstrate a useful technique for both contralateral access as well as thrombolytic infu-sion. This is particularly useful when axillary and bra-chial approaches are too distant or unsuitable for upper extremity access.

Materials and MethodsA 60 year old man presented with an ischemic left leg and multiple healed abdominal, femoral and distal scars from prior operations which included an aorto-bifemoral by-pass grafts as well as a left femoral-popliteal bypass graft with saphenous vein. The right femoral pulse was normal but the left femoral was decreased and distal pulses were absent. Sensation and motor function were present. Af-ter informed consent, the right common femoral artery was accessed with ultrasound and fluoroscopic guidance. A 5French introducer sheath was placed and a reversed curve aortic flush catheter was placed at T-12 for aotogra-

phy, fig. 1. The left graft limb was patent but the femoral-popliteal vein graft was occluded. The profunda femoris artery was patent.

The left limb of the aorto-bifemoral graft was engaged and a 0.035 inch hydrophilic wire was passed to the left profunda femoris artery and anchored in the femoral circumflex vessel for stability, Fig. 2. The reversed curve catheter was exchanged for a 5F hydrophilic catheter.

Citation Best IM. Crossing the High Aortic Graft Bifur-cation for Contralateral Lower Extremity Lysis. J Surg Radiol. 2012 Oct 1;3(4).

CorrespondenCe Irwin M Best, M.D., MBA E-mail [email protected].

reCeived October 25, 2011. aCCepted October 1, 2012. epub October 1, 2012.

Crossing the High Aortic Graft Bifurcation for Contralateral Lower Extremity LysisIrwin M Best, M.D., MBA

Department of Radiology, Emory University School of Medicine, Atlanta, GA.

Abstractoverview Aortic grafts and short infrarenal aortic trunks push the aortic bifurcation cephelad thus narrowing the angle between the graft limbs. This acute angulation makes contralateral access quite challenging. However, as this case illustrated, the use of highly flexible hydrophilic wires and catheters can allow one to gain access to the contralateral limb not only for diagnostic interventions but also for therapeutic interventions. Advantages of this approach are discussed.

Keywords Contralateral graft limb access, retrograde graft limb access

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Best. Crossing High Aortic Graft Bifurcations original artiCle

This new catheter was passed over the hydrophilic guide wire and placed in the profunda femoral artery, fig. 3. The catheter was negotiated into the proximal vein graft and position was verified with a puff of contrast, fig. 4. This showed throm-bus within the vein graft. A Y-adapter was placed at the hub of the 5French hydrophilic catheter and A 2.8 French 120 cm catheter and 018 in. wire were passed through the hydrophilic catheter and advanced into the thrombus, Fig 5.


original artiCle Best. Crossing High Aortic Graft Bifurcations99.6% of cases. However, 21 patients (6.5%) had complication at access site and 65% of these required an operation to fix the complication of brachial thrombosis or pseudoaneurysm4. Such an occurrence would complicate care in an already sur-gically complex patient and possibly limit the use of needed anticoagulation after lytic therapy.

As illustrated, good results might be achieved by using wires and catheters that conform to the patient’s geometry.

References1. Shah PM, Scarton HA and Tsapogas MJ. Geometric anatomy of the

aortic-common iliac bifurcation. J. Anat. (1978), 126, 3, pp. 451-458.

2. Best IM, Butler KL, Bumpers HL. Considerations in catheter retrieval from the arterial system. Cardiovasc Intervent Radiol. 2005 Jan-Feb;28(1):80-2.

3. Cowling MG, Belli A, Buckenham TM. Evaluation and Complications of Direct Graft Punctures in Thrombolysis and other Interventional Techniques. Cardiovascular and Interventional Radiology (1996) 1982-84.

4. Alvarez-Tostado JA, Moise MA, Bena JF, et al. The Brachial artery: a critical access for endovascular procedures. J. Vasc Surg. 2009 Feb;49(2)378-85.

ResultsCoaxial infusion of tissue plasminogen activator (TPA) was started with the 5F catheter proximally, and into the mid por-tion of the thrombosed fem-pop graft via the 2.8 F micro cath-eter. The infusion rate for each catheter was 0.5mg TPA/ hour. Low dose heparin solution was infused via the right femo-ral sheath at 500 units per hour. Figure 6 showed satisfactory graft lysis after 24 hours. Small filling defect below the knee did not inhibit flow and patient had a warm foot with pal-pable pedal pulses.

DiscussionBifurcated aortic grafts placed by both open and endovascu-lar techniques shortened the infrarenal aortic trunk. As this case demonstrated, this shortened trunk converts this angle from the average 43 degrees in a male1 as calculated by Shah et al., to a much steeper hair pin turn. This acute angulation of the aorto-iliac bifurcation made contralateral access quite challenging. Brachial or axillary artery access was not suit-able since the working lengths of available catheters could not provide access to femoral popliteal graft. In special situations where dialysis access grafts are present in the left upper ex-tremity, that site is avoided for fear of complicating the dialysis access and the increased risk of hematomas particularly when thrombolytic infusions are being considered.

The contralateral approach has several advantages in that there is a shorter distance to the target lesion and this distance is within the working range of most diagnostic and therapeu-tic devices. Furthermore, it provides a means of treating any proximal contralateral lesions so that a second ante grade ac-cess to the ipsilateral femoral artery can be obtained if more distal intervention is needed. In patients with high body mass index, this ante grade approach can be particularly difficult in that the access point has to be started high over the abdomi-nal wall or groin pannus to provide a smooth course to the femoral artery.

Moreover, since most grafts are placed anterially onto the ar-tery, gaining access to the hood of the graft can be particularly difficult if the access point is close to the graft. Special tech-niques might have to be employed to maintain access while attempting to direct a guide wire anterially into the graft. Modification of the introducer sheath as noted previously can lead to device to device failure and intravascular retention of a foreign body presenting a new set of challenges2.

The contralateral approach is most advantageous when acute graft thrombosis is the mechanism of graft failure. Should lysis uncover a treatable lesion, a focused intervention can be employed and the point of access can be readily imaged angio-graphically for placement of accurate placement of an addi-tional access site in an area free of thrombus or stenosis. Cowl-ing et al have found direct graft puncture to be beneficial in 31of 41 patients having thombolysis3. In one series by Alvarez-Tostado et al successful brachial artery access was achieved in

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Case Report43-year-old female with no significant past medical his-tory presented to Duke University Medical Center for a second opinion after being seen at an outside institution for initial chief complaint of periumbilical abdominal pain. Contrast-enhanced abdominal CT at the outside institution demonstrated multiple hyperenhancing liver lesions (Figure 1). The liver was also noted to be nodular in appearance with multiple low attenuation septa cours-ing through the hepatic parenchyma. The hepatic veins were unable to be evaluated on the outside institution CT secondary to suboptimal timing of the contrast bolus.

At the outside institution, the patient was found to be clinically asymptomatic from a liver standpoint, specifi-cally without signs of jaundice, weight loss, abnormal bruising, bleeding or tremor. A representative lesion

within the liver was biopsied under ultrasound guidance at the outside institution and pathology was sent to our institution for consultation.

On presentation to our institution, patient underwent a liver MR using gadoxetate disodium (Gd-EOB-DTPA, Eovist/Primovist, Bayer Pharmaceuticals, Wayne, NJ) as the contrast agent. The liver was again noted to be nodu-lar in contour with an overall “nutmeg” appearance from multiple fibrotic bands coursing through the hepatic pa-renchyma. There was hypertrophy of the caudate and left lobes of the liver with associated atrophy of the right he-patic lobe. Multiple focal hyperenhancing lesions were identified on the arterial phase imaging. These lesions were isointense to liver parenchyma on pre-gadolinium T1-weighted images and iso-to hypointense to liver pa-renchyma on T2-weighted images. The lesions were also noted to be hyperintense to the liver parenchyma on 20 minute delayed hepatobiliary phase images (Figure 2). The hepatic veins were able to be evaluated and seen to be occluded; additionally, there was the presence of multi-ple intrahepatic collateral veins draining into the inferior vena cava. The combination of these morphologic find-ings was most consistent with nodular regenerative hy-perplasia (NRH) in the setting of Budd-Chiari syndrome (Figure 3).

The patient underwent extensive testing without clearly

Citation Davis et al. Nodular Regenerative Hyperplasia in the Setting of Budd-Chiari Syndrome: Application of MR with Hepatobiliary Contrast Agents and His-tologic Confirmation. J Surg Radiol. 2012 Oct 1;3(4).

CorrespondenCe Rajan T. Gupta, M.D. E-mail [email protected].

reCeived September 18, 2012. aCCepted October 1, 2012. epub October 1, 2012.

Nodular Regenerative Hyperplasia in the Setting of Budd-Chiari Syndrome: Application of MR with Hepatobiliary Contrast Agents and Histologic ConfirmationDrew E. Davis, M.D.1, Anand S. Lagoo, M.D.2, and Rajan T. Gupta, M.D.1

1. Duke University Medical Center, Department of Radiology, Durham, North Carolina.2. Duke University Medical Center, Department of Pathology, Durham, North Carolina.

Abstractoverview Nodular regenerative hyperplasia in the setting of Budd-Chiari syndrome is an un-common benign finding but critical to diagnose accurately. Its imaging appearance of hyperenhanc-ing lesions on arterial phase imaging on a background of chronic liver disease can raise concern for neoplastic etiologies such as hepatocellular carcinoma. However, the imaging appearance of these lesions on delayed hepatobiliary phase imaging with hepatobiliary MR contrast agents can be ex-tremely useful in excluding hepatocellular carcinoma from the differential diagnosis and confirming nodular regenerative hyperplasia. The findings on histologic examination can also be helpful in understanding the reason for the hyperintensity of these lesions on delayed phase imaging with these hepatobiliary MR contrast agents.

Keywords Contrast MR, MRI, liver disease

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Figure 1 (Above). A. Single axial contrast-enhanced CT im-age through the liver in the arterial phase, approximately 25 seconds after administration of iopamidol (Isovue-300, Bracco Diagnostics, Princeton, NJ) demonstrates a hyper-enhancing lesion in the right hepatic lobe (arrow). B. Axial CT image in the portal venous phase, approximately 70 seconds after administration of iopamidol, demonstrates the right hepatic lobe lesion to be isodense to the liver pa-renchyma (arrow). Also, note the overall lobular contour to the liver (arrowheads).Figure 2 (Right). A. Axial T2-weighted (T2W) 3D gradi-ent echo (GRE) with fat saturation (FS) image prior to the administration of Gd-EOB-DTPA demonstrates a lesion within the right hepatic lobe (arrow) which is isointense to hypointense to surrounding liver parenchyma. B. Axial T1-weighted (T1W) 3D volumetric interpolated breath-hold sequence (VIBE) with FS acquired in the arterial phase (ap-proximately 25 seconds after administration of Gd-EOB-DTPA) shows hyperenhancing lesion (arrow) relative to liver parenchyma in the right hepatic lobe, corresponding to findings seen on outside CT. C. Axial T1W 3D VIBE with FS acquired in the portal venous phase (approximately 70 seconds after administration of Gd-EOB-DTPA) shows the lesion to be isointense (arrow) in the right hepatic lobe. D. Axial T1W 3D VIBE with FS acquired in the delayed phase (approximately 15 minutes after administration of Gd-EOB-DTPA) demonstrates the lesion in the right hepatic lobe (arrow) to be hyperintense to the surrounding liver parenchyma.

Davis et al. MR with Contrast Agents in Budd-Chiari Syndrome original artiCle


original artiCle Davis et al. MR with Contrast Agents in Budd-Chiari Syndrome

Imaging findings at CT, MRI, ultrasound and angiography have been described with this disease entity and are often necessary in diagnosis as a negative biopsy does not exclude this process.2 MR is particularly effective for the diagnosis of Budd-Chiari syndrome as well as defining the associated vascular and parenchymal abnormalities. Evaluation for the occlusion of the hepatic veins, caudate lobe enlargement, in-homogeneous liver enhancement as well as establishing the presence of intrahepatic collateral vessels and hypervascular nodules are the most important roles of imaging in patients with Budd-Chiari syndrome.2

Budd-Chiari syndrome is classified into primary and second-ary types based on etiology. The primary type is caused by hepatic venous outflow obstruction originating from an en-

definable etiology for her Budd-Chiari syndrome. She has been followed by the Hepatology service and currently does not display any overt clinical or laboratory findings to suggest liver failure.

DiscussionThe term, Budd-Chiari syndrome (BCS), is used to describe a rare and potentially fatal disease related to the obstruction of hepatic venous outflow at any level from the small he-patic veins to the junction of the inferior vena cava and right atrium. While sinusoidal obstruction and heart failure share many similarities with Budd-Chiari syndrome and can affect hepatic venous outflow, they are considered separate entities.1

Figure 3. A. Low magnification image (upper left) of the liver biopsy shows wide area of scar like fibrous tissue to the right and nodules of hepatocytes to the left. B. At higher magnification, the fibrous area shows concentric fibrous thickening of vessels (short arrow), to the point of complete obliteration (long arrow). A small artery is seen close to the obliterated vessel (arrowhead). Thin walled, dilated vascular channels (C) are also present, but ducts or ductules are not seen. These features suggest possible central location of this fibrous scar. (Trichrome, 4x and 10x). C. At the interface between the scar like fibrosis (upper right corner) and hepatic parenchyma, areas of ductular proliferation (arrows) are noted. (H&E, 40x). D. Areas of dilated and congested sinusoids (long arrow) are present close to a central area of fibrosis in upper left corner (short arrows) consistent with outflow obstruction. (H&E, 40x).

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Chiari Syndrome so that the most correct diagnosis can be made.

ConclusionUtilization of newer hepatobiliary MR contrast agents can help to detect and characterize lesions in the setting of Budd-Chiari syndrome. Specifically, the retention of contrast ma-terial on delayed HB phase imaging can help to differentiate benign conditions such as nodular regenerative hyperplasia from neoplastic entities such as hepatocellular carcinoma.

DisclosuresThis project was performed at Duke University Medical Cen-ter, Departments of Radiology and Pathology, Durham, NC. There is no external or internal funding for this project. Dis-closures: DED, ASL: None; RTG: Consultant and Speakers Bureau, Bayer Pharma AG

References1. Valla DC. The diagnosis and management of the Budd-Chiari syn-

drome: consensus and controversies. HEPATOLOGY 2003; 38: 793–803.

2. Brancatelli G, Vilgrain V, Federle MP, et al. Budd-Chiari syndrome: spectrum of imaging findings. AJR Am J Roentgenol 2007;188:W168–W176.

3. Janssen HL, Garcia-Pagan JC, Elias E, Mentha G, Hadengue A, Valla DC. European Group for the Study of Vascular Disorders of the Liv-er. Budd-Chiari syndrome: A review by an expert panel. J Hepatol. 2003;38:364–71.

4. Noone TC, Semelka RC, Siegelman ES, Balci NC, Hussain SM, Kim PN, Mitchell DG. Budd-Chiari syndrome: spectrum of appearances of acute, subacute, and chronic disease with magnetic resonance imag-ing. J Magn Reson Imaging. 2000;11:44–50

5. Erden A. Budd-Chiari syndrome: a review of imaging findings. Eur J Radiol 2007;61:44–56.

6. Brancatelli G, Federle MP, Grazioli L, Golfieri R, Lencioni R. Benign regenerative nodules in Budd-Chiari syndrome and other vascular disorders of the liver: radiologic-pathologic and clinical correlation. RadioGraphics 2002;22:847–862.

7. Brancatelli G, Federle MP, Grazioli L, Golfieri R, Lencioni R. Large regenerative nodules in Budd-Chiari syndrome and other vascular disorders of the liver: CT and MR imaging findings with clinicopatho-logic correlation. AJR Am J Roentgenol 2002; 178:877–883.

8. Reimer P, Schneider G, Schima W. Hepatobiliary contrast agents for contrast-enhanced MRI of the liver: properties, clinical development and applications. Eur Radiol 2004; 14:559-578

9. Ba-Ssalamah A, Uffmann M, Saini S, Bastati N, Herold C, Schima W. Clinical value of MRI liver-specific contrast agents: a tailored exami-nation for a confident non-invasive diagnosis of focal liver lesions. Eur Radiol 2009; 19:342-357

10. Ringe KI, Husarik DB, Sirlin CB, Merkle EM. Gadoxetate Disodium–Enhanced MRI of the Liver: Part 1, Protocol Optimization and Lesion Appearance in the Noncirrhotic Liver. AJR Am J Roentgenol 2010; 195:13-28

11. Cruite I, Schroeder M, Merkle EM, Sirlin CB. Gadoxetate Disodium–Enhanced MRI of the Liver: Part 2, Protocol Optimization and Le-sion Appearance in the Cirrhotic Liver. AJR Am J Roentgenol 2010; 195:29-41

doluminal lesion such as a thrombus or membrane. The sec-ondary type is related to hepatic venous outflow not originat-ing from within the venous system, typically associated with external compression.3 Budd-Chiari syndrome can also be classified into acute, subacute and chronic subtypes. Patients with chronic disease are at risk for development of nodular regenerative hyperplasia.4 These patients with chronic end-stage liver disease are also at increased risk for the develop-ment of hepatocellular carcinoma and it is important to dis-tinguish nodular regenerative hyperplasia from hepatocellular carcinoma.5

Nodular regenerative hyperplasia in the setting of BCS are typically multiple homogenously hyperenhancing areas on arterial phase imaging. These areas can also demonstrate hyperintensity on pre-gadolinium T1-weighted imaging and iso- to hypointensity to liver parenchyma on T2-weighted im-aging.6 The pre-gadolinium T1-weighted imaging character-istics of NRH may help with distinction from hepatocellular carcinoma which is typically hypointense to the liver paren-chyma on T1-weighted imaging and hyperintense to the liver parenchyma on T2-weighted images.6,7

Another potential means by which to distinguish NRH from hepatocellular carcinoma is the appearance of the lesions on delayed hepatobiliary phase imaging with some of the newer hepatobiliary-specific gadolinium-based MR contrast agents, which are commercially available in the United States. Two such agents are gadobenate dimeglumine (Gd-BOPTA, MultiHance, Bracco Diagnostics, Princeton, NJ) and more recently, gadoxetate disodium or gadoxetic acid (Gd-EOB-DTPA, Eovist/Primovist, Bayer Pharmaceuticals, Wayne, NJ).8-

12 These contrast agents have imaging properties of conven-tional extracellular agents during the dynamic phase13,14 and have value in hepatobiliary (HB) phase imaging. After intra-venous injection of these agents, part of the contrast is taken up by hepatocytes and excreted via the biliary system while the remainder is excreted via the kidneys.10 In patients with normal hepatic function, the HB phase usually occurs within 10 to 20 min with gadoxetate disodium and 60 to 120 min with gadobenate dimeglumine due to different degrees of bili-ary versus renal excretion with the agents (50% biliary, 50% renal for gadoxetate disodium and 3-5% biliary, 95-97% re-nal for gadobenate dimeglumine).10, 11, 14-18 Histologically, areas of NRH demonstrate an increased arterial blood supply and functioning hepatocytes which helps to explain their hyper-enhancement. There are also metaplastic bile ductules within the larger regenerative areas which lead to focal abnormal bili-ary excretion of the contrast agent and therefore, their unique appearance of being hyperintense to the liver parenchyma on delayed HB phase imaging.7,10 In contrast, most hepatocellular carcinomas will demonstrate wash out on late dynamic phase and delayed HB phase imaging and appear hypointense to the liver parenchyma. Of note, from a histological perspective, it can be difficult to differentiate focal nodular hyperplasia from nodular regenerative hyperplasia unless the pathologist is pro-vided information on the surrounding hepatic architecture; therefore, it is critical to make the imaging diagnosis of Budd-


original artiCle Davis et al. MR with Contrast Agents in Budd-Chiari Syndrome12. Seale MK, Catalano OA, Saini S, Hahn PF, Sahani DV. Hepatobiliary-

specific MR contrast agents: role in imaging the liver and biliary tree. Radiographics 2009; 29:1725-1748

13. Vogl TJ, Kummel S, Hammerstingl R, et al. Liver tumors: comparison of MR imaging with Gd-EOB-DTPA and Gd-DTPA. Radiology 1996; 200:59-67.

14. Dahlstrom N, Persson A, Albiin N, Smedby O, Brismar TB. Contrast-enhanced magnetic resonance cholangiography with Gd-BOPTA and Gd-EOB-DTPA in healthy subjects. Acta Radiol 2007; 48:362-368

15. Grazioli L, Morana G, Federle MP, et al. Focal nodular hyperplasia: morphologic and functional information from MR imaging with gadobenate dimeglumine. Radiology 2001; 221:731-739

16. Hamm B, Staks T, Muhler A, et al. Phase I clinical evaluation of Gd-EOB-DTPA as a hepatobiliary MR contrast agent: safety, pharmacoki-netics, and MR imaging. Radiology 1995; 195:785-792

17. Petersein J, Spinazzi A, Giovagnoni A, et al. Focal Liver Lesions: Evalu-ation of the Efficacy of Gadobenate Dimeglumine in MR Imaging--A Multicenter Phase III Clinical Study. Radiology 2000; 215:727-736

18. Carlos RC, Hussain HK, Song JH, Francis IR. Gadolinium-ethoxy-benzyl-diethylenetriamine pentaacetic acid as an intrabiliary contrast agent: preliminary assessment. AJR Am J Roentgenol 2002; 179:87-92

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IntroductionDuodenal varices are a rare complication in patients with portal hypertension. The prevalence of ectopic variceal bleeding accounts for 2-5% of all variceal bleeding; of this, only 17% of ectopic variceal bleeding occurs in the duodenum1. Though rare, hemorrhage from duodenal varices is life-threatening, with up to a 40% mortality rate from the initial bleeding episode2. Diagnosis is dif-ficult, and insufficient evidence exists to demonstrate the best treatment option when hemorrhage occurs. Here we

report a case of a patient with life-threatening bleeding from duodenal varices detected with multi-detector heli-cal CT with multiplanar reconstruction, and treated with surgical ligation after failed endoscopic therapy. It serves to provide further evidence of the usefulness of multi-detector helical CT with multiplanar reconstruction in detecting ectopic varices. Furthermore, it reminds us that ectopic varices, although uncommon, should be consid-ered in cases where an upper gastrointestinal bleeding source is not clearly identifiable in patients with known liver disease.

Case ReportThe patient was a 69 year old male who presented just after midnight to the emergency department with nau-sea, vomiting, and several bloody bowel movements con-taining bright red blood and clots. He also complained of weakness, fatigue, and lightheadedness, as well as right-sided abdominal pain. He denied recent illness, fevers,

Citation Larson et al. A Case Report of Fatal Upper Gas-trointestinal Bleed Arising from Duodenal Varices Sec-ondary to Undiagnosed Portal Hypertension. J Surg Radiol. 2012 Oct 1;3(4).

CorrespondenCe Lisa A. Miller, MD E-mail [email protected].

reCeived July 17, 2012. aCCepted October 1, 2012. epub October 1, 2012.

A Case Report of Fatal Upper Gastrointestinal Bleed Arising from Duodenal Varices Secondary to Undiagnosed Portal HypertensionJohn V. Larson1, David M. Bartholomew MD2, Elizabeth A. Steensma MD2, Leandra H. Burke2, John D. Ebersole MD3, Lisa A. Miller MD2

1. College of Human Medicine, Michigan State University, Lansing, MI2. Department of Surgery, Western Michigan University School of Medicine, Kalamazoo, MI3. Bronson Advanced Radiology Services, Kalamazoo, MI

Abstractoverview Duodenal varices are an unexpected source of upper gastrointestinal hemorrhage, and are associated with a high mortality. The prevalence of ectopic variceal bleeding accounts for 2-5% of all variceal bleeding; of this, only 17% of ectopic variceal bleeding occurs in the duode-num1. Diagnosis is difficult, and insufficient evidence exists to demonstrate the best treatment option when hemorrhage occurs. We report a case of a 69 year old male with a history of chronic alcoholism who presented to the emergency department with nausea, vomiting, and several epi-sodes of hematochezia containing bright red blood and clot material. Diagnostic workup in the ER included multi-slice helical computed tomography (CT) with multiplanar reconstruction, and re-vealed a network of large tortuous blood vessels running near the second portion of the duodenum between the inferior vena cava and portal vein. The patient was emergently treated with endoscopic therapy and clipping of the vessel. This failed, and he was subsequently taken to the operating room for suture ligation of the bleeding duodenal varices. Our case is unique in that the suspected source of bleeding was detected by multi-slice helical CT with multiplanar reconstruction. It serves to provide further evidence of the usefulness of multi-detector helical CT with multiplanar recon-struction in detecting ectopic varices, and reminds us that although uncommon, ectopic varices should be considered in cases where an upper gastrointestinal bleeding source is not clearly identi-fiable in patients with known liver disease.

Keywords duodenal varices, portal hypertension, hemorrhagic shock

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Larson et al. Duodenal Varices original artiCle

chills, cough, shortness of breath, chest pain, dysuria, hematu-ria, and hematemesis.

His past medical history included hypertension, gastroesoph-ageal reflux disease, and chronic back pain. His surgical his-tory was significant for lumbar laminectomy. His medications included Omeprazole, ibuprofen, and hydrocodone. Family history was noncontributory. The patient had a history of heavy smoking, but had quit several years prior. He denied any illicit drug use, but reported heavy alcohol intake for the past five years. Notably, he had quit drinking abruptly several days prior to admission.

On physical exam, the patient was afebrile, and demonstrated a heart rate of 114 beats per minute, blood pressure of 134/83 mmHg, and a respiratory rate of 22. He was lethargic but ori-ented to person, place, and time. He generally appeared ill, with pale nonjaundiced skin and conjunctiva. Cardiac exam was notable only for tachycardia. His bilateral lung fields were clear to auscultation and his abdomen was soft, mildly dis-tended, with mild right-sided tenderness to deep palpation. No rebound tenderness, rigidity, or guarding were noted. Bowel sounds were diminished. On rectal exam, dark blood and clot were noted. His extremities revealed no cyanosis,

clubbing, or edema. A nasogastric (NG) tube was placed, which revealed bilious aspirate with no frank blood present; however, the aspirate was hemoccult positive.

The patient’s initial laboratory data demonstrated a white blood cell count of 6.5 x103/mm3 (normal range 4-11), hemo-globin of 9.3 gm/dL (normal range 12-16), and platelet count of 112 x103/mm3 (normal range 140-440). His sodium was 141 mmol/L (normal range 135-145), potassium 4.8 mmol/L (nor-mal range 3.5 – 5.3), blood urea nitrogen 17 mg/dL (normal range 6-20), creatinine 0.8 mg/dL (normal range 0.6-1.1), as-partate aminotransferase 134 U/L (normal range 0-37), ala-nine aminotransferase 63 U/L (normal range 6-37), lipase 65 U/L (normal range 16-63), and tropinin T was less than 0.01 ng/mL (normal range 0.00-0.03). The patient’s lactic acid level was 7.9 mmol/L (normal range 0.7-2.5). INR was elevated at 1.6 (normal value around 1.0), and PTT was 28 seconds (nor-mal range 23-32). An emergent CT scan of the abdomen and pelvis initially revealed a mild degree of mucosal thickening in the area of the cecum, possibly reflecting colitis, and mild distention of the stomach with fluid. The bowel was otherwise unremarkable.

The medical intensivists were consulted for admission. While

Figure 1. Axial contrast enhanced CT images through the junction of the second and third portions of the duodenum. 1a, White arrow denotes varix arising from the superior mesenteric vein, embedded in the wall of the duodenum.

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original artiCle Larson et al. Duodenal Varices

agogastroduodenoscopy revealed mild non-bleeding esopha-geal varices with a normal stomach. Minimal hemosiderin stained bile was noted in the antrum, with a large amount of bright red blood in the duodenum. Just distal to the ampulla, a subcentimeter erosion with adherent clot was noted. The base was injected with epinephrine, and upon withdrawal of the needle, a single continuous stream of blood was observed. This was clipped, successfully achieving hemostasis.

Following the procedure, interventional radiology was con-sulted for mesenteric arteriogram with possible embolization. During this consultation, the CT was reexamined demonstrat-ing the sequelae of portal hypertension, and noted a network of large tortuous blood vessels running near the second por-tion of the duodenum between the inferior vena cava and portal vein. An attempt at coil embolization of the duodenal varices was planned, however the patient began having mas-sive bright red blood around his NG tube and through his nares while in the ICU. He was profoundly hypotensive and tachycardic. He was therefore taken to the operating room for

in the emergency department, the patient had non-bloody emesis, and an additional episode of hematochezia passing blood and clots. His blood pressure dropped by responded to a normal saline bolus. Two units of typed and crossed packed red blood cells were started, and the patient was transferred to the ICU for ongoing resuscitation and monitoring. Two units of fresh frozen plasma and 10 mg of vitamin K were given to correct the elevated INR, esomeprazole was started, and a central venous line and arterial line were placed. The patient was also started on a Clinical Institute Withdrawal Assessment protocol. Gastroenterology and General Surgery consults were emergently obtained.

The patient’s follow up hemoglobin at 8 am was 7.6 gm/dL, which was concerning for ongoing gastrointestinal hemor-rhage. His vitals included a blood pressure of 91/68 mmHg, heart rate 120 bpm, respiratory rate 22 breaths per minute, and oxygen saturation 99% on 4 L nasal cannula. Lactic acid had increased to 9.4 mmol/L. As the bleed had not been local-ized, upper endoscopy was performed at the bedside. Esoph-

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Figure 2. Coronal reconstructed CT images through the second and third portions of the duodenum. 2a, White arrow better delineates varix originating from the superior mesenteric vein. 2b, Varix embedded in the lateral duodenal wall. Curved arrows 2c, 2d, demonstrate circuitous route the varix takes inferiorly ultimately draining into the posterior, lateral aspect of the IVC, white arrows, 2c, 2d.

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Upon re-exploration, the duodenal wall was friable, and there were numerous areas of hemorrhage from the bowel wall de-spite numerous attempts to achieve hemostasis. The abdomen was again packed, allowing anesthesia to continue with ag-gressive resuscitation. After a period of time, a final attempt was made to control the remaining bleeding vessels from the bowel wall with clamps and ties. This was successful, and no large bleeding vessels remained. The patient, however, contin-ued to have ongoing oozing from raw surfaces and the skin edges. The abdomen was packed with lap pads, and the pa-tient transferred back to the ICU for continued resuscitation.

In total, the operative time was approximately 90 minutes, and the patient received a total of 33 units of PRBCs, 25 units of FFP, 5 units of Cryoprecipitate, five 6-packs of platelets, and 1500 ml of crystalloid. His estimated blood loss was calculat-ed to be 23 Liters total, before and during the case. Through-out the case, the patient was euthermic, and his systolic blood pressure ranged from 75 to 110 mmHg.

Post operatively, the patient was transferred back to the inten-

emergency laparotomy, and the massive transfusion protocol was initiated.

Upon entry of the abdomen, clear ascitic fluid was noted, the stomach and small bowel were distended with blood, and a frankly cirrhotic liver was visualized. The duodenum was then kockerized, and an enterotomy was made at the second portion of the duodenum. There was a massive efflux of old, dark blood. The surgeon’s finger was then inserted into the lumen of the duodenum and the endoscopically placed clips were palpated. The enterotomy was opened further distally, allowing direct visualization of the lumen and erosion. Pro-fuse bleeding was identified from the bowel wall along the edges of the enterotomy and from the lesion. Clamps and ties were placed for initial control, and the lesion was oversewn with a 2-0 silk and packs were put in place. This allowed for initial control of the bleeding, and anesthesia was allowed to catch up. The patient continued to be hypotensive with a sys-tolic blood pressure of 80-90 mmHg while receiving blood products, coagulation factors, and pressor support.

Figure 3. Volume rendered, color-coded, 3D reconstructed image demonstrating circuitous course of duodenal varix (pink). Varix arises from the superior mesenteric vein (blue) and drains into the inferior vena cava (yellow). Duodenum (white), aorta (red) for reference. (Courtesy of John Sherwood, MD, Advanced Radiology Services, Kalamazoo, MI)


original artiCle Larson et al. Duodenal Varicestosomiasis, venoocclusive disease, congenital malformations, postoperative shunt thrombosis, and intra-abdominal adhe-sions related to prior surgery6,9. Diagnosis is usually based on findings obtained by endoscopy or angiography. Diagnosis can be quite difficult however, as duodenal varices are difficult to identify on endoscopy due to their serosal and submucosal location10. Furthermore, conventional endoscopy is unable to reach the distal site of the duodenum, and angiography oc-casionally fails to depict duodenal varices due to inappropri-ate catheter cannulation to collateral vessels 11. The pathology may also not be recognized as it is so rare, or may be mistaken for other more common forms of pathology, such as duode-nal ulcers. Capsule endoscopy allows for the possibility to see small intestinal mucosa, and is reported to be sensitive in detecting obscure gastrointestinal bleeding 12. CT angiog-raphy also has been reported as efficient in detecting duode-nal varices 5. Multi-slice helical CT has also been shown to be effective in depicting duodenal varices as a cause of massive upper gastrointestinal bleeding, along with recent reports of the effectiveness of multi-detector helical CT with multiplanar reconstruction, suggesting that this may play an increasingly important role in the detection of ectopic intestinal varices in patients with cirrhosis and gastrointestinal bleeding 13,14.

Treatment of variceal hemorrhage in the upper gastrointestinal tract is largely standardized 1,15. However, there is insufficient evidence to demonstrate the best treatment option for duode-nal variceal bleeding due to the limited number of reports of duodenal varices cases, and the lack of randomized control trials relating to the management of this condition. After ini-tial resuscitation, there are several treatment options available. These include: vasoactive medications, endoscopic injection sclerotherapy and variceal ligation, TIPS procedure, endovas-cular obliteration, and surgical interventions such as surgical variceal ligation and sclerotherapy, surgical shunt placement, or segmental bowel resection 1. Endoscopic treatment is one of the most reasonable options, as it can provide both diagnosis and the potential for less invasive intervention and treatment in the form of sclerotherapy and ligation 15.However, the ef-ficacy of endoscopic variceal ligation is short term and limited to small varices, and endoscopic injection sclerotherapy ap-pears to be less effective against duodenal varices and also has a risk of perforation after the procedure 1,16,17. TIPS is a means of effectively treating acute variceal hemorrhage in patients refractory to endoscopic treatment, and in patients whose gastrointestinal varices are difficult to access by endovascular intervention, or who are poor surgical candidates 1,9. It is ef-fective in decompressing an elevated portosystemic pressure gradient, but decreases hepatic clearance by reducing blood flow through the portal vein, and promotes hepatic encepha-lopathy by increasing porto-systemic shunt blood flow 15-18. TIPS with concomitant endovascular embolization have also been reported to be effective, with the added benefit of ad-dressing both the portal hypertension and the source of the hemorrhage 9,19 . Embolization of bleeding duodenal varices using percutaneous transhepatic or balloon-occluded retro-grade transvenous obliteration has been described in several case reports and is an accepted alternative for the manage-

sive care unit. Upon arrival, the patient’s INR was 1.5, with a PTT of 51 seconds. Hemoglobin was 7.2 gm/dL, platelet count 47 x103/mm3, and fibrinogen 167 mg/dL. His pH was 7.33 (normal range 7.35-7.45), CO2 40 mmHg (normal range 35-45), O2 175 mmHg (normal range 80-90), and base deficit 4.9 mEq/L (normal range 0-2.5). Further resuscitation was contin-ued with correction of the patient’s acidosis and coagulopathy. Despite maximal attempts at optimizing the patient’s physiol-ogy, he continued to be hypotensive and tachycardic, consis-tent with ongoing blood loss. Consideration for a transjugular intrahepatic portosystemic shunt (TIPS) was made, but the patient was deemed too unstable and unlikely to survive the procedure. After a discussion with the family, surgery, and the critical care team, it was determined by all that further op-erative intervention would be futile. The decision to withdraw care was made, and comfort measures were implemented. He expired shortly thereafter.

DiscussionOur report describes an unusual case of upper gastrointesti-nal hemorrhage arising from ectopic varices located in the sec-ond and third portion of the descending duodenum. The pa-tient’s initial presentation was confounded by the symptom of hematochezia, which may represent an upper gastrointestinal bleed, but is more indicative of a lower gastrointestinal source. Second, the patient’s CT scan was initially read with changes suggesting ischemic colitis, which is also indicative of a lower gastrointestinal bleed. Finally, the nasogastric aspirate did not contain frank blood, further confounding the patient’s presen-tation as a lower gastrointestinal source. Despite this unusual presentation, an upper gastrointestinal source was not ruled out prematurely, and a timely endoscopy was performed.

Duodenal varices were first described in 1931 by Alberti et al3.

As these varices are outside the gastroesophageal junction, they are referred to as ectopic varices. Anatomically, they usu-ally consist of a single vessel with associated afferent and ef-ferent vessels forming a retroperitoneal portosystemic shunt4. The afferent vessel arises from either the superior or inferior pancreaticoduodenal vein or from the superior mesenteric vein, and the efferent vessel is thought to arise from one of the many retroperitoneal veins draining into the inferior vena cava 4. These communications between intestinal or retroperi-toneal tributaries of the superior and inferior mesenteric veins with the inferior vena cava are called the veins of Retzius 5. Duodenal varices, therefore, are considered dilated veins of Retzius located in the pancreaticoduodenal region. The duo-denal bulb is reported to be the most common location, with decreasing frequency as one travels distally down the duode-num6,7. A more recent study, however, reported duodenal vari-ces to commonly occur in the descending part of the duode-num, occasionally co-existing with varices in the esophagus, stomach, and duodenal bulb8.

Duodenal varices most frequently result from cirrhosis of the liver, portal vein thrombosis, or obstruction of the splenic vein and inferior vena cava 6. Other rare etiologies include schis-

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12. Pennazio M, Santucci R, Rondonotti E, Abbiati C, Beccari G, Rossini FP, De Franchis R. Outcome of patients with obscure gastrointesti-nal bleeding after capsule endoscopy: report of 100 consecutive cases. Gastroenterology 2004;126:643-653

13. Weishaupt D, Pfammatter T, Hilfiker PR, Wolfensberger U, Marincek B. Detecting bleeding duodenal varices with multislice helical CT. AJR Am J Roentgenol 2002;178:399-401

14. Yoshida S, Watabe H, Omata M. Usefulness of multi-detector helical CT with multiplanar reconstruction for depicting the duodenal varices with multiple collateral shunt vessels. Hepatol Int 2010;4:775-778

15. Stanley AJ, Hayes PC. Portal hypertension and variceal hemorrhage. Lancet 1997;350:1235-1239

16. Yoshida Y, Imai Y, Nishikawa M, Nakatukasa M, Kurokawa M, Shibata K, Shimomukai H, Shimano T, Tokunaga K, Yonezawa T. Successful endoscopic injection sclerotherapy with n-butyl-2-cyanoacrylate fol-lowing the recurrence of bleeding soon after endoscopic ligation for ruptured duodenal varices. Am J Gastroenterol 1997;92:1227-1229

17. Tsuji H, Okano H, Fujino H, Satoh T, Kodama T, Takino T, Yoshimu-ra N, Aikawa I, Oka T, Tsuchihashi Y. A case of endoscopic injec-tion sclerotherapy for a bleeding duodenal varix. Gastroenterol Jpn 1989;24:60-64

18. Sahagun G, Benner KG, Saxon R, Barton RE, Rabkin J, Keller FS, Rosch J. Outcome of 100 patients after transjugular intrahepatic porto-systemic shunt for variceal hemorrhage. Am J Gastroenterol 1997;92:1444-1452

19. Lopera JE, Arthurs B, Scheuerman C, Sandoz C, Petersosn S, Castane-da-Zuniga W. Bleeding Duodenal: Varices Treatment by TIPS and Transcatheter Embolization. Cardiovasc Intervent Radiol 2008;31:431-434

20. Menu Y, Gayet B, Nahum H (1987) Bleeding duodenal varices: Diag-nosis and treatment by percutaneous portography and transcatheter embolization. Gastrointest Radiol 12:111-113

21. Sonomura T, Horihata K, Yamahara K, et al. (2003) Ruptured duo-denal varices successfully treated with balloon-occluded retrograde transvenous obliteration: Usefulness of microcatheters. AJR Am J Roentgenol 181:725-727

22. Kaji T, Tamura J, Matsumoto M, et al. (1993) Superior mesenteric vari-ces and splenic renal shunt with portal hypertension: A case report of liver cirrhosis with complications. J Int Med Res 21:58-65

23. Ozaki CK, Hansen M, Kadir S (1989) Transhepatic embolization of su-perior mesenteric varices in portal hypertension. Surgery 105:446-448

ment of life threatening bleeding20,21,22 . This was the initial endovascular consideration in our patient in order to expedite the patient’s stability prior to TIPS. However, this method is difficult to perform in patients with multiple afferent vessels, and is only a temporary measure as it does not alter portal pressures, allowing new collaterals to develop or pre-existing varices to recanalize 20,23 . Surgical shunt placement or surgi-cal variceal ligation may be necessary to control hemorrhage in patients that sclerotherapy has failed 2. Although surgical ligation and sclerotherapy is more invasive than other proce-dures, it allows for the possibility to achieve curative effects on duodenal varices, especially in patients with reserved liver function and complicated shunt vessels 14.

Although rare, duodenal varices should remain in the differ-ential diagnosis of upper gastrointestinal hemorrhage, espe-cially in individuals with portal hypertension or known liver disease. The diagnosis remains challenging. However, with the aid of multi-slice helical CT scans with multi-planar recon-struction, in addition to endoscopy, this rare and unexpected source of hemorrhage can be detected. As demonstrated in this case, the treatment of ectopic variceal bleeding is problematic, and likely requires a multi-disciplinary approach combining gastroenterology, interventional radiology and surgery.

DisclosuresThe authors have no conflicts of interest, financial or other-wise, pertaining to this case report.

References1. Norton ID, Andrews JC, Kamath PS. Management of ectopic varices.

Hepatology 1998;28:1154-8.

2. Khouqueer F, Morrow C, Jordan P. Duodenal varices as a cause of massive upper gastrointestinal bleeding. Surgery 1987;102:548-52

3. Alberti W. Uber den roentgenologischen Nachweis von Varizen in Buolbus duodeni. Fortschro Geb Roentgenstr 1931; 43: 60-5.

4. Hashizume M, Tanoue K, Ohta M, et al. (1993) Vascular anatomy of duodenal varices: Angiographic and histopathological assessments. Am J Gastroenterol 88:1942-1945

5. Ibukuro K, Tsukiyama T, Mori K, Inoue Y. Veins of Retzius at CT dur-ing arterial portography: anatomy and clinical importants. Radiology 1998;209:793-800

6. Amin R, Alexis R, Korzis J. Fatal ruptured duodenal varix: a case re-port and review of literature. Am J Gastroenterol 1985;80:13-8.

7. Tanaka T, Kato K, Taniguchi I, Takagi K, Takeyama N, Tazawa Y. A case of ruptured duodenal varices and review of the literature. Jpn J Surg 1988;18:595-600

8. Liu Y, Yang J, Yang Y. Clinical characteristics and endoscopic treatment with cyanoacrylate injection in patients with duodenal varices. Scan-dinavian J Gastroenterol 2009;44:1012-16

9. Haskal, ZJ, Scott M, Rubin RA, Cope C (1994) Intestinal varices: Treat-ment with transjugular intrahepatic portosystemic shunt. Radiology 191:183-187

10. Sukigara M, Koyama I, Komazaki T, et al. Bleeding varices located in the second portion of the duodenum. Jpn J Surg 1987;17:130-5

11. Perchik L, Max T. Massive hemorrhage from varices of the duodenal loop in a cirrhotic patient. Radiology 1963;80:641-645


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IntroductionTrichotillomania, meaning obsession with one’s hair, is a rare disorder that was first described over 100 years ago by Hallopeau. It is characterized by repetitive rituals performed with hair after it has been removed, and has a prevalence of 0.6%– 1.6%. 1 This disorder has a strong female predilection and typically affects patients in child-hood and adolescence. Approximately 30% of patients who suffer from trichotillomania also engage in tricho-phagia, or the compulsive eating of one’s hair. Of this subset an even smaller percentage, around 1%, require surgical intervention due to complications of the result-ing trichobezoars, which are indigestible masses of hair that become lodged in the gastrointestinal tract. 2 To date, the number of people with trichophagia who develop trichobezoars is unclear. One study of nearly 200 patients with trichotillomania reported no cases of trichobezoars,

3 whereas other studies have reported a 25%-37.5% preva-lence of trichobezoar in those who engage in trichophagy.

4,5

Baudamant described the first case of trichobezoar in 1779. 6 When hair is ingested it is retained in gastric folds

and is resistant to peristalsis due to its smooth surface. As increasing amounts of hair are ingested, the motion of peristalsis acts to impact the hair into an indigestible mass that continues to grow, eventually forming a cast of the stomach. Many trichobezoars go unnoticed until they become large enough to cause symptoms ranging from abdominal pain, chronic anorexia, failure to thrive, vom-iting, and acute obstruction.

When severe they can result in complications including mucosal erosion, ulceration or perforation. Moreover in-tussusception, obstructive jaundice, protein-losing enter-opathy, pancreatitis and even death have been reported in the literature. 7-12 If trichophagia continues without com-plication, trichobezoars may continue to grow and extend past the pylorus. This situation of so called Rapunzel syndrome was first described by Vaughan et al in 1968 to described a gastric trichobezoar with an extended tail in to the duodenum and caused symptoms of obstruction.

12 Since, the definition of Rapunzel syndrome has varied to describe the extent to which the tail extends, ranging from beyond the pylorus 13-15 to the large bowel. 16-18 Others rely solely on the presence of obstructive symptoms. 15

We report a case of a 20 year-old African-American female with an 8-year history of trichotillomania and trichopha-gia. She had sought psychiatric treatment 6 months prior to presentation but this did not eliminate the behavior. The patient presented with complaints of 2 months of epigastric pain and loose stools, eventually leading to one week of inability to tolerate solid food. She also noted a 10-15 pound weight loss in the months prior to presen-tation. An acute abdominal series revealed a large het-erogeneous opacity displacing the transverse colon infe-riorly (Figure 1). Initial attempts at endoscopic removal

Citation Reid et al. Case of Rapunzel Syndrome: With a Review of Diagnosis and Treatment. J Surg Radiol. 2012 Oct 1;3(4).

CorrespondenCe Todd W. Costantini, MD E-mail [email protected].

reCeived September 10, 2012. aCCepted October 1, 2012. epub October 1, 2012.

Case of Rapunzel Syndrome: With a Review of Diagnosis and TreatmentChris Reid MD,1 Hop Tran Cao MD,1 Leslie Kobayashi MD,2 Raul Coimbra MD, PhD,2 Todd W. Costantini MD2

1. Department of Surgery, University of California San Diego Health Sciences, San Diego, CA2. Division of Trauma, Surgical Critical Care, and Burns, Department of Surgery, University of California San Diego Health Sciences, San Diego, CA

Abstractoverview Rapunzel Syndrome has been used to describe a large gastric trichobezoar with tail that extends beyond the pylorus of variable length. It is a rare diagnosis associated with trichopha-gia. Related to its rarity and non-specific presentation it poses a diagnostic challenge. We describe the case of a young woman with trichotillomania and trichophagia who presented with signs of obstruction and was found to have Rapunzel syndrome, which was treated with laparotomy. We review the epidemiology, diagnosis and treatment of this condition.

Keywords trichotillomania, trichophagia, Rapunzel syndrome, trichobezoar

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with the aid of mechanical disruption proved unsuccessful. Subsequently abdominal computed tomography displayed a heterogeneous mass occupying the stomach and extending to the proximal jejunum. Diffuse wall thickening and edema was present throughout the stomach and extending to the third portion of the duodenum (Figure 2). Because of the extent of the mass, further endoscopic treatment was felt unlikely to be successful. As such the patient was referred to the Acute Care Surgery Service for surgical removal of the mass.

The patient was taken to the operating room where an upper midline laparotomy, followed by a 10-centimeter gastrostomy was performed. Upon opening the gastric wall a large, firm mass with associated tail forming a cast of stomach and en-tirety of duodenum extending in to jejunum was encountered (Figure 3). Her post-operative recovery was remarkable for a delay in return of gastric functioning, attributed to a chronic distention of her stomach. This responded well to conservative management. She was discharged with psychiatry follow up.

DiscussionThere are approximately 30 cases of Rapunzel syndrome that have been documented in the literature. 15 Each case involved a female patient, except for a single case involving a male patient whom was in actuality eating his sister’s hair. 19 There is no

description to date regarding the number of years or quantity of hair one must be consuming to result in this peculiar syn-drome. Invasive intervention is required on approximately 1% of patients who engage in trichophagia and it is uncertain as to why some go on to experience symptoms while others do not. Regardless, this syndrome can result in serious morbidity and even mortality. 7

Patients without a significant trichobezoar burden are diffi-cult to diagnose and may present with non-specific symptoms including abdominal pain, inability to tolerate oral intake, or vomiting. As the time of residence of the trichobezoar and its size increase, there is a higher likelihood of experiencing worsening symptoms and deranged laboratory abnormalities. Plain films may be suggestive of, but are rarely diagnostic for trichobezoars when used alone. Studies have shown ultra-sound to be effective in diagnosing up to 88% of cases. 20,21 The diagnostic test with the best sensitivity is abdominal CT with contrast, which is reported to identify up to 97% of bezoars, 22

but a definitive diagnosis is best achieved by direct visualiza-tion via endoscopy.

Smaller gastric trichobezoars may be amendable to endoscop-ic removal, however the size and complexity of the masses in Rapunzel syndrome warrants treatment via laparotomy. Gort-er et al reported in their review in 2010 that of 40 documented cases of trichobezoar only 5% were successfully extracted en-doscopically. 5 The authors note that this modality may be bet-ter suited to diagnosis than for treatment.

Seven case reports on the use of laparoscopy in the treat-ment of trichobezoar have been reported in the literature. 23-28 A review of these cases showed a tendency for longer more complex operations, sometimes employing the assistance of endoscopy, but with improved cosmetic result, decreased hospital stay and post operative complications. However, this technique was aborted in two cases and makes inspection of the rest of the bowel for satellite trichobezoars more difficult.

Reid et al. Case of Rapunzel Syndrome original artiCle

Figure 1. Abdominal plain film displaying a large heteroge-neous mass displacing the transverse colon inferiorly. This represented an enlarged stomach containing the trichobe-zoar. A radiopaque object is also seen in the stomach, consistent with ingested pill.

Figure 2. Axial computed tomography showing the stom-ach filled with heterogeneous material, as well as diffuse wall thickening. The tail of the trichobezoar can be seen in the duodenum.


original artiCle Reid et al. Case of Rapunzel Syndrome

ConclusionRapunzel syndrome is a rare presentation of what is a rare disorder, trichophagia. Seen almost exclu-sively in females it is often diagnosed with some de-lay, due to its non-specific presentation. Literature regarding this syndrome and its treatment is not extensive but it is believed that laparotomy should be the surgeon’s primary treatment choice.

DisclosuresThe authors have no disclosures or conflicts of in-terest related to this manuscript.

References1. O’Sullivan RL, Mansueto CS, Lerner EA, Miguel EC. Characterization of trichotillomania. A phenomenological mod-el with clinical relevance to obsessive-compulsive spectrum dis-orders. Psychiatr Clin North Am. 2000;23(3):587-604.

2. Bouwer C, Stein DJ. Trichobezoars in trichotilloma-nia: Case report and literature overview. Psychosom Med. 1998;60(5):658-660.

3. Christenson GA, Crow SJ. The characterization and treatment of trichotillomania. J Clin Psychiatry. 1996;57 Suppl 8:42-7; discussion 48-9.

4. Bhatia MS, Singhal PK, Rastogi V, Dhar NK, Nigam VR, Taneja SB. Clinical profile of trichotillomania. J Indian Med As-soc. 1991;89(5):137-139.

5. Cohen LJ, Stein DJ, Simeon D, et al. Clinical profile, comorbidity, and treatment history in 123 hair pullers: A survey study. J Clin Psychiatry. 1995;56(7):319-326.

6. Faria AP, Silva IZ, Santos A, Avilla SG, Silveira AE. The rapunzel syndrome - a case report: Trichobezoar as a cause of

intestinal perforation. J Pediatr (Rio J). 2000;76(1):83-86.

7. Ventura DE, Herbella FA, Schettini ST, Delmonte C. Rapunzel syn-drome with a fatal outcome in a neglected child. J Pediatr Surg. 2005;40(10):1665-1667.

8. Schreiber H, Filston HC. Obstructive jaundice due to gastric trichobe-zoar. J Pediatr Surg. 1976;11(1):103-104.

9. Mehta MH, Patel RV. Intussusception and intestinal perforations caused by multiple trichobezoars. J Pediatr Surg. 1992;27(9):1234-1235.

10. Hossenbocus A, Colin-Jones DG. Trichobezoar, gastric polyposis, pro-tein-losing gastroenteropathy and steatorrhoea. Gut. 1973;14(9):730-732.

11. Shawis RN, Doig CM. Gastric trichobezoar associated with transient pancreatitis. Arch Dis Child. 1984;59(10):994-995.

12. Vaughan ED,Jr, Sawyers JL, Scott HW,Jr. The rapunzel syndrome. an unusual complication of intestinal bezoar. Surgery. 1968;63(2):339-343.

13. Singla SL, Rattan KN, Kaushik N, Pandit SK. Rapunzel syndrome--a case report. Am J Gastroenterol. 1999;94(7):1970-1971.

14. Hirugade ST, Talpallikar MC, Deshpande AV, Gavali JS, Borwankar SS. Rapunzel syndrome with a long tail. Indian J Pediatr. 2001;68(9):895-896.

15. Naik S, Gupta V, Naik S, et al. Rapunzel syndrome reviewed and rede-fined. Dig Surg. 2007;24(3):157-161.

16. Curioso Vilchez WH, Rivera Vega J, Curioso Abriojo WI. Rapunzel syndrome: Case report and literature review. Rev Gastroenterol Peru. 2002;22(2):168-172.

17. West WM, Duncan ND. CT appearances of the rapunzel syndrome:

In Rapunzel syndrome this technique appears inappropriate due to large size and complex shape, and has been reported to date once and this was unsuccessful. 21

There have been 100 laparotomies performed for trichobezoar with a 100% success rate at removal reported. 12 patients ex-perienced complications in this series. 21 The most common complication was bowel perforation during removal, followed by minor wound infection and then paralytic ileus. This treat-ment modality allows direct visualization of all aspects of the upper gastrointestinal tract that may be involved, as well as adequate control to protect against fracture of the mass. More-over, it is much quicker that laparoscopy and allows for easier examination for satellite trichobezoars.

Finally, all patients require psychiatric referral and long term follow up. There are several treatment strategies described however there appears to be no difference in responses to psychotherapy, behavior therapy, clomipramine, or fluoxetine. Additionally none of these treatments were shown to provide lasting aide in symptoms. 5 A thorough review of the litera-ture could not identify the recurrence rate of trichophagia or trichobezoar after surgical intervention. There are at least three recurrences documented but to date no studies have thoroughly described this. 29-31

Figure 3. Removed trichobezoar which appears as a cast of stomach and duodenum.

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Reid et al. Case of Rapunzel Syndrome original artiCle

An unusual form of bezoar and gastrointestinal obstruction. Pediatr Radiol. 1998;28(5):315-316.

18. Faria AP, Silva IZ, Santos A, Avilla SG, Silveira AE. The rapunzel syn-drome - a case report: Trichobezoar as a cause of intestinal perfora-tion. J Pediatr (Rio J). 2000;76(1):83-86.

19. Alsafwah S, Alzein M. Small bowel obstruction due to trichobe-zoar: Role of upper endoscopy in diagnosis. Gastrointest Endosc. 2000;52(6):784-786.

20. Ripolles T, Garcia-Aguayo J, Martinez MJ, Gil P. Gastrointestinal be-zoars: Sonographic and CT characteristics. AJR Am J Roentgenol. 2001;177(1):65-69.

21. Gorter RR, Kneepkens CM, Mattens EC, Aronson DC, Heij HA. Man-agement of trichobezoar: Case report and literature review. Pediatr Surg Int. 2010;26(5):457-463.

22. Malpani A, Ramani SK, Wolverson MK. Role of sonography in tricho-bezoars. J Ultrasound Med. 1988;7(12):661-663.

23. Palanivelu C, Rangarajan M, Senthilkumar R, Madankumar MV. Trichobezoars in the stomach and ileum and their laparoscopy-assist-ed removal: A bizarre case. Singapore Med J. 2007;48(2):e37-9.

24. Kanetaka K, Azuma T, Ito S, et al. Two-channel method for retrieval of gastric trichobezoar: Report of a case. J Pediatr Surg. 2003;38(2):e7.

25. Nirasawa Y, Mori T, Ito Y, Tanaka H, Seki N, Atomi Y. Laparoscopic removal of a large gastric trichobezoar. J Pediatr Surg. 1998;33(4):663-665.

26. Meyer-Rochow GY, Grunewald B. Laparoscopic removal of a gastric trichobezoar in a pregnant woman. Surg Laparosc Endosc Percutan Tech. 2007;17(2):129-132.

27. Hernandez-Peredo-Rezk G, Escarcega-Fujigaki P, Campillo-Ojeda ZV, et al. Trichobezoar can be treated laparoscopically. J Laparoendosc Adv Surg Tech A. 2009;19(1):111-113.

28. Levy RM, Komanduri S. Images in clinical medicine. trichobezoar. N Engl J Med. 2007;357(21):e23.

29. Duncan ND, Aitken R, Venugopal S, West W, Carpenter R. The rapun-zel syndrome. report of a case and review of the literature. West Indian Med J. 1994;43(2):63-65.

30. Eryilmaz R, Sahin M, Alimoglu O, Yildiz MK. A case of rapunzel syn-drome. Ulus Travma Acil Cerrahi Derg. 2004;10(4):260-263.

31. Memon SA, Mandhan P, Qureshi JN, Shairani AJ. Recurrent rapunzel syndrome - a case report. Med Sci Monit. 2003;9(9):CS92-4.


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IntroductionDiaphragmatic hernias can be congenital or traumatic. Re-pair of this condition often depends on size and surgeon experience with different techniques. Often, a synthetic mesh is required for repair. When choosing a mesh mate-rial, one must consider the different properties unique to each material for the individual patient. This case report is an example of a unique presentation of a mesh erosion and the imaging modalities used for diagnosis.

PresentationA 70-year-old male presented to the acute care depart-ment for the evaluation of productive cough of brown, foul smelling mucous. Patient had a history of gastric adenocarcinoma treated with neoadjuvant chemotherapy (MAGIC trial), followed by total gastrectomy with D2 ret-roperitoneal lymphadenectomy with en block splenecto-my and resection of the diaphragm with a Gore-Tex patch repair. He reported four recurrent episodes of community acquired pneumonia in a six month period, halitosis in addition to his cough. The workup included an esophago-gastroscopy, which showed esophageal mucosal changes consistent with short segment Barrett’s esophagus. This was treated with focal thermal ablation. The patient’s per-sistent cough had been treated with multiple rounds of

antibiotics and a two month course of steroids with no palliation of symptoms. Imaging performed during the last six months included multiple chest x rays, which showed non-resolving left lower lobe consolidation. As-sociated symptoms during this time period were anorexia and weight loss (10 lbs over a five month period). The patient denied fevers, chills, hematuria, dysuria, hemato-chezia, diarrhea/constipation, sick contacts, or a family history of immune disorders.

DiagnosisComputed tomography of the chest was ordered to con-firm this consolidation (Figure 1). CT revealed a colobron-chial fistula that had occurred with erosion of the mesh that had been previously placed. The mesh had eroded in the colon, and was currently in the descending colon. Af-ter surgical consultation was obtained, recommendation for diversion around the effected segment was made. The patient was started on preoperative antibiotics and taken to the operating room.

ManagementA bypass was performed with a side to side primary anastomosis allowing for a bypass of the effected gastro-intestinal tract. Exploration of the peritoneal cavity did not reveal any further fistulas or sites of infection. The patch was left intralumenally for the patient to pass. His post-operative recovery was uneventful and the patient was discharged home a week after surgery. The patient has been doing well, with no respiratory tract symptoms since surgery.

Citation Sarcu et al. A 70 Year Old Male with Recurrent Pneumonia. J Surg Radiol. 2012 Oct 1;3(4).

CorrespondenCe David Sarcu, MD E-mail [email protected].

reCeived April 29, 2012. aCCepted October 1, 2012. epub October 1, 2012.

A 70 Year Old Male with Recurrent PneumoniaDavid Sarcu, MD,1,2 Rodrigo Arrangoiz, MD,2 James C. Watson, MD2

1. Department of Otolaryngology, Temple University Hospital, Philadelphia, Pennsylvania2. Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania

Abstractoverview A 70 year old male presents with recurrent pneumonia despite adequate antiobiotic therapy shortly after having a total gastrectomy for gastric adenocarcinoma with primary mesh re-pair. On imaging, a colobronchial fistula is evident secondary to mesh erosion into the colon. This illustrates the usefulness early imaging can provide in illustrating mesh erosion.

Keywords mesh, complications, erosion, diaphragmatic hernia, CT, computed tomography

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Sarcu et al. Recurrent Pneumonia original artiCle

DiscussionDiaphragmatic hernias (DH) can be broken down into two main types, congenital and traumatic. Congenital diaphrag-matic hernias (CDH) are secondary to a developmental ab-normality of the diaphragm. These often present at birth with

pulmonary complications due to displacement of abdomi-nal contents into the thorax. Rarely, CDH can present dur-ing adulthood, where an asymptomatic defect that has been present since birth, suddenly herniates due to trauma or an unknown trigger. DH can be further classified as the more common Bochdalek (posterolateral defects) and the less common Morgagni (anterior midline, usually right sided). Traumatic hernias are the other main type of DH, most often seen with blunt and penetrating trauma.1

Repair of these defects are done with the goal of closing the defect while maintaining as close to a tension free repair as possible. For defects larger than 20 to 30 cm2, mesh reinforce-ment is often necessary.1,5,6 As more and more patches with natural and synthetic materials enter the market, the ques-tion becomes which offers the best therapeutic options with the lowest risk for complications.2

Currently, surgeon preference plays the largest role in deter-mining the type of material to use. The disadvantages of syn-thetic materials include having up to 6% secondary wound infections, graft dehiscence, seroma formation, insufficient tensile strength, and secondary chest wall deformities in pediatric cases. Autologous grafts are reported to have bet-ter outcomes, but tend to lead to a much longer procedure which carries its own risks, secondary to the mobilization of muscle flaps.3 The efficacy of a biological bovine pericar-dial repair patch was tested in one study for diaphragmatic repair. Primary outcomes included its biocompatibility, rate of wound infection, and secondary calcification after repair. Zardo et al in a series of seven patients, performed full thick-ness diaphragmatic resection. Five had the patch shaped ex-actly to match the defect, two had the patch placed over the native diaphragm to repair the defect. After median follow up of 12 months, 1 patient with mesothelioma had died of cardiopulmonary complications. Of the remaining six, five, assessed their quality of life on a standardized SF-36 health survey to be good to excellent. One patient did form a late bronchopleural fistula four and a half years after lobectomy and 16 months after an ipsilateral en block chest wall and diaphragm resection. Although a small sample size, it was reasoned that synthetic bovine patches provide a reasonable alternative to flap procedures and other types of synthetic patches.3

There are limited studies looking at specific mesh materi-als. The patient in this vignette had his diaphragm defect re-paired with a Gore-Tex mesh. In one study using a compos-ite patch of Gore-Tex/Marlex, 137 congenital diaphragmatic hernias were repaired over an 11 year period. Seventy-nine of these patients had primary repair compared to 46 that had patch repairs. Twenty-eight of the patch patients survived the repair, and one of these patients (3.57%) went on to develop

a recurrence (median follow up of 47 months).2

In a similar retrospective review, 188 children underwent sur-gery for CDH. Fifty-one infants (27%) could not be repaired with primary closure, 19 had muscle flap repair, 32 had pros-thetic patch repair (15 goretex, 9 marlex, 5 surgisis, 3 silastic).

Figure 1. CT chest performed at presentation. The mesh is not-ed in the descending colon.

Figure 2. CT chest performed at presentation. There is evidence of a colobronchial fistula.


original artiCle Sarcu et al. Recurrent Pneumonia

DisclosuresThe authors have no disclosures or conflicts of interest relat-ing to this manuscript.

References1. Palanivelu C, Rangarajan M, et al: Laparoscopic repair of adult dia-

phragmatic hernias and eventration with primary sutured closure and prosthetic reinforcement: a retrospective study. Surg Endosc. 2009 May;23(5):978-85.

2. Riehle KJ, Magnuson DK, Waldhausen JH. Low recurrence rate after Gore-Tex/Marlex composite patch repair for posterolateral congenital diaphragmatic hernia. J Pediatr Surg. 2007 Nov;42(11):1841-4.

3. Zardo P, Zhang R, et al: Biological materials for diaphragmatic repair: initial experiences with the PeriGuard Repair Patch®. Thorac Cardio-vasc Surg. 2011 Feb;59(1):40-4. Epub 2011 Jan 17.

4. Nasr A, Struijs MC, et al: Outcomes after muscle flap vs prosthetic patch repair for large congenital diaphragmatic hernias. J Pediatr Surg. 2010 Jan;45(1):151-4.

5. Rice GD, O’Boyle CJ, et al: Laparoscopic repair of Bochdalek hernia in an adult. Aust N Z J Surg 2001 71:443–445.

6. Kitano Y, Lally KP, Lally PA Congenital diaphragmatic hernia study group: late-presenting congenital diaphragmatic hernia. J Pediatr Surg 2005 40:1839–1843.

7. Khanna, A, Finch, G Paraoesophageal herniation: A review. Surgeon. 2011 Apr;9(2):104-11.

Postoperative bowel obstruction occurred in three muscle flap patients and one patch patient (P = 0.2). Ten recurrences oc-curred, two after a muscle flap, eight after the prosthetic flap (P = 0.3). This paper demonstrated in a relatively large patient population that the postoperative complications with a mesh were comparable to that of the primary closure group.4

Furthermore, the surgical approach used is another variable in outcome. Laparoscopic techniques have improved post op-erative morbidity for many types of abdominal surgery. For diaphragmatic hernias, one study looked at 21 patients that underwent laparoscopic diaphragmatic hernia repair. Eleven of these patients were symptomatic, with symptoms includ-ing vomiting, upper abdominal pain, problems breathing, and retrosternal discomfort. The patients were repaired with in-tracorporeal sutures as well as a polypropylene mesh. All 11 symptomatic patients had their symptoms completely abate. With a follow up mean of 24 months, one patient (4.7%) had a CT confirmed recurrence 10 months after surgery. As this paper notes, a mesh for reinforcement is necessary in defects larger than 20 to 30 cm2.1,5,6 Also, by suturing the large defect, a flat surface is provided for easier placement of the mesh, there-by decreasing the risk of the mesh extruding through the de-fect. The type of mesh chosen is difficult to compare as there have been no randomized controlled trials comparing their re-spective efficacies. However, polypropylene is known to cause excessive bowel adhesions, making a composite or expanded polytetrafluoroethylene (ePTFE) mesh a more ideal choice.1

Other hernia studies involving the diaphragm show similar evidence supporting the use of mesh for repair. In a review paper of paraesophageal hernia management, Khanna and Finch discuss the controversy of mesh vs. no mesh. Random-ized controlled trials have shown decreased recurrence of hia-tal hernias with use of mesh.7 The problem arises with the fact that the diaphragm is constantly moving with breathing, coughing, etc., leading to reports of ulceration, stricture, dys-phagia, and erosion of the prosthesis into the esophagus. Ero-sion into surrounding structures has been reported with poly-propylene, nylon, and teflon pledges.7 More inert structures like PTFE and human acellular dermal matrix patches are suggested. Ultimately, only four studies were deemed to have suitable designs, and addressed symptom recurrence follow-ing hiatal hernia repair.7 One hundred and nineteen patients were evaluated and a low recurrence rate was found with ac-ceptable levels of morbidity and mortality, suggesting a strong place for mesh repair for hiatal hernia repair.7

Although the literature is limited, studies show mesh can be a suitable adjuvant to hernia repair, especially when defect size warrants it. One must bare in mind the complications that can occur, especially erosion into surrounding tissues, as occurred with the patient in the vignette presented. Ideally, as more data is collected on mesh repair, an ideal synthetic material that minimizes erosion and attachment to bowel while still main-taining strength and closure will be developed.

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IntroductionDeaths from pancreatic ductal adenocarcinoma rank fourth among cancer-related mortality in the United States. In the year 2011, the incidence of pancreatic can-cer numbered 44,030, with 37,660 reported deaths. The five-year survival rate for patients with pancreatic cancer is approximately 6% and efforts at improving outcomes over the past 30 years have remained relatively unsuccess-ful.1 Of the primary pancreatic malignancies, pancreatic ductal adenocarcinoma is the most common histological subtype and is associated with the greatest mortality bur-den; hence, mention of ‘pancreatic cancer’ in our review article will refer to ductal adenocarcinoma unless stated

otherwise. Curative resection is the most important fac-tor for determining survival in patients with pancreatic adenocarcinoma.2 This article will explore the surgical management of patients with pancreatic adenocarcino-ma, with focus on pre-operative staging, operative strate-gies, and future and experimental approaches.

MethodsA computerized search was made of the Medline data-base from January 1970 to June 2012 using keywords re-lated to pancreatic adenocarcinoma (‘pancreatic ductal adenocarcinoma’ or ‘pancreatic adenocarcinoma’ or ‘pan-creatic cancer’). References from all articles retrieved were subsequently studied for any additional articles. Letters, reviews without original data, and non-English language articles were excluded. For each publication, the full manuscript was obtained. Studies were assessed for re-sults specific to pancreatic adenocarcinoma and all other histological types of pancreatic cancer were excluded. P values less than 0.05 were used to determine significance of measured associations.

Citation Ecker, BL. Pancreatic Cancer - Surgical Prog-ress and Future Management. J Surg Radiol. 2012 Oct 1;3(4).

CorrespondenCe Brett L. Ecker E-mail [email protected].

reCeived August 1, 2012. aCCepted October 1, 2012. epub October 1, 2012.

Pancreatic Cancer - Surgical Progress and Future ManagementBrett L. Ecker, Edward W. Chu, Malika Garg MD, Celia M. Divino MDDepartment of Surgery, Mount Sinai School of Medicine, New York, New York.

Abstractpurpose Deaths from pancreatic ductal adenocarcinoma rank fourth among cancer-related mortality in the United States. Curative resection is the single most important factor determining survival in patients with pancreatic adenocarcinoma. This review explores the surgical manage-ment of pancreatic adenocarcinoma, with attention to pre-operative staging, operative strategies, and future experimental approaches.Methods A computerized search was made of the Medline database from January 1970 to June 2012 using keywords related to pancreatic adenocarcinoma (‘pancreatic ductal adenocarci-noma’ or ‘pancreatic adenocarcinoma’ or ‘pancreatic cancer’). References from all articles retrieved were subsequently studied for any additional articles. Letters, reviews without original data, and non-English language articles were excluded. Studies were assessed for results specific to pancreatic adenocarcinoma. All other histological types of pancreatic cancer were excluded. ConClusion Pancreatic ductal adenocarcinoma is a major oncologic burden with poor prognosis despite multi-modality therapy. Improvements in surgical strategies have expanded the degree of re-sectable cases. Despite improved perioperative outcomes over the last three decades, there remains poor long-term survival for both surgical and non-surgical patients. Continued collaboration be-tween surgical oncologists, medical and radiation oncologists, and research scientists will improve cure rates and overall survival for affected patients.

Keywords pancreatic adenocarcinoma, surgery, diagnostic laparoscopy, pancreaticoduodectomy, pancreatectomy, whipple, jaundice, CA 19-9, vascular resection, lymph node ratio

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Ecker et al. Surgical Management of Pancreatic Adenocarcinoma original artiCle

DiscussionRisk Factors and Clinical PresentationDevelopment of pancreatic adenocarcinoma has been linked to tobacco use and familial susceptibility. Cigarette smoking poses one of the greatest environmental risks. Compared to patients with no cigarette smoking history, the relative risk for pancreatic cancer among active smokers ranged from 1.75 to 2.13, depending on smoking intensity, duration, and pack-years.3,4 Chronic pancreatitis, obesity, diabetes mellitus, and non-O blood group have also been found to increase the risk of pancreatic cancer.5,6,7,8

Approximately 5-10% of patients with pancreatic cancer have a positive family history.9.10 First and second degree family members of early-onset pancreatic cancer patients, defined as occurrence of cancer prior to age 50, experience greater risk of developing pancreatic cancer than those of late-onset pan-creatic cancer patients. The magnitude of this risk is propor-tional to the number of first-degree relatives affected by pan-creatic cancer and inversely proportional to the age at which pancreatic cancer is discovered.11 While the complete genetic basis for these familial associations are not known, BRCA2 and PALB2 germline mutations have been observed in up to 17% of familial pancreatic cancers.12,13

The presenting symptoms of pancreatic cancer depend on its location and the extent of disease. Classically, pancreatic malignancy presents with a combination of abdominal pain, jaundice and weight loss. Abdominal pain is reported by 79% of patients on presentation. Jaundice results from obstructive cholestasis, which is most commonly associated with cancer in the head of the pancreas. Painless jaundice occurs more

commonly than pain with jaundice and in may portend a more favorable prognosis.14

Staging of Pancreatic Adenocarcinoma

The Role of Staging ModalitiesPancreatic cancer staging is based on the TMN classification scheme developed by the American Joint Committee on Can-cer. The size of the tumor (T), involvement of regional lymph nodes (M), and presence of distant metastasis (N) are features used to estimate the extent and surgical resectability of the pancreatic cancer. Distant metastases and tumor encasement > 180° of the superior mesenteric artery (SMA) or celiac ar-tery (CA) are considered unresectable states by current guide-lines.15 A summary of the TMN classification scheme is shown in Table 1.

Staging is determined by specialized pancreatic comput-erized tomography ( CT) or magnetic resonance imaging (MRI) with contrast enhancement. The correlation between CT classification of resectability and intraoperative findings was 69 - 87% in recent studies.16,17 The large variation in range was likely a result of the quality of the imaging as well as the characteristics used by each institution to define resect-able disease.18 MRI has yet to demonstrate an advantage over helical CT in the detection of pancreatic cancer. Two studies have found that MRI was superior to CT for the detection of liver metastases, although the results fell short of significance by virtue of the small number of patients in each study.19,20 However, MRI has still been found to improve pre-operative assessment of respectability.21

Diagnostic laparoscopy (DL) with peritoneal cytology and laparoscopic ultrasonogra-phy has also been used to improve pre-operative stag-ing and identification of surgical candidates. There is considerable debate re-garding the cost-effective-ness and utility of DL.22 Some have suggested that all cases of radiographical-ly resectable disease should

Table 1. Staging of Pancreatic Ductal Carcinoma92

Stage Tumor Lymph Node Distant Metastases Characteristics

IA T1 N0 M0 Tumor limited to the pancreas, ≤ 2 cm

IB T2 N0 M0 Tumor limited to the pancreas, >2 cm

IIA T3 N0 M0 Tumor extends beyond the pancreas but without involve-ment of the celiac axis or the SMA

IIB T1, T2 or T3 N1 M0 Regional lymph node metastasis

III T4 N0 or N1 M0 Tumor involves the celiac axis or the superior mesenteric artery

IV T1, T2, T3 or T4 N0 or N1 M1 Distant metastasis

Table 2. Survival for Pancreatectomy Patients with Pancreatic Ductal Adenocarcinoma93

Stage 5-Year Survival (%) Median Survival (months)

IA 31.4 24.1

IB 27.2 20.6

IIA 15.7 15.4

IIB 7.7 12.7

III 6.8 10.6

IV 2.8 4.5


original artiCle Ecker et al. Surgical Management of Pancreatic Adenocarcinoma

Surgical candidates who present with obstructive jaundice can either proceed directly to surgery or undergo endoscopic stent placement to relieve hyperbilirubinemia with postponement of surgery to a later date. Hyperbilirubinemia leads to hepatic dysfunction and impaired mitochondrial activity that can persist up to 6 weeks post-obstruction.33 Early randomized trials found that hyperbilirubinemia increased perioperative morbidity.34 However, with the transition from percutaneous to endoscopic stenting, routine preoperative biliary drainage has become a less favorable option as studies have demon-strated no significant safety hazard for patients who proceed directly to surgery.35 In addition, patients who undergo preop-erative biliary drainage are at an increased risk for complica-tions from ERCP.36 While its role in surgical patients may be limited, preoperative biliary drainage will continue to be clini-cally relevant for patients with cholangitis and as a bridge to surgery in patients whom obstructive tumors are down-staged with neoadjuvant chemotherapy.

Goals of Surgery

Post-Operative Prognostic Factors Despite improvements in operative mortality and increasing resection rates, only 15 to 25% of patients survive five years beyond curative-intent surgery.37,38 Tumor stage remains the most important prognostic factor in pancreatectomy patients to date. The overall five-year survival for patients after pan-createctomy is summarized in Table 2. The prognosis for pa-tients who undergo pancreatic resection has also been associ-ated with pathological factors including histologic grade, and relative and absolute decreases (postoperative value <200) in tumor marker CA19-9.39,40 Resection margin and lymph node status are additional prognostic indicators.

undergo DL to exclude occult metastasis to the liver and peri-toneum, and to prevent patients with positive DL findings from undergoing laparotomy.23 CT-occult metastatic disease has been documented in 4-13% of patients at time of lapa-rotomy, which could have been detected earlier by laparoscopy in most cases.16,24 The yield of DL has been documented as high as 31% in the identification of occult metastasis for ra-diographically resectable disease, especially in cases of locally advanced cancer.25 Some of practitioners advocate the use of objective findings to determine the risk of unresectability and the selective use of DL.26 Preoperative CA 19-9 levels can assist in predicting stage and survival as it is associated with a high-er tumor burden. In one study, CA 19-9 levels below 100 cor-related with the absence of metastatic disease, as confirmed by diagnostic laparoscopy.27 Limitations include the biomarker’s lack of specificity for pancreatic adenocarcinoma and its in-accuracy in Lewis-negative phenotypes , which represent ap-proximately 5% of the general population.28,29,30

Laparoscopic ultrasonography has been proposed to improve assessment of retroperionteal tumor-vessel relationship and intraparenchymal hepatic metastases. In one study, laparo-scopic ultrasonography provided imaging of the portal vein, superior mesenteric vein, hepatic artery, and superior mesen-teric artery in greater than 90% of cases, and led to a change in surgical treatment in 14% of patients in whom standard lapa-roscopic examination was equivocal.31

Some patients require additional diagnostic studies. Endo-scopic ultrasonography (EUS) is useful in cases where no pancreatic lesion is visible by CT. Additionally, EUS can help elucidate tumor-vessel relationships or questionable lymphat-ic involvement,32 and guide fine-needle aspiration to obtain cytology samples. ERCP can also aid in tissue collection via ductal brushing and lavage, and is allows for endoscopic stent placement to relieve obstructive cholestasis.

The Role of Biliary Drainage

Figure 1. Contrast-enhanced CT venous phase image of a hypodense, poorly-defined pancreatic head mass.

Figure 2. Contrast-enhanced CT arterial phase image of enlarged Courvoisier’s gallbladder (GB), dilated distal pancreatic duct (PD), dilated distal common hepatic duct (CHD) and dilated low-inserting cystic duct (CD). The ex-tensive biliary and pancreatic duct dilatation suggests ob-structive cholestasis.

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ing from two Japanese retrospective reviews.53,54 Subsequently, a meta-analysis of several randomized control trials failed to confirm that pancreatoduodenectomy with extended lymph-adenectomy improves overall survival.55.56,57,58 Nevertheless, metastatic lymph nodes have independent prognostic signifi-cance.59 The presence or absence of nodal disease is not as valuable as the lymph node ratio (calculated as the number of positive nodes relative to the total number resected), which has been shown to improve assessment of post-operative prognosis.60,61 Riediger and colleagues confirmed the value of the lymph node ratio, and even found that patients with a single disease-positive lymph node had comparable overall survival to N0 patients, but prognosis significantly fell with two or more positive lymph nodes.62 There is some evidence that after two positive lymph nodes, there is a linear relation-ship between number of positive nodes and median survival.63

Surgical Strategies

Tumors of the Pancreatic HeadSeventy-eight percent of pancreatic adenocarcinomas are found in the pancreatic head and the remaining 22% are dis-tributed evenly between the body and tail. Tumors in the pan-creatic head are 7 times more likely to present with stage I than IV disease compared to tumors of the pancreatic tail, and are generally more amenable to surgical resection.64 Hence, the primary discussion of surgical interventions for pancreatic cancer will be related to the operative management of tumors of the pancreatic head. Four surgical options exist: “Whipple” pancreatoduodectomy (PD), pylorus-preserving pancreato-duodectomy (PPPD), total pancreatectomy and regional pan-createctomy.

In 1975, the Whipple procedure was an unfavorable surgery, with high morbidity and no survival benefit compared to pal-

Resection Margin StatusThe resection margin describes the absence of tumor cells at the limits of the resection field. An R0 resection is defined as the absence of tumor on both gross and microscopic analyses; an R1 resection is defined as a grossly negative resection with microscopically positive margins; and an R2 resection is de-fined as a grossly positive margin.41 There is no international consensus on the histologic definition of R1 for pancreatic cancer, and outside of North America, R1 often refers to the presence of tumor within 1 mm of the surgical margin.42 There is some evidence to suggest that expanding the definition of R1 from microscopic involvement to a 1-mm border has no impact on overall survival.43 Moreover, when margin clear-ance is examined as a function of long-term survival, there is no significant difference in overall survival until resection margins greater than 1.5-mm are achieved.44The SMA margin is the most common positive margin following pancreatecto-my, as perineural extension of the tumor into the autonomic plexus surrounding the SMA is rarely palpable or visible.45,46,47

An R0 resection margin, has demonstrated survival benefit in multiple studies, while the impact of an R1 resection margin on overall survival is a topic of continued debate.48,49 Evi-dence has shown that R1 has independent prognostic signifi-cance in retrospective analysis, yet others have found that R1 predicts poor survival on univariate but not multivariate anal-ysis.2,50,51 Neoptolemos et al. determined that resection margin status was no longer a predictor of outcome on multivariate analysis after accounting for tumor grade and nodal status.52 Raut et al. also found that R1 status did not independently af-fect survival on multivariate analysis. R0 vs. R1 status did not influence patterns of first recurrence nor the relative rates of local, regional, and distant sites for first recurrence47. Further research is needed to clarify the prognosis of R1 resections.

Nodal StatusMore extensive surgery to include radical lymph node dissec-tion initially appeared to benefit survival, with support deriv-

Figure 3. MRI venous phase T1-weighted image of pan-creatic adenocarcinoma (PA), which does not invade the adjacent superior mesenteric vein (SMV) and superior mesenteric artery (SMA).

Figure 4. Illustration of adenocarcinoma in the pancreatic head with invasion of the SMV. Note the intimate relation-ship between the pancreas and the SMA and SMV (insert). SMV: superior mesenteric vein; SMA: superior mesenteric artery; IVC: inferior vena cava; LRV: left renal vein.53



mortality, and low survival rates (3% at 3 years).75 Literature regarding the efficacy of the regional pancreatectomy has stalled since 1996, at which time Fortner reported a median 30-day mortality rate of 5.3%, and 33% 5-year survival for tu-mors <2.5 cm and 12% 5-year survival for tumors >2.5 cm.76 There has been no prospective trial to evaluate the relative benefit of regional pancreatectomy compared to PD, PPPD, and TD . However, since Fortner’s original publication, ma-jor developments in radiological and surgical techniques have resulted in improved vascular resection and reconstruction at the time of pancreaticoduodenectomy.

Borderline Resectable DiseaseGiven that curative resection provides the greatest potential survival benefit, surgical strategies have expanded to include resections for nearby vascular involvement. In contrast to Fortner’s regional PD, pancreaticoduodenectomy with vascu-lar resection has been implemented for the sole purpose of achieving negative resection margins. Primary cancers with tumor-associated deformity or reconstructible occlusion of the superior mesenteric vein (SMV), portal vein (PV), or SMV/PV confluence is considered as borderline resectable.15

Fuhrman et al. demonstrated no differences in perioperative morbidity, mortality or margin positivity in patients who un-derwent pancreaticoduodenectomy with resection of isolated venous involvement. The need for venous resection did not have an impact on survival duration, with a reported median survival of approximately 2 years.77 Patients who undergo ve-nous resection have comparable nodal positivity and tumor histology compared to patients who do not undergo venous resection.78 The data suggests that isolated venous involve-ment is a function of tumor location rather than a marker of aggressive tumor behavior.

The development of venous thrombosis as a complication of venous resection,, has been shown to occur in 17% of patients at a mean time of 11.9 months. Approximately half of patients

liative surgical bypass.65 Over the last thirty years, operative mortality and 1-year survival rates have greatly improved. Sur-gical treatment with curative intent has become the strongest predictor of survival.66 Even margin-positive PD is associated with improvements in median survival as compared to pallia-tive bypass in locally advanced disease.67 Long-term survival rates, however, continue to be poor.68

A head-to-head comparison of PD with or without pylorus re-section by randomized control trials demonstrated no signifi-cant difference in overall survival of pylorus-preserving pan-creaticoduodenectomy (PPPD) as compared to the Whipple procedure.69,70,71 There have been inconsistent results regarding improvements in operative time, blood loss and volume of blood transfused during PPPDas well as postoperative inci-dence of delayed gastric empyting .69,70,71

Extensive surgical options include total and regional pancre-atectomy. Total pancreatectomy (TP) was developed to achieve wider margins of resection, avoid tumor spillage and avoid the complications of pancreatic fistula. Compared to patients who undergo PD, TP patients have more lymph nodes harvested and are more likely to have negative margins upon surgical resection.50, However, single institution series from Memorial Sloan-Kettering and Johns Hopkins have showed no overall survival benefit in patients who undergo TP.72,73 Moreover, the pancreatic exocrine insufficiency and brittle diabetes resulting from TP leads to patient-reported declines in functional and symptom-based scales.74

The regional PD includes en bloc regional lymph node dis-section and resection of the portal vein (Type I) or a locally involved major artery (Type II). In 1973, Fortner found these extended resections useful to improve resectability rates, al-though the procedure was associated with high morbidity,

Figure 5. MRCP with evidence of external compression (red arrow) of common bile duct (CBD) and pancreatic duct (PD). Also note external compression on the distal pancreatic duct by the mass (yellow arrow).

Figure 6. 3D MRCP of an enlarged gallbladder (GB) and “double duct” sign of enlarged common bile duct (CBD) and pancreatic duct (PD). Note, there is also mild dilata-tion of the intrahepatic biliary tree (IBT).

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resection.

Arterial resection includes pancreaticoduodenectomy with re-moval and reconstruction of the celiac axis or superior mesen-teric artery (SMA). Arterial tumor extension is classified as T4, and had traditionally been considered as a contraindication for surgery. However, there is growing evidence that challenges the exclusion of arterial involvement from surgical manage-ment. Bachellier et al. demonstrated no significant increase in postoperative morbidity or mortality for patients undergoing arterial resection.80. Martin II et al. observed a mean overall survival length of 22 months for 3 patients who underwent hepatic artery resection and a mean overall survival length of 11.5 months in patients who underwent SMA resection.81

Operative Management of Tumors of the Distal PancreasRarely, tumors of the distal pancreas can be detected early in their course, permitting surgical intervention. When in-dicated, curative resection for lesions in the body or tail can improve survival, nearly doubling median survival time to achieve long-term survival rates comparable to resections for pancreatic head lesions.82 Moreover, recent retrospective analy-sis supports the application of distal pancreactomy for locally

received anticoagulation with aspirin, warfarin or clopidogrel, but did not experience a significant reduction in thrombosis rates. A limitation of the study is the variety of venous recon-struction methods used (primary lateral venorrhaphy, PTFE graft, primary end-to-end repair and autologous vein graft).79 There has been no head-to-head comparison of reconstruc-tion techniques for pancreaticoduodenectomy with venous

Figure 7. Transabdominal ultrasound of pancreatic head mass.

Figure 8. Diagnosis and staging algorithm adapted from the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Pancreatic Adenocarcinoma V.2.2012. All recommendations are cat-egory 2A. Reproduced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Pancreatic Adenocarcinoma V.2.2012. © 2012 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of the NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES™, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc.15



experience pain relief with endoluminal stenting and avoid the need for palliative surgery.85 Moreover, recent prospective studies have demonstrated that prophylactic duodenal, biliary or double bypass surgery neither reduces the need for subse-quent hospitalization prior for pain control nor decreases the proportion of patients requiring future palliative intervention. Hence, there is accumulating evidence to favor non-operative palliative procedures in lieu of surgical management of non-resectable disease.

Future and Experimental StrategiesAdvances in the detection of tumor, both operatively and in the pathology specimen, will aid surgical management. Re-cent application of monoclonal antibodies against tumor-as-sociated antigens has identified occult nodal spread in lymph nodes that were found to be free of metastasis on routine histopathologic examination. Bogoevski et al. found that pa-tients with R0 resections, who were free of nodal involvement by both histopathologic and immunohistochemical analysis were twice as likely to survive the observational period with-out recurrence when compared to patients with R0 resec-tions and histopathologically negative nodal disease, but with positive immunohistochemical staining.87 Most significantly, an isolated nodal microenvironment influenced both mean relapse-free and overall survival on multivariate analysis. Im-munocytologically detected metastasis in peritoneal lavage and bone marrow aspirates have similarly been predictive of

advanced pancreatic adenocarcinoma following neoadjuvant chemoradiation. Preliminary support from a small retrospec-tive series of distal pancreatectomy with en bloc celiac axis resection achieved a 91% R0 resection rate. Carefully selected Stage III patients with lesions in the distal pancreas experi-enced median disease-free and overall survival rates of 21 and 26 months, respectively.83

Palliative ManagementMost patients with pancreatic adenocarcinoma present with advanced disease that precludes curative surgical manage-ment. Palliation of pain and biliary and duodenal obstruction have been managed both surgically and medically.

Pain control via chemical splanchnicectomy can be performed at the time of non-therapeutic laparotomy or as a percuta-neous procedure for those staged non-operatively. Chemical neurolysis reduces narcotic requirements and can more than double the mean number of pain-free months for those with-out pain at presentation. In addition to improved quality of life, patients treated with chemical splanchnicectomy dem-ostratated significantly longer survival than patients undergo-ing medical management for pain control.84

Surgical bypass has become less common given the advances in endoluminal biliary and duodenal stenting. Single institu-tion data from Memorial Sloan-Kettering has suggested that 98% of patients with unresectable periampullary cancer can

Figure 9. Role of biliary drainage in cases complicated by cholangitis adapted from the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Pancreatic Adenocarcinoma V.2.2012. All recommendations are category 2A. Reproduced with permission from the NCCN Clinical Practice Guidelines in Oncol-ogy (NCCN Guidelines®) for Pancreatic Adenocarcinoma V.2.2012. © 2012 National Comprehensive Cancer Net-work, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of the NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDE-LINES™, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc.

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8. Wolpin BM, Chan AT, Hartge P, Chanock SJ, Kraft P, Hunter DJ, Giovannucci EL, Fuchs CS. ABO blood group and the risk of pancre-atic cancer. J Natl Cancer Inst. 2009 Mar 18;101(6):424-31.

9. Shi C, Hruban RH, Klein AP. Familial pancreatic cancer. Arch Pathol Lab Med 2009;133:365-74.

10. Ghadirian, P., P. Boyle , A. Simard , J. Baillargeon , P. Maisonneuve , C. Perret. Reported family aggregation of pancreatic cancer within a population-based case-control study in the Francophone community in Montreal, Canada. Int J Pancreatol 1991;10:183–196.

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overall survival.88

New technologies are being developed to improve surgical resections by enhancing the surgeon’s ability to distinguish tumor from normal pancreatic tissue.89,90 Preclinical trials in an orthotopic mouse model of pancreatic cancer have demon-strated that fluorescence-guided surgery (FGS) can improve complete tumor resection, decrease tumor burden and im-prove disease-free survival.91 The utility of these technologies in human patients warrants further investigation.

ConclusionPancreatic ductal adenocarcinoma is a major oncologic bur-den with poor prognosis despite multi-modality therapy. Sur-gical outcomes have improved over the last three decades, but there is much room for improvement in all aspects of treat-ment. Continued collaboration between surgical, medical and radiation oncologists has the greatest promise for improving cure rates and overall survival for affected patients and their families.

DisclosuresThe authors have no disclosures or conflicts of interest related to this manuscript.

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IntroductionAn 81 year-old male with a medical history notable for atrial fibrillation, aortic and mitral stenosis and severe coronary artery disease was admitted for evaluation of a 6 month history of melena. Upper endoscopy, colonoscopy and capsule study two months prior to presentation only demonstrated non-bleeding colonic diverticula. A tagged red blood cell scan on admission demonstrated proximal jejunal hemorrhage (A, arrow). The patient underwent angiography in the interventional radiology suite with gelfoam embolization of the visualized bleeding site (B). Following the procedure, the patient developed worsen-ing abdominal pain with peritonitis localized to upper abdomen associated with lactate acidemia. He under-went a focused exploratory laparotomy, during which a 10 cm necrotic segment of jejunum was identified (C), resected, and repaired with a jejunojejunal anastomosis. His postoperative course was complicated by hypoten-sion requiring vasopressors, but he eventually recovered without adverse consequences.

The safety and efficacy of superselective embolization for management of lower gastrointestinal bleeding has been studied in small cohorts.1-8 The most common complica-tions are bowel ischemia (3-10%) and recurrent hemor-rhage (10-20%).1-5 Ischemic complications occur most fre-quently in the context of angioembolization for colonic bleeding, due to the lack of abundant collateral arterial supply. Ischemic complications in more proximal lower gastrointestinal bleeding are rare, likely because of the

more redundant collateral circulation to the small bowel. Patients who initially undergo embolization and subse-quently require surgical intervention have a demonstra-bly higher rate of anastamotic leak. While there is a role for superselective angioembolization in the management of lower gastrointestinal bleeding, we recommend small bowel resection with primary anastomosis as the ini-tial step in good operative candidates and patients with massive hemorrhage in whom a delay in treatment can be detrimental. However, especially in small bowel low-er gastrointestinal hemorrhage, it is imperative that the bleeding source is identified preoperatively. This can be accomplished with angiography without or with provoca-tion. It is helpful to the surgeon for the angiographer to leave the catheter parked in the mesenteric vessel adjacent

Citation Susarla, SM. Jejunal Necrosis following Angio-embolization for Lower Gastrointestinal Hemorrhage. J Surg Radiol. 2012 Oct 1;3(4).

CorrespondenCe Claudius Conrad, MD, PhD E-mail [email protected].

reCeived February 7, 2012. aCCepted October 1, 2012. epub October 1, 2012.

Jejunal Necrosis following Angioembolization for Lower Gastrointestinal HemorrhageSrinivas M. Susarla, DMD, MD, MPH, David R. King, MD, Claudius Conrad, MD, PhDDepartment of Surgery, Massachusetts General Hospital, Boston, MA, USA.

Abstractoverview The safety and efficacy of superselective embolization for management of lower gas-trointestinal bleeding has been studied in small cohorts.. This image presentation illustrates that angioembolization can be the initial and sole treatment modality for patients with recurrent bleed-ing.

Keywords angioembolization, GI bleed, jejunum, bowel necrosis, ischemic necrosis

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Susarla et al. Jejunal Necrosis original artiCle

to the bleeding site in order to facilitate intra-operative identification of the cul-prit small bowel loop. For patients in an intermediate risk category, where the risks of laparotomy might outweigh the risks of recurrent bleeding, angioemboliza-tion can be considered the initial and sole treatment modality.

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IntroductionA 54-year-old man underwent VATS lung resection for a left upper lobe tumour. Prior inspection of the CT im-ages suggested abnormal bronchovascular anatomy (Fig-ure 1). At surgery, abnormalities of both the bronchial and pulmonary arterial anatomy were identified (Figure 2). There were separate bronchi arising from the left main bronchus for the lingular and upper lobe trisegment (an-terior, apical and posterior segments) (Figure 3). The pulmonary arterial branch to the superior segment of the lower lobe originated very proximally from the left pulmonary artery and then took a course lateral to the

abnormal trisegment bronchus as shown in figures one and two. Consequently, the trisegement bronchus had the main pulmonary arterial trunk to the lower lobe running medial to it and the abnormal branch to the superior seg-ment running laterally. The anatomy was carefully delin-eated before proceeding to a VATS left upper lobe trisge-mentectomy and adenectomy.

Awareness of the possibility of structural abnormalities is essential with VATS resection and mandates careful study of imaging and operative findings.

Citation Woolley, S. Abnormal Anatomy Encountered During VATS Left Upper Lobe Trisegmentectomy. J Surg Radiol. 2012 Oct 1;3(4).

CorrespondenCe Michael Hughes E-mail [email protected]

reCeived October 9, 2011. aCCepted October 1, 2012. epub October 1, 2012.

Abnormal Anatomy Encountered During VATS Left Upper Lobe TrisegmentectomySteve Woolley MBBS1, Michael Hughes, MBChB1, Graham McKillop, MBChB2, William S Walker MBChB1

1. Department of Thoracic Surgery, Royal Infirmary of Edinburgh.2. Department of Radiology, Royal Infirmary of Edinburgh.

Abstractoverview Abnormalities of pulmonary vasculature and bronchial anatomy are of key impor-tance in performing lung resections especially via a VATS approach. This series of images illustrates the need to be aware of structural abnormalities when completing thoracic procedures.

Keywords Anatomy, Pulmonary artery/veins, thoracoscopy/VATS

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