upper extremity lymphedema after axillary lymph …

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Lymphology 49 (2016) 44-56

UPPER EXTREMITY LYMPHEDEMA AFTER AXILLARY LYMPH NODE DISSECTION:

PROSPECTIVE LYMPHOSCINTIGRAPHIC EVALUATION

A. Szuba, A. Chachaj, M. Koba-Wszedybyl, R. Hawro, R. Jasinski, R. Tarkowski,M. Bebenek, K. Szewczyk, J. Forgacz, A. Jodkowska, D. Jedrzejuk, M. Landwójtowicz,

D. Janczak, I. Malicka, K. Pawlowska, M. Piwowarczyk, U. Pilch, M. Wozniewski

Division of Angiology (AS,AC) and Department of Surgery (DJ), Wroclaw Medical University & 4th Military Hospital in Wroclaw; Departments of Internal Medicine (MK-W,AJ), Oncology andGynecological Oncology (RH,RT,KS), and Endocrinology (DJ,ML), Wroclaw Medical University;Faculty of Physiotherapy, University School of Physical Education (RH,RJ,IM,KP,MP,UP,MW); andLower Silesian Oncology Center (RT,MB,KS,JF), Wroclaw, Poland

ABSTRACT

This prospective study was designed toevaluate changes in upper extremity lymphaticdrainage after ALND in comparison to thepreoperative status using lymphoscintigraphy.The study enrolled 44 women (mean age:57.95; range: 35-80) with a new diagnosis ofunilateral invasive breast carcinoma who hadbeen scheduled to undergo ALND. This was asubstudy of the physiotherapeutic project, inwhich subjects after ALND were randomizedinto 4 groups treated with: 1) rehabilitationexercises; 2) manual lymphatic drainage; 3) pneumatic compression pump; and 4)education only. Clinical evaluation whichincluded arm measurements and lymphoscin-tigraphy was performed in every subject beforesurgery and 3 times after surgery (1-6 weeks,1 and 2 years after ALND). Follow-up wascompleted in 44 subjects at 1 year and in 32subjects at 2 years. Lymphedema diagnosiswas made in 4 subjects 1 year after ALND(9%) and in 8 subjects 2 years after ALND(25%). Among them, respectively, only 50%and 62% noticed and reported lymphedema.Quantitative analysis of lymphoscintigramsand photoplethysmography results did not

reveal upper extremities lymphatic transportand/or venous function impairment after theALND procedure. Qualitative analysis oflymphoscintigrams revealed most commonlydisappearance of previously functional lymphnodes and appearance of dermal backflow insubjects who developed lymphedema.Conversely, appearance of functional lymphnodes in different locations after ALND mayindicate protection from development of upperextremity lymphedema.

Keywords: breast cancer, axillary lymph node dissection (ALND), lymphedema,lymphoscintigraphy, lymphatic transport,photoplethysmography, prospectiverandomized control study

Arm lymphedema is a frequentcomplication of breast cancer therapy andaffects 20-40% women with a delay of months to years after surgery. Aggressivecancer treatment may increase the risk oflymphedema (1-3). The condition is associ-ated with a number of physical symptoms,such as pain, impaired function of theaffected arm, infection, and occasionally skinmalignancy. It is also a cause of psychological

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morbidity (anxiety, depression, and emotional distress) that further negativelyaffects activities of daily living and worsenssurvivors’ overall quality of life (4,5).

The pathophysiology of arm lymph-edema after breast cancer treatment is notfully understood. Disruption of lymphaticsdue to axillary lymph nodes dissection(ALND) and radiation therapy are recognizedas the major pathophysiological factors (6).The history of infection in the arm on the sideof breast surgery and obesity are the otherwell recognized risk factors of breast cancerrelated lymphedema (3,6,7).

However, the majority of women afterALND do not develop arm lymphedema inspite of the same treatment. Assumedpathomechanisms of arm lymphedema afterALND are: deterioration of newly developedcollateral circulation by fibrous scar andradiation therapy, lymphatic pump failuredue to lymphatic overload, and venoushypertension caused by axillary/subclavianvein stenosis or occlusion. Conversely,protective mechanisms include: existence ofadditional extraaxillary lymphatic pathwaysand development of peripheral lymphovenouscommunications (8).

At this point, it is not possible to identifypatients who will develop lymphedema aftercancer treatment. We designed this prospec-tive study to evaluate changes in upperextremity lymphatic drainage after ALND incomparison to the preoperative status usinglymphoscintigraphy. The prospective studymay lead to better understanding of patho-genesis of breast cancer related lymphedema.

MATERIAL AND METHODS

Patients

We have prospectively recruited 44women (mean age: 57.95; range: 35-80) with a new diagnosis of unilateral invasive breastcarcinoma who were scheduled to undergooperation, including ALND. ALND wasperformed by an experienced team of

oncological surgeons. The standard surgicalprocedure has been fully described previously(9). In brief, regardless of the clinical axillarylymph node (ALNs) status, the removal oflevels I, II and III nodal tissue in one blocwas performed in every case. The axillaryvein was the upper limit of the range ofsurgery and the posterior wall of the axilla(including subscapularis, latissimus dorsi andteres major muscles) was clearly seen duringeach surgery.

The subjects enrolled into our study werethe participants in a larger physiotherapeuticproject and agreed to have additional lympho-scintigraphies according to our protocol. All recruited subjects were randomized intoone of 4 groups regarding physiotherapy afterALND: 1) rehabilitation exercises (n=11); 2) manual lymphatic drainage (n=16); 3)pneumatic compression pump (n=12); and 4)educational program only (n=5). The subjectswere followed for two years after ALND. The physiotherapy program was initiated one day after the surgery and conducted 5times a week for 4 weeks. If lymphedema was diagnosed in a participating subject,immediate decongestive lymphatic therapy(DLT) including compression, manuallymphatic drainage, pneumatic pump, andskin care was initiated.

The study was approved by the LocalBioethical Committee of the WroclawMedical University and all subjects gaveinformed written consent prior to inclusion inthe study. Selected demographic and medicalparameters are presented in Table 1.

Study Design

The study protocol for all subjectsincluded: physical examination, measure-ments of both upper limbs circumferences in4 cm intervals, lymphoscintigraphy, andphotoplethysmography. Evaluation wasperformed before surgery, 1-6 weeks aftersurgery, and 1, and 2 years later.

Lymphedema diagnosis in our subjectswas made when both of the following


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diagnostic criteria were fulfilled: 1) upperextremity circumference measurements weremeasured at 4 cm distance: the upper limb

edema was defined as at least 2.0 cm circum-ference difference increase at minimum 2 armlevels, and 2) upper extremity edema volume

TABLE 1 Demographic and Medical Parameters of the Subjects


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increase: the upper limb edema was definedas at least 200 ml difference between operatedarm and not operated arm, adjusted for thepre-op difference between arm volumes. Armvolume was calculated from arm circum-ferences measured at 4 cm distances using the formula for a truncated cone (10).

Lymphoscintigraphy

Bilateral subcutaneous injection of 0.25mCi of 99mTc-Nanocoll was performedsimultaneously in both hands in the secondand the third interdigital space (total dose per subject amounted 1mCi).

Static acquisitions were obtained 10minutes and 2 hours after the injection. Thisprocedure was performed preoperatively andwas repeated further 3 times: 1-6 weeks, 1 year and 2 years after the surgery.

ALNs status before and after ALND wasevaluated in every subject qualitatively andquantitatively.

Qualitative analysis was performed forevery patient independently by two physicians.The patients were divided into the followinggroups:

(1) disappearance of previouslyfunctional lymph nodes,

(2) appearance of dermal backflow(accumulation of the radiotracer within thesubcutis/skin),

(3) lymph nodes seen in the samelocalization,

(4) lymph nodes seen in the same andadditionally in different locations,

(5) lymph nodes seen in differentlocations, and

(6) lymphocele.For quantitative analysis, symmetrical

regions of interest (ROIs) were placed overthe injection site and over the axilla on eachlymphoscintigram. Radioactivity in ROIswere measured 10 minutes after injection(ROI0) and 2 hours later (ROI2h), before andafter ALND.

Quantification of lymphatic transportwas performed by calculation for each upper

extremity before and 3 times after surgery (1-6 weeks, 1 year, and 2 years after ALND)the following parameters:

(1) Axillary ratio 2 hours post injection(AR2h): the radioactivity was measured atROI over axilla 2 hours post injection(ROIax.) to radioactivity of symmetrical ROIover injection site (ROIinj.) for each upperextremity before and 3 times after surgery byusing the formula: AR2h = (ROIax. / ROIinj.);

(2) AR2h ratio = AR2h operated arm /AR2h non-operated arm was calculated forevery subject before and 3 times after ALND;

(3) Tracer disappearance rate from theinjection site 2 hours post injection (TD2h):the radioactivity was measured at ROI overboth sites of injection (ROIinj.) for each upperextremity before and 3 times after ALND byusing the formula: TD2h = (ROIinj.

0 /ROIinj.

2h);(4) Tracer disappearance ratio (TD2h

ratio) = TD2h operated arm / TD2h non-operated arm was calculated for every patientbefore and 3 times after ALND.

Photoplethysmography

Venous photoplethysmography wasperformed to evaluate the effect of ALND onvenous flow in the upper extremities. Venousphotoplethysmography of upper limbs wasperformed with Rheo Dopplex II PPG (HNEMedical) in subjects before and after ALNDon the days of lymphoscintigraphy. Examina-tion was performed in the sitting positionwith upper extremities allowed to hang down.The photoplethysmographic sensor wasplaced on the dorsal side of the wrist and thesubjects then performed 10 rhythmical elbowflexions. The photoplethysmographic curvewas recorded during the exercises. Thevenous pump index (Vp) and venous refillingtime (RT) were automatically calculatedusing software provided by manufacturer(HNE Medical Inc.).

Statistical Methods


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Statistical analysis was performed usingStatistica for Windows 12. Differencesbetween lymphoscintigraphic and photo-plethysmographic parameters before andafter ALND were evaluated using t-test fordependent samples. Comparisons of quanti-tative parameters of lymphoscintigrams insubjects with and without lymphedema wereevaluated using t-test for independentsamples. Differences were consideredsignificant when p was < 0.05.

RESULTS

Follow-up has been at 1 year for 44subjects and at 2 years for 32 subjects. 2subjects died and 10 withdrew their consentprior to the 2 years follow-up visit.

Lymphedema was diagnosed on the basisof circumferential measurements in 4 subjectsat 1 year after ALND (9%) and in 8 subjectsat 2 years after ALND (25%). Among them,only 50% (2/4) 1 year after ALND and 62%

(5/8) 2 years after ALND were aware of ownlymphedema.

Qualitative analysis of lymphoscintigramsrevealed that disappearance of previouslyfunctional lymph nodes and appearance ofdermal backflow 1 or 2 years after ALNDwere the lymphoscintigraphic features morefrequently present in subjects with lymph-edema. 1 year after ALND, ALNs werevisualized in 36 of 40 examined breast cancersurvivors without lymphedema (90%) incomparison to 2 of 4 breast cancer survivorswith lymphedema (50%). 2 years after ALND,ALNs were visualized on lymphoscintigramsin all examined breast cancer survivorswithout lymphedema (100%) in comparisonto 6 of 8 breast cancer survivors withlymphedema (75%). Table 2 presents thelymphoscintigraphic features observed inlymphoscintigrams in subjects with and with-out lymphedema 1 and 2 years after ALND.

Analysis of lymphoscintigramsperformed 1-6 weeks after ALND in subjects

TABLE 2 Lymphoscintigraphic Features in Women With and Without Lymphedema


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TABLE 3Lymphoscintigraphic Features in Women With and Without History of Adjuvant Chemotherapy

TABLE 4Lymphoscintigraphic Features in Women With and Without History of Adjuvant Radiotherapy


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Fig. 1. Lymphoscintigrams of a subject who developed lymphedema (case 1). Lymphoscintigraphy prior to thesurgery reveals symmetric axillary lymph nodes. 3 weeks after left ALND, no axillary lymph nodes (ALNs) on theleft side were seen and draining set filled with tracer/lymph. 1 and 2 years after surgery no ALNs are visualized onthe operated side and accumulation of the radiotracer within the subcutis/skin (“dermal backflow”) is present. Arm edema (lymphedema) became evident at 2 years.

Fig. 2. Lymphoscintigrams of a subject with lymphedema (case 2). Prior to the surgery weak and slightly asymmetricvisualization of ALNs. Three weeks after left side ALND, patchy and diffuse accumulation of radiotracer is seenin the arm on the operated side consistent with acute lymphedema (although still minimal volume change). 1 and 2years after surgery, no ALNs are visualized on the operated side and accumulation of the radiotracer within thesubcutis/skin (“dermal backflow”) is present with measurable arm edema (lymphedema).

who developed lymphedema 1 or 2 years after ALND (n=8) and subjects without upperextremity lymphedema 1 or 2 years afterALND (n=36) revealed the following featureson postoperative lymphoscintigrams associ-ated with development of lymphedema after1-2 years: (1) appearance of dermal backflow[in 2 subjects with lymphedema (25%) and in

1 subject without lymphedema (2.7%)]; (2)presence of lymph nodes in the same andadditional different locations [in 2 subjectswith lymphedema (25%) and in 4 subjectswithout lymphedema (11.1%)]; and (3)lymphocele [in 2 subjects with lymphedema(25%) and in 5 subjects without lymphedema(13.9%)].


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Presence of lymph nodes in the samelocation (seen in the group with lymphedemain 5 subjects (62.5%) and in the groupwithout lymphedema in 24 subjects (66.7%))was not associated with future lymphedemadiagnosis. Both lack of any lymph nodevisualization without lymphocele and lymphnodes only seen in different locations wererarely seen on early lymphoscintigrams (notpresent in subjects with lymphedema and,respectively in 1 subject and 2 subjects in thegroup without lymphedema).

Tables 3 and 4 presents the lympho-scintigraphic features observed inlymphoscintigrams 1 and 2 years after ALND in subjects with and without history of application of adjuvant chemo- andradiotherapy.

Figs. 1-4 present the examples oflymphoscintigraphic alterations that arepresent more often in subjects withlymphedema. Fig. 5 shows the example oflymphoscintigram in women withoutlymphedema.

Fig. 3. Lymphoscintigrams of a subject with lymphedema (case 3). Prior to surgery, slightly asymmetric visualizationof ALNs is seen. Three weeks after right side ALND, a proximal lymph node (possibly supraclavicular) is visualized.1 and 2 years after surgery, a supraclavicular LN is visualized on the operated side and slight accumulation of theradiotracer within the subcutis/skin (“dermal backflow”) is present with arm edema (lymphedema) at 2 years.

Fig. 4. Lymphoscintigrams of a subject with lymphedema (case 4). Prior to the surgery, symmetric visualization ofALNs is seen. Three weeks after left side ALND, axillary LNs are still visualized. 1 and 2 years after surgery axillaryLNs are still visualized. At 2 years after ALND, intercalated LNs on the operated side are better visualized, thereis slight accumulation of the radiotracer within the subcutis/skin (“dermal backflow”) and measurable arm edema(lymphedema).


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Quantitative analysis of lymphoscinti-grams revealed that the lymphatic transportfrom the upper extremities was not affectedby the ALND procedure. Table 5 displays nostatistical difference in lymphoscintigraphicaxillary ratio and tracer disappearance rateratio (AR2h ratio and TD2h ratio) before andafter ALND. Table 6 demonstrates thecomparison of AR2h ratio and TD2h ratio insubjects with and without lymphedema.

These differences ware also statistically notsignificant.

Photoplethysmography results also showthat venous function was not affected by thesurgery. Table 7 presents the values of venouspump index (Vp) and venous refill time (RT)of the upper extremity on the operated side.They did not differ statistically relevantlybefore and after ALND.

Fig. 5. Lymphoscintigrams of a subject without lymphedema (case 5). Prior to the surgery, symmetric visualizationof ALNs is seen. Three weeks after right side ALND, no ALNs are visualized on the operated side. 1 and 2 yearsafter surgery, a supraclavicular LN is visualized on the operated side and arm edema is not present.

TABLE 5Differences Between Lymphoscintigraphic Axillary Ratio (AR2h) and

Tracer Disappearance Rate (TD2h) Before and After ALND


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TABLE 6Comparison of AR2h and TD2h in Women With and Without Lymphedema

TABLE 7Photoplethysmography Results: Venous Pump Index and

Venous Refill Time of the Upper Extremity on the Operated Side Before and After ALND


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DISCUSSION

In this prospective study, the overallincidence of objectively diagnosed lymph-edema at 1-2 years after ALND was 9% and25%, which is consistent with other reports(1-3). Circumference difference above 2 cm atminimum 2 arm levels and upper extremityedema volume increase of at least 200 mlwere our cut-off point for the diagnosis oflymphedema. Dominant arms can benaturally up to 2 cm in circumference and200 ml in volume greater that non-dominant(11-13). Unlike in the majority of studies, weincluded arm measurements before surgery to our study protocol. This way we were ableto control and recognize a truer increase ofupper extremity circumference and volumedue to operation and adjuvant treatment.

The incidence of lymphedema based onobjective measurements in many cases doesnot reflect the prevalence of lymphedemareported by affected women. In our study,only half of the subjects from lymphedemagroup after 1 year after ALND and 62.5% ofwomen after 2 years after ALND reported tohave arm edema. On the other hand, approxi-mately 20% of subjects in the group withoutlymphedema diagnosed using our criteriacomplained to suffer from this condition.Subjects in the group with lymphedema morefrequently complained of upper extremitypain and functional impartment, which is inagreement with published reports ondisability and lymphedema (4,5).

Subjects with lymphedema in our studyhad greater BMI, more frequently history ofhypertension, history of radical mastectomyand adjuvant therapy (radiotherapy,chemotherapy, hormone therapy), which isalso in agreement with other studies onlymphedema risk factors (2,6,7,14).

Removal of a greater number of lymphnodes during ALND is the most importantrisk factor of lymphedema. It can beexplained by the greater disruption of upperextremity lymphatic drainage pathwaysduring more extensive axillary surgery. The

sentinel lymph node biopsy (SLNB) lowersthe incidence of lymphedema to the level of3-7%. Recent studies demonstrated that theremoval of more than 5 axillary lymph nodessignificantly increases the risk of lymphedema.After the removal of 10 or more lymph nodes,the prevalence of arm lymphedema increasesin an approximately linear manner (3,14,15).Removal of up to five lymph nodes has been suggested to be safe with respect tolymphedema (16). However, Britton et al.demonstrated that in 13 of 15 women,lymphatic drainage from upper extremity and from the breast were separated but in the other 2 of 15 patients, sentinel lymphnode (SLN) was joint (17). Patients with SLNwithin the common lymphatic drainagepathway for breast and upper extremity maybe at increased risk of developing lymph-edema after ALND.

In our study, ALNs after ALND werevisualized significantly more often onlymphoscintigrams in breast cancer survivorswithout lymphedema in comparison tosubjects with this complication, and thisfinding may indicate a protective effectagainst lymphedema. This supports ourearlier findings in which the presence offunctional ALNs seen by lymphoscintigraphyin subjects after breast cancer surgery andALND was associated with lower frequencyof lymphedema development (18). Presenceof ALNs after ALND may be due to a lowernumber of nodes resected during surgery.However, recent studies confirm that ALNsthat remain after ALND are not the ones that were missed during the surgery. Theirpresence is rather a natural consequence ofclassic surgical technique of level I+II+IIIALND procedure that does not allow removalof all ALNs in the majority of operatedsubjects. There may also be a hereditarypredisposition to breast cancer relatedlymphedema development, provided, that is,by individual anatomical arrangement ofaxillary lymph nodes (9,16).

Early lymphedema may develop withoutlymphoscintigraphic evidence of impaired


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lymphatic drainage. However, our studyshows that there are some characteristiclymphoscintigraphic features that are presentmore often in subjects with lymphedemadiagnosis. Disappearance of previouslyfunctional lymph nodes and appearance ofdermal backflow seem to correlate withlymphedema development. Conversely,presence of lymph nodes in differentlocalization after surgery seems to indicate aprotective effect. Their presence could be areflection of collateral lymphatic pathwayswhich were recruited, and they may be seenas a compensatory mechanism afterimpairment of axillary lymphatic system.

We were also searching for characteristicfeatures of lymphoscintigrams performedearly after ALND that may help predictdevelopment of lymphedema 1 or 2 yearsafter surgery. This analysis indicates thatdermal backflow, presence of lymph nodes in the same and additionally in differentlocations, and lymphocele were more commonin women who developed lymphedema after 1 and 2 years.

Our study also indicates that history of adjuvant chemotherapy and radiotherapyis associated with similar lymphoscinti-graphic features as lymphedema onset, i.e.,disappearance of previously functionallymphnodes and appearance of dermalbackflow.

Taking into account that subjects whowere enrolled in our study were the partici-pants in the rehabilitation project, theprevalence and severity of lymphedemamight be lower than in the average popula-tion of breast cancer survivors. Differenttypes of rehabilitation may influence lymphdrainage and lymphoscintigraphic patterns.Unfortunately, our subgroups were too smallto examine these data. Published studies havedemonstrated that physiotherapy treatmentimproves upper extremity function afterALND. It also helps to identify presence oflymphedema at its earliest stage, and earlytreatment prevents progression to the chronicphase of the disease, associated with fibrosis

and lipid deposition in the subcutaneoustissue that is more difficult to treat (19).

CONCLUSIONS

Our study shows that pre- and post-surgical lymphoscintigraphy cannot predictthe risk of lymphedema development.However, we have found some characteristiclymphoscintigraphic features that are presentmore often in subjects who developedlymphedema. Disappearance of previouslyfunctional lymph nodes and appearance ofdermal backflow seems to be associated withlymphedema development. In contrast,presence of lymph nodes in differentlocalization after ALND may indicate someprotection from lymphedema development.

ACKNOWLEDGMENT

The study was supported by the PolishMinistry of Science and Higher EducationGrant N40406631/3041.

REFERENCES

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2. Yen, TW, X Fan, R Sparapani, et al: Acontemporary, population-based study oflymphedema risk factors in older women withbreast cancer. Ann. Surg. Oncol. 16 (2009),979-988.

3. Paskett, ED, MJ Naughton, TP McCoy, et al:The epidemiology of arm and hand swellingin premenopausal breast cancer survivors.Cancer Epidemiol. Biomarkers Prev. 16(2007), 775-782.

4. Chachaj, A, K Malyszczak, K Pyszel, et al:Physical and psychological impairments ofwomen with upper limb lymphedemafollowing breast cancer treatment.Psychooncology 19 (2010), 299-305.

5. Smoot, B, J Wong, B Cooper, et al: Upperextremity impairments in women with orwithout lymphedema following breast cancertreatment. J. Cancer Surviv. 4 (2010), 167-178.


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6. Kwan, ML, J Darbinian, KH Schmitz, et al:Risk factors for lymphedema in a prospectivebreast cancer survivorship study: ThePathways Study. Arch. Surg. 145 (2010),1055-1063.

7. Vignes, S, M Arrault, A Dupuy: Factorsassociated with increased breast cancer-related lymphedema volume. Acta. Oncol. 46(2007), 1138-1142.

8. Szuba A, SG Rockson: Lymphedema:Anatomy, physiology and pathogenesis. Vasc.Med. 2 (1997), 321-326.

9. Szuba, A, Z Chachaj, M Koba-Wszedybylb, et al: Axillary lymph nodes and armlymphatic drainage pathways are sparedduring routine complete axillary clearance inmajority of women undergoing breast cancersurgery. Lymphology 44 (2011), 103-112.

10. Casley-Smith, JR: Measuring andrepresenting peripheral oedema and itsalterations. Lymphology 27 (1994), 56-70.

11. Schunemann, H, N Willich: [Lymphedemaafter breast carcinoma. A study of 5868cases]. Dtsch. Med. Wochenschr. 122 (1997),536-541.

12. Segerstrom, K, P Bjerle, S Graffman, et al:Factors that influence the incidence ofbrachial oedema after treatment of breastcancer. Scand. J. Plast. Reconstr. Surg. HandSurg. 26 (1992), 223-227.

13. Szuba, A, WS Shin, HW Strauss, et al: The third circulation: Radionuclidelymphoscintigraphy in the evaluation oflymphedema. J. Nucl. Med. 44 (2003), 43-57.

14. Meeske, KA, J Sullivan-Halley, AW Smith, et al: Risk factors for arm lymphedemafollowing breast cancer diagnosis in Blackwomen and White women. Breast CancerRes. Treat. 113 (2009), 383-391.

15. Engel, J, J Kerr, A Schlesinger-Raab, et al:Axilla surgery severely affects quality of life:Results of a 5-year prospective study in breastcancer patients. Breast Cancer Res. Treat. 79(2003), 47-57.

16. Goffman, TE, C Laronga, L Wilson, et al:Lymphedema of the arm and breast inirradiated breast cancer patients: risks in anera of dramatically changing axillary surgery.Breast J. 10 (2004), 405-411.

17. Britton, TB, CK Solanki, SE Pinder, et al:Lymphatic drainage pathways of the breastand the upper limb. Nucl. Med. Commun. 30(2009), 427-430.

18. Szuba, A, A Pyszel, D Jedrzejuk D, et al:Presence of functional axillary lymph nodesand lymph drainage within arms in womenwith and without breast cancer-relatedlymphedema. Lymphology 40 (2007), 81-86.

19. Singh C, M De Vera, KL Campbell KL: Theeffect of prospective monitoring and earlyphysiotherapy intervention on arm morbidityfollowing surgery for breast cancer: A pilotstudy. Physiother. Can. 65 (2013), 183-191.

Andrzej Szuba MD, PhDProfessor of Medicine Department of Internal MedicineWroclaw Medical University &

4th Military Hospital in Wroclaw Weigla 5 street50- 981 Wroclaw, Poland Phone/fax: +48 71 7660599 Email: [email protected]


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