A role for metformin in the treatment of Dupuytren disease?

Dupuytren disease (DD) is a hand-localized fibrotic disorder characterized by a scar-like, collagen-rich cord. Treatment usually comprises surgical removal of the cord, but is associated with a high relapse rate, in some cases requiring finger amputation. There is currently no consensual medical approach for treating DD. Numerous preclinical studies have highlighted antifibrotic properties of metformin, and the aim of this study was to assess a potential antifibrotic role of metformin in DD. Fibroblasts from DD cords (DF) and phenotypically normal palmar fascia (PF) were extracted from surgical specimens and cultured. The fibrotic status of DF and PF was compared at baseline, and under profibrotic (TGF-ß stimulation) and antifibrotic (metformin stimulation) conditions, using quantitative RT-PCR, western blot, immunocytochemistry, and a functional fibroblast contraction assay. At baseline, DF showed higher levels of fibrotic markers and contraction capacity compared with PF. Both types of fibroblasts responded to TGF-ß stimulation. Treatment of DF and PF with metformin did not affect basal levels of fibrotic markers and contraction but largely prevented their induction by TGF-ß. In conclusion, our data show that metformin inhibits TGF-ß-induced expression of fibrotic markers and contraction in hand-derived fibroblasts. This supports the case for a clinical trial to assess the repurposing of metformin as an adjuvant to surgery, to prevent, reduce, or delay recurrence in at-risk DD patients.

Surgical treatment of secondary lymphedema of the upper limb by stepped microsurgical lymphaticovenous anastomoses.

OBJECTIVE: The incidence of lymphedema following treatment for breast cancer ranges between 10 and 50% after complete axillary dissection and gives rise to severe functional discomfort in patients. Results of lymphaticovenous anastomoses (LVA) in surgical treatment of lymphedema appear to be favorable. However, the available literature on this topic is scarce, often with short follow-up times. The aim of this study is to analyze the results of LVA on 31 patients and to review the existing literature. PATIENTS AND METHODS: This study comprised 31 female patients presenting lymphedema of the upper limb following treatment for breast cancer for which surgical treatment was given by microsurgery consisting of three stepped LVA performed in an outpatient setting. RESULTS: The post-LVA arm circumference was measured at three levels (wrist, forearm, and arm) in 31 female patients. Mean follow-up time was 12.8 months. Reduction in the circumference was 22.5, 21.32, and 30.2%, respectively, in the wrist, forearm, and arm. Functional improvement was observed in the majority (84%) of patients ranging from moderate to substantial. Only 2 patients had no result. The only patients to experience recurrence were those with a high level of lymphedema. CONCLUSION: The review of the current literature and the present study revealed modest results in terms of decreased excess volume, although a major improvement in function points to LVA as a useful technique in this indication. Progress in imaging techniques has enhanced the results achieved with this procedure, although further studies on recurrence rates are needed with a follow-up greater than 1 year.

Morbidity, mortality, and oncological outcomes of 401 consecutive cytoreductive procedures with hyperthermic intraperitoneal chemotherapy (HIPEC).

PURPOSE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are a novel curative treatment option for selected patients with peritoneal carcinomatosis (PC). We aimed to report the mortality rate and the most frequent grade III-IV adverse events and to identify associated prognostic markers. We report oncological outcomes and major prognostic factors influencing overall survival (OS) and disease-free survival. METHODS: A total of 401 CRS plus HIPEC procedures were performed on 356 patients. Mortality, grade III-IV adverse events, OS, disease-free survival, and prognostic factors were studied. RESULTS: Based on Common Terminology Criteria for Adverse Events (CTCAE of the National Cancer Institute 2006), mortality rate was 1 % and overall rate of morbidity grade III-IV was 12.5 %. In multivariate analysis, only the number of digestive anastomoses (>1) significantly correlated with adverse events with an odds ratio of 2.8 (p = 0.032). OS was related to histological type of PC, with a median survival reaching 47.6 months for PC of ovarian cancer origin, 45.8 months for that of colorectal origin, 64.2 months for peritoneal mesothelioma, and 8.1 months for PC of gastric cancer origin. Over half the patients with pseudomyxoma are still alive. Major prognostic factors influencing survival were histological type, World Health Organization performance status (WHO PS) (hazard ratio (HR) = 3.56), operating time (HR = 0.45), previous chemotherapy (HR = 2.04), number of peritonectomies (HR = 2.03), and completeness of cytoreduction score (HR = 3.12). Disease-free survival across all groups was 16.8 months. CONCLUSION: The low mortality rate and 12.5 % grade III-IV morbidity of CRS and HIPEC are acceptable when weighed against overall oncologic survival. This multimodal treatment appears feasible for selected patients and trained centers.