Lymphedema Rates Following Axillary Lymph Node Dissection With and Without Immediate Lymphatic Reconstruction: A Prospective Trial.

BACKGROUND: Immediate lymphatic reconstruction (ILR) has been proposed to decrease lymphedema rates. The primary aim of our study was to determine whether ILR decreased the incidence of lymphedema in patients undergoing axillary lymph node dissection (ALND). METHODS: We conducted a two-site pragmatic study of ALND with or without ILR, employing surgeon-level cohort assignment, based on breast surgeons' preferred standard practice. Lymphedema was assessed by limb volume measurements, patient self-reporting, provider documentation, and International Classification of Diseases, Tenth Revision (ICD-10) codes. RESULTS: Overall, 230 patients with breast cancer were enrolled; on an intention-to-treat basis, 99 underwent ALND and 131 underwent ALND with ILR. Of the 131 patients preoperatively planned for ILR, 115 (87.8%) underwent ILR; 72 (62.6%) were performed by one breast surgical oncologist and 43 (37.4%) by fellowship-trained microvascular plastic surgeons. ILR was associated with an increased risk of lymphedema when defined as ≥10% limb volume change on univariable analysis, but not on multivariable analysis, after propensity score adjustment. We did not find a statistically significant difference in limb volume measurements between the two cohorts when including subclinical lymphedema (≥5% inter-limb volume change), nor did we see a difference in grade between the two cohorts on an intent-to-treat or treatment received basis. For all patients, considering ascertainment strategies of patient self-reporting, provider documentation, and ICD-10 codes, as a single binary outcome measure, there was no significant difference in lymphedema rates between those undergoing ILR or not. CONCLUSION: We found no significant difference in lymphedema rates between patients undergoing ALND with or without ILR.

[Preventive axillary lymphovenous anastomoses simultaneously with lymph node dissection in the treatment of breast cancer for prevention of lymphedema of the upper limb (LYMPHA technique)]. / Preventivnoe nalozhenie limfovenoznykh anastomozov v podmyshechnoi oblasti odnomomentno s limfaticheskoi dissektsiei pri lechenii raka molochnoi zhelezy dlya profilaktiki limfedemy verkhnei konechnosti (metodika LYMPHA).

OBJECTIVE: To analyze the effect the LYMPHA technique on the incidence of upper limb lymphedema in patients with breast cancer after complete axillary lymph node dissection. MATERIAL AND METHODS: There were 89 patients with breast cancer and signs of metastatic lesion of axillary lymph nodes who underwent complete axillary lymph dissection. In group 1 (41 patients), the LYMPHA technique was used simultaneously with lymph node dissection; in group 2 (48 patients) - lymph node dissection alone. RESULTS: The follow-up period was 1 year. The LYMPHA technique prolonged surgery and decreased duration of postoperative lymphorrhea. The incidence of upper limb lymphedema was 9.8% and 22.9%, respectively. CONCLUSION: The LYMPHA technique was effective for prevention of upper limb lymphedema after complete axillary lymph node dissection in the treatment of breast cancer.

Oncologic safety of axillary lymph node dissection with immediate lymphatic reconstruction.

PURPOSE: Immediate lymphatic reconstruction (ILR) at the time of axillary lymph node dissection (ALND) can reduce the incidence of lymphedema in patients with breast cancer. The oncologic safety of ILR is unknown and has not been reported. The purpose of this study was to evaluate if ILR is associated with increased breast cancer recurrence rates. METHODS: Patients with breast cancer who underwent ALND with ILR from September 2016 to December 2020 were identified from a prospective institutional database. Patient demographics, tumor characteristics, and operative details were recorded. Follow-up included the development of local recurrence as well as distant metastasis. Oncologic outcomes were analyzed. RESULTS: A total of 137 patients underwent ALND with ILR. At cancer presentation, 122 patients (89%) had clinically node positive primary breast cancer, 10 patients (7.3%) had recurrent breast cancer involving the axillary lymph nodes, 3 patients (2.2%) had recurrent breast cancer involving both the breast and axillary nodes, and 2 patients (1.5%) presented with axillary disease/occult breast cancer. For surgical management, 103 patients (75.2%) underwent a mastectomy, 22 patients (16%) underwent lumpectomy and 12 patients (8.8%) had axillary surgery only. The ALND procedure, yielded a median of 15 lymph nodes pathologically identified (range 3-41). At a median follow-up of 32.9 months (range 6-63 months), 17 patients (12.4%) developed a local (n = 1) or distant recurrence (n = 16), however, no axillary recurrences were identified. CONCLUSION: Immediate lymphatic reconstruction in patients with breast cancer undergoing ALND is not associated with short term axillary recurrence and appears oncologically safe.

One key to fit all locks? Routine internal drainage to minimize seromas during thigh lift surgeries.

INTRODUCTION: Obesity is a worldwide epidemic. Complication rates after body contouring surgeries in massive weight loss patients were quite high, with seroma development being the second most common complication, reported rates averaging 15%-40%, Methods described to reduce the annoying high rate of seroma did not have a statistically significant difference in reducing seromas. METHODS: Our aim was to find a universal solution that could be used with any body-contouring surgery to manage seromas. We tried this novel technique initially on thigh lifts. Instead of wading in the jungle of methods aiming at preventing seromas, we contemplated a drainage channel that would continuously drain any fluid accumulation. The idea was borrowed from the hypothesis of Thompson on lymphoedema management. By excising an area of deep fascia overlying the Vastus Medialis muscle, the muscle would be directly exposed to any seroma fluid and would imbibe it as blotting paper. Furthermore, this technique would open new drainage channels between the superficial and deep lymphatics. This technique was tried in 20 patients, with the excision of deep fascia carried only in one limb. The other limb was left as a control. Rates of seroma formation were noted and duration before it dried up. FINDINGS: This technique significantly reduced the incidence of detected seromas and the amount of seroma fluid. CONCLUSION: This technique reduced the incidence of seroma formation, and is recommended for routine use during all thigh lift surgeries.

Human skin fibrosis: up-regulation of collagen type III gene transcription in the fibrotic skin nodules of lower limb lymphoedema.

OBJECTIVES: To investigate the cellular and molecular pathophysiology involved in the development of fibrotic skin of grade-3 lymphoedema patients with a focus on collagen types. METHODS: Fibrotic and normal skin biopsy samples obtained from grade-3 lymphoedema patients and normal individuals, respectively, were analysed by histopathology, quantitative real-time PCR and immunohistochemistry to examine collagen gene expression. RESULTS: Histopathologic analysis revealed epidermal changes such as orthokeratosis, hypergranulosis and irregular acanthosis in the skin biopsies. The thickened dermis contained nodules of haphazardly arranged thick collagen bundles. Real-time PCR data showed significant (P-value 0.0003) up-regulation of Collagen type I and type III gene transcripts in the fibrotic skin of patients resulting in 38.94-fold higher transcription of Collagen type III alpha-1 gene than of Collagen type I alpha-1 gene. Semi-quantification of the per cent of haematoxylin-DAB-stained area of immunohistochemistry images also showed significant (P < 0.0001) enhancement of both collagen proteins in the fibrotic skin of patients vs. normal human skin. CONCLUSIONS: Gene transcript analysis revealed significant up-regulation of Collagen type III vs. Collagen type I in fibrotic skin of limb nodules from patient biopsies. Histopathological and immunohistochemical analysis also revealed enhancement of Collagen types I and III in fibrotic vs. normal skin. The findings of this preliminary study indicate the potentially significant involvement of Collagen type III in the development of the fibrotic skin of grade-3 lymphoedema patients.

OBJECTIFS: Etudier la physiopathologie cellulaire et moléculaire impliquée dans le développement de la fibrose cutanée chez les patients atteints de lymphœdème de grade 3 en mettant l'accent sur les types de collagène. MÉTHODES: Des échantillons de biopsie cutanée fibrotique et normale obtenus respectivement de patients atteints de lymphœdème de grade 3 et d'individus normaux ont été analysés par histopathologie, par PCR quantitative en temps réel et par immunohistochimie pour examiner l'expression des gènes de collagène. RÉSULTATS: L'analyse histopathologique a révélé des changements épidermiques tels que l'orthokératose, l'hypergranulose et l'acanthose irrégulière dans les biopsies cutanées. Le derme épaissi contenait des nodules de faisceaux de collagène épais disposés au hasard. Les données de PCR en temps réel ont montré une régulation à la hausse significative (P = 0.0003) des transcrits des gènes de collagène de type I et III dans la peau fibrotique des patients, résultant en une transcription 38,94 fois plus élevée du gène alpha-1 du collagène de type III par rapport à celui du gène alpha-1 du collagène de type I. La semi-quantification du pourcentage de zone colorée à l'hématoxyline-DAB des images d'immunohistochimie a également montré une amélioration significative (P < 0.0001) des deux protéines de collagène dans la peau fibrotique des patients par rapport à la peau humaine normale. CONCLUSIONS: L'analyse de transcription génétique a révélé une régulation à la hausse importante du collagène de type III par rapport à celle du collagène de type I dans la peau fibrotique des nodules des membres provenant de biopsies de patients. L'analyse histopathologique et immunohistochimique a également révélé une amélioration du collagène de types I et III dans la peau fibrotique pa rapport à la peau normale. Les résultats de cette étude préliminaire indiquent l'implication potentiellement significative du collagène de type III dans le développement de la peau fibrotique des patients atteints de lymphœdème de grade 3.

Surgical Approach to Lymphedema Reduction.

PURPOSE OF REVIEW: For patients who have or may develop lymphedema due to oncologic resection, surgical options are available to prevent and treat this chronic disease. Here, we review the current pathophysiology, classification systems, surgical preventive techniques, and treatment options for lymphedema reduction. RECENT FINDINGS: Preventive surgical techniques, including de-escalation of axillary surgery, sentinel lymph node biopsy (SLNB), axillary reverse mapping (ARM), and lymphedema microsurgical preventive healing approach (LYMPHA), have been shown to reduce the incidence of lymphedema. Water displacement remains the gold standard for measuring limb volume and classification of lymphedema; however, lymphoscintigraphy and ICG lymphography are two novel imaging techniques that are now utilized to characterize lymphedema and guide management. Complete decongestive therapy (CDT) remains the mainstay of treatment. Vascularized lymph node transfer (VLNT) and lymphovenous bypass have shown promising results, particularly in advanced lymphedema stages. Combination therapy, incorporating both surgical and non-surgical approaches to lymphedema, yields best patient outcomes. Lymphedema is a chronic disease wherein management requires a combination of surgical and conservative treatments. Standardization in lymphedema staging, key outcome indicators, and quantitative data will be critical to establish the absolute best practices in lymphedema diagnosis and treatment.

Lymphaticovenous anastomosis: Treatment of a persistent breast seroma.

Lymphaticovenous anastomoses are mainly used in secondary limbs lymphedema. They also can be used to treat iatrogenic seroma. This technique was used to treat a patient with a painful breast seroma that appeared after a mastectomy with axillary dissection, resistant to multiple ponctions and persistent 8 months after. Pre operative both lymphoscintigraphy and lympho-MRI have been performed and we identified lymphatic ducts responsible for the seroma. The one involved in the seroma was also the preferential drainage network of the arm. Innoperative, we performed an indocyanine green angiography to map those lymphatic ducts. A total capsulectomy of the breast seroma has been performed. An incision was made in front of lymphatics selected for lymphaticovenous anastomoses on the anterior axilla face. We performed two microscopic lymphaticovenous anastomoses. The patient was followed up at one, three, six months and one year post operative. No recurrence occurred during the follow-up. At six month the arm perimeter reduced of two centimeters. Lymphoscintigraphy and lympho-MRI were performed at six month showing a disappearance of the drainage asymmetry and collateralities of the upper limb; and no measurable volume in projection of the right breast area. Lymphaticovenous anastomoses may be an effective therapeutic solution for resistant seroma after node dissection. Lymphoscintigraphy and lympho IRM are very useful in those cases.

A Lymphedema Surveillance Program for Breast Cancer Patients Reveals the Promise of Surgical Prevention.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is one of the most significant survivorship issues in breast cancer management. Presently, there is no cure for BCRL. The single greatest risk factor for developing BCRL is an axillary lymph node dissection (ALND). Lymphatic Microsurgical Preventative Healing Approach (LYMPHA) is a surgical procedure to reduce the risk of lymphedema in patients undergoing an ALND. We present our single institution results after offering LYMPHA in the context of an established lymphedema surveillance program. MATERIALS AND METHODS: A retrospective review of our lymphedema surveillance program at the University of Florida was performed over a 2-year period (March 2014-March 2016). LYMPHA was offered to patients undergoing ALND beginning in March 2015. Patients who developed lymphedema were compared with those who did not. Demographics and potential risk factors for development of lymphedema such as age, body mass index, clinical stage, radiotherapy, and chemotherapy were reviewed. RESULTS: Eighty-seven patients participated in the surveillance program over the study period with an average age of 60 y (range 32-83) and body mass index of 30 kg/m2 (range 17-46). The single most significant risk factor for the development for lymphedema was an ALND (P < 0.001). One of 67 patients undergoing a sentinel lymph node biopsy developed lymphedema (1.5%). Four of 10 patients who underwent an ALND alone developed lymphedema (40%). One of 8 patients in the ALND + LYMPHA group developed transient lymphedema (12.5%). CONCLUSIONS: Offering LYMPHA with ALND decreased our institutional rate of lymphedema from 40% to 12.5%. Long-term follow-up and randomized control trials are necessary to further elucidate the promise of this surgical technique to reduce the incidence of BCRL.

A novel pilot animal model for the surgical prevention of lymphedema: the power of optical imaging.

BACKGROUND: Breast cancer-related lymphedema affects more than 400,000 survivors in the United States. In 2009, lymphatic microsurgical preventive healing approach (LYMPHA) was first described as a surgical technique to prevent lymphedema by bypassing divided arm lymphatics into adjacent veins at the time of an axillary lymph node dissection. We describe the first animal model of LYMPHA. METHODS: In Yorkshire pigs, each distal hind limb lymphatic system was cannulated and injected with a different fluorophore (human serum albumin-conjugated indocyanine green or Evans Blue). Fluorescence-assisted resection and exploration imaging system was used to map the respective lymphangiosomes to the groin. Baseline lymphatic clearance of each hind limb lymphangiosome was obtained by measuring the fluorescence of each dye from centrally obtained blood samples. A lymphadenectomy versus lymphadenectomy with LYMPHA was then performed. The injections were then repeated to obtain clearance rates that were compared against baseline values. RESULTS: Human serum albumin-conjugated indocyanine green and Evans Blue allowed for precise lymphatic mapping of each respective hind limb using fluorescence-assisted resection and exploration imaging. Lymphatic clearance from the distal hind limb dropped 68% when comparing baseline clearance versus after a groin lymphadenectomy. In comparison, lymphatic clearance dropped only 21% when comparing baseline clearance versus a lymphadenectomy with LYMPHA. CONCLUSIONS: We describe the first animal model for LYMPHA, which will enable future studies to further evaluate the efficacy and potential limitations of this technique. Of equal importance, we demonstrate the power of optical imaging to provide real-time lymphatic clearance rates for each hind limb.

Immediate lymphatic reconstruction.

Although surgical and medical treatment options are available for the treatment of chronic lymphedema, there is no cure. Recent advances in microsurgery have provided an opportunity to perform immediate lymphatic reconstruction after lymphadenectomy for disease prevention. In this review, we provide the historical background leading to a paradigm shift in performing this procedure. We will also discuss the current evidence for immediate lymphatic reconstruction, potential oncologic procedures amenable to this approach, and detail ongoing challenges.

[Angiosarcoma in primary lymphoedema: A rare complication]. / Angiosarcome sur lymphœdème primaire du membre inférieur : une complication rare.

BACKGROUND: Chronic lymphoedema is classically complicated by recurring episodes of cellulitis. Degeneration to the angiosarcoma form (Stewart-Treves syndrome) is much less common. It occurs mainly in the upper limbs following surgery or radiotherapy for mammary neoplasia. Herein we report a rare case of Stewart-Treves syndrome (STS) of the lower limb as a complication of congenital lymphoedema. PATIENTS AND METHODS: A 69-year-old woman treated for bilateral lower-limb oedema present for 30years developed painful necrotic lesions in her left lower limb. A diagnosis of angiosarcoma was made based on biopsy of a nodular lesion. Since surgical excision was precluded by the extent of the lesions, chemotherapy was initiated with paclitaxel 175mg/m2 every 21days. The outcome was rapidly unfavourable and the patient died at her home during the third course of treatment. DISCUSSION: Angiosarcoma is an extremely rare complication of primary lymphoedema; treatment is poorly codified and the prognosis is unfavourable.

[Use of indocyanine green angiography in oncological and reconstructive breast surgery]. / Utilisation du vert d'indocyanine en chirurgie sénologique et reconstruction mammaire.

The Indocyanine green (ICG) is a soluble dye that is eliminated by the liver and excreted in bile. When illuminated by an near-infrared light, the ICG emits fluorescence in the near-infrared spectrum, which can be captured by a near-infrared camera-handled device. In case of intravenous injection, ICG may be used as a marker of skin perfusion. In case of interstitial injection, it may be useful for lymphatic network mapping. In oncological and reconstructive breast surgery, ICG is used for sentinel lymph node identification, to predict mastectomy skin flap necrosis, to assess the perfusion of free flaps in autologous reconstruction and for diagnosis and treatment of upper limb secondary lymphedema. Intraoperative indocyanine green fluorescence might also be used to guide the excision of nonpalpable breast cancer.

[Lymphedema of the lower limbs: Initial manifestation of gastric linitis plastica]. / Lymphœdème des membres inférieurs révélant une linite gastrique.

BACKGROUND: Primary lymphedemas are constitutional abnormalities of the lymphatic system. Secondary lymphedemas occur after damage to the lymphatic system, mainly after cancer treatments or tumour mass compression. There are many other causes, including filariasis, which is nonetheless very rare in France. PATIENTS AND METHODS: A 52-year-old man presented with a two-month history of increased size of the left leg. He was asymptomatic and in good general condition. Clinical examination revealed non-pitting lymphedema and ipsilateral hydrocele without loco-regional compressive lymph node. Initial extensive explorations were unremarkable. Lymphoscintigraphy revealed low tracer fixation in the left leg. The symptoms continued to worsen, with exacerbation and bilateralization of the lymphedema. Two months later, axillary lymph nodes appeared corresponding to metastasis from a signet-ring cell carcinoma. Despite two lines of chemotherapy, the patient died 8 months later due to multiple metastatic disease. DISCUSSION: Our case is remarkable because the lymphedema was not related to extrinsic compression and was the first symptom of gastric cancer. In the absence of compression, endo-lymphatic micro-metastases could constitute the causative process. Acquired lymphedema of the lower limbs must be recognized as a potential early symptom of gastric carcinoma and should therefore prompt further investigations.

[Nursing role and TPE in patients with lymphoedema of the limbs]. / Rôle infirmier et ETP chez les patients atteints de lymphœdèmes des membres.

Lymphoedema, primary and secondary after cancer treatment, is a chronic condition which has a significant impact on patients' quality of life. Therapeutic education plays an important role in the initial care and in the follow-up of these conditions.

[Algorithm for surgical treatment of limb lymphedema]. / Traitement chirurgical du lymphœdème des membres : algorithme de prise en charge.

Whether primary or secondary, limb lymphedema is a relatively common disease whose impact on the quality of life of patients is important. Although the microsurgical reconstruction techniques seem to be the techniques of choice in the treatment of limb lymphedema, no consensus about treatment of limb lymphedema has yet been defined. Considering the advantages and disadvantages of surgical techniques and their impact on the quality of life of patients, we propose a surgical treatment algorithm of limb lymphedema.

[Sirolimus-induced lymphedema in a kidney-transplant recipient: Partial recovery after changeover to tacrolimus]. / Lymphœdème induit par le sirolimus chez une greffée rénale : amélioration après remplacement par le tacrolimus.

BACKGROUND: Lymphedema induced by mTOR inhibitors is a side-effect rarely reported to date. PATIENTS AND METHODS: Long-lasting bilateral lower-limb lymphedema with left predominance developed in a 71-year-old stable renal transplant recipient after 40 months of sirolimus treatment. Although no change in lymphedema was observed after 21 months despite dosage reduced, it improved markedly after changeover to tacrolimus. DISCUSSION: Regardless of the individual drug, mTOR inhibitors can cause lymphedema. This effect may be countered through substitution with tacrolimus. CONCLUSION: Physicians should be aware of lymphedema as a side-effect of mTOR inhibitors. It can be improved by substitution with tacrolimus. However, early withdrawal of mTOR inhibitors is recommended before irreversible lymphedema occurs.

[Massive localized lymphedema]. / Lymphœdèmes massifs localisés.

BACKGROUND: Massive localized lymphedema (MLL) is a benign soft-tissue lesion that usually presents as a large and isolated mass in morbidly obese adults. PATIENTS AND METHODS: We report the case of a 39-year-old woman presenting obesity and multiple MLL. There was a large tumor in the left groin and two smaller lesions on the backs of the thighs. DISCUSSION: MLL is a benign tumor that must be removed wherever possible because such tumors may degenerate into angiosarcomas in 13% of cases. MLL is probably secondary to a prolonged obstruction of lymphatic vessels due to marked excess of adipose tissue.

[Risk factors associated with leg erysipelas (cellulitis) in sub-Saharan Africa: A multicentre case-control study]. / Facteurs de risque associés à l'érysipèle de jambe en Afrique subsaharienne: étude multicentrique cas-témoins.

BACKGROUND: Acute bacterial cellulitis of the leg (erysipelas) is a common problem involving considerable morbidity in dermatology practice in Africa. Previous studies conducted in Europe and North Africa have highlighted lymphoedema and toe-web intertrigo as independent factors associated with leg erysipelas. The aim of this case-control study was to identify risk factors associated with leg erysipelas in sub-Saharan Africa, within a different socio-economic and culture context. PATIENTS AND METHODS: We conducted a prospective case-control study in hospital dermatology departments in 8 sub-Saharan African countries over a 12-month period (October 2013 to September 2014). Each case of acute leg cellulitis was matched with 2 controls for age (±5 years) and sex. We analysed the general and local factors. RESULTS: During the study period, 364 cases (223 female, 141 male) were matched with 728 controls. The mean age was 42.15±15.15 years for patients and 42.11±36 years for controls. Multivariate analysis showed the following to be independent risk factors associated with leg erysipelas in our study: obesity (odds ratio [OR]=2.82 ; 95% confidence interval: 2.11-3.76), lymphoedema (OR=3.87, 95%CI: 2.17-6.89), voluntary cosmetic depigmentation (OR=4.29, 95%CI: 2.35-7.83), neglected traumatic wound (OR=37.2, 95%CI: 24.9-57.72) and toe-web intertrigo (OR=37.86, 95%CI: 22.27-64.5). CONCLUSION: The results of this study confirms the major role of local risk factors (toe-web intertrigo, lymphoedema) previously identified in other geographical settings. However, the originality of our study consists of the identification of voluntary cosmetic depigmentation as a risk factor for leg erysipelas in sub-Saharan Africa.

Non-endemic cases of lymphatic filariasis.

OBJECTIVE: Several cases of lymphatic filariasis (LF) have been reported in non-endemic countries due to travellers, military personnel and expatriates spending time in and returning from endemic areas, as well as immigrants coming from these regions. These cases are reviewed to assess the scale and context of non-endemic presentations and to consider the biological factors underlying their relative paucity. METHODS: Cases reported in the English, French, Spanish and Portuguese literature during the last 30 years were examined through a search of the PubMed, ProMED-mail and TropNet resources. RESULTS: The literature research revealed 11 cases of lymphatic filariasis being reported in non-endemic areas. The extent of further infections in recent migrants to non-endemic countries was also revealed through the published literature. CONCLUSIONS: The life-cycle requirements of Wuchereria and Brugia species limit the extent of transmission of LF outside of tropical regions. However, until elimination, programmes are successful in managing the disease, there remains a possibility of low rates of infection being reported in non-endemic areas, and increased international travel can only contribute to this phenomenon. Physicians need to be aware of the signs and symptoms of lymphatic filariasis, and infection should be considered in the differential diagnosis of people with a relevant travel history.