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Abstract Background The pathogenesis of colorectal neoplasia is still unresolved but has been associated with alterations in epithelial clearance of xenobiotics and metabolic waste products. The aim of this study was to functionally characterize the transport of cyclic nucleotides in colonic biopsies from patients with and without colorectal neoplasia. Methods Cyclic nucleotides were used as model substrates shared by some OATP- and ABC-transporters, which in part are responsible for clearance of metabolites and xenobiotics from the colonic epithelium. On colonic biopsies from patients with and without colorectal neoplasia, molecular transport was electrophysiologically registered in Ussing-chamber set-ups, mRNA level of selected transporters was quantified by rt-PCR, and subcellular location of transporters was determined by immunohistochemistry. Results Of four cyclic nucleotides, dibuturyl-cAMP induced the largest short circuit current in both patient groups. The induced short circuit current was significantly lower in neoplasia-patients (p = 0.024). The observed altered transport of dibuturyl-cAMP in neoplasia-patients could not be directly translated to an observed increased mRNA expression of OATP4A1 and OATP2B1 in neoplasia patients. All other examined transporters were expressed to similar extents in both patient groups. Conclusions OATP1C1, OATP4A1, OATP4C1 seem to be involved in the excretory system of human colon. ABCC4 is likely to be involved from an endoplasmic-Golgi complex and basolateral location in goblet cells. ABCC5 might be directly involved in the turnover of intracellular cAMP at the basolateral membrane of columnar epithelial cells, while OATP2B1 is indirectly related to the excretory system. Colorectal neoplasia is associated with lower transport or sensitivity to cyclic nucleotides and increased expression of OATP2B1 and OATP4A1 transporters, known to transport PGE2.

Endoscopic retrograde cholangiopancreatography (ERCP) has until now always been performed using a reusable non-sterile duodenoscope. The introduction of the new single-use disposable duodenoscope makes it possible to perform perioperative transgastric and rendezvous ERCP in an almost sterile manner. It also eliminates the risk of patient-to-patient transmission of infection in non-sterile settings. We present four patients who underwent different types of ERCP using a sterile single-use duodenoscope. This case report aims to demonstrate the use and the many potential advantages of the new disposable single-use duodenoscope in both sterile and non-sterile settings., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: A subgroup of patients with benign colonic neoplasia is unsuitable for standard endoscopic treatment modalities. These patients may benefit from a combined endoscopic and laparoscopic surgical (CELS) approach. A CELS procedure may even be an option for some patients with a small malignant lesion where resection of the colon may be associated with an excessively high risk of proced-ure-related morbidity and mortality., Methods: All patients considered for a CELS procedure were evaluated at a multidisciplinary team conference. The CELS procedures were performed as laparoscopy-assisted endoscopic mucosal resections or endoscopy-assisted laparoscopic resections., Results: A total of 25 patients were included. Five patients had a malignant and 20 patients had a benign lesion. Two patients with histologically verified malignant lesions pre-operatively had CELS performed due to severe co-morbidity. In one patient with initially benign biopsies, the resected CELS specimen revealed adenocarcinoma. This patient subsequently underwent oncological resection (no residual disease). In the last two cases, the lesions were assessed during CELS and they exhibited endoscopically malignant features. Consequently, both patients underwent immediate oncological segmental colon resection., Conclusions: CELS is a feasible treatment for colonic neoplasia where endoscopic resection alone is not technically possible. In case of severe co-morbidity ruling out segmental resection in patients diagnosed with T1 or T2 colorectal cancer, CELS treatment may be considered., Funding: none., Trial Registration: This study was assessed by The National Committee on Health Research Ethics (SJ-593), which concluded that the study required no approval from the Committee. The study was approved by the Danish Data Protection Agency (REG-126-2017). ., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Aim: To investigate functional duodenal abnormalities in functional dyspepsia (FD) and the role of serotonin (5-hydroxytryptamine, 5-HT) in mucosal ion transport and signalling., Methods: Duodenal mucosal biopsies were obtained from 15 patients with FD and 18 healthy controls. Immunohistochemistry was used to study the number of 5-HT-containing cells and real-time polymerase chain reaction for expression of 5-HT receptors 1A, 1B, 2A, 2B, 3A, 3B, 3C, 3D, 3E, 4 and 7, as well as expression of the serotonin re-uptake transporter (SERT) gene SLC6A4 and tryptophan hydroxylase 1 (TPH1). Biopsies were mounted in Ussing chambers for evaluation of basal and 5-HT-stimulated short-circuit current (SCC)., Results: Conductance was lower in FD [42.4 ± 4.7 mS/cm(2) (n = 15) vs 62.5 ± 4.5 mS/cm(2) (n = 18), P = 0.005]. 5-HT induced a dose dependent rise in SCC in both FD (n = 8) and controls (n = 9), the rise was lower in FD (P < 0.001). Mean number of 5-HT stained cells per high power field was the same [34.4 ± 8.4 in FD (n = 15) and 30.4 ± 3.7 in controls (n = 18), P = 0.647]. The following genes were highly expressed: 5-HT receptor HTR3E, HTR4, HTR7, SERT gene (SLC6A4) and TPH1. Differences in expression levels were observed for HTR3E (higher expression in FD, P = 0.008), HTR7 (lower expression in FD, P = 0.027), SLC6A4 (higher expression in FD, P = 0.033) and TPH1 (lower expression in FD, P = 0.031)., Conclusion: Duodenal ion transport in response to exogenous 5-HT is abnormal in FD patients and associated with high expression of the HTR3E receptor and the serotonin transporter.

The presence of gastrin-releasing peptide (GRP) was studied in extracts of porcine pancreata. Gel filtration and high-pressure liquid chromatographic profiles of these extracts as monitored with both C-terminally and N-terminally directed radioimmunoassays against GRP showed pancreatic GRP to consist of one main form, namely the 27-amino acid peptide originally extracted from porcine stomach, and small amounts of a C-terminal fragment identical with the C-terminal 10-amino acid peptide. Gastrin-releasing peptide-like immunoreactivity released from the isolated perfused porcine pancreas during electrical vagal stimulation was shown by gel filtration to consist of the same two forms. By use of immunocytochemical techniques employing an antiserum directed against its N terminus, GRP was localized to varicose nerve fibers in close association with the exocrine tissue of the porcine pancreas in particular. Some fibers were found penetrating into pancreatic islets also. Immunoreactive nerve cell bodies as well as fibers were found within intrapancreatic ganglia. The potency of GRP in stimulating exocrine as well as endocrine secretion from the porcine pancreas, its presence in close contact with both acini and islets, and its release during vagal stimulation indicate that GRP may have a role in the parasympathetic regulation of endocrine and exocrine secretion from the pig pancreas.

Using a newly developed radioimmunoassay for porcine gastrin-releasing peptide in plasma, we studied the pharmacokinetics of this peptide after infusing it into pigs at two dose levels. The disappearance of the peptide from plasma was characterized by two components, a fast one (t 1/2 1.4 min) and a slow one (t 1/2 6.6 min). With the same assay the release of gastrin releasing-peptide from the stomachs of 8 pigs that had been catheterized for selective sampling of fundic and antral blood was studied during vagal and splanchnic stimulation with or without acute adrenalectomy at neutral, acidic, and alkaline intragastric pH. Electrical stimulation of the vagal nerves resulted in a marked increase in both antral and fundic gastrin-releasing peptide release, whereas splanchnic stimulation was without effect. The effects of nerve stimulation were neither influenced by intragastric pH nor by adrenalectomy. Because of its presence in nerves in all layers of the gastric wall, its potent effect on gastrin release, and its release after vagal stimulation, gastrin-releasing peptide is likely to play a role in the vagal control of gastrin release, gastric motility, and acid secretion.