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Background: Cholecystectomy in patients with idiopathic acute pancreatitis (IAP) is controversial. A randomized trial found cholecystectomy to reduce the recurrence rate of IAP but did not include preoperative endoscopic ultrasonography (EUS). As EUS is effective in detecting gallstone disease, cholecystectomy may be indicated only in patients with gallstone disease. This study aimed to determine the diagnostic value of EUS in patients with IAP, and the rate of recurrent pancreatitis in patients in whom EUS could not determine the aetiology (EUS-negative IAP). Methods: This prospective multicentre cohort study included patients with a first episode of IAP who underwent outpatient EUS. The primary outcome was detection of aetiology by EUS. Secondary outcomes included adverse events after EUS, recurrence of pancreatitis, and quality of life during 1-year follow-up. Results: After screening 957 consecutive patients with acute pancreatitis from 24 centres, 105 patients with IAP were included and underwent EUS. In 34 patients (32 per cent), EUS detected an aetiology: (micro)lithiasis and biliary sludge (23.8 per cent), chronic pancreatitis (6.7 per cent), and neoplasms (2.9 per cent); 2 of the latter patients underwent pancreatoduodenectomy. During 1-year follow-up, the pancreatitis recurrence rate was 17 per cent (12 of 71) among patients with EUS-negative IAP versus 6 per cent (2 of 34) among those with positive EUS. Recurrent pancreatitis was associated with poorer quality of life. Conclusion: EUS detected an aetiology in a one-third of patients with a first episode of IAP, requiring mostly cholecystectomy or pancreatoduodenectomy. The role of cholecystectomy in patients with EUS-negative IAP remains uncertain and warrants further study. [ABSTRACT FROM AUTHOR]

Background & Aims: Data regarding health‐related quality of life (HRQoL) in primary sclerosing cholangitis (PSC) are sparse and have only been studied cross‐sectionally in a disease which runs a fluctuating and unpredictable course. We aim to describe HRQoL longitudinally by using repeated measurements in a population‐based cohort. Methods: Every 3 months from May 2017 up to August 2020, patients received digital questionnaires at home. These included the EQ‐5D, 5‐D Itch, patient‐based SCCAI and patient‐based HBI. The SF‐36, measuring HRQoL over eight dimensions as well as a physical component summary (PCS) and mental component summary (MCS) score, was sent annually. Data were compared with Dutch reference data and a matched IBD disease control from the population‐based POBASIC cohort. Mixed‐effects modelling was performed to identify factors associated with HRQoL. Results: Three hundred twenty‐eight patients completed 2576 questionnaires. A significant reduction of small clinical relevance in several mean HRQoL scores was found compared with the Dutch reference population: 46.4 versus 48.0, p =.018 for PCS and 47.5 versus 50.5, p =.004 for MCS scores. HRQoL outcomes were significantly negatively associated with coexisting active IBD (PCS −12.2, p <.001 and MCS −12.0, p <.001), which was not the case in case of quiescent IBD. Decreasing HRQoL scores were also negatively associated with increasing age (PCS −0.1 per 10 years, p =.002), female sex (PCS ‐2.8, p <.001), diagnosis of AIH overlap (PCS ‐3.7, p =.059), end‐stage liver disease (PCS ‐3.7, p =.015) and presence of itch (PCS ‐9.2, p <.001 and MCS −3.1, p =.078). The odds of reporting a clinically relevant reduction in EQ‐5D scores showed seasonal variation, being lowest in summer (OR = 0.48 relative to spring, p =.037). In patients with liver transplant, HRQoL outcomes were comparable to the Dutch general population. Conclusions: PSC patients report impaired HRQoL of small clinical relevance compared with the general population. After liver transplantation, HRQoL scores are at comparable levels to the general population. HRQoL scores are associated with potentially modifiable factors such as itch and IBD activity. [ABSTRACT FROM AUTHOR]

Background: Targeted molecular imaging may improve tumor cell identification during diagnosis and resection of pancreatic ductal adenocarcinoma (PDAC). Although many molecular imaging biomarkers are (over)expressed in PDAC, intertumoral heterogeneity of biomarker expression hampers universal tracer administration. Preoperative, patient-specific screening and selection of the most optimal biomarker could therefore improve tumor delineation. Objective: This study evaluated whether fine-needle biopsy (FNB) specimens could be used to preoperatively predict biomarker expression in the corresponding primary PDAC specimen. Methods: Expression of previously identified PDAC biomarkers αvβ6, CEACAM5, EGFR, mesothelin, Lea/c/x, and sdi-Lea on FNB and corresponding primary tumor (PT) specimens (n = 45) was evaluated using immunohistochemistry and quantified using a semi-automated image analysis workflow. Results: Biomarker expression on FNB and PT tissues showed high concordance (∆H-score ≤ 50), i.e. was present in 62% of cases for αvβ6, 61% for CEACAM5, 85% for EGFR, 69% for mesothelin, 76% for Lea/c/x, and 79% for sdi-Lea, indicating high concordance. Except for αvβ6, biomarker expression on FNB tissues was positively correlated with PT expression for all biomarkers. Subgroup analyses showed that neoadjuvant therapy (NAT) had no major and/or significant effect on concordance, expression difference and, except for mesothelin, correlation of biomarker expression between FNB and PT tissues. Conclusion: This study demonstrated that biomarker expression in FNB tissues is predictive for PT expression, irrespective of the application of NAT. These findings thereby provide the foundation for the clinical application of an FNB-based biomarker-screening workflow, eventually facilitating a patient-specific approach of molecular imaging tracer administration in PDAC. [ABSTRACT FROM AUTHOR]

Background & Aims: Primary sclerosing cholangitis (PSC) is a progressive, cholestatic liver disease which greatly impacts the lives of individuals. Burden of disease due to shortened life expectancy and impaired quality of life is ill‐described. The aim of this study was to assess long‐term disease burden in a large population‐based registry with regard to survival, clinical course, quality adjusted life years (QALYs), medical consumption and work productivity loss. Methods: All PSC patients living in a geographically defined area covering ~50% of the Netherlands were included, together with patients from the three liver transplant centres. Survival was estimated by competing risk analysis. Proportional shortfall of QALYs during disease course was measured relative to a matched reference cohort using validated questionnaires. Work productivity loss and medical consumption were evaluated over time. Results: A total of 1208 patients were included with a median follow‐up of 11.2 year. Median liver transplant‐free survival was 21.0 years. Proportional shortfall of QALYs increased to 48% >25 years after diagnosis. Patients had on average 12.4 hospital contact days among which 3.17 admission days per year, annual medical costs were €12 169 and mean work productivity loss was 25%. Conclusions: Our data quantify for the first time disease burden in terms of QALYs lost, clinical events, medical consumption, costs as well as work productivity loss, and show that all these are substantial and increase over time. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound-guided fine needle aspirations (EUS-FNA) of pancreatic masses suffer from sample errors and low-negative predictive values. Fiber-optic spectroscopy in the visible to near-infrared wavelength spectrum can noninvasively extract physiological parameters from tissue and has the potential to guide the sampling process and reduce sample errors. We assessed the feasibility of single fiber (SF) reflectance spectroscopy measurements during EUS-FNA of pancreatic masses and its ability to distinguish benign from malignant pancreatic tissue. A single optical fiber was placed inside a 19-gauge biopsy needle during EUS-FNA and at least three reflectance measurements were taken prior to FNA. Spectroscopy measurements did not cause any related adverse events and prolonged procedure time with ~5 min. An accurate correlation between spectroscopy measurements and cytology could be made in nine patients (three benign and six malignant). The oxygen saturation and bilirubin concentration were significantly higher in benign tissue compared with malignant tissue (55% versus 21%, p = 0.038; 166 µmol/L versus 17 µmol/L, p = 0.039, respectively). To conclude, incorporation of SF spectroscopy during EUS-FNA was feasible, safe, and relatively quick to perform. The optical properties of benign and malignant pancreatic tissue are different, implying that SF spectroscopy can potentially guide the FNA sampling. [ABSTRACT FROM AUTHOR]

Background: Data are scarce on the efficacy and safety of motorized spiral enteroscopy (MSE). No data are available on the utility of this technique in patients with surgically altered gastrointestinal (GI) anatomy. We aimed to evaluate the safety and efficacy of MSE in patients with suspected small-bowel disease, including those with surgically altered GI anatomy.Methods: A multicenter prospective observational, uncontrolled study evaluated MSE in consecutive patients with suspected small-bowel pathology and an indication for diagnostic and/or therapeutic intervention.Results: A total of 170 patients (102 men; median age 64 years, range 18-89) were included. The overall diagnostic yield was 64.1 %. Endotherapy was performed in 53.5 % of procedures. The median total procedure times for the antegrade and retrograde approaches were 45 minutes (interquartile range [IQR] 30-80) and 40 minutes (IQR 30-70), respectively. When total (pan)enteroscopy was intended, this was achieved at rate of 70.3 % (28.1 % by antegrade approach and 42.2 % by a bidirectional approach). Surgically altered GI anatomy was present in 34 /170 of all procedures (20.0 %) and in 11 /45 of the successful total enteroscopy procedures (24.4 %). Propofol sedation or general anesthesia were used in 92.9 % and 7.1 % of the procedures, respectively. Minor adverse events were observed in 15.9 % of patients, but there were no major adverse events.Conclusion: MSE seems to be an effective and safe endoscopic procedure. Total (pan)enteroscopy can be achieved, in one or two sessions, even in the presence of surgically altered GI anatomy. The total procedure time is relatively short. For both antegrade and retrograde MSE procedures, propofol sedation seems sufficient and safe. [ABSTRACT FROM AUTHOR]

Endoscopic sphincterotomy and stone extraction are widely performed as a primary intervention for patients with common bile duct (CBD) stones, with or without cholangiosepsis, with a high success rate and a relatively low complication rate [1]. When CBD stone removal is not successful, a plastic stent can be placed as a salvage therapy to achieve drainage, especially in the septic patient. [Extracted from the article]

Bariatric surgery is the most effective treatment for obesity and improves several manifestations of the metabolic syndrome, including nonalcoholic fatty liver disease. Strict nutritional counseling after bariatric surgery is a key in realizing these outcomes. When postoperative nutrient intake or nutrient uptake is compromised, bariatric surgery can also lead to severe hepatic complications. Here, we describe 3 cases of acute liver injury and acute liver failure caused by bariatric surgery, all with different management strategies and outcomes. [ABSTRACT FROM AUTHOR]

The association between intraoperative bile cultures and infectious complications after pancreatoduodenectomy remains unclear. This cohort study and meta-analysis aimed to determine the predictive role of intraoperative bile cultures in abdominal infectious complications after pancreatoduodenectomy. The cohort study included 114 patients undergoing pancreatoduodenectomy. Regression analyses were used to estimate the odds to develop an organ space infection (OSI) or isolated OSI (OSIs without a simultaneous complication potentially contaminating the intraabdominal space) after a positive bile culture. A systematic review and meta-analysis was performed on abdominal infectious complications (Mantel-Haenszel fixed-effect model). The positive bile culture rate was 61%, predominantly in patients after preoperative biliary drainage (98% vs 26%, p < 0.001). OSIs occurred in 35 patients (31%) and isolated OSIs in nine patients (8%) and were not associated with positive bile cultures (OSIs: odds ratio = 0.6, 95% CI = 0.25–1.23, isolated OSIs: odds ratio = 0.77, 95% CI = 0.20–3.04). In the meta-analysis, 15 studies reporting on 2047 patients showed no association between positive bile cultures and abdominal infectious complications (pooled odds ratio = 1.3, 95% CI = 0.98–1.65). Given the rare occurrence of isolated OSIs and similar odds for patients with positive and negative bile cultures to develop abdominal infectious complications, routine performance of bile cultures should be reconsidered. [ABSTRACT FROM AUTHOR]

MRI surveillance in a cohort of CDKN2A-p16-Leiden mutation carriers with a 20% lifetime risk of PDAC led to increased resection rates and improved survival. Patients with screen-detected PDAC were evaluated for main pancreatic duct (MPD) abnormalities in this retrospective review. Since 2000 annual MRI and optional EUS was performed in mutation carriers. Data of patients with screen-detected PDAC was collected on gender, age at diagnosis, site of tumor, size, outcome of surgery, pathology findings and survival. All MRIs were re-evaluated for MPD abnormalities. 23 PDAC were detected in 22 (10%) of 217 mutation carriers, 10 (45%) males and 12 (55%) females. The mean age at diagnosis was 59.8 years (range 39.2–74.3 years). Revision of the MRI/MRCP revealed a lesion and dilatation of the MPD in 8 of the 22 patients. In 5 of 7 patients with PDAC detected during follow-up, the previous MRI showed MPD dilatation without evidence of tumor. The mean size of PDAC was 12.3 mm (range 5–19 mm). All tumors were resectable. MPD dilation is common in patients with screen-detected PDAC. Abnormalities on MRI during surveillance of high-risk individuals requires intense follow-up or prompt treatment, as early treatment results in a better prognosis. [ABSTRACT FROM AUTHOR]

Highlights • 74% of patients with a tumor <20 cc at baseline developed a complete response (cCR). • Patients who didn't respond to EBRT, were unlikely to benefit from a BT boost. • A BT dose–response effect was observed for clinical and endoscopic proctitis. • Ulceration at the tumor site occurred in 78% of patients with a BT CTV D2cc >14 Gy. Abstract Purpose The HERBERT study was a dose-finding feasibility study of a high-dose rate endorectal brachytherapy (HDREBT) boost after external beam radiotherapy (EBRT) in elderly patients with rectal cancer who were unfit for surgery. This analysis evaluates the association of patient, tumor and dosimetric parameters with tumor response and toxicity after HDREBT in definitive radiotherapy for rectal cancer. Patients and methods The HERBERT study included 38 inoperable patients with T2-3N0-1 rectal cancer. Thirteen fractions of 3 Gy EBRT were followed by three weekly HDREBT applications of 5–8 Gy per fraction. Clinical and dosimetric parameters were tested for correlation with clinical complete response (cCR), sustained partial/complete response (SR), patient reported bowel symptoms, physician reported acute and late proctitis (CTCAE v3) and endoscopically scored toxicity. Results Thirty-five patients completed treatment and were included in the current analyses. Twenty of 33 evaluable patients achieved a cCR, the median duration of a sustained response was 32 months. Tumor volume at diagnosis showed a strong association with clinical complete response (OR 1.15; p = 0.005). No dose–response correlation was observed in this cohort. Prescribed dose to the brachytherapy CTV (D90) correlated with acute and late physician reported proctitis while CTV volume, CTV width and high dose regions in the CTV (D1cc/D2cc) were associated with endoscopic toxicity at the tumor site. Conclusion Tumor volume is the most important predictive factor for tumor response and a higher dose to the brachytherapy CTV increases the risk of severe clinically and endoscopically observed proctitis after definitive radiotherapy in elderly patients with rectal cancer. [ABSTRACT FROM AUTHOR]

Summary: Background: After liver transplantation primary sclerosing cholangitis (PSC), the condition returns in the transplanted liver in a subset of patients (recurrent primary sclerosing cholangitis, rPSC). Aim: To define risk factors for rPSC. Methods: We searched Pubmed, Embase, Web of Science, and Cochrane library for articles published until March 2018. Studies addressing risk factors for developing rPSC were eligible for inclusion. A random effects meta‐analysis was conducted using hazard ratios (HR) as effect measure. Study quality was evaluated with the Newcastle Ottawa scale. Statistical analysis was performed using Cochrane Review Manager. Results: The electronic database search yielded 449 results. Twenty‐one retrospective cohort studies met the inclusion criteria for the review; 14 were included in the meta‐analysis. The final cohort included 2159 patients (age range 31‐49 years, 68.8% male), of whom 17.7% developed rPSC. Colectomy before liver transplantation, HR 0.65 (95% CI: 0.42‐0.99), cholangiocarcinoma before liver transplantation, HR 2.42 (95% CI: 1.20‐4.86), inflammatory bowel disease, HR 1.73 (95% CI: 1.17‐2.54), donor age, HR 1.24 (95% CI 1.0‐1.45) per ten years, MELD score, HR 1.05 (95% CI: 1.02‐1.08) per point and acute cellular rejection, HR of 1.94 (95% CI: 1.32‐2.83) were associated with the risk of rPSC. Conclusions: Multiple risk factors for rPSC were identified. Colectomy before liver transplantation reduced the risk of rPSC. [ABSTRACT FROM AUTHOR]

Summary: Background: Azathioprine (AZA) and mercaptopurine (MP) are the cornerstone of steroid‐sparing strategies in autoimmune hepatitis (AIH). Up to 20% of patients do not tolerate or respond to these regimens. Aim: To evaluate retrospectively the tolerability and efficacy of tioguanine (thioguanine) (TG) therapy in selected patients with AIH and AIH variant syndromes. Methods: Records of 52 patients who received TG therapy were retrieved from nine hospitals in the Netherlands. Indications for TG treatment were intolerable side effects on AZA or MP (n = 38), insufficient response (n = 11) or first‐line treatment (n = 3). Treatment efficacy was defined as normalisation of serum aminotransferases and serum immunoglobulin G. Results: No serious adverse events occurred in patients treated with TG during a median follow‐up of 18 months (range 1‐194). Treatment was well tolerated in 41 patients (79%), whereas four had tolerable (8%) and seven (13%) intolerable side effects. Thirty‐eight patients were treated with TG after intolerable side effects on AZA or MP; 29 patients continued TG therapy of whom 24 (83%) achieved complete biochemical remission, four (14%) had incomplete and one (3%) had no response; nine discontinued treatment. Seven of 11 patients with insufficient response to AZA or MP were responsive to TG, three with complete and four with incomplete biochemical remission; four discontinued due to intolerance (n = 2) and non‐response (n = 2). TG was effective in all AIH patients as first‐line maintenance treatment. Conclusion: In our retrospective review of TG therapy in selected patients with AIH or AIH variants who previously failed on AZA or MP, TG appeared tolerable with biochemical efficacy. [ABSTRACT FROM AUTHOR]

Optimizing therapy of post-transplant HCV recurrence remains important, especially in advanced liver disease. We evaluated daclatasvir ( DCV) plus sofosbuvir ( SOF), with or without ribavirin ( RBV), in patients with post-liver transplant recurrence in a real-world European cohort at high risk of decompensation or death within 12 months. Recommended treatment was DCV 60 mg plus SOF 400 mg once daily for 24 weeks; RBV use/shorter treatment duration was at physicians' discretion. Patients ( N = 87) were 70% male, 93% white, and mostly infected with HCV genotypes 1b (48%), 1a (32%), or 3 (9%); 37 (43%) had cirrhosis (16 decompensated), five had fibrosing cholestatic hepatitis. Sustained virologic response at post-treatment week 12 ( SVR12) was 94% (80/85) in a modified intention-to-treat analysis: 95% (58/61) without RBV and 92% (22/24) with RBV, with no virologic failures. SVR12 was 100% (80/80) in an as-observed analysis excluding five nonvirologic failures. Four patients (5%) discontinued therapy for adverse events ( AEs); 16 (18%) experienced serious AEs. One patient died on treatment and five during follow-up. Most AEs were associated with advanced liver disease and unrelated to therapy. No clinically significant drug-drug interactions were observed. DCV + SOF ± RBV was well tolerated and achieved high SVR12 (94%) in patients with post-transplant HCV recurrence, including patients with severe liver disease. [ABSTRACT FROM AUTHOR]

Orthotopic liver transplantation ( OLT) with donation after circulatory death ( DCD) often leads to a higher first week peak alanine aminotransferase ( ALT) and a higher rate of biliary nonanastomotic strictures ( NAS) as compared to donation after brain death ( DBD). This retrospective study was to evaluate whether an association exists between peak ALT and the development of NAS in OLT with livers from DBD ( n = 399) or DCD ( n = 97) from two transplantation centers. Optimal cutoff value of peak ALT for risk of development of NAS post- DCD- OLT was 1300 IU/l. The 4-year cumulative incidence of NAS after DCD- OLT was 49.5% in patients with a high ALT peak post- OLT, compared with 11.3% in patients with a low ALT peak. ( P < 0.001). No relation between peak ALT and NAS was observed after DBD- OLT. Multivariate analysis revealed peak ALT ≥1300 IU/l [adjusted hazard ratio ( aHR) = 3.71, confidence interval ( CI) (1.26-10.91)] and donor age [ aHR = 1.04, CI 1.00-1.07] to be independently associated with development of NAS post- DCD- OLT. A peak ALT of <1300 IU/l carries a risk for NAS similar to DBD- OLT. Thus, in DCD- OLT, but not in DBD- OLT, peak ALT discriminates patients at high or low risk for NAS. [ABSTRACT FROM AUTHOR]