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BACKGROUND Treatment of advanced lymphedema requires not only restoration of physiological lymph drainage, but also excision of fibrotic tissue and excess skin. The aim of this study is to show how the combination of double vascularized lymph node transfers (VLNTs) and a modified radical reduction with preservation of perforators (RRPP) can accomplish both of these treatment goals. METHODS Between 2010 and 2016, 16 patients (15 female and one male) with extremity lymphedema underwent a combined double gastroepiploic VLNTs and modified RRPP. Demographics, outcomes including circumference reduction rates, preoperative and postoperative lymphoscintigraphy, complications, and responses to the Lymphedema Quality of Life (LYMQOL) questionnaire were analyzed. RESULTS All flaps survived. The mean follow-up period was 14.2 months (range, 12-19). The mean circumference reduction rate was 74.5% ± 6.9% for the upper limb and 68.0% ± 4.2% for the lower limb. There were no major complications. Minor complications, including numbness and hyperesthesia, were treated conservatively. LYMQOL showed a 2.7-fold quality-of-life improvement (P

Background This study evaluated the long-term clinical outcomes among different vascularized lymph node transfers (VLNT) used at our institution. Methods Between July 2010 and July 2016, all patients with International Society of Lymphology (ISL) stages II-III who underwent VLNT were evaluated. Demographic and clinical data (limb circumference, infectious episodes, lymphoscintigraphic studies) were recorded pre-operatively. Clinical outcomes, complications, and additional excisional procedures were analyzed post-operatively. At least 2-year follow-up was required for inclusion. Results Overall, 83 patients (Stage II:47, Stage III:36) met the inclusion criterion. Mean follow-up was 32.8 months (range, 24-49). Lymph node flaps used were groin (n = 13), supraclavicular (n = 25), gastroepiploic (n = 42), ileocecal (n = 2), and appendicular (n = 1). Total mean circumference reduction rate was 29.1% (Stage II) and 17.9% (Stage III) (P

Vascularized lymph node (VLN) transfer has been of high interest in the past decade for the treatment of lymphedema, since it has been shown to be effective in reducing limb volumes, decreasing infectious episodes and improving quality of life. Multiple donor sites have been described in the quest for the optimal one. Herein, we describe a novel lymph node flap option based on the ileocolic artery and vein. The ileocecal vascularized lymph node (IC-VLN) flap was used in the management of a 33-year-old male patient with lower extremity lymphedema secondary to left inguinal trauma. The patient had previously underwent a pedicled omentum flap transposition with minimal improvement in limb size and persistent episodes of infection. At 15 month follow-up, the IC-VLN flap improved the lymphatic drainage in the affected limb with a mean limb circumference reduction rate of 26.3%. No donor site complications or further episodes of infection were noted. According to our findings, the IC-VLN flap may be another option for VLN transfer in very selected cases. Nevertheless, larger series with a longer follow-up are required to analyze the efficacy and long-term results of this flap.

Vascularized lymph node transfer has demonstrated promising results for the treatment of extremity lymphedema. In an attempt to find the ideal donor site, several vascularized lymph nodes have been described. Each has a common goal of decreasing morbidity and avoiding iatrogenic lymphedema while obtaining good clinical results. Herein, we present the preliminary clinical outcomes of an intra-abdominal lymph node flap option based on the appendicular artery and vein used for the treatment of extremity lymphedema. A 62 year-old woman with moderate lower extremity lymphedema, on chronic antibiotics because of recurrent infections and unsatisfactory outcomes after conservative treatment underwent a vascularized appendicular lymph node (VALN) transfer. At a follow-up of 6 months, the reduction rate of the limb circumference was 17.4%, 15.1%, 12.0% and 9% above the knee, below the knee, above the ankle and foot respectively. In addition, no further episodes of infection or other complications were reported after VALN transfer. Postoperative lymphoscintigraphy demonstrated that the VALN flap was able to improve the lymphatic drainage of the affected limb. According to our findings, the use of VALN transfer minimizes donor-site morbidity, avoids iatrogenic lymphedema and may provide a strong clearance of infection because of the strong immunologic properties of the appendiceal lymphatic tissue in selected patients. Despite these promising results, further research with larger number of patients and longer follow- up is needed.

Between 2010 and 2016, 110 patients with extremity lymphedema underwent vascularized lymph node (VLN) transfer: groin (G-VLN = 20), supraclavicular (SC-VLN = 54), and right gastroepiploic (RGE-VLN = 36) open and laparoscopic approach. Herein, we discuss the pearls and pitfalls for VLN harvest and compare donor site morbidity and complications. Lymphatic leakage: G-VLN (n = 1) and SC-VLN (n = 1) and one hematoma: SC-VLN were found. Laparoscopic harvest of the RGE-VLN reduces donor site morbidity. However, surgeons experience is imperative to minimize donor site morbidity and complications. J. Surg. Oncol. 2017;115:37-42. © 2016 Wiley Periodicals, Inc.

BACKGROUND Drug repurposing of phentolamine, an α-adrenoceptor antagonist, as an anticancer agent has been studied in human castration-resistant prostate cancer (CRPC). METHODS Cell proliferation was examined by sulforhodamine B and CFSE staining assays. Cell cycle progression and mitochondrial membrane potential (ΔΨm) were detected by flow cytometric analysis. Protein expression was detected by Western blotting. Effect on tubulin/microtubule was determined using confocal immunofluorescence microscopic examination, microtubule assembly detection, tubulin turbidity assay, and binding assay. Several assessments were used to characterize apoptotic signaling pathways and combinatory effect. RESULTS Phentolamine induced anti-proliferative effect in PC-3 and DU-145, two CRPC cell lines, and P-glycoprotein (P-gp) overexpressing cells. This effect was not significantly reduced in paclitaxel-resistant cells. Rhodamine 123 efflux assay showed that phentolamine was not a P-gp substrate. Phentolamine induced mitotic arrest of the cell cycle and formation of hyperdiploid cells, followed by an increase of apoptosis. Mitotic arrest was confirmed by cyclin B1 up-regulation, Cdk1 activation, and a dramatic increase of mitotic protein phosphorylation. Both in vitro and cellular identification demonstrated that phentolamine, similar to paclitaxel, induced tubulin polymerization and formation of multiple nuclei. Besides, it did not compete with paclitaxel binding on tubulin. Phentolamine induced the phosphorylation and degradation of Bcl-2 and Bcl-xL, two anti-apoptotic Bcl-2 family members, and the loss of ΔΨm indicating the induction of mitochondrial damage. It ultimately induced the activation of caspase-9, -8, and -3 and apoptotic cell death. Moreover, combination treatment with phentolamine and paclitaxel caused a synergistic apoptosis. CONCLUSIONS The data suggest that phentolamine is a potential anticancer agent. In contrast to a wide variety of microtubule disrupting agents, phentolamine induces microtubule assembly, leading to mitotic arrest of the cell cycle which “in turn” induces subsequent mitochondrial damage and activation of related apoptotic signaling pathways in CRPC cells. Furthermore, combination between phentolamine and paclitaxel induces a synergistic apoptotic cell death. Phentolamine has a simple chemical structure and is not a P-gp substrate. Optimization of phentolamine structure may also be a potential approach for further development. Prostate 75:1454–1466, 2015. © 2015 Wiley Periodicals, Inc.