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).

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.

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.

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.

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.

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.

Diclofenac does not reduce the risk of acute pancreatitis in patients with primary sclerosing cholangitis after endoscopic retrograde cholangiography.

BACKGROUND: The European Society of Gastrointestinal Endoscopy recommends rectal indomethacin or diclofenac before endoscopic retrograde cholangiopancreatography (ERCP) to prevent post-ERCP pancreatitis. However, data on the prophylactic effect in patients with primary sclerosing cholangitis (PSC) are lacking. METHODS: This was a retrospective case-control study. In 2009-2018, a total of 2000 ERCPs were performed in 931 patients with PSC. Case procedures (N = 1000 after November 2013) were performed after administration of rectal diclofenac. Control procedures (N = 1000 before November 2013) were performed with the same indication but without diclofenac. Acute post-ERCP pancreatitis and other ERCP-related adverse events (AEs) were evaluated. RESULTS: Post-ERCP pancreatitis developed in 49 (4.9%) procedures in the diclofenac group and 62 (6.2%) procedures in the control group (p = 0.241). No difference existed between the groups in terms of the severity of pancreatitis or any other acute AEs. The risk of pancreatitis was elevated in patients with native papilla: 11.4% in the diclofenac group and 8.7% in the control group (p = 0.294). In adjusted logistic regression, diclofenac did not reduce the risk of pancreatitis (odds ratio (OR) = 1.074, 95% confidence interval 0.708-1.629, p = 0.737). However, in generalised estimation equations with the advanced model, diclofenac seemed to diminish the risk of pancreatitis (OR = 0.503) but not significantly (p = 0.110). CONCLUSION: In this large patient cohort in a low-risk unit, diclofenac does not seem to reduce the risk of post-ERCP pancreatitis in patients with PSC. The trend in the pancreatitis rate after ERCP is decreasing. The evaluation of the benefits of diclofenac among PSC patients warrants a randomised controlled study targeted to high-risk patients and procedures.

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.

Yield of prolonged wireless pH monitoring in achalasia patients successfully treated with pneumatic dilation.

BACKGROUND: Gastro-oesophageal reflux disease (GORD) is a long-term complication of achalasia treatments. The aim of our study was to evaluate the yield of prolonged wireless pH monitoring in patients with successfully treated achalasia and its influence on proton pump inhibitor (PPI) use. METHODS: Twenty-five patients with achalasia who underwent prolonged wireless pH monitoring after a successful treatment with pneumatic dilation were enrolled. pH variables were analysed in the first 24 hours of monitoring to determine if tracings were indicative of GORD; the same variables were analysed in the following 24-hour period in order to obtain a worst-day diagnosis of GORD. PPI therapy before and after the test was recorded. RESULTS: Five out of 25 patients had GORD diagnosis during the first day of monitoring and four of them had oesophagitis at endoscopy. During the following days of monitoring four more patients had a diagnosis of GORD. Out of the 25 patients, PPIs were started after the test in six asymptomatic GORD-positive ones, whereas prescription of PPIs was stopped without detrimental effect on symptoms in three GORD-negative patients. CONCLUSIONS: Prolonged wireless pH monitoring is a useful test to be added to endoscopy in order to evaluate GORD and to optimise antisecretory treatment in successfully treated achalasia patients.

Esophageal chemical clearance and baseline impedance values in patients with chronic autoimmune atrophic gastritis and gastro-esophageal reflux disease.

BACKGROUND: The factors influencing new markers of gastro-esophageal reflux disease detected by impedance-pH monitoring - mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave (PSPW) index - need to be evaluated. AIM: To compare endoscopy-negative heartburn with chronic autoimmune atrophic gastritis (CAAG). MATERIALS AND METHODS: 24 patients with CAAG, 25 with non-erosive reflux disease (NERD) and 25 with functional heartburn (FH) were included. In all patients the main impedance-pH monitoring parameters were calculated. RESULTS: CAAG and NERD patients had a number of reflux events (non-acid ones being more common among the former group) which was higher than that found in FH (p<0.001). MNBI decreased progressively in FH (>3000Ohm), CAAG (>2000Ohm) and NERD (<1000Ohm) patients (p=0.0046). The PSPW index was similar between CAAG and NERD patients but significantly lower in comparison to FH (p<0.0001). CONCLUSION: Patients with CAAG have evidence of non-acid reflux based on the high number of reflux events and confirmed by low values of MNBI and PSPW index. MNBI is a strong marker of acid/non-acid reflux-induced mucosal damage, whereas the PSPW index can reliably discriminate patients with reflux from those with FH, independently of the acidity of refluxate.

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.

Clinical course and prognosis of pediatric-onset primary sclerosing cholangitis.

BACKGROUND: The natural history of pediatric-onset primary sclerosing cholangitis (PSC) and overlap with autoimmune hepatitis (PSC/AIH) is poorly known. OBJECTIVE: The aim of this study was to evaluate the clinical outcome of patients with pediatric-onset disease in a tertiary referral center. METHODS: We traced 33 patients (median age at diagnosis 16 years), with PSC or PSC/AIH in cholangiography and liver histology diagnosed between December 1993 and 2011, at Helsinki University Hospital. Diagnostic procedures and long-term follow-up were reassessed until the end of December 2013. RESULTS: PSC was confirmed in all 33 patients; 19 of them had an overlap with AIH. At diagnosis, three of 33 had cirrhosis. Inflammatory bowel disease (IBD) was associated in 76% of the patients, mostly ulcerative colitis (70%); treatment of IBD being a minor determinant of the clinical outcome of liver disease. In the last follow-up (median nine years), all patients were alive, and no malignancy occurred. Most patients (91%) were on ursodeoxycholic acid and 12 PSC/AIH patients on immunosuppression. Endoscopic retrograde cholangiography during follow-up showed a progression of intra-hepatic disease in 12 patients (36%). Four patients (12%) had undergone liver transplantation, and one was listed; no recurrence of the disease in the graft was seen. CONCLUSION: The clinical course and outcome of pediatric-onset PSC and PSC/AIH seem to be favourable in the majority of patients until early adulthood. In about one-third of patients, however, PSC is progressive, challenging the current treatment guidelines and warranting further studies on disease pathogenesis.

A case of pseudoachalasia hiding a malignant pleural mesothelioma.

PURPOSE: Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. We describe a case of MPM with an uncommon onset, characterized by pseudoachalasia as demonstrated with high-resolution manometry (HRM). METHODS: A 56-year-old man was referred to our hospital reporting worsening dysphagia. On the hypothesis of an esophageal motor disorder, the patient was referred for an HRM examination, which revealed features consistent with a diagnosis of type II achalasia. RESULTS: At the time of the first pneumatic dilation the endoscopist stopped the procedure in order to prevent perforation when he noticed only partial expansion of the pneumatic balloon. A CT scan and subsequent CT-guided excisional biopsy revealed an epithelioid pleural mesothelioma infiltrating the muscle wall. Given his good clinical condition, the patient was eligible for chemotherapy with cisplatin 75 mg/m2 and pemetrexed 500 mg/m2, resulting in a good response with partial remission of the disease and resolution of the dysphagia symptoms. CONCLUSIONS: Pseudoachalasia as the first or only manifestation of mesothelioma is a rare occurrence that may expose patients to the risk of diagnostic delay. Close attention should be paid whenever a patient with symptoms and signs consistent with achalasia shows unusual features.

Covered metal stents in endoscopic therapy of biliary complications after liver transplantation.

There is growing interest in using covered self-expandable metal stents for the treatment of benign biliary conditions, and the presence of anastomotic biliary strictures and leaks after liver transplantation provide a valuable opportunity for testing them. The performance of the stents is encouraging, and the technical success rate is high. They provide larger diameter dilation and are easily removed, and can potentially limit costs by reducing the number of procedures needed to treat anastomotic biliary strictures. However, drawbacks such as sub-optimal tolerability and migration may affect both patient management and costs. New stent designs are currently being evaluated. Randomized controlled trials and cost-effectiveness analyses comparing covered metal stents with multiple plastic stent endotherapy are warranted in order to define the role of the former as first-line or rescue treatment.