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Introduction: Cold snare polypectomy (CSP) is a safe and effective procedure for small colorectal polyps ≤9 mm. There are only limited data regarding CSP of larger neoplastic lesions. This study evaluated the efficacy and safety of CSP for polyps between 10 and 15 mm in size., Methods: In this prospective single-arm observational pilot study, patients with a least one polyp 10-15 mm were included. These polyps were preferably removed by CSP using a dedicated hybrid snare. The primary outcome was the histological complete resection rate (CRR) determined by pathologically negative margins of the specimen and no neoplastic tissue obtained from biopsies of the resection site margin. Secondary outcomes were en bloc resection rate, failure of CSP, and incidence of adverse events., Results: A total of 61 neoplastic polyps were removed from 39 patients. Overall CRR was 80.3% (49/61). CSP was feasible in 78.7% (48/61) of polyps and the CRR in this group was 85.4% (41/48). When CSP failed (13/61; 21.3%), lesions were successfully resected by immediate HSP using the same snare with a CRR of 61.5% (8/13) in this group. One patient presented delayed hemorrhage after HSP of a polyp but successful hemostasis was achieved with two hemoclips. No other adverse events occurred. No recurrence was seen on follow-up colonoscopy in cases with incomplete resected polyps., Conclusion: CSP seems to be efficient and safe in removing colorectal polyps up to 15 mm. A hybrid snare seems to be particularly advantageous for these polyps as it allows immediate conversion to HSP if CSP might fail in larger polyps. This trial is registered at ClinicalTrials.gov (NCT04464837)., (© 2023 S. Karger AG, Basel.)

Background/aims: The gut microbiota is altered in irritable bowel syndrome (IBS), and microbiota manipulations by diet or antibiotics can reduce its symptoms. As fecal microbiota transfer (FMT) in IBS is still controversial, we investigated the clinical and side effects of FMT in a cohort of IBS patients with recurrent, treatment refractory symptoms, and studied gut microbiota signatures., Methods: Using an observational, prospective study design, we applied FMTs from one unrelated, healthy donor to 13 IBS patients. Fecal samples of patients and the donor were analyzed by 16S ribosomal RNA amplicon sequencing., Results: On a symptom level, primarily abdominal pain symptoms were reduced after FMT, and no adverse effects were observed. Studying the microbiome, we found an increase in alpha diversity and changes in the composition of the gut microbiota after FMT. Beta diversity changes after FMT were prominent in a subset of 7 patients with microbiota profiles coming very close to the donor. These patients also showed most pronounced visceral pain reduction. The relative abundance of Akkermansia muciniphila was inversely correlated with pain reduction in our cohort., Conclusion: Although exploratory in nature and with a pilot character, this study highlights the potential role of microbiota manipulations in IBS and describes a novel association of intestinal Akkermansia and pain modulation., (© 2018 S. Karger AG, Basel.)

Background: Improving health-related quality of life is a primary target of therapy for patients with inflammatory bowel disease. Physical activity has been demonstrated to improve health-related quality of life in several patient populations with chronic disease. There are very few studies investigating the effects of physical activity on health-related quality of life in inflammatory bowel disease. The primary purpose of this study is to investigate the effects of 10 weeks of moderate physical activity on health-related quality of life in patients with inflammatory bowel disease., Methods: Thirty patients with mild to moderate IBD (Crohn's Disease Activity Index (CDAI) <220 or Rachmilewitz Index (RI) <11) were randomized 1:1 to either supervised moderate-intensity running thrice a week for 10 weeks or a control group who were not prescribed any exercise. Health-related quality of life, symptoms, and inflammation were assessed at baseline and after 10 weeks., Results: Participants were 41 ± 14 years (73% female), had a body mass index of 22.8 ± 4.1 kg/m(2), and an average CDAI or RI of 66.8 ± 42.4 and 3.6 ± 3.1. No adverse events occurred during the 10-week training period. Health-related quality of life, reported as IBDQ total score, improved 19% in the intervention group and 8% in the control group. Scores for the IBDQ social sub-scale were significantly improved in the intervention group compared with controls (ΔIBDQsocial = 6.27 ± 5.46 vs. 1.87 ± 4.76, p = 0.023)., Conclusion: Patients suffering from moderately active IBD are capable of performing symptom-free regular endurance exercise. Our data support the assumption that PA is feasible in IBD patients. PA may furthermore improve quality of life through improvements in social well-being, and may, therefore, be a useful adjunct to IBD therapy., (© 2015 S. Karger AG, Basel.)

Background: In biliary tract cancer, gemcitabine platinum (GP) doublet palliative chemotherapy is the current standard treatment. The aim of this study was to analyze recent trials, even those small and nonrandomized, and identify superior new regimens., Methods: Trials published in English between January 2000 and January 2014 were analyzed, as well as ASCO abstracts from 2010 to 2013., Results: In total, 161 trials comprising 6,337 patients were analyzed. The pooled results of standard therapy GP (no fluoropyrimidine, F, or other drug) were as follows: the median response rate (RR), tumor control rate (TCR), time to tumor progression (TTP) and overall survival (OS) were 25.9 and 63.5%, and 5.3 and 9.5 months, respectively. GFP triplets as well as G-based chemotherapy plus targeted therapy were significantly superior to GP concerning tumor control (TCR, TTP) and OS, with no difference in RR., Conclusion: Triplet combinations of GFP as well as G-based chemotherapy with (predominantly EGFR) targeted therapy are most effective concerning tumor control and survival.

Aim: To determine the long-term effect of argon plasma coagulation (APC) of gastric inlet patches in the cervical esophagus for patients suffering from globus sensation., Methods: We intended to follow up all patients between 2004 and 2011 (n = 49) who received argon plasma ablation of gastric inlet patches for globus sensation at our clinic. Symptoms were assessed by a visual analogue scale (VAS) in 31 of 49 patients. Follow-up endoscopy of the upper gastrointestinal tract was performed to confirm residual or relapsed cervical inlet patches., Results: After a median period of 27 months, APC was assessed as a successful therapy in 23 of 31 patients (74%). VAS scores decreased significantly from 7.6 to 4.0 in the long term. Twenty-two of 31 patients were willing to undergo follow-up endoscopy. Endoscopy revealed recurrent/residual gastric inlet patches after APC in 11 of 22 cases. These patients suffered from a significant relapse of symptoms in the postinterventional period (p < 0.001)., Conclusion: This retrospective study indicates that APC of gastric inlet patches for the treatment of globus sensation might be a sufficient therapy option. Recurrences or residual heterotopic gastric mucosa are possible and seem to be associated with a relapse of symptoms. Therefore, endoscopic follow-up and retreatment might be necessary if globus sensation is not sufficiently eliminated., (© 2013 S. Karger AG, Basel.)

Background: Primary myelofibrosis belongs to the group of myeloproliferative syndromes. Extramedullary hematopoiesis in the liver can lead to portal hypertension., Patient and Methods: We report a case of a patient with life-threatening, endoscopically not treatable bleeding from esophageal varices due to extramedullary hematopoiesis of the liver that was successfully treated with placement of a transjugular intrahepatic porto-systemic stent-shunt (TIPS)., Results: Therapy of variceal bleeding by TIPS insertion was successful. During a 29-month follow-up, no hepatic failure, hepatic encephalopathy, or further variceal bleeding episode occurred., Conclusion: TIPS placement is a well-established procedure for the treatment of complications due to portal hypertension mainly due to liver cirrhosis. This report illustrates that TIPS placement can also be a promising treatment option in patients with primary myelofibrosis and portal hypertension due to extramedullary hematopoiesis., (Copyright © 2012 S. Karger AG, Basel.)

Background/aims: Combined pH-metry/multichannel intraluminal impedance (pH/MII) measurement enables to measure gastroesophageal reflux despite ongoing proton pump inhibitor therapy. The aim of our study was to evaluate the influence of an escalating medical anti-reflux therapy with 40 mg esomeprazole, 80 mg esomeprazole and 80 mg esomeprazole plus baclofen for the treatment of refractory pathological reflux as determined by pH/MII., Methods: Symptomatic patients under 40 mg esomeprazole were screened by pH/MII. Patients with normal values in pH/MII were excluded; all others received 2 x 40 mg esomeprazole for another 4 weeks. Thereafter, the treatment effect was controlled by pH/MII. In the case of persistent pathological reflux, therapy was further escalated by adding baclofen and controlled after 3 months by pH/MII., Results: 45/138 (32.6%) patients showed pathological pH/MII despite ongoing therapy with 40 mg esomeprazole. In these, a significant reduction in liquid/mixed reflux events was observed after administering 2 x 40 mg (mean: 118.3 vs. mean: 66.6; p < 0.001), and pH/MII turned to normal in 32/45 (71.1%). Baclofen was additionally administered to 7/13 patients, which did not lead to a remarkable reduction in reflux events., Conclusion: In patients with abnormal pH/MII and persistent symptoms under 40 mg esomeprazole, we observed a significant reduction in liquid/mixed reflux events after increasing proton pump inhibitor dose up to 80 mg esomeprazole. Further escalation of therapy with baclofen has shown inconclusive results., (Copyright 2009 S. Karger AG, Basel.)

Background/aim: True adenomas of the cardia appear to be extremely rare lesions. There are no data on the natural history and histopathological background of these lesions. We report 3 patients with true adenomas of the cardia., Methods and Results: Three patients with polypoid masses at the cardia below the Z-line were submitted to a tertiary referral center for further diagnosis and therapy. In 2 of the 3 cases Barrett's esophagus with low-grade intraepithelial neoplasia was assumed on the basis of histopathological examination of biopsy specimens taken from the surface of the lesions. Polypectomy was performed in all 3 cases. In 2 of the 3 cases the final histopathological diagnosis of low-grade adenoma of the cardia could only be established after complete removal of the polypoid masses., Conclusions: Adenomas of the cardia can be mistaken for dysplasia arising from Barrett's esophagus, if the diagnosis is based on endoscopic biopsies only. It is, therefore, reasonable to completely remove any suspicious lesions by endoscopy not only for therapeutic but also for diagnostic reasons., (Copyright 2008 S. Karger AG, Basel.)

Background: Globus sensations, hoarseness and chronic cough are suggested to be atypical manifestations of Gastroesophageal Reflux Disease (GERD). The aim of the study was to investigate whether combined pH-metry and multichannel intraluminal impedance monitoring increases the diagnostic yield., Methods: 41 patients with atypical GERD symptoms were included in the study. Globus sensation was the dominant symptom in 23 patients (56.1%). The remaining 18 patients (43.9%) complained mainly about hoarseness or chronic cough. All patients were examined by endoscopy, dual-channel pH-metry and impedance monitoring off-therapy with proton pump inhibitors (PPI). Diagnostic yield of the respective method was determined., Results: A total of 26 patients (63.4%) had pathological findings in any method. The highest diagnostic yield was achieved by combined 24-h pH-metry/impedance measurement (61.0%), followed by solely impedance measurement (48.8%), distal pH-metry (29.3%), endoscopy (22.8%) and proximal pH-metry (17.1%). All patients with a positive PPI-test and 25% of patients (5/20) with a negative PPI-test had a pathological result in pH-metry/impedance., Conclusion: Multichannel intraluminal impedance monitoring increases the diagnostic yield for objective detection of atypical manifestation of GERD. Combined 24-h pH-metry/impedance measurement has the best diagnostic yield for detection of gastroesophageal reflux and has therefore the potential to represent a new diagnostic gold standard.

Objectives: No effective chemotherapy for advanced hepatocellular carcinoma (HCC) exists. Expression of the platelet-derived growth factor receptor (PDGFR) has been demonstrated in HCC, which may derive from hepatic stem cells that express c-kit. The aim of this trial was to evaluate imatinib, a tyrosine kinase inhibitor of PDGFR and c-kit, in patients with advanced HCC and impaired liver function., Patients and Methods: Patients were treated with 400-600 mg imatinib daily. Immunohistochemical staining was performed for PDGFR and c-kit. Response was assessed by CT scans every 8 weeks. For pharmacokinetics studies, 74 plasma samples were assessed., Results: Of the 17 patients enrolled in the study, 15 were evaluable for response. Only 1 tumor was positive for PDGFR and none was positive for c-kit. Grade 3/4 neutropenia occurred in 2 patients (1 had neutropenic fever). There was no objective response, and 5 (33%) patients had stable disease. Median time to treatment failure was 1.8 months in the whole study cohort and 3.7 months in the patients with stable disease. Patients treated with 400 mg imatinib did not significantly differ in pharmacokinetics from patients with chronic myelogenous leukemia (CML)., Conclusion: In this small group of patients with advanced, mostly PDGFR- and c-kit-negative HCC, imatinib showed no therapeutic effect. In contrast to CML patients, the pharmacokinetics of imatinib were not significantly affected by impaired liver function.

Background and Aims: Supramaximal concentrations of cholecystokinin (CCK) or cerulein induce the intracellular activation of trypsinogen and the transcription factor NF-kappaB, a key regulator of inflammatory gene expression. Both events occur early in the development of an acute pancreatitis. The aim of this study was to examine the relationship between intracellular trypsinogen and NF-kappaB activation., Methods: We detected NF-kappaB-binding activity in electromobility shift assays, IkappaB proteolysis in Western analysis and endogenous IkappaB-kinase (IKKalpha and beta) activation using immune complex kinase assays following treatment with CCK in rat pancreatic lobules. To block intrapancreatic trypsinogen activation, a potent and cell-permeable serine-protease inhibitor, Pefabloc, was used., Results: CCK-induced IkappaBalpha degradation and subsequent NF-kappaB activation correlated closely with the catalytic activity of IKKs to phosphorylate IkappaBalpha in vitro. Activation is dose-dependent and peaked at 30 min. Doses of Pefabloc sufficient to inhibit trypsin activation reduced CCK-induced activation of NF-kappaB whereas TNF-alpha-induced NF-kappaB activation was not blocked but slightly increased. Moreover, treatment with Pefabloc as well as another serine protease inhibitor, FUT175, inhibited CCK-induced IKK activation., Conclusion: These results suggest that intrapancreatic activation of trypsinogen may contribute to NF-kappaB signaling via IKK activation in cerulein pancreatitis. This also explains the fact that only doses of CCK which activate trypsinogen induce NF-kappaB activation in pancreatic acinar cells. Thus, trypsinogen activation is likely to modulate signaling events in acinar cells in the initial phase of acute pancreatitis., (Copyright 2002 S. Karger AG, Basel)

Background/aims: The activation of the K-ras gene at codon 12 is thought to be an early genetic event in the multistep pathogenesis of pancreatic cancer. Since the risk of pancreatic cancer is significantly elevated in subjects with chronic pancreatitis, the aim of the present study was to determine the frequency of K-ras mutations in chronic pancreatitis., Methods: Pancreatic DNA from intraoperatively resected tissues of 60 patients with chronic pancreatitis and 11 patients with histologically confirmed pancreatic carcinoma was evaluated by PCR amplification and restriction fragment length polymorphism analysis., Results: In none of the 60 samples of chronic pancreatitis could K-ras mutations be identified using two independent PCR assays. In 5 of 11 patients with pancreatic carcinoma, K-ras mutations in codon 12 were detected., Conclusion: These data indicate that K-ras mutations are rare events in chronic pancreatitis. Alternatively, it is possible that the time span between the occurrence of K-ras mutations and malignant transformation is rather short.

Background: The introduction of recombinant DNA into cells is the initial step toward the development of gene therapy. It has been shown that cationic liposomes are useful vehicles to introduce DNA into colon epithelial cells in vivo., Methods: In the present study we compared the efficacy of different nonviral transfection methods into the colon wall. In anesthetized rats, a double balloon catheter was advanced into the colon and a chloramphenicol acetyltransferase (CAT) reporter plasmid complexed to liposomes, mixed with DEAE dextran, or precipitated with calcium phosphate was instilled. Following 2 days CAT activity was determined in the transfected colon segments., Results: DEAE dextran and liposomes were more effective than calcium phosphate, whereas naked DNA was not taken up by the colon epithelial cells. Reporter gene expression was dose-dependent. Expressing cell types did not differ utilizing the various transfection methods as judged by X-gal staining of colon sections after transfection with a LacZ reporter plasmid., Conclusion: These data indicate that in addition to liposomes, plasmid DNA mixed with DEAE dextran can be taken up by colon epithelial cells. This transfection techniques may prove useful in the development of gene therapy approaches for colon disease.