Experimental data suggest that melatonin decreases inflammatory changes after major liver resection, thus positively influencing the postoperative course. To assess the safety of a preoperative single dose of melatonin in patients undergoing major liver resection, a randomized controlled double-blind pilot clinical trial with two parallel study arms was designed at the Department of General and Transplantation Surgery, Ruprecht-Karls-University, Heidelberg. A total of 307 patients, who were referred for liver surgery, were screened. One hundred and thirteen patients, for whom a major liver resection (≥3 segments) was scheduled, were eligible. Sixty-three eligible patients refused to participate, and therefore, 50 patients were randomized. A preoperative single dose of melatonin (50 mg/kg BW) dissolved in 250 mL of milk was administered through the gastric tube after the intubation for general anesthesia. Controls were given the same amount of microcrystalline cellulose. Primary endpoint was safety. Secondary endpoints were postoperative complications. Melatonin was effectively absorbed with serum concentrations of 1142.8 ± 7.2 ng/mL (mean ± S.E.M.) versus 0.3 ± 7.8 ng/mL in controls (P < 0.0001). Melatonin treatment resulted in lower postoperative transaminases over the study period (P = 0.6). There was no serious adverse event in patients after melatonin treatment. A total of three infectious complications occurred in either group. A total of eight noninfectious complications occurred in five control patients, whereas three noninfectious complications occurred in three patients receiving preoperative melatonin (P = 0.3). There was a trend toward shorter ICU stay and total hospital stay after melatonin treatment. Therefore, a single preoperative enteral dose of melatonin is effectively absorbed and is safe and well tolerated in patients undergoing major liver surgery.

In medical patients with sepsis, early enteral pharmaconutrition with glutamine dipeptides, vitamin C and E, beta-carotene, selenium, zinc, and butyrate in combination with an immunonutrition formula results in significantly faster recovery of organ function compared with control.

In Switzerland a rapid increase in the total overweight population (BMI ≥ 25) from 30.3% to 37.3% and in the obese segment (BMI ≥ 30) from 5.4% to 8.1% was observed between 1992 and 2007. The objective of this study is to produce a projection until 2022 for the development of adult overweight and obesity in Switzerland based on four National Health Surveys conducted between 1992 and 2007. Based on the projection, these prevalence rates may be expected to stabilize until 2022 at the 2007 level. These results were compared with future projections estimated for France, UK, US and Australia using the same model.

IntroductionAndrogen deprivation therapy (ADT) is a mainstay of treatment against advanced prostate cancer (PC). As a treatment goal, suppression of plasma testosterone levels to <50 ng/dl has been established over decades. Evidence is growing though that suppression to even lower levels may add further clinical benefit. Therefore, we undertook a pooled retrospective analysis on the efficacy of 1-, 3-, and 6-month sustained-release (SR) formulations of the gonadotropin-releasing hormone (GnRH) agonist triptorelin to suppress serum testosterone concentrations beyond current standards.MethodsData of 920 male patients with PC enrolled in 9 prospective studies using testosterone serum concentrations as primary endpoint were pooled. Patients aged 42–96 years had to be eligible for ADT and to be either naïve to hormonal treatment or have undergone appropriate washout prior to enrolment. Patients were treated with triptorelin SR formulations for 2–12 months. Primary endpoints of this analysis were serum testosterone concentrations under treatment and success rates overall and per formulation, based on a testosterone target threshold of 20 ng/dl.ResultsAfter 1, 3, 6, 9, and 12 months of treatment, 79%, 92%, 93%, 90%, and 91% of patients reached testosterone levels <20 ng/dl, respectively. For the 1-, 3-, and 6-month formulations success rates ranged from 80–92%, from 83–93%, and from 65–97% with median (interquartile range) serum testosterone values of 2.9 (2.9–6.5), 5.0 (2.9–8.7), and 8.7 (5.8–14.1) ng/dl at study end, respectively.ConclusionIn the large majority of patients, triptorelin SR formulations suppressed serum testosterone concentrations to even <20 ng/dl. Testosterone should be routinely monitored in PC patients on ADT although further studies on the clinical benefit of very low testosterone levels and the target concentrations are still warranted.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-016-0466-7) contains supplementary material, which is available to authorized users.

Twelve overnight fasted, healthy, male volunteers received on separate days a test breakfast consisting of (A) 100 g fresh white bread (providing 50 g starch) and 250 mL drinking water, (B) the same bread with a supplement of 10 g alpha-cyclodextrin dissolved in the drinking water (250 mL), and (C) 250 mL drinking water containing 25 g alpha-cyclodextrin. Capillary and venous blood samples were collected before breakfast and at regular intervals for a period of 3 hours thereafter. Plasma glucose was determined in capillary blood and plasma insulin in venous blood samples. Breakfast (A) let to the expected rise in blood glucose and insulin concentrations. Breakfast (C) did not produce a significant glycemic and insulinemic response, demonstrating that alpha-cyclodextrin is not hydrolyzed to glucose in the human digestive tract. Mild intestinal symptoms after the ingestion of alpha-cyclodextrin were reported by 4 subjects. The postprandial rises of plasma glucose and insulin were significantly smaller after breakfast (B) than (A). Under the conditions of this study, alpha-cyclodextrin reduced the glycemic and insulinemic index of white bread by 57 and 55 %, respectively. The postprandial time profile of plasma glucose and insulin suggests that, in an initial phase, the digestion of starch is inhibited by alpha-cyclodextrin almost completely. Yet, despite the delayed and reduced digestion of starch, the intake of breakfast (B) was not associated with flatulence or any other gastrointestinal symptoms.

The demonstration of a physiological benefit has recently become an indispensible element of the definition of dietary fibers. In the here-reported pilot study, the effect of alpha-cyclodextrin (alpha-CD) on the postprandial glycemic and insulinemic effect of starch was examined. Twelve fasted, healthy male volunteers received, on three subsequent days, a test breakfast consisting of (A) 100 g fresh white bread (providing 50 g starch) and 250 mL drinking water, (B) the same bread with a supplement of 10 g alpha-CD dissolved in the drinking water, and (C) 25 g alpha-CD dissolved in drinking water. Capillary and venous blood was sampled before the breakfast and in regular intervals for a three-hour period thereafter. Glucose was determined in capillary blood and insulin in the plasma of venous blood samples. Breakfast (A) led to a rapid rise in blood glucose and insulin. In breakfast (B), alpha-CD reduced the areas under the curve of blood glucose and insulin significantly by 59% and 57%, respectively, demonstrating that alpha-CD inhibits and thereby delays starch digestion. Treatment (C) was not associated with a rise of blood glucose. Hence, alpha-CD complies with the current definition of dietary fiber in every respect.

447 Background: BTC are aggressive tumors with limited treatment options and poor overall survival. Aberrant FGFR signaling has been implicated in BTC carcinogenesis. Debio 1347 is an orally available selective FGFRi with potent antitumor effect in preclinical model bearing FGFR alterations. Debio 1347 showed encouraging preliminary clinical activity and manageable treatment-emergent adverse events (TEAE) in its first-in-human (FIH) ph1 study (NCT1948297) dose-escalating part. Here we report only results from the BTC pts of this study. Methods: This FIH study enrolled pts with advanced solid malignancies harboring defined activating alterations of FGFR 1, 2, or 3: amplifications (amp), mutations (mut) and translocations (trans). Pharmacokinetics (PK) and pharmacodynamics were serially evaluated in blood, skin and/or tumor tissue. A confirmatory post-hoc analysis was performed centrally for all available biopsies. Results: Eight pts, six with intrahepatic cholangiocarcinoma (iCCA) and two with gallbladder cancer (GBC), were treated with Debio 1347 at doses between 60 and 150 mg orally daily in 28-day cycles. Among the iCCA pts, one had an FGFR2mut, one had an FGFR2 activating deletion (del), and one had an FGFR3mut; the other three had FGFR2trans. One of the two GBC pts had an FGFR3trans, the other one an FGFR2mut. All pts had prior systemic therapy (mostly 2 or 3 lines). The most common TEAEs were hyperphosphatemia (8/8), nail changes (5/8), nausea (5/8), dry mouth (4/8) and stomatitis (3/8). No grade ≥ 3 related TEAE were reported except grade 3 hyperphosphatemia (4/8). PK was comparable to that in pts with other solid malignancies.A partial response lasting up to 48 weeks was observed in an iCCA pt (FGFR2 del exon 5); three additional iCCA pts (FGFR2trans: ROCK1; KIAA1217; DDX21) and one GBC pt (FGFR3-TACC3 trans) had target lesions regression < 30% and stayed on trial between 24 – 37 weeks. Overall disease control was 62.5%. Conclusions: These results suggest that BTC pts with genomic events leading to activation of FGFR2/3 may benefit from treatment with Debio 1347. Further study is ongoing in the expansion cohort of this trial. Clinical trial information: NCT1948297.

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