Characteristics of lymphoedema, in particular midline lymphoedema, after treatment for prostate cancer: a retrospective study.

BACKGROUND: Patients undergoing treatment for prostate cancer may develop lymphoedema of the midline region. This has a substantial impact on a patient's quality of life and its diagnosis is often delayed or missed. Therefore, the purpose of this study is to compare the characteristics of patients with leg and midline lymphoedema to patients with only leg lymphoedema. METHODS: We retrospectively collected patient-, cancer-, lymphoedema- and lymphoedema treatment-related data of 109 men with lymphoedema after treatment for prostate cancer. First, 42 characteristics were compared between both groups. Second, factors predicting presence of midline lymphoedema were explored by multivariable analyses. RESULTS: The mean age of the patients with lymphoedema was 68 ( ±7) years and mean BMI is 28 (±4) kg/m2. Median duration of lymphoedema before the first consultation was 27 (9;55) months. Based on univariable analyses, patients with leg and midline lymphoedema had more frequently upper leg lymphoedema (89% (31/35) vs. 69% (51/74), p = 0.026), skin fibrosis (34% (12/35) vs. 16% (12/74), p = 0.034) and lymphatic reconstructive surgery (9% (3/35) vs. 0% (0/71), p = 0.020) than patients with only leg lymphoedema. Additionally, patients with leg and midline lymphoedema reported less frequently lower leg lymphoedema (77% (27/35) vs. 95% (70/74), p = 0.007). Based on the multivariable analysis, not having lower leg lymphoedema, skin fibrosis, performing self-bandaging and self-manual lymphatic drainage appear to be predictors for having midline lymphoedema. CONCLUSIONS: If patients with lymphoedema after prostate cancer do not have lower leg lymphoedema, have skin fibrosis, perform self-bandaging or self-manual lymphatic drainage, they possibly have midline lymphoedema.

Loss of hypothalamic Furin affects POMC to proACTH cleavage and feeding behavior in high-fat diet-fed mice.

OBJECTIVE: The hypothalamus regulates feeding and glucose homeostasis through the balanced action of different neuropeptides, which are cleaved and activated by the proprotein convertases PC1/3 and PC2. However, the recent association of polymorphisms in the proprotein convertase FURIN with type 2 diabetes, metabolic syndrome, and obesity, prompted us to investigate the role of FURIN in hypothalamic neurons controlling glucose and feeding. METHODS: POMC-Cre+/- mice were bred with Furinfl/fl mice to generate conditional knockout mice with Furin-deletion in neurons expressing proopiomelanocortin (POMCFurKO), and Furinfl/fl mice were used as controls. POMCFurKO and controls were periodically monitored on both normal chow diet and high fat diet (HFD) for body weight and glucose tolerance by established in-vivo procedures. Food intake was measured in HFD-fed FurKO and controls. Hypothalamic Pomc mRNA was measured by RT-qPCR. ELISAs quantified POMC protein and resulting peptides in the hypothalamic extracts of POMCFurKO mice and controls. The in-vitro processing of POMC was studied by biochemical techniques in HEK293T and CHO cell lines lacking FURIN. RESULTS: In control mice, Furin mRNA levels were significantly upregulated on HFD feeding, suggesting an increased demand for FURIN activity in obesogenic conditions. Under these conditions, the POMCFurKO mice were hyperphagic and had increased body weight compared to Furinfl/fl mice. Moreover, protein levels of POMC were elevated and ACTH concentrations markedly reduced. Also, the ratio of α-MSH/POMC was decreased in POMCFurKO mice compared to controls. This indicates that POMC processing was significantly reduced in the hypothalami of POMCFurKO mice, highlighting for the first time the involvement of FURIN in the cleavage of POMC. Importantly, we found that in vitro, the first stage in processing where POMC is cleaved into proACTH was achieved by FURIN but not by PC1/3 or the other proprotein convertases in cell lines lacking a regulated secretory pathway. CONCLUSIONS: These results suggest that FURIN processes POMC into proACTH before sorting into the regulated secretory pathway, challenging the dogma that PC1/3 and PC2 are the only convertases responsible for POMC cleavage. Furthermore, its deletion affects feeding behaviors under obesogenic conditions.