The new definition of dominant stricture in primary sclerosing cholangitis: Prevalence and clinical significance.

BACKGROUND AND AIMS: A new definition of dominant stricture (NDS) has recently been defined for patients with primary sclerosing cholangitis (PSC). Prevalence and clinical features of this, compared to traditional dominant stricture (TDS), have not been reported. METHODS: In this single-centre longitudinal prospective cohort study, all PSC patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) between October 2021 and 2022 were recruited. Symptoms of cholestasis, laboratory values (P-alkaline phosphatase, P-Bilirubin), Helsinki PSC-score, brush cytology findings and need for endoscopic therapy (i.e. dilation, stenting) were prospectively collected. RESULTS: Overall, 228 patients with PSC underwent 248 ERCPs. NDS was detected in 43 (17%; 36 patients) and TDS without NDS (TDS group) was detected in 62 (25%; 58 patients) ERCPs, respectively; in the remaining 143 ERCPs, neither TDS nor NDS was seen (no dominant stricture [NoDS] group). PSC duration (median 8 years) and patient's age did not differ between the three groups; males presented more often with NDS. Patients with NDS were more often symptomatic, had higher cholestatic liver enzymes, advanced bile duct disease and markers of biliary inflammation (p < .001). Patients with NDS needed dilation (81%) and stenting (21%) more often than the TDS group (60% and 5%, respectively). Dysplasia in brush cytology was more common in TDS (5%) and NDS (9%) than in NoDS (3%) groups (p = .04), but did not differ between TDS and NDS groups. CONCLUSIONS: Dominant stricture according to the new definition developed in 17% of PSC patients in our cohort and identifies patients with more advanced disease, biliary inflammation and need of endo-therapy.

Endoscopic therapy of sporadic non-ampullary duodenal adenomas, single centre retrospective analysis.

INTRODUCTION: Although sporadic non-ampullary duodenal adenomas (SNADA) are rare, with the risk of progression to cancer, they deserve therapy. Endoscopic therapy of SNADA is effective, but with the increased risk of complications, endotherapy should be performed in high-volume units. The results of endotherapy of SNADA in our unit are presented. PATIENTS AND METHODS: A total of 97 patients with SNADA had endoscopic resection in 2005-2021 and control endoscopies between 3 and 24 months. Snare polypectomy, endoscopic mucosal resection (EMR), endoscopic band ligation (EBL) and endoloop were used (en bloc 37% and piecemeal 63%). In cases of residual/recurrent adenomas, endotherapy was repeated. RESULTS: The median size of the adenoma was 12 (5-60) mm and most polyps were sessile (25%) or flat (65%). Primary endotherapy eradicated adenomas in 57 (59%) cases. Residual and recurrence rates were 24% (n = 23) and 17% (n = 16) with successful endotherapy in 16 (70%) and 13 (81%) patients. Endotherapy was successful in 86 (89%) patients after a median (range) follow-up of 23 (1-166) months. Four out of 11 patients with failed endotherapy had surgery; seven patients were not fit for surgery. There were no disease-specific deaths or carcinoma. Eleven patients (11%) suffered from complications: perforation requiring surgery (n = 1), sepsis (n = 1), postprocedure bleeding (n = 7), cardiac arrest (n = 1) and coronary infarct (n = 1). The thirty-day mortality was zero. Colonoscopy was performed on 67 (69%) patients with neoplastic lesions in 33% patients during follow-up. CONCLUSIONS: Endotherapy of SNADA is effective and safe. Repeat endotherapy in residual and recurrent adenomas is successful. Careful patient selection is mandatory. Abbreviations: ASA: American Society of Anesthesiologist classification; BMI: body mass index; CT: computed tomography; EBL: endoscopic band ligation; EMR: endoscopic mucosal resection; ESD: endoscopic submucosal dissection; ET: endotherapy; FAP: familial adenomatous polyposis; F: female; LST: laterally spreading tumours; M: male; SD: standard deviation; SNADA: sporadic nonampullary duodenal adenoma.

Transpancreatic biliary sphincterotomy versus double guidewire in difficult biliary cannulation: a randomized controlled trial.

BACKGROUND: Difficult biliary cannulation in endoscopic retrograde cholangiopancreatography (ERCP) increases the risk of post-ERCP pancreatitis (PEP). The purpose of this prospective, randomized, multicenter study was to compare two advanced rescue methods, transpancreatic biliary sphincterotomy (TPBS) and a double-guidewire (DGW) technique, in difficult common bile duct (CBD) cannulation. METHODS: Patients with native papilla and planned CBD cannulation were recruited at eight Scandinavian hospitals. An experienced endoscopist attempted CBD cannulation with wire-guided cannulation. If the procedure fulfilled the definition of difficult cannulation and a guidewire entered the pancreatic duct, randomization to either TPBS or to DGW was performed. If the randomized method failed, any method available was performed. The primary end point was the frequency of PEP and the secondary end points included successful cannulation with the randomized method. RESULTS: In total, 1190 patients were recruited and 203 (17.1 %) were randomized according to the study protocol (TPBS 104 and DGW 99). PEP developed in 14/104 patients (13.5 %) in the TPBS group and 16/99 patients (16.2 %) in the DGW group (P = 0.69). No difference existed in PEP severity between the groups. The rate of successful deep biliary cannulation was significantly higher with TPBS (84.6 % [88/104]) than with DGW (69.7 % [69/99]; P = 0.01). CONCLUSIONS: In difficult biliary cannulation, there was no difference in PEP rate between TPBS and DGW techniques. TPBS is a good alternative in cases of difficult cannulation when the guidewire is in the pancreatic duct.

Cost analysis of a long-term randomized controlled study in biliary duct-to-duct anastomotic stricture after liver transplantation.

Multiple plastic stent (MPS) for biliary anastomotic stricture (AS) after liver transplantation requires multiple procedures with consequent costs. To compare the success, adverse events and treatment-related costs of fully covered self-expandable metal stents (FCSEMS) versus MPS. Thirty liver transplant (LT) patients with clinically relevant naïve AS were prospectively randomized to FCSEMS or MPS, with stent numbers increased at 3-month intervals. Treatment costs per patient were calculated for endoscopic retrograde cholangiopancreatography (including all devices and stents) and overall hospital stay. Radiological success was achieved in 73% of FCSEMS (median indwelling period of 6 mos) and 93% of MPS patients (P = NS) (median period of 11 mos). AS recurrence occurred in 36% of FCSEMS and 7% of MPS patients (P = NS), and AS re-treatment was needed in 53% and 13% (P < 0.01), respectively, during follow-up of 60 (34-80) months. Stents migrated after 29% and 2.6% of FCSEMS and MPS procedures, respectively (P < 0.01). Including re-treatments, long-term clinical success was achieved in 28/30 (93%) patients. Overall treatment-related costs were similar between groups. In the subgroup of LT patients in clinical remission after first-line treatment, treatment costs were 41% lower per FCSEMS patient compared with MPS patients. FCSEMS did not perform better than MPS. FCSEMS migration increased the rate of re-treatment and costs.

Impact of paediatric onset primary sclerosing cholangitis on clinical course and outcome of inflammatory bowel disease: a case-control population-based study in Finland.

Introduction and aim: The aim of this study was to investigate the outcome of a paediatric onset of inflammatory bowel disease (IBD) in a cohort of subjects with primary sclerosing cholangitis (PSC) and in a matched-age population-based control group without PSC. Methods: We identified 28 IBD-PSC cases (median age at IBD diagnosis 12.5 years, 25-75th: 10-16 years) and selected three IBD controls for each case matched for age and year of IBD diagnosis. All data regarding the gastrointestinal tract and liver were collected at diagnosis and at last follow-up (median 15 years). Results: At diagnosis the prevalence of pancolitis was similar between the groups (78% and 79%, respectively p = -.30), but histologic inflammation was milder in IBD-PSC (61% vs 30%, p = .06). At last follow-up (median age 29 years) pancolitis was less frequent (6% and 33%, respectively p = .04) and the remission higher (76% and 47%, respectively p = .08) in IBD-PSC patients than in IBD patients. Panproctolectomy (32% in IBD-PSC and 34% in IBD, p = 1.0) and the rate of pouchitis (62% and 70%, respectively p = .8) were similar. Conclusions: The outcome of paediatric onset IBD in patients with PSC in adulthood seems to be comparable to those with IBD only.

The role of magnetic resonance imaging and endoscopic retrograde cholangiography in the evaluation of disease activity and severity in primary sclerosing cholangitis.

BACKGROUND & AIMS: Endoscopic retrograde cholangiography (ERCP) has been considered the gold standard for the diagnosis and follow-up of primary sclerosing cholangitis, but it has been replaced by less invasive magnetic resonance imaging and cholangiopancreatography (MRI-MRCP). However, the role of these two techniques in the evaluation of disease activity and severity needs to be elucidated. METHODS: Patients with primary sclerosing cholangitis (n: 48, male 31, median age: 35.7; 28.0-44.2) who underwent ERCP and MRI-MRCP within ±3 months for diagnosis or follow-up, were reviewed. ERCP and MRI-MRCP images were scored using the modified Amsterdam score. Serum and biliary cytology markers of disease activity and severity were related to the imaging findings. Agreement on the assessment of the ERCP/MRCP score was calculated by kappa-statistics. Spearman's ρ was calculated when appropriate. RESULTS: The agreement between ERCP and MRCP in scoring bile duct changes for disease severity was only moderate (weighted kappa: 0.437; 95% CI: 0.211-0.644 for intra- and 0.512; 95% CI: 0.303-0.720 for extra-hepatic bile ducts). ERCP and MRCP intra-hepatic scores were associated to the surrogate marker alkaline phosphatase (P = .02 for both). A weak correlation between MRCP score for extra-hepatic bile ducts and liver transplantation/death was found (Spearman's ρ = .362, 95% CI: 0.080-0.590, P = .022). A weak correlation between intra- (Spearman's ρ = .322, 95% CI: 0.048-0.551, P = .022) and extra-hepatic (Spearman`s ρ = .319, 95% CI: 0.045-0.549, P = .025) peribiliary enhancement on contrast-enhanced MRI and severity of biliary cytologic classification was found. CONCLUSIONS: The overall agreement between ERCP and MRI-MRCP in assessing disease severity was moderate for intra- and extra-hepatic bile ducts. MRI-MRCP seems to have a minor role as surrogate marker of disease activity and progression in PSC.

Point shear-wave elastography in chronic pancreatitis: A promising tool for staging disease severity.

BACKGROUND: Objectives: ElastPQ®-pSWE is an ultrasound technique developed to stage disease severity in patients with chronic liver diseases. Little data is available about its application to the pancreas. We aimed to assess the feasibility and reproducibility of pancreatic stiffness (PS) measurements in patients with chronic pancreatitis and their relationship with clinical and laboratory data. MATERIAL AND METHODS: 52 consecutive patients with chronic pancreatitis (CP) (40 males; median age 60 years) underwent hepatic and pancreatic pSWE. Liver stiffness was measured by transient elastography, 42 healthy subjects being controls (25 males; median age 54 years). Pancreatic pSWE inter-observer agreement was analyzed by intraclass correlation coefficient (ICC). The effects of clinical, laboratory and US data on PS measurements were evaluated by linear regression. RESULTS: pSWE was feasible in all the CP patients, but one. Pancreatic stiffness was significantly higher in CP patients than healthy controls (4.3 ± SD 2.4 vs. 2.8 ± SD 1.1 kPa, respectively, p = 0.001). Significantly higher values in the CP group were observed in patients with longer disease duration (>10 vs. ≤10 years) (5.8 ± SD 4 vs. 3.9 ± SD 1.5 kPa, respectively, p = 0.01), on chronic analgesic drugs (6.0 vs. 3.5 kPa, p < 0.05) and with lower body weight (p < 0.05, r = -0.38). At multivariate analysis all the three variables resulted independently associated to the pancreatic stiffness value. The ICC for PS was 0.77. CONCLUSIONS: ElastPQ®-pSWE is promising and reproducible in assessing pancreatic stiffness, which mainly reflects disease length and severity. Accordingly, its use is of potential value in stratifying CP patients by identifying those with a more serious degree of disease.

Surveillance of primary sclerosing cholangitis with ERC and brush cytology: risk factors for cholangiocarcinoma.

OBJECTIVE: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease leading to bile duct strictures and fibrosis, and predisposing to cholangiocarcinoma (CCA). Biliary dysplasia is a known precursor of CCA. In our unit, PSC patients undergo regular surveillance with ERC and brush cytology (BC), and liver transplantation is an option in case with biliary dysplasia. We evaluated the risk factors for biliary dysplasia and CCA based on ERC imaging, BC and liver function tests. PATIENTS AND METHODS: Seven hundred and eighty-eight ERCs were performed with BC for 447 PSC patients. ERC images were evaluated using the modified Amsterdam score, neutrophilic inflammation was assessed in BC, and liver function tests were collected. Ploidy analysis with DNA flow cytometry was performed in cases with advanced PSC or previous suspicious BC/aneuploidy. The endpoint was either a benign disease course (follow-up for ≥2.4 years after the latest ERC), benign histology, biliary dysplasia or CCA. RESULTS: Benign disease course was seen in 424/447 (including 23 cases with biliary dysplasia), and CCA in 17 (3.8%) patients. Gallbladder carcinoma/carcinoma in situ was diagnosed in three patients. Advanced ERC findings, male gender, suspicious BC, aneuploidy in flow cytometry, inflammation, and elevation of ALP, bilirubin, ALT, AST, GGT, CEA and CA19-9 represented significant risk factors for CCA in univariate analysis. CONCLUSIONS: PSC patients with advanced bile duct disease and elevated liver enzymes, CEA or CA19-9, inflammation or suspicious BC are most likely to develop CCA. These patients may benefit from surveillance with BC if early liver transplantation is possible.

Screening primary sclerosing cholangitis and biliary dysplasia with endoscopic retrograde cholangiography and brush cytology: risk factors for biliary neoplasia.

BACKGROUND AND STUDY AIMS: Primary sclerosing cholangitis (PSC) is associated with increased risk of biliary dysplasia and cholangiocarcinoma (CCA). The aim of this study was to evaluate the role of early endoscopic retrograde cholangiography (ERC) with systematic brush cytology to identify risk factors associated with biliary neoplasia. PATIENTS AND METHODS: Patients who were referred for their first ERC for suspicion of PSC between January 2006 and October 2011 were included in the study. Brush cytology specimens were scored as benign, suspicious, or malignant. End points were CCA, biliary dysplasia, benign histology, or benign disease course for ≥ 2 years. RESULTS: PSC was diagnosed in 261 patients (125 men, 136 women), most of whom were asymptomatic (n = 211). Cholangiographic changes were mild in 57.1 %. Men presented with advanced disease more often than women. Brush cytology was benign in 243, suspicious in 16, and malignant in 2 patients. Follow-up completed in 249 patients indicated a benign disease course in 232 patients. Seven patients were diagnosed with CCA and eight had biliary dysplasia in the explanted liver. Thus, 15 patients had biliary neoplasia, and suspicious or malignant brush cytology had been detected in 8 of them at initial brushing. Advanced extrahepatic cholangiographic changes with elevated aminotransferases at diagnosis seemed to be associated with increased risk of biliary neoplasia. CONCLUSIONS: Even in mostly asymptomatic patients with PSC, 42.9 % had advanced disease and 6.9 % presented with suspicious or malignant brush cytology at first ERC. Advanced extrahepatic ERC changes with elevated aminotransferases at diagnosis might be risk factors for biliary neoplasia.

Long-term results of combined ESWL and ERCP treatment of chronic calcific pancreatitis.

OBJECTIVE: Extracorporeal shock wave lithotripsy (ESWL) combined with endotherapy (ET) is the standard treatment for pancreatic duct stones (PDS) in chronic pancreatitis (CP). Our aim was to report the short- and long-term results of ESWL and ET. MATERIAL AND METHODS: Consecutively treated 83 patients with symptomatic PDS using ESWL and ET. Success was defined (i) technically: PDS fragmentation and clearance obtained and (ii) clinically: improvement/resolution of pain. To get information on quality of life, we conducted a phone survey whereby we contacted 64 (89%) patients. The long-term results are presented in those patients with ≥2 years follow-up. RESULTS: Treated PDS with median size of 10 (5-25) mm were located in the head, body, or the tail of the pancreas in 78, 4, and 1 patients, respectively. The primary results were that technical success was achieved in 69 patients (83%) and clinical success in 66 patients (80%). Fourteen patients had technical failure, but eight of them became free of pain. Thus, clinical success can be considered to have been achieved in 74 of 83 patients (89%). In patients with persistent pseudocyst (PC) at the time of ESWL (n = 19), the PC disappeared in a year in 14 patients (74%). The long-term results were obtained from 61 (73%) ESWL- and ET-treated patients. The median follow-up for them was 53 months (range: 24-124) and 57 patients (93%) became pain-free or had less pain. CONCLUSIONS: For patients with CP and PDS ESWL combined with ET is an effective and safe treatment giving favorable long-term results.

Environmental Risk Factors of Pediatric-Onset Primary Sclerosing Cholangitis and Autoimmune Hepatitis.

OBJECTIVES: The aim of this population-based observational case-control questionnaire study was to investigate the possible role of environmental risk factors associated with pediatric-onset autoimmune liver diseases. METHODS: Seventy-one patients with autoimmune liver diseases (<16 years) received a questionnaire with 22 items, evaluating contact with environmental factors (eg, family manners, type of housing, pets) before the diagnosis. Two age- and sex-matched control groups were used: inflammatory bowel disease (IBD; n = 91) and healthy subjects (n = 716; matched also for place of residence at birth). Univariate analysis (odds ratio [OR] and 95% confidence interval) for all variables was calculated. Fisher exact test was performed to depict associations between variables and the multivariate logistic regression to test their interactions. RESULTS: In the final analyses, the responses of 51 autoimmune liver diseases cases (n = 51/71, 72%), 59 IBD controls (n = 59/91, 65%), and 292 healthy controls (n = 292/716, 41%) were investigated. In univariate analysis only having a cat, a dog, and a cat or a dog were risk factors of autoimmune liver diseases (OR varying between 2.6-3.4); no other significant associations (eg, place of residence, number of siblings, family manners) were found. Multivariate logistic regression analyses showed that especially living with a cat in block of flats was a risk factor (OR 3.6, 1.2-10.8). CONCLUSIONS: Living in a close contact with a pet (especially a cat) was a risk factor of autoimmune liver diseases. This finding may suggest an involvement of an unidentified agent (ie, toxin/microbe) among the triggers of these diseases.

Health-related quality of life among patients with primary sclerosing cholangitis.

BACKGROUND & AIMS: To assess health-related quality of life (HRQoL) of patients with primary sclerosing cholangitis (PSC), and to compare it with that of the general population. Also, to examine changes in HRQoL in newly diagnosed PSC patients at a follow-up 1-2 years later, and to compare their HRQoL with HRQoL of newly diagnosed inflammatory bowel disease (IBD) patients. Furthermore, sources of and need for disease-related information among PSC patients were surveyed. METHODS: Primary sclerosing cholangitis patients filled in the survey questionnaire when attending an endoscopic retrograde cholangiography examination. The 15D served as a general HRQoL instrument. The follow-up questionnaire was mailed to the newly diagnosed patients 1-2 years later. RESULTS: No significant difference was seen in 15D scores between PSC patients and general population, but the dimensions of excretion (P < 0.001), depression (P = 0.003), distress (P = 0.003) and vitality (P = 0.005) were significantly lower in PSC. Age and symptoms affected HRQoL but severity of biliary changes did not. Those with newly diagnosed IBD had lower 15D scores than those with PSC. No significant changes were observed in 15D scores of new PSC patients in the follow-up. Many patients were dissatisfied with information received. CONCLUSION: Newly diagnosed PSC patients have better HRQoL than do IBD patients, and no significant HRQoL changes were observed in the mean follow-up of 1.58 years after PSC diagnosis. ERC findings did not correlate with HRQoL or symptoms. HRQoL of PSC patients was mostly comparable with that of general population, but special attention should be paid to patients' psychological well-being.

Dominant stricture in paediatric-onset primary sclerosing cholangitis is associated with impaired prognosis in a long-term follow-up.

BACKGROUND AND OBJECTIVES: The impact of dominant stricture (DS) on the outcomes of paediatric-onset primary sclerosing cholangitis (PSC) is unknown. This study was aimed at investigating the impact of DS on the clinical course and prognosis of patients with paediatric-onset PSC. METHODS: Patients with paediatric-onset PSC diagnosed between January 1993 and May 2017 were identified from hospital records or our PSC registry. Data including clinical, laboratory, cholangiography, and cytology at diagnosis and during follow-up (until July 2023) were reviewed. We graphed the Kaplan-Meier failure function and fitted crude and multivariable Cox model to calculate hazard ratios (HR) and 95% confidence intervals (CI) for selected variables. In these analyses, DS was treated as a time-varying variable. RESULTS: We identified 68 patients (42 males) with paediatric-onset PSC (median age at diagnosis 15 years). The median follow-up was 13 years and the median age at the last follow-up was 27 years. In total, 35 (51%) had concomitant autoimmune hepatitis. DS was diagnosed in 33 patients (48%): in eight at the time of PSC diagnosis (12%) and in 25 (37%) by the end of follow-up. In patients with DS, two developed cirrhosis, seven were transplanted and one patient was operated for a biliary mass with low-grade dysplasia. In patients without a DS, two developed cirrhosis, and four were transplanted; one female was excluded from survival analysis because she already had cirrhosis at the time of PSC diagnosis. Cirrhosis or biliary dysplasia or needing liver transplantation for these indications were more frequent after the development of DS (10/33, adjusted HR 4.26, 95%CI: 1.26-14.4). No cholangiocarcinomas or deaths occurred during the follow-up. CONCLUSIONS: DS was present at diagnosis or developed during follow-up in about half of the patients with paediatric-onset PSC and was associated with impaired outcome.

NGS of brush cytology samples improves the detection of high-grade dysplasia and cholangiocarcinoma in patients with primary sclerosing cholangitis: A retrospective and prospective study.

BACKGROUND: Biliary dysplasia, a precursor of cholangiocarcinoma (CCA), is a common complication of primary sclerosing cholangitis. Patients with high-grade dysplasia (HGD) or early CCA who have received oncological treatment are candidates for liver transplantation. The preoperative diagnosis of CCA or HGD is challenging, and the sensitivity of biliary brush cytology (BC) is limited. METHODS: By using next-generation sequencing (NGS), we retrospectively analyzed archived tissue samples (n=62) obtained from explanted liver tissue and CCA samples to identify oncogenic mutations that occur during primary sclerosing cholangitis carcinogenesis. BC samples were prospectively collected from patients with primary sclerosing cholangitis (n=97) referred for endoscopic retrograde cholangiography to measure the diagnostic utility of NGS combined with BC compared with traditional cytology alone. RESULTS: Mutations in KRAS, GNAS, FLT3, RNF43, TP53, ATRX, and SMAD4 were detected in archived CCA or HGD samples. KRAS, GNAS, TP53, CDKN2A, FBXW7, BRAF, and ATM mutations were detected in prospectively collected brush samples from patients with histologically verified CCA or HGD. One patient with low-grade dysplasia in the explanted liver had KRAS and GNAS mutations in brush sample. No mutations were observed in brush samples or archived tissues in liver transplantation cases without biliary neoplasia. While KRAS mutations are common in biliary neoplasms, they were also observed in patients without biliary neoplasia during surveillance. CONCLUSIONS: In summary, NGS of BC samples increased the sensitivity of detecting biliary neoplasia compared with traditional cytology. Performing NGS on BC samples may help diagnose HGD or early CCA, benefiting the timing of liver transplantation.

Magnetic resonance cholangiography in the diagnosis of dominant strictures in pediatric-onset primary sclerosing cholangitis.

BACKGROUND: Magnetic resonance cholangiopancreaticography (MRCP) has become the primary imaging modality in primary sclerosing cholangitis (PSC). Endoscopic retrograde cholangiopancreaticography (ERCP) is recommended when a dominant stricture (DS) of bile ducts is suspected in MRCP. However, MRCP criteria for DS are lacking. AIMS: To evaluate the diagnostic accuracy of MRCP in the diagnosis of DS in patients with pediatric-onset PSC. METHODS: ERCP and MRCP images of patients with pediatric-onset PSC (n=36) were evaluated for the presence of DS applying the diameter-based ERCP criteria. The diagnostic accuracy of MRCP in detecting DS was calculated using ERCP as the gold standard. RESULTS: The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and accuracy of MRCP for detecting DS were 62%, 89%, 5.6, 0.43, and 81%. Most common reasons for incongruent ERCP/MRCP assessment were (1) MRCP stenosis not fulfilling the diameter criteria of ERCP, resulting in false negative MRCP evaluation, and (2) lack of filling pressure in MRCP, resulting in false positive MRCP evaluation. CONCLUSION: The high positive likelihood ratio of MRCP in detecting DS suggests that MRCP is a useful tool in the follow-up of PSC. However, diameter limits of DS should probably be less strict in MRCP than in ERCP.

Occupational radiation dose from gastrointestinal endoscopy procedures with special emphasis on eye lens doses in endoscopic retrograde cholangiopancreatography.

Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) procedures may result in remarkable radiation doses to patients and staff. The aim of this prospective study was to determine occupational exposures in gastrointestinal endoscopy procedures, with a special emphasis on eye lens dose in ERCP. Methods Altogether 604 fluoroscopy-guided procedures, of which 560 were ERCPs belonging to four American Society for Gastrointestinal Endoscopy procedural complexity levels, were performed using two fluoroscopy systems. Personal deep-dose equivalent H p (10), shallow-dose equivalent H p (0.07), and eye lens dose equivalent H p (3) of eight interventionists and H p (3) for two nurse dosimeters were measured. Thereafter, conversion coefficients from kerma-area product (KAP) for H p (10), H p (0.07), and H p (3) were determined and dose equivalents per procedure to an operator and assisting staff were estimated. Further, mean conversion factors from H p (10) and H p (0.07) to H p (3) were calculated. Results The median KAP in ERCP was 1.0 Gy·cm 2 , with mobile c-arm yielding higher doses than a floor-mounted device ( P  < 0.001). The median H p (3) per ERCP was estimated to be 0.6 µSv (max. 12.5 µSv) and 0.4 µSv (max. 12.2 µSv) for operators and assisting staff, respectively. The median H p (10) and H p (0.07) per procedure ranged from 0.6 to 1.8 µSv. ERCP procedural complexity level ( P  ≤ 0.002) and interventionist ( P  < 0.001) affected dose equivalents. Conclusions Occupational dose limits are unlikely to be exceeded in gastrointestinal endoscopy practice when following radiation-hygienic working methods and focusing on dose optimization. The eye lens dose equivalent H p (3) may be estimated with sufficient agreement from the H p (10) and H p (0.07).

PNPLA3 allele frequency has no impact on biliary bile acid composition or disease course in patients with primary sclerosing cholangitis.

BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease that leads to bile duct strictures, cholestasis, and biliary cirrhosis. PNPLA3 (patatin-like phospholipase domain containing 3), regulates cellular lipid synthesis by converting lysophosphatidic acid into phosphatidic acid. Isoleucine mutation to methionine at position 148 (I148M) causes a loss of this function. Only two studies, with contradictory results, have evaluated the role of PNPLA3 in PSC. The rs738409(G) variant of PNPLA3 has been associated with an increased risk for transplantation in male patients with dominant strictures (DS). The study aimed to evaluate the PNPLA3 allele frequency effect on the clinical outcomes, progression, and prognosis of PSC. Furthermore, we analyzed the impact of PNPLA3 on phospholipid and bile acid composition to evaluate the effect of the PNPLA3 status on UDCA response. PATIENTS AND METHODS: We recruited 560 patients prospectively and collected clinical and laboratory data as well as liver histology and imaging findings. PNPLA3 (CC, CG, GG) alleles were analyzed with TaqManTM. We also analyzed bile acids (BA), cholesterol and phospholipids and individual BA from a sample aspirated during endoscopic retrograde cholangiography (ERC). RESULTS: Among the recruited patients, 58.4%, 35.7% and 5.9% had the wild (CC), heterozygous (CG) and homozygous (GG) alleles, respectively. The PNPLA3 haplotype did not impact bile composition or individual BA. In addition, we found no differences in age at diagnosis, disease progression, liver fibrosis or survival between the cohorts. CONCLUSIONS: The PNPLA3 I148M variant had no significant impact on on bile composition, including UDCA content, clinical outcomes, progression of liver fibrosis, hepatobiliary cancer risk, liver transplantation, or overall survival.

Quantitative bile and serum proteomics for the screening and differential diagnosis of primary sclerosing cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by biliary strictures, cholestasis, and a markedly increased risk of cholangiocarcinoma. New markers for the screening and differential diagnosis of PSC are needed. In this pilot study, we have analyzed both the bile and serum proteomic profiles of 80 PSC patients and non-PSC controls (n = 6 for bile and n = 18 for serum). AIM: The aim of this study was to discover candidates for new biomarkers for the differential diagnosis of PSC. METHODS: Bile and serum samples were processed and subsequently analyzed using ultra performance liquid chromatography-ultra definition mass spectrometry (UPLC-UDMSE). Further analysis included statistical analyses such as receiver operating characteristic curve analysis as well as pathway analysis using Ingenuity Pathway Analysis. RESULTS AND CONCLUSIONS: In bile, we discovered 64 proteins with significantly different levels between the groups, with fold changes of up to 129. In serum, we discovered 112 proteins with significantly different levels. Receiver operating characteristic curve analysis found multiple proteins with high area under the curve values, up to 0.942, indicating that these serum proteins are of value as new non-invasive classifiers of PSC. Pathway analysis revealed multiple canonical pathways that were enriched in the dataset, which have roles in bile homeostasis and metabolism. We present several serum proteins that could serve as new blood-based markers for the diagnosis of PSC after further validation. The measurement of serum levels of these proteins could be of use in the screening of patients with suspected PSC.

Diagnostic yield of 96-h wireless pH monitoring and usefulness in patients' management.

OBJECTIVE: To get insight into usefulness of 96-h wireless monitoring in diagnosis of gastro-esophageal reflux disease (GERD) and in patients' management. MATERIAL AND METHODS: 51 patients who underwent 96-h wireless and 51 matched patients who underwent 24-h traditional pH monitoring were enrolled and retrospectively contacted with a structured telephone interview. RESULTS: In the wireless group, the 96-h recording improved (p < 0.05) the diagnostic yield compared with the first 48-h recording by allowing Symptom Association Probability to be measured in eight more patients and by decreasing indeterminate tests from 11 to 5. After pH monitoring, concordance between results of the test and treatment for GERD was higher in the wireless compared with the traditional group, 78% versus 58% of the patients (p < 0.05). Both improvement/disappearance of the clinically relevant symptom and satisfaction (score of 1-10) at time of the telephone interview were however similar in the two groups, 73% versus 65% and 7.0 versus 6.5. CONCLUSIONS: Wireless pH monitoring prolonged to 96 h increased the likelihood to exclude/confirm GERD as the cause of the clinically relevant symptoms in those patients with an indeterminate result for GERD after the first 48 h. Outcome was however similar to the one of traditional pH monitoring.

Use of thiopurines is not a risk factor for post-ERC pancreatitis in patients with primary sclerosing cholangitis.

INTRODUCTION: Risk of post-ERC pancreatitis (PEP) in patients with primary sclerosing cholangitis (PSC) is 1-7.8%. PSC is often associated with inflammatory bowel disease and autoimmune hepatitis, which are usually treated with thiopurines. The role of thiopurines in PEP risk is still unclear. AIMS AND METHODS: We evaluated the thiopurine use in PEP. The data of 354 PSC patients who underwent 985 ERCs between 2009 and 2018 were collected. 177 patients treated with thiopurines (study group, SG) and 177 controls (CG) were matched with a propensity score (PSM). Odds ratios (ORs) with 95% confidence interval (95% CI) were calculated. Multivariable logistic regression analysis and generalized linear mixed model were performed. The P-value <0.05 was significant. RESULTS: In matched data, 472 ERCs were performed in SG and 513 in CG. Thiopurines were used in 373/472 (79.0%) ERCs in SG. The PEP rate was 5.3% in SG and 5.7% in CG (p = 0.889). Unintentional pancreatic duct cannulation (OR 1.28, 95%CI 1.07-1.51, p = 0.004), and periampullary diverticulum (OR 4.87, 95%CI 1.72-11.98, p = 0.001) increased the risk of PEP. CONCLUSION: Prior or present thiopurine use did not increase the risk of PEP.