The G protein-coupled receptors, GPR41 and GPR43, are activated by short-chain fatty acids (SCFAs), with distinct rank order potencies. This study investigated the possibility that SCFAs modulate intestinal motility via these receptors. Luminal SCFA concentrations within the rat intestine were greatest in the caecum (c. 115 mmol L(-1)) and proximal colon. Using similar concentrations (0.1-100 mmol L(-1)), SCFAs were found to inhibit electrically evoked, neuronally mediated contractions of rat distal colon, possibly via a prejunctional site of action; this activity was independent of the presence or absence of the mucosa. By contrast, SCFAs reduced the amplitude but also reduced the threshold and increased the frequency of peristaltic contractions in guinea-pig terminal ileum. In each model, the rank-order of activity was acetate (C2) approximately propionate (C3) approximately butyrate (C4) > pentanoate (C5) approximately formate (C1), consistent with activity at the GPR43 receptor. GPR43 mRNA was expressed throughout the rat gut, with highest levels in the colon. However, the ability of SCFAs to inhibit neuronally mediated contractions of the colon was similar in tissues from wild-type and GPR43 gene knockout mice, with identical rank-orders of potency. In conclusion, SCFAs can modulate intestinal motility, but these effects can be independent of the GPR43 receptor.

Previous studies have demonstrated mixed inhibitory and facilitatory effects of 5-hydroxytryptamine-4 (5-HT(4)) receptor agonists on electrical field stimulation (EFS)-induced responses in human isolated colon. Here we report three types of responses to EFS in human isolated colon circular muscle: monophasic cholinergic contraction during EFS, biphasic response (nitrergic relaxation during EFS followed by cholinergic contraction after termination of EFS) and triphasic response (cholinergic contraction followed by nitrergic relaxation during EFS and a tachykininergic contraction after EFS). The effects of two 5-HT(4) receptor agonists, prucalopride and tegaserod were then investigated on monophasic responses only. Each compound inhibited contractions during EFS in a concentration-dependent manner. In the presence of N(omega)-nitro-l-arginine methyl ester (l-NAME) however, prucalopride and tegaserod enhanced the contractions in a concentration-dependent manner. In strips where the tone was elevated with substance-P and treated with scopolamine, EFS-induced relaxations were enhanced by the two agonists. The above observed effects by the two agonists were abolished by 5-HT(4) receptor antagonist SB-204070. The two agonists did not alter the tone raised by substance-P in the presence of scopolamine and l-NAME and did not affect carbachol-induced contractions in the presence of tetrodotoxin. These results suggest that in the circular muscle of human colon, 5-HT(4) receptor agonists simultaneously facilitate the activity of neurones which release the inhibitory and excitatory neurotransmitters, nitric oxide and acetylcholine respectively.

Objective: Despite the low local toxicity of the used agents, Cisplatin-based chemotherapy (CBP) for patients with testicular germ cell tumors (TGCT) is mostly delivered via a central venous access (CVA). Since 2008, CBP is given peripherally in our hospital. Methods: Medical reports of TGCT patients who received CBP between September 1991 and August 2014 were evaluated. Complications regarding the way of administration (CVA vs. peripheral venous catheter [PVC]) were classified according to the Common Terminology Criteria of Adverse Events. The complication rates were compared using chi square test and propensity score matching. Results: During 288 cycles in 109 patients, 85 complications (29.5%) were observed with similar rates for overall (PVC 31.3%, CVA 29.9%; p = 0.820) and grade I complications (21.3%, 25.4%; p = 0.470). More grade II complications were observed in the PVC group (10.0 vs. 1.5%; p < 0.001). Grade III complications requiring invasive treatment were found only in the CVA group (3.0%; p = 0.120). Using propensity score matching, no differences in overall (p = 0.950), grade I (p = 0.540) and grades II/III (p = 0.590) complications were seen. Conclusion: The peripheral and central administration of CBP has similar overall complication rates. Despite more grade II complications, the peripheral administration of CBP is a safe alternative for TGCT patients. Additionally, no severe grade III complications occurred.

The critical appraisal process assures quality of the available information and the tool is applicable to all healthcare related internet resources. The process is discussed with respect to colorectal cancer information resources and will be equally useful to healthcare professional and public. The healthcare professionals can apply the tool in practice and advise the public more confidently on internet information.

Objective: The study aimed to calculate direct medical costs (DMC) during the first year of diagnosis and to evaluate the impact of guideline changes on treatment costs in clinical stage (CS) I testicular germ cell tumor (TGCT) patients in a German healthcare system. Materials and Methods: Healthcare expenditures as DMC during the first year of diagnosis for 307 TGCT patients in CS I treated at our institution from 1987 to 2013 were calculated from the statutory health insurance perspective using patient level data. Three periods were defined referring to the first European Association of Urology (EAU) guideline in 2001 as well as to subsequent major guideline changes in 2005 and 2010. Data source for cost calculations were the German Diagnosis Related Groups system for inpatient stays (version 2014) and the German system for reimbursement of outpatient care (EBM – Einheitlicher Bewertungsmaßstab, edition 2014). Results: During our 25 years of study period, mean DMC in the first year after diagnosis for the entire cohort of TGCT patients in CS I almost halved from EUR 13.000 to EUR 6.900 (p < 0.001). From 1987 to 2001, DMC for CS I seminomatous germ cell tumor (SGCT) patients were EUR 13.790 ± 4.700. From 2002 to 2010, mean costs were EUR 10.900 ± 5.990, and from 2011 to 2013, mean costs were EUR 5.190 ± 3.700. For CS I non-seminomatous germ cell tumor (NSGCT) patients, from 1987 to 2001, mean DMC were EUR 11.650 ± 5.690. From 2002 to 2010, mean costs were EUR 11.230 ± 5.990, and from 2011 to 2013, mean costs were EUR 11.170 ± 7.390. Follow-up examinations became less frequent over time, which caused a significant cost reduction for NSGCT (p = 0.042) while costs remained stable for SGCT. When adding costs of relapse treatment, active surveillance (AS) was the most cost-effective adjuvant treatment option in CS I NSGCT whereas one course carboplatin or AS caused similar expenditures in SGCT patients. Conclusion: The introduction of the EAU guidelines in 2001 caused a decrease in DMC in CS I seminoma patients. This cost reduction mainly took place due to the declining importance of radiation therapy. No substantial changes were seen in patients with CS I NSGCT. Costs for follow-up care also diminished, but to a lesser degree. Even when considering expenditures for relapse treatment, AS remained cost-effective in CS I TCGT patients. Our data show that evidence-based medicine in TGCT can reduce DMC in the first year after diagnosis.