Endoscopic full-thickness resection of benign and malignant colon lesions with one-year follow up in a Danish cohort.

BACKGROUND: Endoscopic full-thickness resection (EFTR) has been shown to be a feasible and safe technique in several studies since the introduction of the full-thickness resection device (FTRD®). This study aimed to describe our clinical experience and long-term follow up in in patients who underwent EFTR of benign and malignant colon lesions using FTRD. METHODS: All patients with difficult adenomas or early adenocarcinomas referred for an EFTR to two centres in Denmark were included in this prospective consecutive study. The primary outcome was technical success with R0 resection and relapse-free follow up. The secondary outcome was procedure-related adverse events. RESULTS: Twenty-six patients were enrolled in the study. Technical success was achieved in 81% patients and R0 resection rate was 86%. Full-thickness resection was achieved in 86% patients. In 13 patients with malignant lesions, we obtained follow-up in 10 cases (two patients underwent surgery and one was non-compliant). Findings of the three-month follow up showed no residual tumour in all 10 cases. At the 12-month follow up, one patient had a late relapse. There were no residual or recurrent adenomas in the benign subgroup. Overall, adverse events were observed in 11.5% (3/26) patients with a perforation rate of 7.7%. CONCLUSION: EFTR with FTRD proves to be an additional technique for the treatment of difficult non-lifting colorectal lesions. For malignant lesions, EFTR is technically safe and feasible and can potentially treat small early low-risk tumours; however, some cases may require subsequent surgery according to the histological staging observed in the resected specimen.

A Pilot Study Showing Acute Inhibitory Effect of GLP-1 on the Bone Resorption Marker CTX in Humans.

Bones have been suggested to be a target for glucagon-like peptide -1 (GLP-1); however, studies of the effects on human bones so far have given diverging results. We hypothesized that GLP-1, together with glucagon-like peptide-2 and glucose-dependent insulinotropic polypeptide, plays a role in the gut-bone axis. We examined the acute effect of three GLP-1 receptor ligands [GLP-1 (7-36)amide, GLP-1 (9-36)amide, and exenatide] on markers of bone remodeling. Eight healthy, normal-weight participants, with a mean age of 24.3 years, were studied for 4 days in a double-blinded, randomized clinical trial. Blood was collected before and after s.c. injection of GLP-1 (7-36)amide (1.5 nmol/kg), GLP-1 (9-36)amide (1.5 nmol/kg), exenatide (2.4 nmol/subject), or saline. Plasma was analyzed for bone markers and for osteoprotegerin (OPG), PTH, and IGF-1 levels. All ligands were tested in vitro for their cAMP-inducing activity on the human GLP-1 receptor. GLP-1 (7-36)amide decreased CTX-levels, compared with placebo (area under the curve [AUC] ±SD 0 to 120 min = -2143 ± 1294 % × min versus -883 ± 1557 % × min; p < 0.05). No difference was observed between placebo and GLP-1 (9-36)amide, or between placebo and exenatide, although exenatide had a similar potency as GLP-1 (7-36)amide for cAMP formation in vitro (EC50 of 0.093 and 0.054 nmol/L). However, exenatide reached maximum plasma concentration at 90 min versus 15 min for GLP-1 (7-36)amide, and plasma CTX was significantly decreased during the second hour of the study after exenatide injections compared with placebo (AUC ±SD -463.1 ± 218 % × min and -136 ± 91 % × min; p < 0.05). There was no effect of the injections on bone formation markers (P1NP and osteocalcin) or on OPG, PTH and IGF-1 levels. In conclusion, we show that GLP-1 receptor agonists, but not the primary metabolite GLP-1 (9-36)amide, decrease bone resorption, and suggest that GLP-1 may be part of the gut-bone axis. © 2019 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Combined endoscopic laparoscopic surgical treatment of advanced adenomas and early colon cancer.

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). .

[Oesophageal vascular ectasia in a patient with anaemia].

This case report describes the findings of oesophageal vascular ectasia (OVE) in a patient with known gastric antral vascular ectasia, who presented with anaemia. OVE is a very rare endoscopic finding and therefore a diagnostic challenge. An 85-year-old male was admitted due to anaemia. He went through a gastroscopic examination where severe OVE changes were seen, along with newfound oesophageal varices. There was no need for treating the OVE, but the findings coupled with the knowledge of the varices led to the diagnosis of portal thrombosis.

Acute effects of glucagon-like peptide-1, GLP-19-36 amide, and exenatide on mesenteric blood flow, cardiovascular parameters, and biomarkers in healthy volunteers.

Glucagon-like peptide-1 (GLP-1, GLP-17-36amide) and its sister peptide glucagon-like peptide 2 (GLP-2) influence numerous intestinal functions and GLP-2 greatly increases intestinal blood flow. We hypothesized that GLP-1 also stimulates intestinal blood flow and that this would impact on the overall digestive and cardiovascular effects of the hormone. To investigate the influence of GLP-1 receptor agonism on mesenteric and renal blood flow and cardiovascular parameters, we carried out a double-blinded randomized clinical trial. A total of eight healthy volunteers received high physiological subcutaneous injections of GLP-1, GLP-19-36 amide (bioactive metabolite), exenatide (stable GLP-1 agonist), or saline on four separate days. Blood flow in mesenteric, celiac, and renal arteries was measured by Doppler ultrasound. Blood pressure, heart rate, cardiac output, and stroke volume were measured continuously using an integrated system. Plasma was analyzed for glucose, GLP-1 (intact and total), exenatide and Pancreatic polypeptide (PP), and serum for insulin and C-peptide. Neither GLP-1, GLP-19-36 amide, exenatide nor saline elicited any changes in blood flow parameters in the mesenteric or renal arteries. GLP-1 significantly increased heart rate (two-way ANOVA, injection [P = 0.0162], time [P = 0.0038], and injection × time [P = 0.082]; Tukey post hoc GLP-1 vs. saline and GLP-19-36amide [P < 0.011]), and tended to increase cardiac output and decrease stroke volume compared to GLP-19-36 amide and saline. Blood pressures were not affected. As expected, glucose levels fell and insulin secretion increased after infusion of both GLP-1 and exenatide.

Glucagon-like Peptide 1 Receptor Signaling in Acinar Cells Causes Growth-Dependent Release of Pancreatic Enzymes.

Incretin-based therapies are widely used for type 2 diabetes and now also for obesity, but they are associated with elevated plasma levels of pancreatic enzymes and perhaps a modestly increased risk of acute pancreatitis. However, little is known about the effects of the incretin hormone glucagon-like peptide 1 (GLP-1) on the exocrine pancreas. Here, we identify GLP-1 receptors on pancreatic acini and analyze the impact of receptor activation in humans, rodents, isolated acini, and cell lines from the exocrine pancreas. GLP-1 did not directly stimulate amylase or lipase release. However, we saw that GLP-1 induces phosphorylation of the epidermal growth factor receptor and activation of Foxo1, resulting in cell growth with concomitant enzyme release. Our work uncovers GLP-1-induced signaling pathways in the exocrine pancreas and suggests that increases in amylase and lipase levels in subjects treated with GLP-1 receptor agonists reflect adaptive growth rather than early-stage pancreatitis.

[A targeted effort can secure a good and educating clinical stay for medical students].

The medical education at the University of Copenhagen introduces the student to clinical life through a number of clinical courses. In this article we describe measures taken to secure a good and educating stay on the department during a five-week course. We describe the process, procedures, planning, executing and evaluation of the five-week clinical course. The evaluation through direct feedback and subsequent electronic form is commented and essential learning points are discussed.

[Autoimmune pancreatitis is a differential diagnosis to pancreatic cancer].

Autoimmune pancreatitis is a rare benign inflammatory disease, treated with steroids. It consists of two clinical and histological distinct types, type 1 and type 2. Type 1 is part of an IgG4-related multiorgan disease, while type 2 is pancreas-specific. We here present a case of each type illustrating the difficult diagnostic process and how it can be misinterpreted as pancreatic carcinoma or cholangiocarcinoma. Though autoimmune pancreatitis is rare it should be considered as a differential diagnosis to pancreatic cancer.

Barrett's esophagus. Diagnosis, follow-up and treatment.

Barrett's Esophagus (BE) is a premalignant condition in the esophagus. Esophageal adenocarcinomas have the fastest increase of incidence of all solid tumors in the western world. BE is defined as areas with macroscopic visible columnar epithelium and intestinal metaplasia oral of the anatomical gastroesophageal junction. The extent of the endoscopic findings is described by the Prague classification. The metaplasia is histologically confirmed by the presence of intestinal metaplasia. The diagnosis of BE can only be made by a combined macroscopic and microscopic examination. The histological description should include evaluation of dysplasia, and if present it should be classified as low or high grade dysplasia. All patients are offered relevant antireflux treatment with PPI or surgery. Ablation or mucosal resection of metaplastic epithelia with or without low grade dysplasia is experimental and it is not recommended outside controlled studies. Treatment of high grade dysplasia and carcinoma in situ is handled in departments treating esophageal cancer. Follow-up with endoscopy and biopsy can be offered. Follow-up endoscopy with biopsy can only be recommended after thorough information to the patients, as evidence for the value is scarce.

The effect of Glucagon-Like Peptide-2 on mesenteric blood flow and cardiac parameters in end-jejunostomy short bowel patients.

BACKGROUND: Exogenous Glucagon-Like Peptide-2 (GLP-2) treatment improves intestinal wet weight absorption in short bowel syndrome (SBS) patients. In healthy subjects, administration of GLP-2 increases small intestinal blood flow. The aim of the study was to evaluate the effect of GLP-2 on mesenteric blood flow and dynamic changes in cardiac parameters in SBS patients with jejunostomy and varying length of remnant small intestine. METHODS: 8 SBS patients with end-jejunostomy and less than 200 cm small intestine were given GLP-2, 1600 µg subcutaneously (SC), or isotonic saline in a double blinded manner. At 0, 30 and 60 min plasma GLP-2 was measured, and from 0 to 90 min, blood flow in the superior mesenteric artery (SMA) and the celiac artery (CA) was measured using Doppler ultrasound (US), and cardiovascular variables were measured by continuous impedance cardiography and finger plethysmography. RESULTS: Plasma GLP-2 concentrations increased significantly in the GLP-2 group, whereas no changes were seen in the placebo group. Compared to baseline, GLP-2 SC elicited a 19.4% decrease (p<0.01) in the resistance index (RI) and a 97.6% increase in time averaged maximal velocity (TAMV) in the SMA (P<0.01). In the CA there were no significant changes in RI or TAMV in the GLP-2 or placebo group. Blood flow and length of remaining intestine were correlated (RI: y=0.14+4.3, R=0.83, p=0.01 and TAMV: y=1.21+21.3, R=0.63, p=0.09). GLP-2 non significantly increased cardiac output (CO), stroke volume (SV) and significantly increased heart rate (HR) compared to baseline. CONCLUSION: Subcutaneous GLP-2 increased SMA blood flow in end-jejunostomy SBS patients with less than 200 cm of remaining small intestine. The increase in blood flow correlated with the length of remaining intestine, suggesting that the increase is coupled to the metabolic actions of GLP-2 on the gut rather than effects on the vasculature.

[Intestinal tuberculosis as a differential diagnosis of inflammatory bowel disease]. / Intestinal tuberkulose som differentialdiagnose til inflammatorisk tarmsygdom.

Intestinal tuberculosis (ITB) is a rare differential diagnosis of inflammatory bowel disease (IBD) in Denmark. In the presented case, a 44-year-old native Danish man was examined for IBD symptoms. Colonoscopy and microscopy of colonic biopsies suggested IBD. The patient was started on steroid therapy, but without effect so tumour necrosis factor alpha therapy was planned. Routine interferon-gamma release assay was normal, but chest X-ray revealed an apical infiltration. New tests on the colonic biopsies using polymerase chain reaction were positive for Mycobacterium tuberculosis and the patient was treated for ITB and pulmonary tuberculosis.

[Severe hyperkalemia in combination with gastroenteritis in previously colectomized patient]. / Svaer hyperkaliaemi ved gastroenteritis hos kolektomeret patient.

Severe hyperkalemia is a life-threatening condition that causes primarily cardiac and muscular dysfunction with potentially fatal consequences. This case report describes a case of severe hyperkalemia (9,1 mmol/l) caused by acute prerenal failure due to dehydration. The severe dehydration was caused by a combination of reduced fluid intake due to gastroenteritis and a hampered capacity for intestinal fluid absorption, due to previous colectomy. The patient developed classic signs of hyperkalemia with electrocardiogram changes and muscular dysfunction.

The effect of glucagon-like peptide-2 on arterial blood flow and cardiac parameters.

BACKGROUND: Glucagon-like peptide-2 (GLP-2) is known to increase mesenteric blood flow. The aim of the study was to evaluate the effect of GLP-2 on blood flow in different vascular sites, and dynamic changes in cardiac parameters. METHODS: 10 healthy volunteers were given 450 nmol subcutaneous (SC) GLP-2 or isotonic saline (5 subjects) in a single blinded manner. During the following 90 min, blood flow in the superior mesenteric artery (SMA), celiac artery (CA), renal artery (RA), common carotid artery (CCA) was measured using Doppler ultrasound (US), and cardiovascular variables were measured by impedance cardiography and finger plethysmography. Plasma GLP-2 was measured at times 0, 30 and 60 min. RESULTS: Compared to the placebo group, GLP-2 elicited a 27% decrease in the resistance index (RI) and a 269.4% increase in Time Averaged Maximal Velocity (TAMV) in the SMA (P<0.01). CA, RA and CCA: There were no significant changes in RI or TAMV in the GLP-2 or placebo group, and no change in CA diameter. Cardiac parameters: GLP-2 increased cardiac output (CO), stroke volume (SV) and heart rate (HR) compared to baseline (respectively: 15.3, 4.81 and 8.2% (P<0.001, P<0.01 and P<0.01)). The CO, SV and HR changes were not significantly different from the placebo group. Mean plasma GLP-2 serum levels in the placebo group at times 0, 30 and 60 min were 22.8, 23.4 and 23.2 pmol/l. In the GLP-2 group 20.3, 1273 and 1725 pmol/l. CONCLUSION: SC GLP-2 increased SMA blood flow, as previously shown, but elicited no changes in other vascular sites. CO and HR increased significantly, presumably due to the increased mesenteric blood flow.

[Acute esophageal necrosis]. / Akut øsofageal nekrose.

Acute esophageal necrosis (AEN), necrotizing esophagitis or "black esophagus", is a rare condition with less than 100 reported cases in the world literature. The condition arises due to necrosis of the esophageal mucosa leading to macroscopically black tissue. The condition is associated with a relatively poor prognosis with an overall mortality due to comorbidity of 32-36%. This case report describes a patient with AEN in the full length of the esophagus secondary to ischaemia due to bleeding and hypoperfusion. The patient died after 48 hours due to multi-organ failure.

Glucagon-like peptide-2 increases mesenteric blood flow in humans.

OBJECTIVE: Mesenteric blood flow is believed to be influenced by digestion and absorption of ingested macronutrients. We hypothesized that the intestinotrophic hormone, GLP-2 (glucagons-like peptide 2), may be involved in the regulation of mesenteric blood flow. Changes in mesenteric blood flow were measured by Doppler ultrasound scanning of the superior mesenteric artery (SMA). The aim of the study was to demonstrate the influence of GLP-2 on this flow, expressed as changes in resistance index (RI). MATERIAL AND METHODS: A homogeneous group of 10 fasting healthy volunteers completed a 2-day trial. On day 1, a standard meal was given, and RI measured in the SMA. On day 2, GLP-2 was infused intravenously (IV) at rates of 0.5, 1.0 and 2.0 pmol/kg/min over 3 x 45 min separated by a 15-20 min rest period. After a further 15-20 min of rest, 450 nmol synthetic GLP-2 was given subcutaneously (SC). RI in the SMA was measured before, during and after the meal and GLP-2 infusions. RESULTS: After IV infusion of GLP-2, the following decreases in RI were observed: 0.5 pmol/kg/min: 2.7% (range 0-6.3%), 1.0 pmol/kg/min: 6.7% (range 0.4-15.9%), 2.0 pmol/kg/min: 15.3% (range 9.6-22.7%) p<0.00802. When given SC, GLP-2 elicited a maximum average change in RI of 15.6% (range 5.0-28.1%). The standard meal elicited a 14.7% (range 8.8-21.6%) change, p<0.020 There was a similar change in RI over time (0-90 min) after a standard meal and after subcutaneous GLP-2, p<0.005. CONCLUSIONS: Our study showed a significant association between IV and SC administration of synthetic GLP-2 and changes in mesenteric blood flow. An exponential dose-response relationship was observed after IV infusion. The meal-induced changes in mesenteric blood flow over time were similar to those obtained by SC GLP-2. Thus, our results support the hypothesis that GLP-2 is an important regulator of mesenteric blood flow.