Emerging Treatment Options in Inflammatory Bowel Disease: Janus Kinases, Stem Cells, and More.

BACKGROUND: Treatment of inflammatory bowel diseases (IBD) has tremendously improved during the last 20 years; however, a substantial fraction of patients does not respond to available therapies or lose response, and new strategies are needed. SUMMARY: Two pharmacological principles have been successfully used for IBD treatment: inhibition of cellular signaling and interference with leukocyte trafficking. Besides tumor necrosis factor, interleukin (IL)-23 is a promising drug target, and antibodies for the combined inhibition of IL-23 and IL-12 (ustekinumab and briakinumab) or selective IL-23 inhibition (brazikumab, risankizumab, and mirikizumab) seem to be effective in Crohn's disease (CD) with emerging evidence also for ulcerative colitis (UC). Janus kinase (JAK) mediates intracellular signaling of a large number of cytokines. Tofacitinib is the first JAK inhibitor approved for UC, and the JAK inhibitors filgotinib and upadacitinib showed potential in CD. Leukocyte trafficking can be inhibited by interference with lymphocyte integrin-α4ß7 or endothelial MadCAM-1. The α4ß7 integrin inhibitor vedolizumab is an established treatment in IBD, and long-term data of pivotal studies are now available. Additional molecules with therapeutic potential are α4ß7-specific abrilumab, ß7-specific etrolizumab, and the α4-specific small molecule AJM300. PF-00547659, an antibody against endothelial MadCAM-1, also showed therapeutic potential in UC. Modulation of sphingosine-1-phosphate receptor (S1PR) activity is necessary for the egress of lymphocytes into the circulation, and S1PR modulation results in lymphocyte trapping in lymphatic organs. Ozanimod, an S1PR1 and S1PR5 inhibitor, has been successfully tested in initial studies in UC. Mesenchymal stem cell therapy has been approved for the treatment of complex, active CD fistula, and mesenchymal stem cell therapy might be a paradigm shift for this condition. Autologous stem cell transplantation (ASCT) has been successfully used in CD case series; however, in a randomized trial, a highly stringent endpoint was not met. However, considering positive effects in secondary endpoints, ASCT might be a future treatment of last resort in severe, refractory CD cases, provided that safer protocols can be provided. Key messages: New IBD treatments are successful for a significant fraction of patients. However, new strategies for patient selection, treatment combinations, and/or additional therapies must be developed to serve the need of all IBD patients.

Treatment Algorithms for Crohn's Disease.

BACKGROUND: Treatment of Crohn's disease (CD) patients is complex as therapy choices depend on a variety of factors, such as location and severity of inflammation, disease behavior (inflammatory, stricturing or penetrating) but also comorbidities, extra-intestinal manifestations, the patient's age, and previous therapies. Subsequently, the choice of treatment should be tailored to the individual patient. SUMMARY: This article gives the reader therapy algorithms as a guide through different CD scenarios to support the physician's decision making. New compounds introduced in CD therapy in recent years justify such an update on standard approaches. Ustekinumab and vedolizumab and their positions within the treatment options are discussed. Fistulizing perianal disease and postoperative medical prophylaxis are depicted in separate chapters with own algorithms. Key Messages: In recent years, a variety of new drugs became available to treat patients with CD - especially those who are antitumor necrosis factor (TNF) experienced with ongoing inflammation. The definitive role of vedolizumab and ustekinumab is not yet fully clarified. However, with the advantage of good safety profiles over TNF-inhibitors, these drugs will be more frequently used in the near future, also as first-line biologicals, compared to TNF-inhibitors. Concerning treatment of fistulizing disease, the knowledge of the exact anatomy of the fistula is of major importance. An interdisciplinary discussion involving gastroenterologists, surgeons, and in some cases gynecologists may help to optimize the treatment plan. Regarding the postsurgical setting in CD patients, according to the very recent Cochrane Network meta-analysis, mesalazine should be at least positioned equivalent to thiopurines and TNF-inhibitors, as shown in our algorithm.

Percutaneous tibial nerve stimulation (pTNS): success rate and the role of rectal capacity.

PURPOSE: Percutaneous tibial nerve stimulation (pTNS) was originally developed to treat urinary incontinence. Recently, some case series have also documented its success in the treatment of fecal incontinence. Nevertheless, the mechanism underlying this effect remains unknown but may be related to changes in rectal capacity. The aim of this study was to investigate the success of pTNS for the treatment of fecal urge incontinence and assess the influence of rectal capacity on treatment efficacy. METHODS: All patients undergoing pTNS for fecal incontinence between July 2009 and March 2014 were enrolled in a prospective, observational study consisting of a therapeutic regimen that lasted 9 months. Therapy success was defined as a reduction in the CCI (Cleveland Clinic incontinence) score of ≥50% and patient-reported success. Furthermore, quality of life (Rockwood's scale) and changes in anorectal physiology were recorded. RESULTS: Fifty-seven patients with fecal urge incontinence were eligible, nine of whom were excluded. The success rate was 72.5%. Incontinence events and urge symptoms were significantly reduced after 3 months and at the end of therapy. The median CCI score decreased from 12 to 4 (P < 0.0001), and the quality of life was significantly improved. However, rectal capacity was not significantly related to treatment success before or after therapy. No adverse events were observed. CONCLUSIONS: These results demonstrate that pTNS can improve the symptoms and quality of life of patients with fecal urge incontinence. However, the study fails to demonstrate a correlation between treatment success and changes in rectal capacity.

Effect of morbid obesity, gastric banding and gastric bypass on esophageal symptoms, mucosa and function.

BACKGROUND: Obesity and gastroesophageal reflux disease (GERD) are commonly associated diseases. Bariatric surgery has been shown to have various impacts on esophageal function and GERD. Our aim was to evaluate changes in symptoms, endoscopic findings, bolus passage and esophageal function in patients after primary gastric bypass surgery as compared to patients converted from gastric banding to gastric bypass. METHODS: Obese patients scheduled for laparoscopic Roux-en-Y gastric bypass (naïve-to-bypass) and patients who previously underwent gastric banding and were considered for conversion from gastric banding to gastric bypass (band-to-bypass) were included. Patients rated esophageal and epigastric symptoms (100 point VAS) and underwent upper endoscopy, impedance-manometry, and modified "timed barium swallow" before/after surgery. RESULTS: Data from 66 naïve-to-bypass patients (51/66, 77 % females, mean age 41.2 ± 11.1 years) and 68 band-to-bypass patients (53/68, 78 % females, mean age 43.8 ± 10.0 years) were available for analysis. Esophageal symptoms, esophagitis, esophageal motility abnormalities and impaired esophageal bolus transit were more common in patients that underwent gastric banding compared to those that underwent gastric bypass. The majority of symptoms, lesions and abnormalities induced by gastric banding were decreased by conversion to gastric bypass. Esophagitis was present in 28/68 (41 %) and 13/47 (28 %) patients in the band-to-bypass group, pre- versus postoperatively, respectively, (p < 0.05). The percentage of swallows with normal bolus transit increased following transformation from gastric band to gastric bypass (57.9 ± 4.1 and 83.6 ± 3.4 %, respectively, p < 0.01). CONCLUSIONS: From an esophageal perspective, gastric bypass surgery induces less motility disorders and esophageal symptoms and should be therefore favored over gastric banding in difficult to treat obese patients at risk of repeated bariatric surgery.

The Clinical Relevance of the IBD-Associated Variation within the Risk Gene Locus Encoding Protein Tyrosine Phosphatase Non-Receptor Type 2 in Patients of the Swiss IBD Cohort.

BACKGROUND/AIMS: The single nucleotide polymorphism (SNP) rs1893217 within the gene locus encoding protein tyrosine phosphatase non-receptor type 2 (PTPN2) results in a dysfunctional PTPN2 protein is associated with Crohn's disease (CD) and exists in perfect linkage disequilibrium with the CD- and ulcerative colitis (UC)-associated PTPN2 SNP rs2542151. We investigated associations of PTPN2 SNP rs1893217 and clinical characteristics of inflammatory bowel disease (IBD) patients. METHODS: One thousand seventy three patients with CD and 734 patients with UC from the Swiss IBD Cohort Study (SIBDCS) were included. Epidemiologic, disease and treatment characteristics were analysed for an association with the presence of one of the rs1893217 genotypes 'homozygous wild-type' (TT), 'heterozygous' (CT) and 'homozygous variant' (CC). RESULTS: About 2.88% of IBD patients were identified with CC, 26.8% with CT and 70.4% with TT genotype. The CC-genotype was associated with the existence of gallstones in CD and pancolitis in UC patients. The presence of the C-allele (i.e. either CC or CT genotype) was associated with the onset of uveitis, but protected from aphthous oral ulcers in CD patients. UC patients carrying a C-allele were diagnosed at an older age but required intestinal surgery more often. The presence of the C-allele was associated with a successful treatment with anti-TNF antibodies in both CD and UC patients. CONCLUSION: IBD patients carrying the C-allele of PTPN2 SNP rs1893217 are at greater risk for developing a severe disease course but are more likely to respond to treatment with anti-TNF antibodies. These findings demonstrate a clinical relevance of this PTPN2 risk variant in IBD patients.

The role of single-balloon colonoscopy for patients with previous incomplete standard colonoscopy: Is it worth doing it?

BACKGROUND: The rate of cecal intubation is a well-recognized quality measure of successful colonoscopy. Infrequently, the standard colonoscopy techniques fail to achieve complete examination. The role of single-balloon overtube-assisted colonoscopy (SBC) in these situations has only been sparsely studied. This prospective single-center study aimed to investigate the technical success (rate of cecal intubation) and the diagnostic gain of SBC. METHODS: The study recruited consecutive patients with previous incomplete standard colonoscopy who were admitted for SBC at our tertiary center in Eastern Switzerland between February 2008 and October 2014. The primary outcome was defined as successful cecal intubation. Data on patient characteristics, indication, technical details of procedure, and outcome were collected prospectively. The Olympus enteroscope SIF-Q180 was used. RESULTS: The study included 100 consecutive patients (median age 70 years; range 38-87 years; 54 % female) who were examined using a single-balloon overtube-assisted technique. The cecal intubation rate was 98 % (98/100). The median time of total procedure was 54 min (range 15-119 min); the median time to reach the cecal pole was 27.5 min (range 4-92 min). Passage of the sigmoid colon was not possible in two cases with a fixed, angulated sigmoid colon. The diagnostic gain was 21 % regarding adenomatous polyps in the right colon. The complication rate was 2 % (2/100, minor) without need for surgery. CONCLUSIONS: This prospective patient cohort study shows that single-balloon colonoscopy is a safe and effective procedure to achieve a complete endoscopic examination in patients with a previous failed standard colonoscopy. A significant diagnostic and therapeutic gain in the right colon justifies additional procedure time.

Patients' perceptions on the impact of coffee consumption in inflammatory bowel disease: friend or foe?--a patient survey.

BACKGROUND: Environmental factors are an integral component in the pathogenesis of inflammatory bowel disease (IBD). There is an increasing interest in nutritive components. While the potential disease-modifying role of coffee has been intensively investigated in a variety of gastrointestinal diseases, the data on the potential impact on IBD is very limited. We aimed to determine the patients' perspective on coffee consumption in IBD. METHODS: We conducted a questionnaire among IBD patients in Switzerland, assessing key questions regarding coffee consumption. Descriptive statistics including chi square testing were used for analysis of questionnaire data. RESULTS: Among a total of 442 patients 73% regularly consume coffee. 96% of patients attributing a positive and 91% of patients attributing no impact of coffee intake on IBD regularly drink coffee and surprisingly even 49% of those patients that assign a negative impact on disease symptoms. Among those patients refraining from regular coffee intake 62% are convinced that coffee adversely influences intestinal symptoms, significantly more in Crohn's disease (CD) than in ulcerative colitis (UC) (76% vs. 44%, p = 0.002). In total, 38% of all study subjects suppose that coffee has an effect on their symptoms of disease, significantly more in CD (54%) compared to UC patients (22%, p < 0.001). Moreover, while 45% of CD patients feel that coffee has a detrimental influence, only 20% of UC patients share this impression (p < 0.001). CONCLUSION: Two thirds of IBD patients regularly consume coffee. More than twice as many CD compared to UC patients attribute a symptom-modifying effect of coffee consumption, the majority a detrimental one. However, this negative perception does not result in abstinence from coffee consumption.

Acute pancreatitis caused by gastric balloon: a case report.

Background: Intragastric balloon (IGB) insertion is a safe and effective method for the treatment of obesity. The most common side effects of the balloon-therapy are nausea/vomiting and abdominal pain, acute pancreatitis has rarely been reported. Case Description: We present the case of a 28-year-old woman who underwent IGB insertion 9 months before onset of intense upper abdominal pain. We confirmed the diagnosis of acute pancreatitis by means of clinical symptoms, serological tests and cross-sectional imaging. Endoscopic removal of the balloon led to a complete resolution of the symptoms. Initial laboratory parameters were normal on admission, only the control of lipase and amylase levels led us to the diagnosis of pancreatitis. On imaging with computed tomography, the filling catheter of the balloon showed to be dislodged in the duodenum. After carrying out a systematic approach, other causes of pancreatitis were ruled out. Conclusions: Laboratory tests including amylase/lipase and adequate imaging should be considered in patients with relevant symptoms after gastric balloon insertion. A possible pathogenesis may be the direct compression and traumatic effect on the pancreas by the balloon or the dislodgement of the catheter into the duodenum and an obstruction/compression of the Papilla. Endoscopic removal of the balloon is not mandatory in every case, it should be decided individually.

Childlessness in Patients with Inflammatory Bowel Disease - Data from the Prospective Multi-center Swiss IBD Cohort Study.

BACKGROUND AND AIMS: Childlessness and infertility represent a frequent and important issue in inflammatory bowel disease (IBD) patients. Nevertheless, until now epidemiological data remains scarce. Therefore, main objectives of this study were to evaluate the rate of childlessness and the cumulative probability of reproduction in female and male IBD patients within the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS), a large prospective multicenter nationwide cohort. METHODS: Prospectively collected data of SIBDCS was used, comprising more than 3,300 patients with Crohn's disease (CD) and ulcerative colitis (UC). We analyzed the following groups of patients: 1) female IBD patients aged ≥40 years and diagnosed before age of 30 years with at least one follow-up, 2) female IBD patients who reported actively trying to conceive, with IBD diagnosed <35 years and with age at enrolment <45 years (longitudinal observation), with at least one follow-up, and 3) childless males who actively tried to conceive. RESULTS: A total of 1,412 female patients from the SIBDCS [843 CD, 539 UC, 30 indeterminate colitis (IC)] with available data were included in our analyses. Out of those 184 females (70.1% CD and 29.9 % UC) were aged ≥ 40 years and have been diagnosed with IBD before the age of 30 years. Among these, 184 women 32.1% were childless. The portion of childless females (36.4%) was significantly higher in CD vs. UC (36.4% vs. 21.8%; p=0.026), equaling a relative risk of childlessness of 1.7 in CD vs. UC. and higher than in the Swiss general population (21%). The mean number of children per female patient was 1.32 (median 1, min 0, max 6), per female with CD 1.12 (median 1, min 0, max 4), per female with UC/IC 1.78 (median 2, min 0, max 6; P=0.001). The longitudinal analysis of female IBD patients trying to conceive revealed that one out of two women neither were pregnant nor had born a child five years after first trying to conceive. CONCLUSIONS: The rate of childlessness in females with CD is higher compared to the general Swiss population, whereas it is similar in women with UC. Moreover, the mean number of children is lower in CD than in UC. Females with CD remain more often childless compared to their UC counterparts. Although the exact underlying mechanisms are largely unknown, this discrepancy should alert healthcare professionals treating CD patients to actively address this topic.

Depressive Symptoms Predict Clinical Recurrence of Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) patients are at high risk for depression, and depression has been shown to affect disease course. We examined interrelations between depression, genetic risk factors for depression, and IBD flares. METHOD: In 1973 patients (1137 Crohn's disease, 836 ulcerative colitis) of the Swiss IBD Cohort Study (SIBDCS), depressive status (hospital anxiety and depression subscale for depression, HADS-D ≥11) was assessed on a yearly basis. We investigated the impact of depression on IBD-relevant clinical outcomes in Cox proportional hazards models. We used active disease (CDAI ≥150 or MTWAI ≥10) and 2 published composite flare definitions-FNCE (physician-reported flare, nonresponse to therapy, new complication, or extraintestinal manifestation) and AFFSST (active disease, physician-reported flare, fistula, stenosis, and new systemic therapy)-as clinical end points. Additionally, 62 preselected single nucleotide polymorphisms (SNPs) were screened for cross-sectional associations with depression, and if present, their predictive value for future depression and clinical deterioration was assessed. RESULTS: Depression was a strong risk factor for disease-related end points, including active disease (adjusted hazard ratio [aHR], 3.55; P < 0.001), AFFSST (aHR, 1.62; P < 0.001), and FNCE (aHR, 1.35; P = 0.019). The SNP rs2522833 was significantly associated with depression at enrollment (q = 0.059). The TC allele of rs588765 was negatively associated with the presence of depression at enrollment (q = 0.050) and after enrollment (aHR, 0.67; P = 0.035) and with fewer active disease states (aHR, 0.72; P = 0.045) during follow-up. CONCLUSION: In IBD, depressive symptoms and inflammatory activity are intimately related. Depressive symptoms were a strong predictor of clinical deterioration, and genetic markers may play a role in this relationship.

Effectiveness of golimumab in patients with ulcerative colitis: results of a real-life study in Switzerland.

BACKGROUND: Tumor necrosis factor (TNF) inhibitors have improved treatment of ulcerative colitis (UC), but loss of response remains a frequent problem. The anti-TNF agent, golimumab, was approved in Switzerland for the treatment of UC in 2014. This study aims to summarize the experience of golimumab in a real-world setting in Switzerland. METHODS: We analyzed real-world data from 1769 UC patients from the Swiss Inflammatory Bowel Disease Cohort (SIBDC) study and performed a chart review of golimumab-treated patients. We extracted the partial Mayo score at t0 (baseline), t1 (2-16 weeks), t2 (17-35 weeks), and t3 (36-89 weeks). The primary endpoint was clinical response at t1, defined as marked improvement in partial Mayo score and objective parameters. Clinical remission was defined as resolution of symptoms and normalization of objective parameters. RESULTS: Our chart review included 103 UC patients with golimumab treatment (5.8% of all SIBDC UC patients); only 16 (15.5%) were anti-TNF naïve. Sixty-three patients remained on golimumab (61.2%) after 180 days, 51 (44.7%) after 365 days, and 34 (33%) after 630 days after the start of treatment. Upon golimumab treatment, the partial Mayo score decreased from 4 [interquartile range (IQR): 2-6] at t0 to 2 (IQR: 0-4) at t1, 1 (IQR: 0-3.5) at t2, and 1 (IQR: 0-3) at t3 (p < 0.001 for all comparisons with t0). The primary endpoint, clinical response at t1, could be evaluated in 52 patients and was met in 15 individuals (28.8%). Clinical remission at t1 was observed in 8 out of 52 patients (15.4%). Golimumab was generally well tolerated, one patient developed meningitis. The most frequent reasons to stop treatment were primary and secondary non-response. CONCLUSION: Golimumab was used in 5.8% of Swiss UC patients, mainly in biologic-experienced individuals. Golimumab treatment was associated with a sustained reduction of symptoms and clinical response in approximately 30% of patients.[ClinicalTrials.gov identifier: NCT00488631].

[Autoimmune hepatitis]. / Autoimmunhepatitis.

Autoimmune hepatitis (AIH) is a chronic, progressive disease of the liver characterized by hypergammaglobulinemia, circulating autoantibodies, and interface hepatitis on biopsy. AIH can occur in all age groups. It affects women more commonly than men (3:1). The spectrum of clinical manifestations is wide and ranges from asymptomatic disease to acute hepatitis or even acute liver failure. Corticosteroids are the drug of choice for induction of remission, azathioprine is the drug of choice for maintenance of remission. Rapid response to immunosuppressive treatment supports the diagnosis and leads to a good long-term prognosis. Therapy should be ideally continued for at least two to four years to minimize the risk of relapse.

Type D personality is associated with depressive symptoms and clinical activity in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) can be exacerbated by stress and depression. Type D personality, characterised by high negative affectivity and social inhibition, represents a vulnerability towards stressors and is associated with adverse outcomes in coronary heart disease. AIMS: To assess the prevalence of Type D personality in IBD patients and investigate potential associations with disease course. METHODS: We tested for associations between Type D (Type D Scale-14), depressive symptoms (Hospital Anxiety and Depression Scale's depression subscore ≥11) and recurrent IBD amongst Swiss IBD cohort patients. We built regression models for cross-sectional and Cox proportional hazards models for time-to-event analyses. IBD disease course was assessed by the future occurrence of active disease (Crohn's Disease Activity Index ≥150/Modified Truelove & Witts activity index ≥10) and several IBD-relevant endpoints. RESULTS: Amongst 2275 patients (1005 ulcerative colitis, 1270 Crohn's disease), 672 (29.5%) had Type D. Type D was a significant risk factor for future active disease (adjusted hazard ratio, aHR: 1.60, corrected P value, q = 0.007) and predicted the future presence of depressive symptoms (aHR: 3.30, P < 0.001). The combination of Type D and depressive symptoms further increased the risk for active disease (aHR: 3.98, q < 0.001). However, Type D associated depressive symptoms seemed to be the main contributor to this effect as Type D's predictive power decreased considerably in models corrected for depressive symptoms (aHR: 1.32, CI: 0.97-1.79, q = 0.292). CONCLUSIONS: Type D personality's prevalence amongst IBD patients was comparable with its prevalence in the general population. Type D was strongly associated with depressive symptoms and showed modest independent associations with IBD prognosis.

Can the CalproQuest predict a positive Calprotectin test? A prospective diagnostic study.

BACKGROUND: Diagnosis of inflammatory bowel disease (IBD) in primary care (PC) is challenging and associated with a considerable diagnostic delay. Using a calprotectin test for any PC patient with abdominal complaints would cause significant costs. The 8-item-questionnaire CalproQuest was developed to increase the pre-test probability for a positive Calprotectin. It is a feasible instrument to assess IBD in PC, but has not yet been evaluated in clinical routine. This study, therefore, aimed to validate whether the CalproQuest increases pretest-probability for a positive fecal Calprotectin. METHODS: Prospective diagnostic trial. The CalproQuest consists of 4 major and 4 minor questions suggestive for IBD. It is considered positive if ≥ 2 major or 1 major and 2 minor criteria are positive. Primary outcome: Sensitivity and specificity of the CalproQuest for Calprotectin levels ≥ 50 µg/g and for positive IBD diagnosis among patients referred to endoscopic evaluation at secondary care level. Secondary finding: Patient-reported diagnostic delay. RESULTS: 156 patients from 7 study centers had a complete CalproQuest and fecal Calprotectin test. The sensitivity and specificity of CalproQuest for Calprotectin ≥ 50 µg/g was 36% and 57%. The sensitivity and specificity of the CalproQuest for positive IBD diagnosis was 37% and 67%. The diagnostic delay was 61 months (SD 125.2). CONCLUSION: In this prospective diagnostic study, the sensitivity and specificity of CalproQuest for Calprotectin levels ≥ 50 µg/g and positive IBD diagnosis were poor. Additional prospective studies concerning the ideal cut-off values, validity and cost-effectiveness of a combined use with the Calprotectin test in the PC setting are necessary.

A Very Rare Cause of a Relapsing Para-Oesophageal Abscess.

Oesophageal involvement in Crohn's disease (CD) is uncommon and most often accompanied by involvement of more distal parts. Its presentation is mostly non-specific, and therefore a diagnosis, especially in isolated oesophageal disease, is difficult. We present the case of a 42-year-old male patient who was referred to our gastroenterology department because of a para-oesophageal abscess. Under antibiotic treatment the abscess healed, but despite great diagnostic efforts, its aetiology remained unclear. Three years later the patient was hospitalized again because of an abscess at the same site. Endoscopy showed disseminated ulcerations of the lower oesophagus, raising suspicion of CD. After excluding other possible causes, we made the diagnosis of isolated CD of the oesophagus. We review the available literature on this topic and discuss the clinical presentation, symptoms, endoscopic findings, and histology as well as treatment of oesophageal CD.

Endoscopic dilation of complete oesophageal obstructions with a combined antegrade-retrograde rendezvous technique.

AIM: To investigate the combined antegrade-retrograde endoscopic rendezvous technique for complete oesophageal obstruction and the swallowing outcome. METHODS: This single-centre case series includes consecutive patients who were unable to swallow due to complete oesophageal obstruction and underwent combined antegrade-retrograde endoscopic dilation (CARD) within the last 10 years. The patients' demographic characteristics, clinical parameters, endoscopic therapy, adverse events, and outcomes were obtained retrospectively. Technical success was defined as effective restoration of oesophageal patency. Swallowing success was defined as either percutaneous endoscopic gastrostomy (PEG)-tube independency and/or relevant improvement of oral food intake, as assessed by the functional oral intake scale (FOIS) (≥ level 3). RESULTS: The cohort consisted of six patients [five males; mean age 71 years (range, 54-74)]. All but one patient had undergone radiotherapy for head and neck or oesophageal cancer. Technical success was achieved in five out of six patients. After discharge, repeated dilations were performed in all five patients. During follow-up (median 27 mo, range, 2-115), three patients remained PEG-tube dependent. Three of four patients achieved relevant improvement of swallowing (two patients: FOIS 6, one patient: FOIS 7). One patient developed mediastinal emphysema following CARD, without a need for surgery. CONCLUSION: The CARD technique is safe and a viable alternative to high-risk blind antegrade dilation in patients with complete proximal oesophageal obstruction. Although only half of the patients remained PEG-tube independent, the majority improved their ability to swallow.

Does caffeine reduce postoperative bowel paralysis after elective laparoscopic colectomy? (CaCo trial): study protocol for a randomized controlled trial.

BACKGROUND: Postoperative bowel paralysis is common after abdominal operations, including colectomy. As a result, hospitalization may be prolonged, thereby leading to increased cost. A recent randomized controlled trial showed that the consumption of regular black coffee after colectomy is associated with a significantly faster resumption of intestinal motility. The mechanism by which coffee stimulates intestinal motility is unknown, but caffeine seems to be the most likely stimulating agent. Thus, the effect of caffeine on postoperative bowel activity after colon surgery will be analyzed in this trial, herein referred to as CaCo. METHODS/DESIGN: Patients scheduled for elective laparoscopic colectomy or upper rectum resection are eligible to participate in this double-blinded, placebo-controlled, randomized trial. Patients fulfilling all inclusion criteria will be allocated after the surgical procedure to one of three treatment arms: 100 mg caffeine, 200 mg caffeine, or placebo (corn starch). Patients will take the capsules containing the study medication three times daily with a meal. The primary endpoint of the study is the time to a solid bowel movement. The study treatment will be stopped after the patient produces a solid bowel movement or has taken ten capsules, whichever occurs first. To determine the colonic passage time, patients will take a capsule with radiopaque markers at breakfast for the first 3 days after surgery. On the fourth day, the location of the markers will be determined with an abdominal X-ray scan. Further secondary objectives are the postoperative morbidity and mortality, well-being, sleeping behavior, and length of hospital stay. The study size was calculated to be 180 patients with an interim analysis occurring after 60 patients. DISCUSSION: From a previous study investigating coffee, evidence exists that caffeine might have a positive influence on the postoperative bowel activity. This double-blinded, placebo-controlled, randomized trial tries to show that caffeine will shorten the postoperative bowel paralysis and, thus, will improve recovery and shorten the hospital stay after colon surgery. TRIAL REGISTRATION: Clinicaltrials.gov NCT02510911 Swiss National Clinical Trials Portal SNCTP000001131.

First report of colonoscopic closure of a gastrocolocutaneous PEG migration with over-the-scope-clip-system.

Percutaneous endoscopic gastrostomy (PEG) is a common practice for long-term nutrition of patients who are unable to take oral food. We report of an 85-year old man with a history of recurrent larynx carcinoma and hemicolectomy many years ago due to unknown reason. Laryngectomy was indicated. Preoperatively a PEG was inserted endoscopically after an abdominal ultrasonography without abnormal findings. Few months after PEG insertion, the patient was evaluated for diarrhea and insufficient feeding without signs of infection or peritonism. An upper endoscopy and computed tomography scan confirmed a buried bumper syndrome with migration of the PEG tube into the colon as a rare complication. He underwent successful colonoscopic removal of the internal bumper and closure of the colonic orifice of the fistula with the over-the-scope-clip system (OTSC). OTSC is an endoscopic device for treatment of bleeding, perforation, leak and fistula in the gastrointestinal tract. To the best of our knowledge, this is the first report of the use of OTSC for colonoscopic closure of a gastrocolocutaneous fistula due to a buried bumper syndrome with transcolonic PEG tube migration.

Unspecific abdominal symptoms and pneumobilia: a rare case of gastrointestinal obstruction.

The case of a 77-year-old woman with symptoms of gastric outlet obstruction is presented. Transabdominal ultrasonography findings were suspicious of Bouveret's syndrome. Upper endoscopy confirmed this diagnosis. Bouveret's syndrome is a rare complication of gallstone disease caused by a bilioenteric fistula leading to gastric outlet obstruction by a gallstone and should be suspected in any patient who presents with pneumobilia without recent endoscopic retrograde cholangiopancreatography or biliary surgery.