Loss of fat mass is a key feature of cancer cachexia and has been attributed to increased adipocyte lipolysis. The mechanism behind this alteration is unknown and was presently investigated. We studied mature s.c. fat cells and differentiated preadipocytes from 26 cancer patients with and without cachexia. Hormone-induced lipolysis and expression of lipolysis-regulating genes were determined together with body composition and in vivo lipolytic activity ( fasting plasma glycerol or fatty acids related to body fat). Body fat was reduced by 40% and in vivo lipolytic activity was 2-fold increased in cachexia (P = 0.001). In mature adipocytes, the lipolytic effects of catecholamines and natriuretic peptide were 2-to 3-fold increased in cachexia (P < 0.001). This was completely counteracted by inhibiting the rate-limiting lipolysis enzyme hormone-sensitive lipase (HSL). In cachexia, the expression levels of HSL mRNA and protein were increased by 50% and 100%, respectively (P = 0.005-0.03), which strongly correlated with in vitro lipolytic stimulation (r = 0.7-0.9). The antilipolytic effect of insulin in mature fat cells and the stimulated lipolytic effect in differentiated preadipocytes were unaltered in cachexia. Patients who lost weight due to other factors than cancer cachexia had no change in adipocyte lipolysis. In conclusion, adipocyte lipolysis is increased in cancer cachexia not due to nonepigenic factors or to weight loss per se, but most probably because of enhanced expression and function of adipocyte HSL. The selective inhibition of this enzyme may prevent fat loss in cancer patients. [Cancer Res 2007;67(11):5531-7]

Objective:The aim of the study was to evaluate if associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) could increase resection rates (RRs) compared with two-stage hepatectomy (TSH) in a randomized controlled trial (RCT).Background:Radical liver metastasis resection offers the only chance of a cure for patients with metastatic colorectal cancer. Patients with colorectal liver metastasis (CRLM) and an insufficient future liver remnant (FLR) volume are traditionally treated with chemotherapy with portal vein embolization or ligation followed by hepatectomy (TSH). This treatment sometimes fails due to insufficient liver growth or tumor progression.Methods:A prospective, multicenter RCT was conducted between June 2014 and August 2016. It included 97 patients with CRLM and a standardized FLR (sFLR) of less than 30%. Primary outcome—RRs were measured as the percentages of patients completing both stages of the treatment. Secondary outcomes were complications, radicality, and 90-day mortality measured from the final intervention.Results:Baseline characteristics, besides body mass index, did not differ between the groups. The RR was 92% [95% confidence interval (CI) 84%–100%] (44/48) in the ALPPS arm compared with 57% (95% CI 43%–72%) (28/49) in the TSH arm [rate ratio 8.25 (95% CI 2.6–26.6); P < 0.0001]. No differences in complications (Clavien–Dindo ≥3a) [43% (19/44) vs 43% (12/28)] [1.01 (95% CI 0.4–2.6); P = 0.99], 90-day mortality [8.3% (4/48) vs 6.1% (3/49)] [1.39 [95% CI 0.3–6.6]; P = 0.68] or R0 RRs [77% (34/44) vs 57% (16/28)] [2.55 [95% CI 0.9–7.1]; P = 0.11)] were observed. Of the patients in the TSH arm that failed to reach an sFLR of 30%, 12 were successfully treated with ALPPS.Conclusion:ALPPS is superior to TSH in terms of RR, with comparable surgical margins, complications, and short-term mortality.

BACKGROUND.Cancer cachexia is an important, negative prognostic marker that has been linked to systemic inflammation and cell death through unclear mechanisms. A key feature of cancer cachexia is loss of white adipose tissue (WAT) because of increased adipocyte lipolysis and possibly reduced lipid synthesis (lipogenesis). In this study, the authors investigated whether alterations in fat cell numbers, lipogenesis, or cytokine and/or leukocyte infiltration could account for some of the functional changes observed in WAT in cancer cachexia.METHODS.Blood and subcutaneous WAT samples were obtained from a 10 weight‐stable patients, from 13 weight losing (cachexia) patients with cancer, and from 5 patients without cancer (noncancer patients) who initially were classified with cancer.RESULTS.Systemic inflammation (increased circulating levels of interleukin 6 [IL‐6]) and enhanced lipolysis were confirmed in the cachectic patients compared with the other patients. However, the messenger RNA expression of IL‐6 and other cytokine or leukocyte markers, as well as WAT secretion of IL‐6, were not altered in the patients with cachexia. Thus, the elevated serum levels of IL‐6 that were observed in cachexia were not derived from WAT. Insulin‐induced lipogenesis in adipocytes from patients with cachexia was the same as that in adipocytes from patients with weight‐stable cancer and from noncancer patients (2.5‐fold maximal stimulation; half‐maximum effective concentration, ∼0.03 nmol/L). Fat cell size was decreased but adipocyte numbers were normal in cancer patients with cachexia, suggesting that there was no major fat cell death.CONCLUSIONS.The current findings indicated that subcutaneous WAT does not contribute to the systemic inflammatory reaction and does not induce adipocyte insulin resistance in cancer cachexia. Moreover, increased fat cell lipolysis, not reduced lipogenesis or adipocyte cell death, appeared to be the primary cause of fat loss in this condition. Cancer 2008. © 2008 American Cancer Society.