Development Of Lymphedema Research Articles

Prophylactic lymphaticovenous anastomoses for resection of soft tissue tumors of the thigh to prevent secondary lymphedema-a retrospective comparative cohort analysis.

Patients with soft tissue tumors of extremities are at risk to develop secondary lymphedema after tumor resection caused by disruption of lymphatic vessels and sclerosis. Subsequently, this study aimed to evaluate the beneficial effects of lymphaticovenous anastomoses (LVAs) after soft tissue tumor resection of the thigh in a prophylactic approach. In a retrospective cohort study, we compared eight patients with a median age of 68.5 years (49-80) who received LVAs in combination with tumor resection for treatment of soft tissue tumors of the thigh region with a prior cohort of 20 patients with a median age of 63.0 years (23-84) who received soft tissue sarcoma resection of the thigh region. All patients of LVA cohort received 1-2 LVAs (mean 1.25± 0.49) at the dorsum of the foot and three patients at the SEKI-point (mean 0.375 ± 0.51). Mean maximum tumor diameter of LVA group was 19.5 ± 5.2cm and 12.3 ± 6.6cm of control group. All patients receiving LVA were assessed for development of lymphedema via bilateral measurements of circumference and assessment of lymphedema quality of life index (LyQLI). One of the eight patients who received LVAs showed moderate impairment in the LyQLI at a follow-up of 12 months while 45% of the control cohort complained about symptoms of secondary lymphedema at a median follow-up of 22 months (p-values LyQLI: p= .018 [physical domain]; p= .018 [psychosocial domain]; p= .020 [practical domain]). LVAs performed in combination with tumor resection of thigh soft tissue tumors reduce negative consequences of lymph stasis and prevent development of secondary lymphedema.

Novel Quantification of Real-Time Lymphatic Clearance: Immediate Lymphatic Reconstruction in a Large-Animal Model.

The real-time quantification of lymphatic flow remains elusive. Efforts to provide a metric of direct lymphatic function are not clinically translatable and lack reproducibility. Early reports demonstrate the promise of immediate lymphatic reconstruction (immediate lymphovenous bypass after lymphadenectomy) to reduce the risk of lymphedema development. However, there remains a heightened need to appraise this technique in a clinically translatable large-animal model. The aim of the authors' experiment was to evaluate the role of molecular imaging in the quantification of real-time lymphatic flow after lymphadenectomy, and lymphadenectomy with lymphovenous bypass using novel fluorophores in a swine model. A lymphadenectomy or lymphadenectomy with subsequent lymphovenous bypass was performed in 10 female swine. After subdermal fluorophore injection, near-infrared molecular imaging of blood samples was used to evaluate change in lymphatic flow after lymphadenectomy versus after lymphadenectomy with lymphovenous bypass. Continuous imaging evaluating fluorescence of the superficial epigastric vein in the torso and adjacent skin was performed throughout all experiments. Findings between modalities were correlated. The near-infrared dye signal in central and peripheral blood samples was often difficult to separate from background and proved challenging for reliable quantification. Venous and skin near-infrared imaging demonstrated a lymphatic clearance rate decrease of 70 percent after lymphadenectomy versus a decrease by only 30 percent after lymphadenectomy with immediate lymphovenous bypass. In this article, the authors describe a noninvasive, swine, large-animal model to quantify lymphatic clearance using skin imaging. The authors' findings were consistent with results yielded from real-time imaging of the vein. The authors believe this model may have important implications for eventual direct translation to the clinical setting.

Relationship of Hand Grip Strength on The Upper Extremity Function, Activities of Daily Living and Physical Activity Level ın Patients with Postmastectomy Lymphedema: A Pilot Study

This study aimed to investigate the relationship of hand grip strength on upper extremity functionality, activities of daily living, and physical activity level in female patients with lymphedema who have undergone breast cancer surgery. A total of 15 female patients with a diagnosis of lymphedema associated with breast cancer treatment were included in the study. The presence and severity of lymphedema were determined by circumference measurement. A hand dynamometer was used to evaluate the hand grip strength. Disabilities of Arm, Shoulder and Hand Questionnaire (DASH); Milliken Activities of Daily Living Scale (MAS);and the long form of the International Physical Activity Questionnaire(IPAQ) were used to evaluate upper extremity functionality, daily living activity, and physical activity level, respectively. The mean age of the patients was 51±10.6 years. DASH score was significantly related with age (r:0.639; p:0,010). The relationship between the hand grip strength of the affected side and the hand grip strength of the unaffected side was statistically positively significant (r:0.756; p:0.001).It was determined that hand grip strength was related to the total MAS value and the DASH score (r:0.609;p:0.016 and r:-0.624; p:0.013, respectively). The relationship between postoperative lymphedema development time with affected side hand grip strength and total MAS score was statistically significant (r:0.574; p:0.025 and r:0.766; p:0.001, respectively). There were no correlations between IPAQ score and hand grip strength, DASH, and MAS values (p>0.05). Considering these results, we concluded that improving hand grip strength in the early period may increase upper extremity functionality and quality of life for these patients.

Immediate lymphatic reconstruction for breast cancer

: Upper extremity lymphedema remains a significant source of morbidity in breast cancer patients despite significant improvements in breast cancer care. The risk of lymphedema is particularly elevated in patients requiring an axillary lymph node dissection and/or adjuvant radiation to treat their disease. Current treatment options for lymphedema, including conservative management or surgery, are limited and are often aimed at improving symptoms and quality of life rather than curing the disease. In this review we describe immediate lymphatic reconstruction, a novel surgical procedure that is done concurrent with axillary lymph node dissection in an effort to prevent the development of breast cancer-related lymphedema. Based on our growing knowledge of the pathophysiology of lymphedema, microsurgical techniques are used at the time of axillary lymph node dissection to perform a lymphovenous bypass between transected, leaking lymphatic channels and an adjacent, small calibre vein in the axilla. Using several objective metrics for short- and long-term surveillance, patients are monitored for the development of postoperative lymphedema. Early outcomes from using this technique have been promising, both in the literature and within our own institutions, demonstrating significant improvements in rates of postoperative lymphedema. However, future study is still required to better understand the long-term efficacy of immediate lymphatic reconstruction.

Risk factors for lymphedema after breast surgery: A prospective cohort study in the era of sentinel lymph node biopsy.

The Objective was to investigate the incidence of lymphedema after breast cancer treatment and to analyze the risk factors involved in a tertiary level hospital. Prospective longitudinal observational study over 3 years post-breast surgery. 232 patients undergoing surgery for breast cancer at our institution between September 2013 and February 2018. Sentinel lymph node biopsy (SLNB) or axillary lymphadenectomy (ALND) were mandatory in this cohort. In total, 201 patients met the inclusion criteria and had a median follow-up of 31 months (range, 1-54 months). Lymphedema was diagnosed by circumferential measurements and truncated cone calculations. Patients and tumor characteristics, shoulder range of motion limitation and local and systemic therapies were analyzed as possible risk factors for lymphedema. Most cases of lymphedema appeared in the first 2 years. 13.9% of patients developed lymphedema: 31% after ALND and 4.6% after SLNB (p <0.01), and 46.7% after mastectomy and 11.3% after breast-conserving surgery (p <0.01). The lymphedema rate increased when axillary radiotherapy (RT) was added to radical surgery: 4.3% for SLNB alone, 6.7% for SLNB + RT, 17.6% for ALND alone, and 35.2% for ALND + RT (p <0.01). In the multivariate analysis, the only risk factors associated with the development of lymphedema were ALND and mastectomy, which had hazard ratios (95% confidence intervals) of 7.28 (2.92-18.16) and 3.9 (1.60-9.49) respectively. The main risk factors for lymphedema were the more radical surgeries (ALND and mastectomy). The risk associated with these procedures appeared to be worsened by the addition of axillary radiotherapy. A follow-up protocol in patients with ALND lasting at least two years, in which special attention is paid to these risk factors, is necessary to guarantee a comprehensive control of lymphedema that provides early detection and treatment.

Therapeutic Targeting of PPAR Signaling in Cancer Treatment-Related Lymphedema

Lymphedema secondary to cancer treatment affects up to 1 in 5 cancer survivors. It is an irreversible late normal tissue toxicity characterized by swelling and scar formation (fibrosis) of the affected limb with physical and psychosocial health consequences for patients. Recent evidence reveals changes in peroxisome proliferator-activated receptor (PPAR) signaling as an underlying pathology of this disease. PPAR agonists have demonstrated therapeutic benefit in other fibrotic conditions; their role in lymphedema, however, remains unclear.In this study, RNA-sequencing of human and murine tissues with and without lymphedema was performed. Samples included: human lymphedema (n = 4), human normal tissue control (n = 5, matched for demographics and cancer history), murine lymphedema (n = 12), and murine control (n = 9). Pathway enrichment analysis was performed. An in vitro model of lymphedema fibrosis using cultured transforming growth factor beta (TGFβ)-stimulated fibroblasts and an in vivo model of lymphedema using a murine surgical model of tail lymphedema were utilized to evaluate the effects of PPAR agonists on gene expression and fibrotic protein expression (pro-collagen Iα1, collagen) in lymphedema compared to controls.RNA-sequencing of tissue from human and murine lymphedema and control subjects identified that suppression of PPAR signaling was a hallmark of lymphedema fibrosis on pathway enrichment analysis (FDR < 0.01). In the murine model, PPAR signaling gene expression changes co-occurred with fibrotic deposition beginning as early as two weeks after lymphedema development, and continued for at least 35 weeks. Treatment of TGFβ-stimulated fibroblasts with a PPAR agonist resulted in an increase in expression of PPAR genes and suppression of COL1α1 gene expression (n≥9 per group, q < 0.05) as well as reduction in the secretion of fibrotic proteins: pro-collagen Iα1 on ELISA (n≥8 per group, P < 0.0001) and collagen I on Western blotting. PPAR agonist treatment of the murine model of lymphedema resulted in a significant reduction in lymphedema fibrosis as measured by trichrome collagen staining (n≥4 per group, P < 0.05).These data, for the first time, demonstrated the value of upregulating PPAR signaling to treat lymphedema. For this condition, which to date, has no cure, repurposing PPAR agonists for lymphedema treatment is a highly promising therapeutic opportunity, which warrants further investigation.

Risk factors for lymphedema and method of assessment in endometrial cancer: a prospective longitudinal multicenter study

ObjectiveThe aim of the study was to determine risk factors for lymphedema of the lower limbs, assessed by four methods, 1 year after surgery for endometrial cancer.MethodsA prospective longitudinal multicenter...

Feasibility and Efficacy Exercises in Women With Lymphedema Post Breast Cancer – A Pilot Study

Research Objectives was to examine the feasibility and efficacy of exercises in women with lymphedema post breast cancer. Breast cancer treatment often results in the development of upper extremity lymphedema. Evidence is lacking on the effects exercise has on lymphedema in breast cancer survivors. This analysis looks to see the impact of exercise programs on lymphedema in breast cancer survivors. Design Retrospective data analysis. Setting The data in this study came from an original research project, Project IMPACT (Improving Mental and Physical ACTivity), that took place in San Antonio, Texas. Participants This analysis included data from a sub-group of 9 participants with lymphedema in at least one of their arms. The original study had 94 participants who were breast cancer survivors. Interventions Project Impact looked at the effects six month exercise interventions on breast cancer survivors: yoga-based exercise, a comprehensive individualized designed program (including aerobic, resistance and flexibility exercises), and exercise of the participant's own choice. Main Outcome Measures Affected side volume, passive range of motion (PROM), and self-reported effects of Lymphedema on daily life measured by the Norman Lymphedema Self-Report Survey (NLSS). All outcomes were measured at the beginning and end of the exercise program. Results All participants completed the exercise program with no adverse events. A significant difference (p < 0.05) was found in four subscales pertaining to the affected upper extremity's forearm and hand in the NLSS. No other significant changes were found. Conclusions The results of this pilot study suggest that it is safe for breast cancer survivors with lymphedema to exercise. Performing exercises can positively reduce some symptoms related to lymphedema. Future studies with bigger sample sizes can help confirm these findings. Author(s) Disclosures The authors also gratefully acknowledge the support of Dr. Amy Lang, the ThriveWell Cancer Foundation, and the START Center for Cancer Care. There are no other disclosures from any of the authors. was to examine the feasibility and efficacy of exercises in women with lymphedema post breast cancer. Breast cancer treatment often results in the development of upper extremity lymphedema. Evidence is lacking on the effects exercise has on lymphedema in breast cancer survivors. This analysis looks to see the impact of exercise programs on lymphedema in breast cancer survivors. Retrospective data analysis. The data in this study came from an original research project, Project IMPACT (Improving Mental and Physical ACTivity), that took place in San Antonio, Texas. This analysis included data from a sub-group of 9 participants with lymphedema in at least one of their arms. The original study had 94 participants who were breast cancer survivors. Project Impact looked at the effects six month exercise interventions on breast cancer survivors: yoga-based exercise, a comprehensive individualized designed program (including aerobic, resistance and flexibility exercises), and exercise of the participant's own choice. Affected side volume, passive range of motion (PROM), and self-reported effects of Lymphedema on daily life measured by the Norman Lymphedema Self-Report Survey (NLSS). All outcomes were measured at the beginning and end of the exercise program. All participants completed the exercise program with no adverse events. A significant difference (p < 0.05) was found in four subscales pertaining to the affected upper extremity's forearm and hand in the NLSS. No other significant changes were found. The results of this pilot study suggest that it is safe for breast cancer survivors with lymphedema to exercise. Performing exercises can positively reduce some symptoms related to lymphedema. Future studies with bigger sample sizes can help confirm these findings.

Lymphatic regeneration after implantation of aligned nanofibrillar collagen scaffolds: Preliminary preclinical and clinical results.

We tested our hypothesis that implantation of aligned nanofibrillar collagen scaffolds (BioBridge™) can both prevent and reduce established lymphedema in the rat lymphedema model. Our authors report clinical cases that demonstrate new lymphatic formation guided by BioBridge™ as seen by near-infrared (NIR) fluoroscopy and magnetic resonance (MR) lymphography. A rat lymphedema model was utilized. A prevention group received implantation of BioBridge™ immediately after lymphadenectomy. A lymphedema group received implantation of BioBridge™ with autologous adipose-derived stem cells (ADSC; treatment group) or remained untreated (control group). All subjects were observed for 4 months after lymphadenectomy. The hindlimb change was evaluated using computed tomography-based volumetric analysis. Lymphagiogenesis was assessed by indocyanine green (ICG) lymphography. Animals in the treatment group showed a reduction in affected limb volume. Animals in the prevention group showed no increase in the affected limb volume. ICG fluoroscopy demonstrated lymph flow and formation of lymphatics toward healthy lymphatics. In the rat lymphedema model, implantation of BioBridge™ at the time of lymph node removal prevents the development of lymphedema. Treatment of established lymphedema with the BioBridge™ and ADSC reduces lymphedema. New lymphatic vessels are demonstrated by NIR fluoroscopy and MR lymphography. These findings have implications for the treatment of lymphedema in human subjects.

An important tool in lymphedema management: validation of Turkish version of the lymphedema breast cancer questionnaire

Purpose This study aimed to perform the psychometric evaluation of the Turkish version of the Lymphedema and Breast Cancer Questionnaire (LBCQ). Methods Patients with BCRL (n = 50) received a Turkish version of the following measurement tools: Lymphedema Functioning, Disability, and Health Questionnaire (Lymph-ICF), Disabilities of the Arm, Shoulder and Hand questionnaire (Quick DASH), LBCQ and Upper Extremity Functional Index (UEFI-20). Patients without BCRL (n = 50) completed only the Turkish LBCQ. Psychometric properties were analyzed with internal consistency, test–retest reliability, ROC analysis, criterion, and discriminant validity. Results The internal consistency of the Turkish LBCQ was strong (Cronbach's α coefficient >0.60). Test–retest reliability was also very strong (intraclass correlation coefficients from 0.79 to 1; p < 0.001). Criterion validity was supported by a moderate correlation of LBCQ with volumetric measurement, skinfold thickness, and questionnaires (Lymph-ICF, UEFI, and Quick DASH) (p < 0.05) via the ROC analysis, the cut-off point was found as “6” in distinguishing individuals with lymphedema and those without. There were significant differences in LBCQ total and subscale scores between participants with and without BCRL (p < 0.05). Conclusions This study clinically confirmed the validity, reliability, and applicability of the Turkish LBCQ in the Turkish population. LBCQ will enable the early detection of lymphedema and will save the country financially with early diagnosis. IMPLICATIONS FOR REHABILITATION The LBCQ was successfully translated, adapted, and validated into the Turkish language. Turkish version of the LBCQ was found to be reliable and valid to evaluate the signs and symptoms of lymphedema in Turkish women with breast cancer. By using LBCQ, rehabilitation professionals can detect lymphedema at an early stage, reduce the cost of lymphedema treatment and prevent the development of advanced lymphedema in their clinics.

SVEP1 IS IMPORTANT FOR MORPHOGENESIS OF LYMPHATIC SYSTEM: POSSIBLE IMPLICATIONS IN LYMPHEDEMA

SVEP1, also known as Polydom, is a large extracellular mosaic protein with functions in protein interactions and adhesion. Since Svep1 knockout animals show severe edema and lymphatic system malformations, the aim of this study is to evaluate the presence of SVEP1 variants in patients with lymphedema. We analyzed DNA from 246 lymphedema patients for variants in known lymphedema genes, 235 of whom tested negative and underwent a second testing for new candidate genes, including SVEP1, as reported here. We found three samples with rare heterozygous missense single-nucleotide variants in the SVEP1 gene. In one family, healthy members were found to carry the same variants and reported some subclinical edema. Based on our findings and a review of the literature, we propose SVEP1 as a candidate gene that should be sequenced in patients with lymphatic malformations, with or without lymphedema, in order to investigate and add evidence on its possible involvement in the development of lymphedema.

Postmastectomic lymphedema prevention: modern possibilities

A three-dimensional computer model of the topographic and anatomical variants of the lymph nodes in the axillary fossa gives reason to doubt the indisputability of the known data on the normal anatomy of the lymph nodes. This mainly concerns the presence of a lateral (shoulder) group of axillary lymph nodes (4-6 nodes), which can be located not only on the medial, but also on the posterior surface of the shoulder. In some cases, this group of axillary lymph nodes is generally absent in its typical place and is in close proximity to the central (intermediate) group of lymph nodes. Attention to the lateral (shoulder) group of lymph nodes is due to the fact that through them lymph drainage occurs from the entire superficial (epifascial) lymphatic system of the volar surface of the upper limb (skin and subcutaneous tissue). From the lateral group of lymph nodes, lymph drainage goes either to the central group or to the deltapectoral lymph nodes. In the course of axillary lymph node dissection of I, II and III levels in breast cancer, it is possible to save only the deltapectal lymph node with its afferent and efferent vessels, which provides full-fledged lymphatic drainage from the dorsolateral surface of the upper limb. But in this situation, without lymphatic drainage (superficial and deep) with preserved lymph production, the inner (volar) part of the upper limb remains, where lymphostasis begins to develop. An exception is the variant of localization of the brachial group of lymph nodes on the posterior surface of the shoulder, in which it is possible to preserve the lateral group of lymph nodes, which does not fall into the block of adipose tissue with other regional lymph nodes, and therefore partially preserve the lymph drainage from the medial surface of the ipsilateral upper limb towards the deltapectoral lymph node. Taking into account the topographic and anatomical variability of the lymph drainage collectors in the axillary fossa and the varied nature of the involvement of lymph nodes in the metastatic process, in each clinical case, the standard preoperative mapping of axillary lymph nodes (reverse lymphatic mapping) does not allow predicting the risk and timing of the development of postoperative upper limb lymphedema. The advantage of our technology two-contrast fluorescent lymphography - is the possibility of visual differentiation of all elements of lymph drainage from the mammary gland (indocyanine green - ICG) and the ipsilateral upper limb (methylene blue - MB). According to the results of the study, it will be possible to clarify the localization of the lateral (shoulder) group of axillary lymph nodes, topographic and anatomical features of the lymphatic drainage collectors in the axillary fossa and indications for lymphovenous shunting for primary surgical prevention of postmastectomy lymphedema of the upper limb.

Lymphatic Function in the Arms of Breast Cancer Patients-A Prospective Cohort Study.

Background:Lymphedema is a highly feared complication of breast cancer treatment, but the underlying complex mechanisms are still unknown. Thus, we investigated the lymphatic morphology and contractility in the lymphatic vessels of arms of high-risk breast cancer patients treated for node-positive early breast cancer.Methods:In this prospective cohort study 32 women treated for unilateral node-positive breast cancer were enrolled and studied 36 ± 23 days after loco-regional radiotherapy. Near-infrared fluorescence imaging was used to assess morphology and function of the superficial lymphatic vessels. Strain-gauge plethysmography was performed to evaluate the capillary filtration of fluid.Both arms were investigated, with the non-treated arm acting as control. The patients were questioned about the presence of lymphedema yearly and finally 574 ± 118 days after ended radiotherapy.Results:Morphologically, 25% of the treated arms expressed lymphatic vessel abnormalities compared to the control arms (p = 0.0048). No difference in functional parameters (maximal pumping pressure, p = 0.20; contraction frequency, p = 0.63; contraction velocity, p = 0.55) was found between the treated and control arms. Patients who later developed lymphedema had a difference in velocity compared to those who did not develop lymphedema (p = 0.02). The capillary filtration rate was similar between the two arms (p = 0.18).Conclusions:Peripheral lymphatic vessels were morphologically changed in the ipsilateral arm in 25% of the patients and patients who later developed lymphedema showed an early increase in velocity. Other functional parameters and capillary filtration were unchanged in this early phase. These discrete changes might be early indicators of later development of lymphedema.

THE EFFICACY OF PHYSIOTHERAPY RECOVERY AFTER A MODIFIED RADICAL MASTECTOMY

Breast cancer is the most common disease in females and the major cause of mortality and morbidity. In reality, 1.67 million new cases of breast cancer are diagnosed around the world, with 458,000 deaths per year. Approximately 89 percent of breast cancer survivors live for a minimum of five years after treatment, but adverse effects can last for months or years after surgery. The most common side effects of the upper limb are pain and joint dysfunction, which is described as having a prevalence range of 12 percent to 51 percent for pain and 1.5 percent to 50 percent for joint dysfunction.(1) The mainstay in primary breast cancer care is surgery.(2) To assess the impact of an early recovery program on shoulder mobility, functional ability, postoperative complications such as seroma, hematoma, and wound infection in patients who had undergone a modified radical mastectomy (MRM)and to assess the impact of variables in clinical practice (e.g., age, education, BMI, previous shoulder problems, number of dissected axillary lymph nodes and metastatic lymph nodes, use of postoperative radiotherapy (RT) and chemotherapy on shoulder mobility, functional ability, and lymphedema development), and lymphedema.(3) Any of these symptoms can result in permanent arm dysfunction. Shoulder exercises are widely prescribed to minimize the impairment of mobility and strength as well as to prevent lymphedema. A variety in clinical services has been established which help mostly in improvement of shoulder range of motion while also reducing the risk of secondary lymphedema. This is the case of a 32-year-old female, resident of Dastur Nagar, Amravati. Housewife by occupation. She has swelling in her right breast so she visited a private hospital in Amravati. There she detected a lump in her right breast and the doctor recommended further treatment to visit AVBRH Hospital, Sawangi Meghe, and Wardha. She underwent a modified radical mastectomy. Patients that have had a mastectomy are always at the possibility of experiencing shoulder pain and adhesive capsulitis and require preventative measures.

Relation Between Early Disturbance of lymphatic transport Visualized With Lymphofluoroscopy and Other Clinical Assessment Methods in Patients With Breast Cancer

IntroductionLymphedema of the upper extremity is one of the most feared complications following breast cancer treatment. Lymphofluoroscopy is a sensitive instrument for detection of lymphedema and visualization of superficial lymphatic transport, thus suitable for early detection. Early detection of lymphedema is important as it can prevent lymphedema to progress into more severe stages and minimalize impact on quality of life and medical costs. ObjectiveTo determine agreement between the presence of early disturbance of the lymphatic transport and outcome of clinical measurement tools evaluating the development of lymphedema. MethodsA prospective study was conducted in 128 breast cancer patients scheduled for breast cancer surgery. Patients were evaluated before surgery and 1, 3-, 6-, 9-, and 12-months’ post-surgery. Cohen's Kappa was used to determine agreement between presence of early disturbance in lymphatic transport and presence of pitting/increased skinfold thickness/increased Percentage Water Content ratio (PWC)/increased arm-hand volume (circumference measures and water displacement). ResultsFor pitting status (Kappa 0.23), for skinfold thickness (Kappa 0.29) and the PWC ratio (Kappa 0.21) a minimal agreement was found. The circumference measurement had a minimal agreement for 5% volume difference (Kappa 0.22) and no agreement for 3% volume difference (Kappa 0.19). Sensitivity was weak for all clinical assessments. The specificity was excellent for pitting status, skinfold thickness, PWC ratio, and for 5% volume difference. For 3% a high specificity was found. ConclusionThe clinical tools assessed in this study were not able to predict an early disturbance of the lymphatic transport seen on lymphofluoroscopy.

Frequency of Early Post-Operative Complications following Modified Radical Mastectomy (MRM) in patients with Breast Carcinoma

Objective: Breast carcinoma is the commonest cancer affecting female gender and is the second major cause of mortality in females globally. Among different surgical options, modified radical mastectomy (MRM) with or without neoadjuvant therapy is the most frequent surgery carried out globally for breast carcinoma. In this study we aimed to determine the frequency of early post-operative complications following modified radical mastectomy (MRM) in patients with breast carcinoma. Material and methods: This dual setting retrospective descriptive study was conducted at General surgery departments of Kuwait Teaching Hospital and MTI-Lady Reading Hospital Peshawar between January, 2018 and June, 2019. A total of 60 patients aged &gt;18 years with biopsy proven stage-I to stage-III breast carcinoma who underwent modified radical mastectomy were included.All patients were followed on weekly basis for six weeks at the out-patient department (OPD) and evaluated for the development of early complications such as seroma/hematoma, flap necrosis and wound infections. Results: Seroma formation found in 9 patients (15%) and wound infection seen in 5 patients (8.3%) were the commonest complications. Conclusion: In our study seroma formation was the most common complication followed by wound infection. Skin flap necrosis, wound dehiscence, hematoma formation and development of early lymphoedema were less common. None of our patients presented with muscle paralysis secondary to nerves injury. Keywords: Breast carcinoma, modified radical mastectomy, complications, seroma, wound infection.

Erysipelas lymphedema: Two case reports and literature review

Erysipelas, a variant of cellulitis, is a superficial dermal bacterial infection. This superficial cutaneous infection may cause lymphangitis with resultant lymphedema in poorly treated cases. Reports of erysipelas preceding lymphedema are rare, rather many have reported the occurrence of erysipelas in patients with subclinical or overt lymphedema. Two case reports of erysipelas preceding lymphedema after appropriate parenteral antibiotics therapy and limb elevation are here presented. Following diagnosis, admission, and commencement of therapy, the second patient (Case 2) discontinued hospital treatment halfway for native treatment and returned after about 3 weeks. All patients recovered successfully but later presented with lymphedema after 8 weeks and 6 weeks, respectively. Both patients made a sustained functional recovery of their limbs with conservative management including elastic compression stocking and limb elevation. Erysipelas infection preceding lymphedema may develop when it occurs, prompt and appropriate treatment modalities for erysipelas infection may forestall the development of lymphedema.

Demographic examination of lymphedema seen in the lower extremities

Background: We aimed to indicate the frequency of this disease according to blood groups, other disease types, age, weight and other demographic characteristics.Methods: We examined total of 236 patients who applied to our clinic because of lower extremity edema within 5 years. All patients had a diagnosis of lymphedema. Patients with a diagnosis of congenital lymphedema or a diagnosis secondary to cancer were excluded. Obesity, presence of venous disease, diabetes mellitus and hypertension which are considered as causes of secondary lymphedema were included in the study. Also the relationship between lymphedema patients and blood groups were evaluated.Results: 81% (n:193) of patients were women. The mean age of the patients was 50.71 (±10.28). All patients had diagnosis of lymphedema. Most of patients (n:189) had bilateral lower extremity edema. Body mass index was above 25 in 149 (63.1%) patients. Deep venous insufficiency accompanied in 75 (31.8%) patients. Perforator vein incompetance was observed with lymphedema in 96 (40.7%) patients. The number of diabetic and hypertensive patients was 64 (27.1%) and 67 (28.4%), respectively. Patients with B type blood group constituted the largest patient profile with a rate of 41.9% (n:99).Conclusions: In our study, demographic characteristics were not statistically corolated to lymphedema development, however, the rate of lymphedema in patients with perforating vein insufficiency was statistically significant (p&lt;0.05, P=0.002). The most important point to be considered here is whether lymphedema plays a role in the development of additional pathology or do additional pathologies trigger the development of lymphedema?

The Role of Metabolism in Modulating Radiation Fibrosis &amp; Lymphedema

With the improvements in cancer diagnosis and therapy, clinical outcome has increased substantially, to the extent that by 2026, there will be >20M cancer survivors in the United States alone. The majority of survivors fare well; however, there is a significant proportion of patients who continue to experience the aftermath of their treatments such as radiation fibrosis (RF) or lymphedema. Until recently, there has been little understanding of the biological basis of RF, which is defined by the aberrant accumulation of extracellular matrix (ECM), leading to reduced tissue elasticity, and potential loss of organ function. The regulation of ECM production and degradation is a complex process, mediated through the production of a myriad of cytokines such as TGFB, and environmental conditions such as hypoxia. We have recently identified that metabolic dysregulation, and in particular, downregulation of fatty acid oxidation (FAO) is a key pathway driving the production and reducing the degradation of collagen, the predominant component of the ECM. Conversely, upregulation of PPAR signaling, a major mediator of FAO, reduced transcription of key ECM genes; whilst increasing internalization and degradation of extracellular collagen. Furthermore, CD36, a membrane transporter of long chain fatty acids, was discovered to play a critical role in regulating the trafficking of collagen and lysosomal degradation. Finally, using a pharmacogenomics approach, caffeic acid was identified to be a compound which can be systemically administered, and reduced RF in pre-clinical models. These data, along with other reports in the literature, strongly point towards the use of metabolic drugs as a therapeutic strategy by which we can mitigate the deleterious effects of RF on cancer patients. More recently, we have also uncovered that metabolic dysregulation likely plays a similar role in the development of lymphedema, a common long-term toxicity in women after breast cancer therapy. Finally, these findings have broad application to the increasing burden of fibrosis beyond cancer, wherein end-stage renal, liver, cardiac, and pulmonary fibrosis accounts for up to 1/3 of the deaths around the world.

The Kinetics of Lymphatic Dysfunction and Leukocyte Expansion in the Draining Lymph Node during LTB4 Antagonism in a Mouse Model of Lymphedema.

The mechanisms of lymphedema development are not well understood, but emerging evidence highlights the crucial role the immune system plays in driving its progression. It is well known that lymphatic function deteriorates as lymphedema progresses; however, the connection between this progressive loss of function and the immune-driven changes that characterize the disease has not been well established. In this study, we assess changes in leukocyte populations in lymph nodes within the lymphatic drainage basin of the tissue injury site (draining lymph nodes, dLNs) using a mouse tail model of lymphedema in which a pair of draining collecting vessels are left intact. We additionally quantify lymphatic pump function using established near infrared (NIR) lymphatic imaging methods and lymph-draining nanoparticles (NPs) synthesized and employed by our team for lymphatic tissue drug delivery applications to measure lymphatic transport to and resulting NP accumulation within dLNs associated with swelling following surgery. When applied to assess the effects of the anti-inflammatory drug bestatin, which has been previously shown to be a possible treatment for lymphedema, we find lymph-draining NP accumulation within dLNs and lymphatic function to increase as lymphedema progresses, but no significant effect on leukocyte populations in dLNs or tail swelling. These results suggest that ameliorating this loss of lymphatic function is not sufficient to reverse swelling in this surgically induced disease model that better recapitulates the extent of lymphatic injury seen in human lymphedema. It also suggests that loss of lymphatic function during lymphedema may be driven by immune-mediated mechanisms coordinated in dLNs. Our work indicates that addressing both lymphatic vessel dysfunction and immune cell expansion within dLNs may be required to prevent or reverse lymphedema when partial lymphatic function is sustained.