Background and Aims: Malfunctions of enteric neurons are believed to play an important role in the pathophysiology of irritable bowel syndrome (IBS). Our aim was to investigate whether neuronal activity in biopsies from IBS patients is altered in comparison to healthy controls (HC).Methods: Activity of human submucous neurons in response to electrical nerve stimulation and local application of nicotine or a mixture of histamine, serotonin, tryptase, and TNF-α (IBS-cocktail) was recorded in biopsies from 17 HC and 35 IBS patients with the calcium-sensitive-dye Fluo-4 AM. The concentrations of the mediators resembeled those found in biopsy supernatants or blood. Neuronal activity in guinea-pig submucous neurons was studied with the voltage-sensitive-dye di-8-ANEPPS.Results: Activity in submucous ganglia in response to nicotine or electrical nerve stimulation was not different between HC and IBS patients (P = 0.097 or P = 0.448). However, the neuronal response after application of the IBS-cocktail was significantly decreased (P = 0.039) independent of whether diarrhea (n = 12), constipation (n = 5) or bloating (n = 5) was the predominant symptom. In agreement with this we found that responses of submucous ganglia conditioned by overnight incubation with IBS mucosal biopsy supernatant to spritz application of this supernatant was significantly reduced (P = 0.019) when compared to incubation with HC supernatant.Conclusion: We demonstrated for the first time reduced neuronal responses in mucosal IBS biopsies to an IBS mediator cocktail. While excitability to classical stimuli of enteric neurons was comparable to HC, the activation by the IBS-cocktail was decreased. This was very likely due to desensitization to mediators constantly released by mucosal and immune cells in the gut wall of IBS patients.

Background and study aims The optimal approach to small subepithelial tumors (SETs) of the upper gastrointestinal tract remains inconclusive. The aim of this study was to evaluate endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) for less invasive tissue sampling of small SETs of the upper gastrointestinal tract. Patients and methods In this prospective observational study patients with small ( ≤ 3 cm) SETs of the upper gastrointestinal tract were eligible and underwent EUS-FNB with a 22-gauge core biopsy needle. The main outcome measure was the diagnostic yield. The number of obtained core biopsies was also assessed. Results Twenty patients were included. The mean SET size was 16 mm (range 10 – 27 mm). EUS-FNB was technically feasible in all cases and no complications were observed. The diagnostic yield was 75 %. Core biopsy specimens were obtained in only 25 % of cases. Conclusion EUS-FNB with a 22-gauge core biopsy needle of small SETs can achieve a definite diagnosis in the majority of cases. However, because core samples cannot regularly be obtained, EUS-FNB seems not to be convincingly superior to standard EUS-FNA in this setting

A cyclosporine (CsA)-based immunosuppression is associated with an increased incidence of cholelithiasis after heart transplantation. It is not known if tacrolimus (Tac) has comparable biliary side effects in humans.We evaluated the incidence of gallbladder sludge and cholelithiasis under Tac-based immunosuppression by ultrasound examinations in 31 cardiac transplants (25 male, 6 female, mean age: 59 ± 11 years). Data were compared to 57 patients (47 male, 10 female, mean age: 58 ± 11 years) who received CsA-based immunosuppression.6 patients receiving Tac and 6 patients receiving CsA had already gallstones prior to transplantation so that finally 25 patients of the Tac group and 51 patients of the CsA group could be evaluated.In the Tac group the incidence of biliary sludge was 4% (1 of 25), of gallstones 28% (7 of 25). In comparison, patients receiving CsA developed biliary sludge in also 4% (2 of 51) and gallstones in 25% (13 of 51). Nine of 42 males in the CsA group (21%) and eight of 20 males in the Tac group (40%) developed either gallstones or sludge (n.s). Six of nine females in the CsA group (67%), but none of five females in the Tac group (0%) developed either gallstones or sludge (p = 0.01).In summary, the incidence of biliary disease in patients with Tac is comparable with CsA-based immunosuppression. We recommend regular sonographical examinations to detect biliary diseases as early as possible. In cases of clinically, laboratory and sonographical signs of cholecystitis cholecystectomy is indicated. It seems that towards lithogenicity female patients benefit more from a Tac-based treatment because the occurrence of gallstones is rare.

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EUS-guided biliary drainage (EUS-BD) has recently gained widespread acceptance as a minimally invasive alternative method for biliary drainage. Even in experienced endoscopy centers, ERCP may fail due to inaccessibility of the papillary region, altered anatomy (particularly postsurgical alterations), papillary obstruction, or neoplastic gastric outlet obstruction. Biliary cannulation fails at first attempt in 5%–10% of cases even in the absence of these factors. In such cases, alternative options for biliary drainage must be provided since biliary obstruction is responsible for poor quality of life and even reduced survival, particularly due to septic cholangitis. The standard of care in many centers remains percutaneous transhepatic biliary drainage (PTBD). However, despite the high technical success rate with experienced operators, the percutaneous approach is more invasive and associated with poor quality of life. PTBD may result in long-term external catheters for biliary drainage and carry the risk of serious adverse events (SAEs) in up to 10% of patients, including bile leaks, hemorrhage, and sepsis. PTBD following a failed ERCP also requires scheduling a second procedure, resulting in prolonged hospital stay and additional costs. EUS-BD may overcome many of these limitations and offer some distinct advantages in accessing the biliary tree. Current data suggest that EUS-BD is safe and effective when performed by experts, although SAEs have been also reported. Despite the high number of clinical reports and case series, high-quality comparative studies are still lacking. The purpose of this article is to report on the current status of this procedure and to discuss the tools and techniques for EUS-BD in different clinical scenarios.