Browsing by Subject "Lymphedema"
Now showing 1 - 10 of 13
Results Per Page
Sort Options
Item 153. Quantification of Lymphangiogenesis in Murine Lymphedema Tail Model Using Intravital Microscopy(Wolters Kluwer, 2023-05-19) Mohan, Ganesh; Khan, Imran; Diaz, Stephanie M.; Neumann, Colby R.; Jorge, Miguel D.; Sinha, Mithun; Gordillo, Gayle M.; Sen, Chandan K.; Hassanein, Aladdin H.; Surgery, School of MedicinePURPOSE: Lymphedema is limb swelling caused by lymphatic dysfunction. It occurs in 30% of patients that undergo axillary lymph node dissection in the treatment of breast cancer. There is no cure for this disease. Understanding the mechanisms of lymphatic growth will play a pivotal role in developing therapeutic strategies against these conditions. Visualization of lymphangiogenesis and functional assessment remains a challenge. Intravital two-photon microscopy (IVM) is a powerful imaging tool for investigating various biological processes in live animals. Tissue nanotransfection technology (TNT) facilitates a direct, transcutaneous non-viral vector gene delivery using a chip with nanochannel poration in a rapid (<100ms) focused electric field. TNT was used in this study to deliver the genetic cargo in the murine tail lymphedema to assess the lymphangiogenesis. The purpose of this study is to experimentally evaluate the applicability of IVM to visualize and quantify lymphatics. METHODS: The murine tail model of lymphedema was utilized. A 3 mm full thickness skin excision and lymphatic vessel disruption was performed 20 mm from the base of the tail in twelve C57BL/6 mice. TNT was applied to the murine tail (day 0) directly at the surgical site with genetic cargo loaded into the TNT reservoir: Group I (control) was given pCMV6 (expression vector backbone alone) (n=6); Group II had pCMV6-Prox1 (n=6). Post-TNT (day 10), a 3 cm segment of murine tail was deskinned distal to the site of occlusion to optimize visualization. FITC-Dextran (2000 kD) injected intradermally at the distal tail region for lymphatic uptake. Lymphatic vessels are visualized at the second skin excision site with the Leica SP8 Confocal/Multiphoton Microscope and assessed for number of branching points to determine the newly formed lymphatics. Lymphatic vessel density was also observed by immunostaining with anti-Podoplanin antibody. RESULTS: The experimental group II exhibited increased branching points (3-fold) using filamentation analysis compared to control group I at the site of TNT treatment (n=6, p<0.05). Increased lymphatic vessel density was also observed with Podoplanin immunostaining post-TNT application. Intensity quantification of immunohistochemistry revealed greater expression of Podoplanin in Group II when compared to Group I (n=6, p<0.05). CONCLUSION: This study demonstrates a novel, powerful imaging tool for investigating lymphatic vessels in live murine tail model of lymphedema. Intravital microscopy can be utilized for functional assessment of lymphatics and visualization of lymphangiogenesis following gene-based therapy.Item 97. Focal Gene Delivery in the Murine Lymphedema Tail Model Using Tissue Nanotransfection Technology (TNT)(Wolters Kluwer, 2022) Mohan, Ganesh; Khan, Imran; Sinha, Mithun; Gordillo, Gayle M.; Sen, Chandan K.; Hassanein, Aladdin H.; Surgery, School of MedicineBackground: Lymphedema is chronic limb swelling resulting from lymphatic dysfunction. It affects an estimated 5 million Americans. There is no cure for this disease. Experimental gene-based therapeutic approaches (e.g., using viral vectors) have had limited translational applicability. Tissue nanotransfection technology (TNT) utilizes a direct, transcutaneous non-viral vector, gene delivery using a chip with nanochannel poration in a rapid (<100ms) focused electric field. This platform technology has been used for various applications in tissue reprogramming. The ability to deliver genetic cargo at a focal, non-global site would have practical clinical potential in lymphedema treatment. The purpose of this study is to experimentally evaluate the applicability of TNT for lymphedema. Methods: The murine tail model of lymphedema was utilized. A 3 mm full thickness skin excision and lymphatic vessel disruption was performed 20 mm from the base of the tail in twelve C57BL/6 mice. TNT was applied to the murine tail (day 0) directly at the surgical site with genetic cargo loaded into the TNT reservoir: Group I (control) was given pCMV6 (expression vector backbone alone) (n=6); Group II had pCMV6-Prox1 (n=6). TNT was applied with square wave pulse electric stimulation (10x10ms pulses, 250 V, 10 mA). The efficiency of gene delivery was assessed through qRT-PCR using primers with SYBR Green fluorescence quantification and immunostaining with anti-Prox1 antibody. Results: The experimental Group II exhibited four-fold increased expression of Prox1 using qRT-PCR compared to control Group I at the site of TNT treatment (P<0.05). Increased expression of Prox1 was also observed with immunohistochemistry 3 days post-TNT application. Intensity quantification of immunohistochemistry revealed greater expression of Prox1 in Group II when compared to Group I (P<0.05). Conclusion: This study demonstrates a novel, focal nanotechnology approach for local genetic cargo delivery in murine tail lymphedema model without the use of viral vectors for transfection. TNT can rapidly and effectively be applied for potentially therapeutic delivery of factors locally at the site of lymphedema.Item ASO Author Reflections: Immediate Lymphatic Reconstruction: A Proactive Approach to Breast Cancer-Related Lymphedema(Springer, 2021-03) Cook, Julia A.; Hassanein, Aladdin H.; Surgery, School of MedicineItem Breast Cancer-Related Lymphedema: A Review of Management and Innovative Surgical Techniques(European Society of Medicine, 2022) Newsom, Keeley D.; Xiang, David; Yang, Alan; Copeland-Halperin, Libby R.; Weiss, Anna; Broyles, Justin M.; Surgery, School of MedicineLymphedema is one of the most feared complications of breast cancer treatment. The objective of this article is to review the basic workup, staging, and diagnostic criteria for lymphedema and to discuss non-surgical and surgical treatments, with a focus on breast-cancer related lymphedema. Non-surgical treatment consists of intensive physical therapy including manual lymphatic drainage via massage, daily compression wraps, and exercises to prevent scarring and increase mobility. Surgical intervention is considered when non-surgical treatment is ineffective or more recently as a preventive measure. Surgical interventions, used once lymphedema has developed, include 1) lympho-venous bypass, which is the anastomosis of lymphatic vessels distal to the site of dermal backflow to neighboring venules to shunt lymphatic drainage away from the area of lymphatic injury; 2) vascularized lymph node transplant, in which lymph nodes are harvested from a donor site with their supporting artery and vein and transferred to the affected recipient site; and 3) debulking procedures including liposuction and direct excision. Preventive surgical interventions include 1) lymphatic microsurgical preventive healing approach, known as LYMPHA, which also utilizes lympho-venous anastomoses but at the time of lymph node dissection to anastomose lymphatic channels transected during lymph node dissection with adjacent veins to preserve lymphatic drainage of the arm; and 2) axillary reverse mapping, which involves tracer or dye injection within the ipsilateral arm before axillary surgery so that the breast surgeons are able to delineate nodal drainage and therefore attempt to spare nodes specific to arm tissue provided they are not the sentinel lymph node. Patient selection is critical for these procedures, and requires a multi-disciplinary approach.Item Compression Therapy for HIV-Associated Kaposi Sarcoma Leg Lymphedema: Results of the Kenyan Improvised Compression for Kaposi Sarcoma Randomized Controlled Trial(American Society of Clinical Oncology, 2022) Chang, Aileen Y.; Karwa, Rakhi; Odhiambo, Haji; Were, Phelix; Fletcher, Sara L.; Tonui, Edith C.; Kohn, Michael A.; Lee, Jeannette; Chang, Di; Lensing, Shelly; Namaemba, Diana Flora; Busakhala, Naftali; Kiprono, Samson K.; Maurer, Toby; Goodrich, Suzanne; Pastakia, Sonak D.; Dermatology, School of MedicinePurpose: Evaluate the effectiveness of compression while receiving chemotherapy compared with chemotherapy alone in the treatment of HIV-associated Kaposi sarcoma (KS) lymphedema. Methods: A randomized controlled trial was conducted in a single oncology clinic in western Kenya (NCT03404297). A computer-generated randomization schedule was used to allocate treatment arms. Randomized block design was used for stratification by lymphedema stage. Participants were HIV positive adults age ≥ 18 years on antiretroviral therapy with biopsy-proven KS associated with leg lymphedema and being initiated on chemotherapy. The intervention was 10 weeks of weekly clinic-based application of two-component paste compression bandages. The primary outcome was change in the Lower Extremity Lymphedema Index (LELI) score from week 0 to week 14. The secondary outcomes were change in the Lymphedema Quality of Life measure (LYMQOL) and change in the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 score from week 0 to week 14. Blinded outcome assessments were conducted. Results: Of 30 participants randomly assigned, 25 eligible patients (chemotherapy [control], n = 13; compression plus chemotherapy [intervention], n = 12) returned at week 14. Change in LELI, LYMQOL, and EORTC QLQ-C30 scores between week 14 and week 0 did not significantly differ by arm. The mean (standard deviation) change in LELI score was -25.9 (34.6) for the control arm compared with -13.3 (29.5) for the intervention arm, P = .340. The difference (95% CI) in the change in LELI score was -12.6 (-39.3 to 14.1). Conclusion: Future studies evaluating a 14-week change in LELI for KS lymphedema should assume a standard deviation of approximately 30. Lessons learned from this pilot trial should inform the development of a larger, multicenter trial to evaluate the effectiveness of compression for KS lymphedema.Item Implementing a Locally Made Low-Cost Intervention for Wound and Lymphedema Care in Western Kenya(Elsevier, 2021) Chang, Aileen Y.; Mungai, Margaret; Coates, Sarah J.; Chao, Tiffany; Odhiambo, Haji Philip; Were, Phelix M.; Fletcher, Sara L.; Maurer, Toby; Karwa, Rakhi; Pastakia, Sonak D.; Dermatology, School of MedicineIn Western Kenya, the burden of chronic wounds and lymphedema has a significant impact on functionality and quality of life. Major barriers to provision of care include availability, affordability, and accessibility of bandages. At the Academic Model Providing Access to Healthcare, dermatologists and pharmacists collaborated to develop a 2-component compression bandage modeled after the Unna boot, using locally available materials, that is distributed through a revolving fund pharmacy network. In partnership with nursing, use of these bandages at a national referral hospital and a few county facilities has increased, but increasing utilization to an expanded catchment area is needed.Item A Murine Tail Lymphedema Model(JoVE, 2021) Hassanein, Aladdin H.; Sinha, Mithun; Neumann, Colby R.; Mohan, Ganesh; Khan, Imran; Sen, Chandan K.; Surgery, School of MedicineLymphedema is extremity swelling caused by lymphatic dysfunction. The affected limb enlarges because of accumulation of fluid, adipose, and fibrosis. There is no cure for this disease. A mouse tail model that uses a focal full thickness skin excision near the base of the tail, resulting in tail swelling, has been used to study lymphedema. However, this model may result in vascular comprise and consequent tail necrosis and early tail swelling resolution, limiting its clinical translatability. The chronic murine tail lymphedema model induces sustained lymphedema over 15 weeks and a reliable perfusion to the tail. Enhancements of the traditional murine tail lymphedema model include 1) precise full thickness excision and lymphatic clipping using a surgical microscope, 2) confirmation of post-operative arterial and venous perfusion using high resolution laser speckle, and 3) functional assessment using indocyanine green near infrared laser lymphangiography. We also use tissue nanotransfection technology (TNT) for novel non-viral, transcutaneous, focal delivery of genetic cargo to the mouse tail vasculature.Item Outcomes analysis of microsurgical physiologic lymphatic procedures for the upper extremity from the United States National Surgical Quality Improvement Program(Wiley, 2022-05) Bamba, Ravinder; Chu, Amanda; Gallegos, Jose; Herrera, Fernando A.; Hassanein, Aladdin H.; Medicine, School of MedicineINTRODUCTION: Physiologic microsurgical procedures to treat lymphedema include vascularized lymph node transfer (VLNT) and lymphovenous bypass (LVB). The purpose of this study was to assess 30-day outcomes of VLNT and LVB using the National Surgical Quality Improvement Program (NSQIP) database. METHODS: NSQIP was queried (2012-2018) for lymphatic procedures for upper extremity lymphedema after mastectomy. Prophylactic lymphatic procedures and those for lower extremity lymphedema were excluded. Outcomes were assessed for three groups: LVB, VLNT, and patients who had procedures simultaneously (VLNA+LVB). Primary outcomes measured were operative time, 30-day morbidities, and hospital length of stay. RESULTS: The study included 199 patients who had LVB (n = 43), VLNT (n = 145), or VLNT+LVB (n = 11). There was no difference in co-morbidities between the groups (p = 0.26). 30-day complication rates including unplanned reoperation (6.9% VLNT vs. 2.3% LVB) and readmission (0.69% VLNT vs. none in LVB) were not statistically significant (p = 0.54). Surgical site infection, wound complications, deep vein thromboembolism, and cardiac arrest was also similar among the three groups. Postoperative length of stay for VLNT (2.5 days± 2.3), LVB (1.9 days± 1.9), and VLNT+LVB (2.8 days± 0.3) did not differ significantly (p = 0.20). Operative time for LVB (305.4 min ± 186.7), VLNT (254 min ± 164.4), and VLNT+LVB (295.3 min ± 43.2) was not significantly different (p = 0.21). CONCLUSIONS: Our analysis of the NSQIP data revealed that VLNT and LVB are procedures with no significant difference in perioperative morbidity. Our results support that choice of VLNT versus LVB can be justifiably made per the surgeon's preference and experience as the operations have similar complication rates.Item Prophylactic Buried Dermal Flap: A Simple Method for Axillary Reconstruction after Lymph Node Dissection(Wolters Kluwer, 2024-09-12) Fallah, Kasra N.; Ahmed, Shahnur; Venardi, Andrew S.; Hulsman, Luci A.; Fisher, Carla S.; Ludwig, Kandice K.; Lester, Mary E.; Hassanein, Aladdin H.; Surgery, School of MedicineBreast cancer-related lymphedema is characterized by progressive limb enlargement and occurs in up to 30% of breast cancer patients following axillary lymph node dissection (ALND). Immediate lymphatic reconstruction (ILR) is a preventative technique used to reduce lymphedema rates by performing lymphovenous anastomoses of disrupted afferent lymphatics. This study presents a novel method of axillary reconstruction following ALND using a buried dermal flap that provides local tissue with intact subdermal lymphatics to the axillary dead space. A single-center retrospective review was performed to assess breast cancer patients who underwent modified radical mastectomy without reconstruction between 2018 and 2023. Groups were divided into those who had ILR alone (group 1) and those who had buried dermal flap with attempted ILR (group 2). There were 31 patients included in this study: 18 patients in group 1 and 13 patients in group 2. Patient demographics, comorbidities, and breast cancer history were similar between the groups. There was no significant difference in the mean number of lymphovenous anastomoses performed (1.6 versus 1.7, P = 0.84). Mean operative time of 224.4 ± 51.9 minutes in group 1 was similar to 223.4 ± 30.4 minutes in group 2 (P = 0.95). We introduce a novel method of axillary reconstruction following ALND using a buried dermal flap that is inset into the axillary dissection space and over the area of ILR. We propose that it is an efficient accessory procedure to augment ILR by providing supplementary intact lymphatic channels to the area of lymphatic injury, while obliterating the axillary dead space.Item Sarcoidosis: A rare cause of penile edema(Elsevier, 2022-07-19) Herodotou, Christopher A.; Burns, Ramzy T.; Whaley, Rumeal; Idrees, Muhammad; Mellon, Matthew J.; Urology, School of MedicineReports of penile sarcoidosis are rare in the literature. We describe the case of a male who presented with several months of distal penile swelling and progressive inability to retract the foreskin. Firm, non-tender subcutaneous nodules were palpated near the base of the penis. The patient ultimately underwent penile skin resection, partial scrotal resection, and split thickness skin graft to the penis after failing multiple conservative treatments. Pathology revealed non-caseating granulomatous lesions which in addition to CT chest findings of bilateral hilar adenopathy suggested a diagnosis of penile sarcoidosis.