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Multimodality Imaging Approach, Staging and Therapy
Assessment of Esophageal Cancer
Erika G. Odisio1, Jeremy J. Erasmus1, Brett Carter1, Carol Wu1, Sonia B. Cuellar1, Myrna C. Godoy1
Department of Diagnostic Radiology, Thoracic Imaging Section1
The University of Texas MD Anderson Cancer Center – Houston –TX – USA
Financial disclosures: Myrna Godoy: Siemens Healthcare
Brett Carter: Amirsys-ElsevierCarol C. Wu: Elsevier,Inc
Description of the 7th edition of the American Joint Committer on Cancer (AJCC) Staging System for esophageal cancer (EC) and proposed changes for the 8th
edition.
Endoscopic esophageal ultrasound (EUS) is the optimal modality to access tumor depth ( T classification ) and has a reported accuracy of 89%.
EUS with ultrasonography-guided biopsy is the first choice for assessment of metastatic locoregional nodes (N status). The main role of CT is to identify suspicious non-locoregional lymph nodes and intrathoracic distant metastatic disease.
CT of the chest and abdomen with intravenous (IV) and oral contrast is the main imaging modality used to detect distant metastasis (cM).
The addition of 18F-2-deoxy-D-glucose (FDG)-positron emission tomography/computed tomography (PET/CT) improves the detection of metastases, especially with advanced cT and cN classifications. PET/CT is also used to assess response after neoadjuvant therapy.
Objectives/Teaching Points
7th Edition of AJCC for ECMajor modifications
Data-driven of 13 institutions based on 4627 esophagectomy patients who had no induction or adjuvant therapy.
Staging based on random forest (RF) analysis.
T classification was changed for Tis and T4 cancers.• Tis: high grade dysplasia including all noninvasive neoplastic epithelium.• T4: T4a or T4b based on resectable or unresectable tumors.
N: any lymph node (LN) from cervical to celiac is considered regional and staging are based on the number of cancer-positive nodes.
M: MX, M1a and M1b were eliminated. Distant metastasis is M1, no distant metastasis M0.
Includes cancer within the 5 cm of the stomach (cardia) that invade the esophagogastric junction (EGJ).
Includes histological grade.
8th Edition of AJCC for ECProposed changes
Expand the data analysis.
Better homogeneity of stage 0 and IV.
Improving homogeneity of stage IIB AC and stages IIA and IIB SCC.
Adding clinical (cStage), postinduction clinical and postdefinitive nonsurgical clinical (ycStage), and post-induction pathologic (ypStage) staging recommendations.
Adding nonesophagectomy survival data, endoscopic treatment in stage 0 and stage IA, and palliative therapy for stage IV.
Adding other nonanatomic tumor analysis that affect survival.
Adding cancer of cervical esophagus (harmonization as was done with GEJ tumors in the 7th edition).
7th Edition of AJCC for EC
Tumor
TX: primary tumor cannot be assessed
T0: no evidence of primary tumor
Tis: high-grade dysplasia
T1a: invasion of lamina propria or muscularis mucosaeT1b: invasion of submucosa
T2: invasion of muscularis propria
T3:invasion of adventitia
T4: invasion of adjacent structures:T4a: resectable (pericardium, pleura, or diaphragm)T4b: unresectable (other structures such as, vertebral body, aorta, trachea, vertebral
body, etc)
Regional Lymph node
NX: regional lymph nodes cannot be assessed
N0: no regional lymph node metastasis
N1: metastasis in 1-2 regional lymph nodes
N2: metastasis in 3-6 regional lymph nodes
N3: metastasis in ≥ 7 regional lymph nodes
Distant MetastasisM0: no distant metastasis
M1: distant metastasis present
Histologic grade
GX: grade cannot be assessed - stage grouping as G1
G1: well differentiated
G2: moderately differentiated
G3: poorly differentiated
G4: undifferentiated – stage group as G3 squamous
Table: 7th edition of AJCC for EC published in 2010
It is based on the deep of mural invasion of the primary tumor. EUS is the most accurate imaging tool for esophageal T score: differentiation of
the 5 histological layers of the esophageal wall. 3th layer: preservation or obliteration determines T1a or T1b disease, respectively 5th layer: preservation or obliteration determines T2 or T3 disease, respectively. Preservation of fat plane between the aorta or left atrium and the tumor excludes
T4 disease.
T score: the primary tumor
EUS probe
Muscularis propria
Submucosa
Interface between the balloon and the superficial mucosaLamina propria and muscularis mucosae
Interface between adventitia and surrounding tissues
Layers of esophageal wall. (a) Schematic and (b) EUS image.
a b
T score: the primary tumor
T1b tumor in a 82-year-old woman. (a) Axial contrast-enhanced CT image at the level of the ventricles show a suspected small intramural mass in the lower esophagus (arrow). (b) EUS image shows smooth, eccentric wall thickening (**), with focal obliteration of the submucosa (3th layer, arrows), biopsy-proven adenocarcinoma (AC). (c) This lesion was not appreciated by fused PET/CT.
a b c
**
Important considerations: EUS is the optimal modality to access tumor depth ( T classification ) and has a
reported accuracy of 89%. CT has poor sensitivity for depiction of the primary mass (approximately 67%
compared to EUS) PET/CT is not useful and should not be performed in the evaluation of early stage
esophageal cancer (cTis and cT1). PET/CT has low sensibility for detection of EGJ adenocarcinoma that secrete mucin.
EUS potential limitations: operator-dependence, peritumoral edema (overstating), stenosis (may restrict
evaluation and biopsy sampling in up to 30% of the patients). Blurring of the normal 5 layer wall pattern can be consistent with either post
treatment inflammatory effect or tumor staging after neoadjuvant therapy secondary to fibrosis and adherence.
T score: the primary tumor
Stenotic esophageal AC with GEJ involvement in a 69-year-old man that presented with progressive dysphagia. (a) Axial contrast-enhanced CT image show an eccentric distal esophageal mass (arrow). (b) Fused PET /CT image shows FDG uptake of the lesion with SUV max of 12. (c,d) EGD image shows exophytic, friable and estenotic esophageal mass. (f) EUS shows T3 tumor penetrating the adventitia (arrow). (g) EUS shows peritumoral lymph node (arrow) biopsy-proven locoregional metastatic disease.
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Nodal classification allows risk stratification for overall survival after surgery and it is an independent predictor of survival in esophageal cancer.
N score is based in the number of involved locoregional lymph nodes.
Any paraesophageal node located from the cervical to celiac region is considered locoregional, independent of the site of the primary esophageal tumor.
The rich lymphatic plexus surrounding the esophagus permits bidirectional tumor spread and development of “skip metastases” to nodes at other levels, without the first involvement of lymph nodes at the same level of the primary tumor, and are found in up to 20% of resected tumors.
EUS with ultrasonography-guided biopsy is superior to both CT and PET/CT for N staging with sensitivity, specificity and accuracy of 89%, 75% and 84%, respectively.
N score: locoregional LN
EUS criteria for pathologic LN is based on size (>1 cm) and morphology (round with hypoechoic central echo pattern).
EUS with fine needle aspiration (FNA) biopsy permits cytologic confirmation of LN metastases. CT and PET-CT are important to show suspicious nonregional LN for FNA biopsy.
N score: locoregional LN
EUS image show round lymph node with hypoechoic central echo pattern (arrows) suspicious for metastatic disease in a 64 year-old woman presenting esophageal GEJ adenocarcinoma . EUS-FNA was positive for locoregional metastatic disease.
AC of the esophagus (uT3N2) in a 75-year-old man presenting dysphagia. (a,b,c) Axial contrast-enhanced CT images show enlarged right paratracheal LN (arrow); concentric thickening of the distal esophageal wall (*) with adjacent LN (arrow) and extension of the esophageal mass to the cardia (arrow), respectively. (d,e,f) Fused PET/CT images at same levels of “a”, “b”, “c”, respectively, show high FDG uptake of respective structures. (g,h,i) EUS images show enlarged, hypoechoic and round right paratracheal LN ( FNA positive for locoregional metastatic disease ); peritumoral LN correspondent to images “b” and “e”; and esophageal mass with obliteration of adventitia (arrows on image “I”), respectively. The patient received induction chemotherapy with minimal response (persistent GEJ tumor, not shown) and proceed with definitive concurrent chemoradiation.
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SUV max= 9.9
SUV max= 20.1
SUV max= 7.5
SUV max= 20.1
CT limitations: Criteria for pathologic LN is based on
short-axis diameter only (> 1 cm). Overstaging: inflammatory LN. Understaging: LN < criteria size with
microscopic metastatic foci, conglomeration of lymph nodes, LN adjacent to the esophageal mass may not be distinguish from the mass.
PET/CT limitations: Understaging: FDG uptake of primary
tumor not distinguished from locoregional LN (“ Bloom effect”).
Overstaging: inflammatory LN.
N score: locoregional LN
Surveillance of distal EC status post-chemoradiation in a 61-year-old man. (a) EUS image shows irregular thickening of the distal esophagus with blurring of the normal 5 layer wall pattern consistent with either post treatment inflammatory effect or tumor (arrows). (b) Fused PET/CT image at same level of “a” shows FDG metabolic activity with [SUV max] = 3.91 that may be related with primary neoplasm and/or treatment-related changes (arrow). Endoscopic FNA reveled recurrent AC.
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CT of the chest and abdomen with IV and oral contrast is the main imaging modality used to detect distant metastasis (cM).
T4B: CT provides evaluation of extension within aorta and trachea in staging T4B (non resectable).
The addition of FDG PET/CT improves the detection of metastases, especially with advanced cT and cNclassifications. PET/CT is also used to assess response after neoadjuvant therapy.
M score: distant disease
Metastatic esophageal AC of the GEJ in a 70-year-old men with right shoulder pain. (a) Axial contrast-enhanced CT at the level of the shoulders shows no abnormalities. (b) Fused PET/CT at same level of “a” shows high FDG uptake in the subscapularismuscle (arrow). FNA was positive for metastatic tumor. The patient underwent chemoradiation therapy (CRT) .
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M score: distant disease
Metastatic esophageal adenocarcinoma of the GEJ with peritoneal carcinomatosis in a 58-year-old men. (a,b) Axial contrast-enhanced CT and fused PET/CT image sat same level show distal esophageal wall thickening with high FDG uptake (SUV max of 22.3), extending into the stomach along the lesser curvature (arrow), compatible with a gastroesophageal malignancy. Note mesenteric and peritoneal soft-tissue nodules consistent peritoneal carcinomatosis (*) in “a”. (c,d) Fused PET/CT images show signs of left lower paratracheal, paraaortic and subcarinal nodal metastatic disease presented with high FDG uptake. (e) Whole-body anterior maximal intensity projection image of PET/CT shows extensive metastatic abdominal disease.
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fMetastatic esophageal adenocarcinoma (cT3N2M1) in a 73 -year-old woman with progressive dysphagia and weight loss. (a,b) Axial contrast-enhanced CT and fused PET/CT images show circumferential distal esophageal wall thickening (arrows) with high FDG uptake (SUVmax of 28). (c,d) Axial contrast-enhanced CT and PET/CT images show distal extension of the mass towards the proximal aspect of the stomach with high FDG uptake (arrows). (e,f) Axial contrast-enhanced CT and fused PET/CT images of an enlarged LN adjacent to the left carotid and left subclavian arteries with high FDG uptake with a SUVmax of 21.2. (g,h) Axial contrast-enhanced CT and fused PET/CT images show distal retroperitoneal lymph node with high FDG uptake with a SUVmax of 32.2.
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The most common histological types of esophageal cancer are the squamous cell carcinoma (SCC) and adenocarcinoma (AC), which together represented more than 90% of malignant esophageal tumors.
AC has a better prognosis than SCC independent of staging (5-year survival rate after resection of 42% compared with 30% for SCC).
Tumor histopathologic type, grade and location
Squamous cell carcinoma Adenocarcinoma SCC arises from progression of a dysplasic epithelium.
Malignant degeneration of underlying Barrett’s epithelium.
The incidence is three times higher in African Americans than Caucasians, and increases with age, peaking in the 7th decade.
It shows increased incidence most notably among white males.
In up to 65% of the cases, SCC arises above the level of the carina.
Three-fourths of the cases are seen at the distal esophagus.
Risk factors: moderate to heavy alcohol consumption, tobacco use, lower socioeconomic status, tylosis (autosomal-dominant syndrome characterized by oral precursor lesions, palmoplantar keratoderma and high risk of EC) .
The majority of cases are linked with Barrett's esophagus (substitution of stratified squamous epithelium by columnar epithelium). Obesity has been attributed as a risk factor (gastroesophageal reflux secondary to the increase of abdominal girth).
Signet ring cell (SRC) carcinoma:
Distinct histologic subtype of AC with predominant component ( > 50% of the tumor) composed of SRC in the stroma.
SRC carcinoma of the esophagus or GEJ is associated with an advanced stage at presentation, respond less well to induction therapy and presents decreased overall survival when compared with non-SRC histopathology.
Tumor histopathologic type, grade and location
A hematoxylin and eosin–stained slide of esophageal adenocarcinoma with signet ring cell features (arrows). (Original magnification ×400.) (Credit: Enlow JM et al, Ann Thorac Surg, 2013
Synchronic SCC of the esophagus (T3N2M0) in a 63-year-old woman with a history of progressive weight loss and dysphagia. (a,b) Axial contrast-enhanced CT images show concentric thickening of the distal esophageal wall and a smaller mural mass at proximal esophagus (arrows), respectively. (c,d) Fused PET/CT images at same levels show high FDG uptake of the distal esophageal wall (SUVmax 15.9 ) and proximal esophageal wall ( SUVmax 4.2). (e) EUS shows upper paratracheal lymph node. Fine needle aspiration (FNA) was consistent with metastatic locoregional SCC.(f) EUS shows T3 staging at level of distal esophageal mass, with the obliteration of the adventitia (arrow). No evidence of distant metastatic disease.
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Tumor staging, comorbidities and age should be taken in consideration to define the best therapy assessment.
Esophagectomy remains the primary treatment for EC when the tumor is resectable and clinical conditions permits.
T1a (high grade dysplasia and intramucosal cancer limited to the muscularismucosa) have low risk of LN involvement, estimated between 0 to 2%, and can be management with endoscopic therapy [endoscopic submucosal resection (EMR) and radiofrequency ablation in selected cases]. Indications for esophagectomy are incomplete EMR or failure of endoscopic treatment.
T1b and T2 have increased risk of lymph node metastases compared with T1a secondary to the muscularis mucosa invasion. Esophagectomy is indicated if clinical condition permits.
Locally advanced EC can be managed with combined modality treatment, including definitive chemoradiation therapy (CRT) and neoadjuvantchemotherapy and radiotherapy and esophagectomy.
Surgical resection or definitive CRT should still be offered to patients with complete metabolic response on PET/CT since residual microscopic tumor cannot be detected.
Supportive care treatment for nonsurgical patients includes esophageal stent placement, percutaneous gastrostomy, chemotherapy, radiotherapy.
EC treatment
Esophageal SCC in situ/high grade squamous dysplasia (Tis) in a 46-year-old man , discovered during evaluation of esophageal FDG uptake on PET/CT for surveillance of Hodgkin’s lymphoma. (a,b) Fused PET/CT images within 2 months interval show increased FDG uptake area in the esophageal wall ( from SUVmax of 4.05 on image “a” to SUV max of 6.34 on image “b”). (c) EUS image at this time with no abnormal findings. FNA biopsy was performed and was positive for in situ/high grade squamous dysplasia (Tis). (d) EGD using staining chromoscopy with Lugol’s solution revels some areas of decreased uptake on the esophageal wall without mucosal irregularity or nodularity (arrows) that was treated with radiofrequency (RFA) ablation. Follow-up PET/CT after RFA showed no FDG activity at the treated location (not shown).
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Stenotic esophageal SCC T4N2 after chemoradiation in a 72-year-old man with dementia who underwent supportive care. (a) Axial contrast-enhanced CT image shows 5.4 cm soft tissue mass involving the distal esophagus (arrows). (b) Coronal contrast-enhanced CT image shows the longitudinal extension of the esophageal mass. (c) Fused PET/CT image shows high FDG uptake with SUVmax of 11.7 at same level of “a”. (d) Axial contrast-enhanced CT image shows interval placement of esophageal stent (arrows) for palliative care. Patient posteriorly underwent gastrostomy.
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Palliative care of EC
b d
T3 tumor in a 68-year-old man who underwent Ivor-Lewis esophagectomy 8 years earlier and presented with pathology concerning for positive proximal margin . EGD follow-up (not shown) demonstrated nonbleeding ulcer at the level of the anastomosis. (a) Axial contrast-enhanced CT image does not show definite abnormality at the esophagogastrostomy anastomosis (arrow). (b) Fused PET/CT image at same level of “”a”” shows focal metabolic activity with SUVmax of 4.1, suspicious fro residual/recurrent disease (arrow). (c) EUS image shows an eccentric mass (**), with focal obliteration of the adventitia (5th layer, arrow), biopsy-proven recurrence of adenocarcinoma at the corresponding area.
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Therapy assessment of EC
Therapy assessment of ECResponse evaluation
e
PET-CT has an important role in the evaluation of residual tumor tissue after CRT to predictive EC outcome and prevent futile surgery when interval metastases are detected.
PET-CT study should be done before endoscopic biopsy and 3 weeks after the end of CRT to avoid false-positive study due to inflammatory changes.
Decrease in SUV max of 35% - 60% between baseline staging and post CRT imaging correlate to pathologic response within the esophageal tumor.
Persistent FDG uptake ≥ 4 correlate to persistent viable macroscopic malignancy and poor outcome.
CT cannot evaluate presence of residual tumor after CRT and EUS-FNA have limitations related with fibrosis, treatment-related inflammation and stenosis.
Surgical resection or definitive CRT should still be offered to patients with complete metabolic response on PET-CT since residual microscopic tumor cannot be detected.
Therapy assessment of ECResponse evaluation
Esophageal adenocarcinoma in a 59-year-old men (T3N2) presented with progressive weight loss. (a,b) Fused PET/CT images show distal esophageal mass ( SUVmax of 7.0 ) and 2.0 cm left gastric LN with FDG uptake ( SUVmax of 3.5), respectively (arrows). FNA of left gastric LN showed poorly differentiated AC. Patient completed induction chemotherapy followed by chemoradiation. (c) Restaging fused PET/CT image shows decrease in FDG uptake of the esophageal mass with SUVmax of 3.2, demonstrating metabolic response of the tumor. The previously biopsied LN resolved (not shown). Patient underwent esophagectomy with complete pathologic response. (d,e) Axial CT-enhanced image after 12 and 18 months, respectively, show subsolid nodule in the left upper lobe that has increase in size and attenuation , biopsy-proven metastatic adenocarcinoma.
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Therapy assessment of ECResponse evaluation
Esophageal AC in a 64-year-old woman (T3N0). (a) Fused PET/CT image shows high FDG uptake on the distal esophagus with SUVmax of 23.6 (arrow). (b) Restaging fused PET/CT image post neoadjuvant chemoradiation with docetaxel and 5-fluorouracil shows decreased FDG uptake ( SUVmax of 6.2 ), possibly related residual disease or inflammatory changes related to therapy. Endoscopic esophageal biopsy was negative at this time and minimally invasive esophagectomy was performed. Surgical pathology revealed 40% viable tumor with no nodal involvement (pT3N0) (c,d) Restaging fused PET/CT images after 2 years show high FDG uptake characterizing distant metastatic disease to the right shoulder and liver, respectively (arrows).
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Future Trends: Biomarkers
Therapy assessment of EC
The RNA expression of thymidylate synthase (TS) in the blood is a potential bad prognostic marker in patients with neoadjuvant-treated EC. Patients with TS expression above 0.78 had a median survival of 1.1 years compared to 2.6 years in patients with TS expression lower than 0.78 (p=0.031, log rank test).
Periostin is an extracellular matrix protein that participates in motility and cell adhesion in the tumor microenvironment. Preclinical models using evaluating probes have demonstrated that specific imaging of periostin in esophageal SCC is feasible using a target PET tracer. This probe could play a role in the future for early detection, post-surgical follow up and with in situ characterization of primary and metastatic lesions using PET/CT images.
The biomarker TP53 divides EC patients into 2 categories with markedly different outcomes: patients with a normal TP53 marker status may experience notable benefits from neoadjuvant chemotherapy with cisplatin/fluorouracil, whereas those with a mutant TP53 marker status appear to be at risk for lack of response.
• Kayani B, Zacharakis E, Ahmed K, Hanna GB. Lymph node metastases and prognosis in oesophageal carcinoma--a systematic review. Eur J Surg Oncol. Sep 2011;37(9):747-753.
• Prenzel KL, Bollschweiler E, Schroder W, et al. Prognostic relevance of skip metastases in esophageal cancer. Ann Thorac Surg. Nov 2010;90(5):1662-1667.
• Howard JM, Johnston C. Patterns of lymphatic drainage and lymph node involvement in esophageal cancer. Abdom Imaging. Apr 2013;38(2):233-243.
• Rasanen JV, Sihvo EI, Knuuti MJ, et al. Prospective analysis of accuracy of positron emission tomography, computed tomography, and endoscopic ultrasonography in staging of adenocarcinoma of the esophagus and the esophagogastric junction. Ann Surg Oncol. Oct 2003;10(8):954-960.
• Godoy MC, Bruzzi JF, Viswanathan C, et al. Multimodality imaging evaluation of esophageal cancer: staging, therapy assessment, and complications. Abdom Imaging. Oct 2013;38(5):974-993.
• Cuellar SL, Carter BW, Macapinlac HA, et al. Clinical staging of patients with early esophageal adenocarcinoma: does FDG-PET/CT have a role? J Thorac Oncol. Aug 2014;9(8):1202-1206.
• Zhang Y. Epidemiology of esophageal cancer. World J Gastroenterol. Sep 14 2013;19(34):5598-5606.• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA: A Cancer Journal for Clinicians. 2015;65(1):5-29.• Lewis RB, Mehrotra AK, Rodriguez P, Levine MS. From the radiologic pathology archives: esophageal neoplasms: radiologic-pathologic
correlation. Radiographics. Jul-Aug 2013;33(4):1083-1108.• Shimizu M, Ban S, Odze RD. Squamous dysplasia and other precursor lesions related to esophageal squamous cell carcinoma. Gastroenterol
Clin North Am. Dec 2007;36(4):797-811, v-vi.• Daly JM, Fry WA, Little AG, et al. Esophageal cancer: results of an American College of Surgeons Patient Care Evaluation Study. J Am Coll Surg.
May 2000;190(5):562-572; discussion 572-563.• Siewert JR, Ott K. Are squamous and adenocarcinomas of the esophagus the same disease? Semin Radiat Oncol. Jan 2007;17(1):38-44.• Brown LM, Devesa SS. Epidemiologic trends in esophageal and gastric cancer in the United States. Surg Oncol Clin N Am. Apr 2002;11(2):235-
256.• Blaydon DC, Etheridge SL, Risk JM, et al. RHBDF2 mutations are associated with tylosis, a familial esophageal cancer syndrome. Am J Hum
Genet. Feb 10 2012;90(2):340-346.• Devesa SS, Blot WJ, Fraumeni JF, Jr. Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer. Nov
15 1998;83(10):2049-2053.• Mao WM, Zheng WH, Ling ZQ. Epidemiologic risk factors for esophageal cancer development. Asian Pac J Cancer Prev. 2011;12(10):2461-2466.• Hvid-Jensen F, Pedersen L, Drewes AM, Sorensen HT, Funch-Jensen P. Incidence of adenocarcinoma among patients with Barrett's esophagus.
N Engl J Med. Oct 13 2011;365(15):1375-1383.• Hoyo C, Cook MB, Kamangar F, et al. Body mass index in relation to oesophageal and oesophagogastric junction adenocarcinomas: a pooled
analysis from the International BEACON Consortium. Int J Epidemiol. Dec 2012;41(6):1706-1718.• Vaughan TL, Davis S, Kristal A, Thomas DB. Obesity, alcohol, and tobacco as risk factors for cancers of the esophagus and gastric cardia:
adenocarcinoma versus squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev. Mar 1995;4(2):85-92.• Rosch T. Endosonographic staging of esophageal cancer: a review of literature results. Gastrointest Endosc Clin N Am. Jul 1995;5(3):537-547.• Riquet M, Saab M, Le Pimpec Barthes F, Hidden G. Lymphatic drainage of the esophagus in the adult. Surg Radiol Anat. 1993;15(3):209-211.
References
• van Vliet EP, Heijenbrok-Kal MH, Hunink MG, Kuipers EJ, Siersema PD. Staging investigations for oesophageal cancer: a meta-analysis. Br J Cancer. Feb 12 2008;98(3):547-557.
• Siewert JR, Stein HJ, Feith M, Bruecher BL, Bartels H, Fink U. Histologic tumor type is an independent prognostic parameter in esophageal cancer: lessons from more than 1,000 consecutive resections at a single center in the Western world. Ann Surg. Sep 2001;234(3):360-367; discussion 368-369.
• von Rahden BH, Stein HJ, Feith M, Becker K, Siewert JR. Lymphatic vessel invasion as a prognostic factor in patients with primary resected adenocarcinomas of the esophagogastric junction. J Clin Oncol. Feb 1 2005;23(4):874-879.
• Yamashina T, Ishihara R, Nagai K, et al. Long-term outcome and metastatic risk after endoscopic resection of superficial esophageal squamous cell carcinoma. Am J Gastroenterol. Apr 2013;108(4):544-551.
• Tachimori Y, Kato H, Watanabe H. Surgery for thoracic esophageal carcinoma with clinically positive cervical nodes. The Journal of Thoracic and Cardiovascular Surgery. 12// 1998;116(6):954-959.
• Lerut T, Nafteux P, Moons J, et al. Three-field lymphadenectomy for carcinoma of the esophagus and gastroesophageal junction in 174 R0 resections: impact on staging, disease-free survival, and outcome: a plea for adaptation of TNM classification in upper-half esophageal carcinoma. Ann Surg. Dec 2004;240(6):962-972; discussion 972-964.
• Heidari P, Esfahani S, Turker NS, et al. Imaging of the secreted extracellular periostin, an important marker of invasion in tumor microenvironment in esophageal cancer. J Nucl Med. Jun 11 2015.
• Grimminger PP, Maus MK, Bergenthal J, et al. Prognostic impact of blood biomarkers TS and DPD in neoadjuvant-treated esophageal cancer patients. Anticancer research. Mar 2015;35(3):1297-1302.
• Kandioler D, Schoppmann SF, Zwrtek R, et al. The biomarker TP53 divides patients with neoadjuvantly treated esophageal cancer into 2 subgroups with markedly different outcomes. A p53 Research Group study. J Thorac Cardiovasc Surg. Nov 2014;148(5):2280-2286.
• D'Journo XB, Thomas PA. Current management of esophageal cancer. J Thorac Dis. May 2014;6 Suppl 2:S253-264.• Rice TW, Blackstone EH. Esophageal cancer staging: past, present, and future. Thorac Surg Clin. Nov 2013;23(4):461-469.• Stiekema J, Vermeulen D, Vegt E, et al. Detecting interval metastases and response assessment using 18F-FDG PET/CT after neoadjuvant
chemoradiotherapy for esophageal cancer. Clin Nucl Med. Oct 2014;39(10):862-867.• Nafteux PR, Lerut TE, Villeneuve PJ, et al. Signet ring cells in esophageal and gastroesophageal junction carcinomas have a more aggressive biological behavior.
Ann Surg. Dec 2014;260(6):1023‐1029.• Enlow JM, Denlinger CE, Stroud MR, Ralston JS, Reed CE. Adenocarcinoma of the esophagus with signet ring cell features portends a poor prognosis. Ann
Thorac Surg. Dec 2013;96(6):1927‐1932.• Yendamuri S, Huang M, Malhotra U, et al. Prognostic implications of signet ring cell histology in esophageal adenocarcinoma. Cancer. Sep 1
2013;119(17):3156‐3161.• Cuellar SL, Carter BW, Macapinlac HA, et al. Clinical staging of patients with early esophageal adenocarcinoma: does FDG‐PET/CT have a role? J Thorac Oncol.
Aug 2014;9(8):1202‐1206.• Fuster D, Mayoral M, Rubello D, et al. Is there a role for PET/CT with esophagogastric junction adenocarcinoma? Clin Nucl Med. Mar 2015;40(3):e201‐207.
References
