Transmission of oral microbiota to the biliary tract during endoscopic retrograde cholangiography.

BACKGROUND: Endoscopic retrograde cholangiography (ERC) possesses a translocation risk of microbes to the biliary system. We studied bile contamination during ERC and its impact on patients' outcome in a real-life-situation. METHODS: Ninety-nine ERCs were analyzed and microbial samples were taken from the throat before and from bile during ERC and from irrigation fluid of the duodenoscope before and after ERC. RESULTS: 91.2% of cholangitis patients had detectable microbes in the bile (sensitivity 91%), but the same was true for 86.2% in the non-cholangitis group. Bacteroides fragilis (p=0.015) was significantly associated with cholangitis. In 41.7% of ERCs with contaminated endoscopes these microbes were found in the bile after the procedure. Analysis of duodenoscopes' irrigation liquid after ERC matched the microbial bile analysis of these patients in 78.8%. Identical microbial species were in throat and in bile samples of the same ERC in 33% of all cases and in 45% in the non-cholangitis group. Transmission of microbes to the biliary tract did not result in more frequent cholangitis, longer hospital stays, or worse outcome. CONCLUSIONS: During ERC bile samples are regularly contaminated with microbes of the oral cavity but it did not affect clinical outcome.

Decline in acute upper gastrointestinal bleeding during COVID-19 pandemic after initiation of lockdown in Austria.

BACKGROUND: COVID-19 has spread rapidly around the world. The Austrian government implemented a lockdown on 16 March to contain further spread of the disease. We investigated the effects of lockdown on acute upper gastrointestinal (GI) bleeding in Austria. METHODS: We contacted 98 Austrian hospitals performing emergency endoscopies. The hospitals were asked to report upper GI endoscopies performed for recent hematemesis, melena, or both, and exhibiting endoscopically visible signs of bleeding. The study period was from 3 weeks before (calendar Week 9) to 3 weeks after (Week 14) initiation of the lockdown. RESULTS: 61 % of Austrian hospitals, and importantly all major state hospitals, responded. A total of 575 upper GI bleedings occurred during the 3 weeks before and 341 during the 3 weeks after initiation of lockdown (40.7 % reduction). There was a 54.6 % decline in nonvariceal bleeding events at Week 14 compared with Week 9 (89 vs. 196), whereas rates of variceal hemorrhage did not change (15 vs. 17). CONCLUSIONS: National lockdown resulted in a dramatic decrease in upper GI bleeding events in Austrian hospitals.

CCBE1 mutation causing sclerosing cholangitis: Expanding the spectrum of lymphedema-cholestasis syndrome.

A 52-year old patient presented with lymphedema, protein loosing enteropathy, and sclerosing cholangitis and was diagnosed with lymphedema cholestasis syndrome (LCS). Cholangioscopy revealed dilated lymphatic vessels obstructing the bile duct and compound heterozygosity for collagen and calcium-binding epidermal growth factor domain-containing protein 1 (CCBE1) mutations was identified defining a novel type of LCS. (Hepatology 2017;66:286-288).

Endoscopic radiofrequency ablation for malignant biliary obstruction: a nationwide retrospective study of 84 consecutive applications.

BACKGROUND: Biliary radiofrequency ablation (RFA) using the Habib™ EndoHBP catheter is a new endoscopic palliation therapy for malignant biliary obstruction. The aim of this study was to assess the feasibility and safety of this technique. METHODS: In this nationwide retrospective study of prospectively collected clinical data, all patients treated by biliary RFA in Austria between November 2010 and December 2012 were included. Procedure-related complications, adverse events within 30 days post-intervention, stent patency, and mortality rates were investigated. RESULTS: A total of 58 patients (31 male, 27 female, median age 75 years) underwent 84 RFA procedures at 11 Austrian referral centers for biliary endoscopy. The predominant underlying condition was Klatskin tumor (45 of 58 cases). All 84 RFA procedures were feasible without technical problems. A partial liver infarction was induced by RFA in a 49-year-old Klatskin tumor patient. During 30 days after each RFA procedure, five cases of cholangitis, three cases of hemobilia, two cases of cholangiosepsis, and one case each of gallbladder empyema, hepatic coma, and newly diagnosed left bundle branch block occurred. Median stent patency after last electively performed RFA was 170 days (95 % CI 63-277) and was almost significantly different between metal and plastic stenting (218 vs. 115 days; p = 0.051). Median survival was 10.6 months (95 % CI 6.9-14.4) from the time of the first RFA in each patient and 17.9 months (95 % CI 10.3-25.6) from the time of initial diagnosis. CONCLUSIONS: Except for one severe interventional complication (hepatic infarct), RFA presented as a technically feasible and safe therapeutic option for the palliative treatment of malignant biliary obstruction. The good results of stent patency and survival in this study should be proven in prospective (controlled) trials to further quantify the efficacy of this promising new technique.

Bleeding Dieulafoy lesions of the small bowel: a systematic study on the epidemiology and efficacy of enteroscopic treatment.

BACKGROUND: Dieulafoy lesions consist of aberrant submucosal arteries, which can cause severe GI bleeding. The predominant location of Dieulafoy lesions is the upper GI tract. OBJECTIVE: To our best knowledge, this is the first systematic study on the frequency of bleeding from Dieulafoy lesions in the small bowel and the efficacy of enteroscopic therapy regarding primary hemostasis and long-term follow-up. DESIGN: Multicenter, retrospective, observational study. SETTING: Nine Austrian centers doing double-balloon enteroscopy or single-balloon enteroscopy. PATIENTS: This study involved 284 consecutive patients who were referred for double-balloon enteroscopy or single-balloon enteroscopy because of suspicion of mid-GI bleeding. INTERVENTION: A total of 317 double-balloon enteroscopy and 78 single-balloon enteroscopy procedures were performed in 284 patients with suspected mid-GI bleeding. MAIN OUTCOME MEASUREMENTS: Demographic, clinical, procedural, and outcome data were collected. RESULTS: A Dieulafoy lesion in the small bowel was identified as the source of mid-GI bleeding in 3.5% of patients, with a mean of 1.5 enteroscopy sessions required per diagnosis. In 9 cases the Dieulafoy lesion was found by enteroscopy from an oral approach, and in 1 patient the lesion was found by an anal approach. In all patients primary endoscopic hemostasis was successful. Eight of 10 patients were free from rebleeding episodes (median follow-up 14.5 months, interquartile range 10.0-17.5 months). In 2 of 10 patients, rebleeding occurred, and a surgical intervention was necessary. LIMITATIONS: Retrospective study. CONCLUSION: Bleeding from Dieulafoy lesions of the small bowel seems to occur more frequently than previously estimated. Most of these lesions are located in the proximal jejunum and can be managed successfully by enteroscopy. After successful endoscopic hemostasis, rebleeding episodes occur in only 20% of patients.

Intramural duodenal hematoma after upper gastrointestinal endoscopy.

BACKGROUND: Intramural hematoma of the duodenum is a very rare condition. It is mostly seen after blunt abdominal trauma in children. There are only few cases of intramural duodenal hematoma after upper gastrointestinal endoscopy. Most of them are associated with coagulation disorders. The optimal treatment strategy for this condition is still under debate. CASE PRESENTATION: We present the case of a 21-year-old woman who had undergone an upper gastrointestinal endoscopy for dyspepsia and protracted singultus. Work-up included biopsies. Immediately after the procedure, the patient developed an intramural hematoma causing complete duodenal obstruction. The patient was treated conservatively and recovered within three weeks without any sequelae. CONCLUSION: Uncomplicated cases of intramural hematoma may be treated conservatively with total parenteral nutrition, fluid and electrolyte replacement.

Targeting NAD immunometabolism limits severe graft-versus-host disease and has potent antileukemic activity.

Acute graft-versus-host disease (aGVHD) and tumor relapse remain major complications after allogeneic hematopoietic stem cell transplantation. Alloreactive T cells and cancer cells share a similar metabolic phenotype to meet the bioenergetic demands necessary for cellular proliferation and effector functions. Nicotinamide adenine dinucleotide (NAD) is an essential co-factor in energy metabolism and is constantly replenished by nicotinamide phosphoribosyl-transferase (Nampt), the rate-limiting enzyme in the NAD salvage pathway. Here we show, that Nampt blockage strongly ameliorates aGVHD and limits leukemic expansion. Nampt was highly elevated in serum of patients with gastrointestinal GVHD and was particularly abundant in human and mouse intestinal T cells. Therapeutic application of the Nampt small-molecule inhibitor, Fk866, strongly attenuated experimental GVHD and caused NAD depletion in T-cell subsets, which displayed differential susceptibility to NAD shortage. Fk866 robustly inhibited expansion of alloreactive but not memory T cells and promoted FoxP3-mediated lineage stability in regulatory T cells. Furthermore, Fk866 strongly reduced the tumor burden in mouse leukemia and graft-versus-leukemia models. Ex vivo studies using lymphocytes from GVHD patients demonstrated potent antiproliferative properties of Fk866, suggesting potential clinical utility. Thus, targeting NAD immunometabolism represents a novel approach to selectively inhibit alloreactive T cells during aGVHD with additional antileukemic efficacy.

Photodynamic therapy with polyhematoporphyrin for malignant biliary obstruction: A nationwide retrospective study of 150 consecutive applications.

BACKGROUND: Photodynamic therapy (PDT) is a palliative treatment for malignant biliary obstruction. OBJECTIVE: The objective of this article is to assess the feasibility and safety of this technique. METHODS: In this nationwide, retrospective study of prospectively collected clinical data, all patients treated with PDT using polyhematoporphyrin in Austria from March 2004 to May 2013 were included. Feasibility, adverse events, stent patency and mortality rates were investigated. RESULTS: Eighty-eight patients (54 male, 34 female, median age 69 years) underwent 150 PDT procedures at seven Austrian referral centers for biliary endoscopy. The predominant underlying disease was Klatskin tumor (79/88). All PDT procedures were feasible without technical issues. Cholangitis was the most frequent adverse event (21/88). Stent patency was 246 days (95% CI 203-289) median and was significantly longer for metal than for plastic stents (269 vs. 62 days, p < 0.01). The median survival was 12.4 months (95% CI 9.7-14.9 m) calculated from first PDT and 15.6 months (95% CI 12.3-18.7 m) calculated from initial diagnosis. In patients suffering from biliary tract cancer, Cox regression revealed the number of PDT treatment sessions as the only independent predictor of survival at a multivariate analysis (p = 0.048). CONCLUSION: PDT using polyhematoporphyrin was feasible and safe in this nationwide analysis. Survival data suggest a benefit of PDT in this unselected real-life patient population. Prospective trials comparing PDT to other palliative treatments will help to define its role in the management of malignant biliary obstruction. The study is registered at ClinicalTrials.gov number: NCT02504957.

Treatment of intractable pruritus in drug induced cholestasis with albumin dialysis: a report of two cases.

Cholestatic liver injury can be caused by a variety of drugs and is difficult to treat. We report two patients, a 22 year old male and a 55 year old female, with drug induced cholestasis caused by anabolic-androgenic steroids (silabolin and nandrolone) and by fluoxetine, respectively. Both patients presented with massive jaundice and severe pruritus resulting in sleep deprivation and suicide ideation. Laboratory examination revealed signs of cholestasis. Medical treatment was ineffective; therefore, extracorporeal albumin dialysis using the molecular adsorbent recirculating system (MARS) was started. Three treatments with a mean duration of 16 hours were performed in each patient. The procedure was well tolerated by the patients and resulted in a sustained relief of pruritus as well as in a decline of plasma bilirubin and serum 3alpha-hydroxy bile acid levels. The mean plasma bilirubin concentration decreased from 25.27 mg/dl to 10.7 mg/dl; the mean serum 3alpha-hydroxy bile acid concentration decreased from 299 micromol/L to 88 micromol/L. After 2 months, the pruritus had nearly vanished in both patients, and there was a further decline of bilirubin levels after discharge from hospital. In conclusion, extracorporeal albumin dialysis appears to be a therapeutic option in severe drug induced cholestasis refractory to medical treatment.

Posttraumatic splenic artery aneurysm presenting as occult gastrointestinal bleeding.

A 53-year-old man presented with a 19-month history of gastrointestinal bleeding. Repeated endoscopic investigation of the upper and lower intestine showed no source of bleeding. When the patient collapsed due to massive gastrointestinal hemorrhage he was referred to our center. Gastroscopy showed a large, bulging tumor protruding from the posterior gastric wall. The consistency of this tumor was soft and the overlying mucosa appeared smooth and intact. Endoscopic ultrasound and contrast-enhanced computerized tomography scan identified a partly thrombosized splenic artery aneurysm (SAA). Arteriography of the celiac trunk confirmed the SAA diagnosis; the SAA was subsequently occluded by coils. So far, four months after discharge, the patient is in excellent health and no further episode of gastrointestinal bleeding has occurred. SAA is a very rare cause of upper gastrointestinal bleeding, but it must be considered when no other common bleeding source can be detected.

Long-term outcome of endoscopic treatment of biliary strictures after liver transplantation.

Biliary strictures are one of the most common complications following liver transplantation (LT), with an incidence of 5.8-34%. Endoscopic techniques have been successfully used to treat biliary complications; however, the long-term efficacy and safety of this treatment option has not yet been fully elucidated. This prospective study was performed to determine the efficacy and safety of endoscopic management of biliary complications after LT and its impact on long-term patient and graft survival. Biliary strictures were suspected in the presence of elevated liver parameters and/or abnormal abdominal sonography and subsequently diagnosed by endoscopic retrograde cholangiography (ERC). The mean follow-up was 39.8 (range, 0.3-98.2) months after first ERC. Between October 1992 and December 2003, a total of 515 patients underwent LT. Biliary complications were diagnosed in 84 patients (16.3 %). Anastomotic strictures (AS) alone were found in 65 (12.6%) and nonanastomotic strictures (NAS) in 19 patients (3.7%). Long-term success was observed in 77% of patients with AS. In patients with NAS, partial long-term responses could be achieved in 63% of patients. Five patients (6.2%) required a percutaneous and 6 (7.4%) patients a surgical approach. In conclusion, the long-term outcome for patients with post-liver transplant biliary strictures after endoscopic treatment is excellent, especially for patients with AS. Development of NAS reduces graft but not patient survival after endoscopic therapy.

Bactobilia after liver transplantation: frequency and antibiotic susceptibility.

After liver transplantation (LT), bactobilia occurs frequently in patients, leading in some cases to cholangitis and biliary sepsis. The present study is the first to investigate bactobilia after LT, and it gives an overview of predisposing factors for bactobilia, the microbial spectrum in the bile of LT patients, and the antibiotic susceptibility. A total of 172 endoscopic retrograde cholangiography (ERC) procedures were performed in 66 LT patients between 1 month and 5.8 years after LT. Bile samples were examined microbiologically. Sixty-eight nontransplanted patients without cholestasis, but requiring ERC for other reasons served as a control group. Of 172 samples obtained from LT patients, 126 (73.3%) were positive for microbes. A total of 236 organisms were isolated: 114 (48.3%) gram-positive bacteria, 92 (39.0%) aerobic gram-negative, 8 (3.4%) anaerobes, and 22 (9.3%) fungi. Ciprofloxacin and amoxycillin/clavulanic acid showed the best susceptibility results among oral antibiotics and piperacillin/tazobactam and imipenem/cilastatin among intravenous preparations. In contrast, only 15.7% of non-LT patients showed bactobilia. In conclusion, our study shows that bactobilia is a problem in patients after LT and that it is not only a contamination from endoscopic intervention. Mechanical obstruction, plastic stents, gallstones, and papillotomy increase the risk of bactobilia significantly. In our cohort we had the best antibiotic susceptibility results for positive cultures in LT patients with piperacillin/tazobactam, ciprofloxacin, or amoxycillin/clavulanic acid.

Treatment of refractory cholestatic pruritus after liver transplantation with albumin dialysis.

Albumin dialysis has been shown to improve the outcome in patients with cholestatic liver failure caused by chronic liver disease. This study reports 7 liver transplant recipients who were treated with albumin dialysis for intractable pruritus of different origin (ductopenic graft rejection, non-anastomotic strictures, and recurrence of hepatitis C). Treatment with histamine (H1) blockers, opioid antagonists, and cholestyramine had not been effective. The Molecular Adsorbent Recirculating System (MARS; Teraklin, Rostock, Germany) was used for albumin dialysis. All patients presented with numerous scratch marks, 6 of whom had a pronounced icterus. Six patients (86%) responded to 3 consecutive treatments with significant reduction of pruritus. The mean pruritus score, which was quantified by a visual analog scale (VAS), decreased from 9.7 +/- 0.5 to 3.7 +/- 0.8 (SD). The mean duration of 1 treatment was 15.6 hours. The procedure was well tolerated by all patients. The mean total serum bilirubin in patients who responded to therapy declined from 19.11 +/- 16.96 mg/dL (SD) before MARS therapy to 9.24 +/- 3.52 mg/dL after treatment. The mean serum concentration of 3 alpha-hydroxy bile acids decreased from 192.67 +/- 58.12 micromol/L (SD) to 42.33 +/- 31.58 micromol/L (SD). Follow-up in 3 cases showed sustained improvement of pruritus lasting for more than 3 months. In 3 patients, however, pruritus relapsed. One patient, who showed severe pruritus, without relevant elevation of serum bile acids before treatment, did not respond to albumin dialysis. Our data indicate that MARS is an effective therapeutic option for patients with intractable cholestatic pruritus.