-
Journal of Hepatology Sep 2021Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many... (Meta-Analysis)
Meta-Analysis
BACKGROUNDS & AIMS
Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening.
METHODS
We combined new and existing genotype data for 10,516 cases and 20,772 controls from 5 European and 2 East Asian cohorts.
RESULTS
We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57 genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, which each play key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, JAK-STAT signalling, and differentiation of T helper (T)1 and T17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some of which are well-established in the treatment of other autoimmune disorders.
CONCLUSIONS
This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders.
LAY SUMMARY
Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10,516 people with PBC and 20,772 healthy individuals recruited in Canada, China, Italy, Japan, the UK, or the USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these 'candidate genes' to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC.
Topics: Genome-Wide Association Study; Humans; Liver Cirrhosis, Biliary
PubMed: 34033851
DOI: 10.1016/j.jhep.2021.04.055 -
Gut Oct 2023In up to 20% of patients, the aetiology of acute pancreatitis (AP) remains elusive and is thus called idiopathic. On more detailed review these cases can often be...
OBJECTIVE
In up to 20% of patients, the aetiology of acute pancreatitis (AP) remains elusive and is thus called idiopathic. On more detailed review these cases can often be explained through biliary disease and are amenable to treatment. Findings range from biliary sludge to microlithiasis but their definitions remain fluid and controversial.
DESIGN
A systematic literature review (1682 reports, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines) analysed definitions of biliary sludge and microlithiasis, followed by an online international expert survey (30 endoscopic ultrasound/hepatobiliary and pancreatic experts; 36 items) which led to definitions of both. These were consented by Delphi voting and clinically evaluated in a retrospective cohort of patients with presumed biliary pancreatitis.
RESULTS
In 13% of original articles and 19.2% of reviews, microlithiasis and biliary sludge were used synonymously. In the survey, 41.7% of experts described the term 'sludge' and 'microlithiasis' as identical findings. As a consequence, three definitions were proposed, agreed on and confirmed by voting to distinctly discriminate between biliary sludge (hyperechoic material without acoustic shadowing) and microlithiasis (echorich calculi of ≤5 mm with acoustic shadowing) as opposed to larger biliary stones, both for location in gallbladder and bile ducts. In an initial attempt to investigate the clinical relevance in a retrospective analysis in 177 confirmed cases in our hospital, there was no difference in severity of AP if caused by sludge, microlithiasis or stones.
CONCLUSION
We propose a consensus definition for the localisation, ultrasound morphology and diameter of biliary sludge and microlithiasis as distinct entities. Interestingly, severity of biliary AP was not dependent on the size of concrements warranting prospective randomised studies which treatment options are adequate to prevent recurrence.
Topics: Humans; Pancreatitis; Retrospective Studies; Prospective Studies; Acute Disease; Consensus; Gallstones
PubMed: 37072178
DOI: 10.1136/gutjnl-2022-327955 -
Annals of Medicine and Surgery (2012) Apr 2021POPF derives from the pancreatic stump, which follows pancreatic resection and the pancreatoenteric anastomosis following pancreaticoduodenectomy. Since 1978 sealants... (Review)
Review
BACKGROUND
POPF derives from the pancreatic stump, which follows pancreatic resection and the pancreatoenteric anastomosis following pancreaticoduodenectomy. Since 1978 sealants have been used in pancreatic surgery to prevent pancreatic fistula after resection of the pancreatic head and tail or for the management of trauma and the treatment of low-output pancreatic fistula. Different types of fibrin sealants have been evaluated for their potential to reduce the occurrence of POPF.
METHODS
A systematic search of the electronic literature was performed using PubMed, Cochrane Library, and Scopus databases to obtain access to all publications, especially clinical trials, randomised controlled trials, and systematic reviews concerning fibrin sealants pancreatic surgery. Searching for "fibrin sealants pancreas," we found a total of 73 results on Pubmed, 61 on Scopus, and 14 on Cochrane Library (148 total results).
RESULTS
Eighteen studies were found on literature, following the criteria already described, concerning the use of fibrin sealants in pancreatic surgery. All articles described were published in the period between 1989 and 2019.Most of these were single centre studies. A total of 1032 patients were enrolled in this review. In the studies, sealants were used to reinforce pancreatic anastomoses and for the occlusion of the main pancreatic duct.
CONCLUSION
CR-POPF is a fearful complication of pancreatic surgery; among the possible solutions to reduce the risk of onset, sealants were used on the pancreatic stump; today the sealants should be considered such as an option to reduce the CR-POPF, but the routine use in clinical practice has to be validated.
PubMed: 33898024
DOI: 10.1016/j.amsu.2021.102244 -
International Journal of Surgery... Dec 2016Duct-to-mucosa and invagination are two commonly used techniques of pancreaticojejunostomy (PJ) after pancreaticoduodenectomy. Previously, we conducted a systematic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Duct-to-mucosa and invagination are two commonly used techniques of pancreaticojejunostomy (PJ) after pancreaticoduodenectomy. Previously, we conducted a systematic review comparing the safety and efficacy of the two PJ techniques. Here, we added new evidence and updated our previous conclusion.
METHODS
We systematically searched multiple databases and included randomized controlled trials (RCTs) comparing duct-to-mucosa and invagination techniques of PJ. The quality of evidence was assessed using Jadad score, and reporting bias was evaluated using funnel plots. Meta-analysis was performed using a random-effects model. Risk ratio (RR) and 95% confidence interval (CI) were calculated. The primary outcome was pancreatic fistula, and the secondary outcomes included mortality, reoperation, morbidity and postoperative hospital stay. Trial sequential analysis was performed to calculate the required information size.
RESULTS
Seven RCTs with 850 participants were included. No significant difference was detected in the rates of pancreatic fistula (RR 0.98, 95% CI 0.63 to 1.53), mortality (RR 0.94, 95% CI 0.40 to 2.18), reoperation (RR 1.23, 95% CI 0.69 to 2.20) and morbidity (RR 0.98, 95% CI 0.82 to 1.16) between the two groups. However, patients who underwent duct-to-mucosa PJ had a significantly shorter postoperative hospital stay (mean difference -2.80, 95% CI -5.08 to -0.52). Trial sequential analysis showed that another 279 participants were needed for conclusive results.
CONCLUSIONS
Given the current evidence, duct-to-mucosa PJ did not decrease the rates of pancreatic fistula and other adverse events as compared to invagination PJ; however, it did reduce postoperative hospital stay. Further RCTs are needed.
Topics: Anastomosis, Surgical; Humans; Intestinal Mucosa; Length of Stay; Mortality; Pancreatic Ducts; Pancreatic Fistula; Pancreaticoduodenectomy; Pancreaticojejunostomy; Postoperative Complications; Randomized Controlled Trials as Topic; Reoperation; Safety
PubMed: 27826046
DOI: 10.1016/j.ijsu.2016.11.008 -
Translational Gastroenterology and... 2017The prevalence of pancreatic cystic echinococcosis (PCE) in the world is low ranging between 0.2% and 0.6%. The diagnosis of PCE is easy when it is associated to other... (Review)
Review
The prevalence of pancreatic cystic echinococcosis (PCE) in the world is low ranging between 0.2% and 0.6%. The diagnosis of PCE is easy when it is associated to other location such as liver, it became difficult when PCE was isolated simulating other diagnosis such as pseudocyst, a choledochal cyst, serous or mucinous cystadenoma and cystadenocarcinoma. This systematic review aimed to provide evidence-based answer to the following questions: (I) what are the efficient tools to affirm the diagnosis of isolated PCE and (II) what are the best therapeutic strategy for the PCE? An electronic search was performed by two authors (W Dougaz, I Bouasker). Medline, Scopus, Embase, Web of Science, Google Scholar and Cochrane collaboration were consulted. The keywords used were "cyst", "echinococcosis", "hydatid cyst" and "pancreas". All abstracts were analyzed followed by extraction of the full text by the same two authors (W Dougaz, I Bouasker), all divergences were resolved by discussion with C Dziri. Recommendations were based on Oxford's classification: (I) what are the efficient tools to affirm the diagnosis of PCE? -ultrasound remains the cornerstone of diagnosis. Magnetic resonance imaging (MRI) reproduces the ultrasound defined features of CE better than computed tomography (CT). MRI with heavily T2-weighted series is preferable to CT. Pancreatic duct MRI should be promising to identify a fistula between PCE and pancreatic duct (level of evidence 3-recommendation B); (II) what are the best therapeutic strategy for the PCE? -surgery is the main treatment of PCE. Open approach is validated. The decision depends of the location of PCE: head body and/or tail of the pancreas (level of evidence 5-recommendation D): for the head of the pancreas, the tendency is toward conservative surgery. For body and/or tail of the pancreas, the tendency is toward radical surgery. Medical treatment (albendazole) should be prescribed 1 week before surgery and 2 months during postoperative period (level II evidence and grade C recommendation).
PubMed: 29354762
DOI: 10.21037/tgh.2017.11.13 -
Endoscopy International Open Sep 2022Placement of a covered (C)-self-expandable metal stent (SEMS) has been recently investigated as an alternative endoscopic treatment for main pancreatic duct stricture... (Review)
Review
Placement of a covered (C)-self-expandable metal stent (SEMS) has been recently investigated as an alternative endoscopic treatment for main pancreatic duct stricture (MPDS) in chronic pancreatitis. Our aim was to carry out a systematic review and meta-analysis of studies quantifying efficacy and safety of C-SEMSs in the management of MPDS. A multiple database search was performed, including MEDLINE, Embase and Cochrane Library, from January 2000 to September 2020, to identify studies reporting the efficacy and safety of C-SEMSs in patients with MPDS. Stricture and pain resolution were investigated. Other outcomes included technical success, stent migration, stricture recurrence and need for repeated stent placement. Pancreatitis, severe abdominal pain requiring stent removal and de-novo stricture were recorded as complications. Nineteen studies were identified, which included a total of 300 patients. C-SEMSs showed a pooled stricture resolution rate of 91 % [95 % confidence interval (CI), 85 %-96 %] and a pooled pain resolution rate of 92 % (95 % CI, 85 %-98 %). The pooled proportion for stricture recurrence was equal to 6 % (95 % CI, 1 %-14 %), while stent migration occurred in 33 of 300 patients, the pooled proportion being 7 % (95 % CI 1 %-15 %). The pooled mean stent duration was 133 days (95 % CI, 100-166 days). The most common complication was pancreatitis (3 %, 95 % CI 0 %-8 %), while de-novo stricture pooled proportion was 2 % (95 % CI, 0 %-5 %). C-SEMSs are effective and safe in the treatment of MPDS. However, there is a significant need for further high-quality, well-designed studies to produce evidence-based data on short and long-term efficacy, safety, costs of C-SEMSs, and also optimal stent duration.
PubMed: 36118636
DOI: 10.1055/a-1880-7430 -
Histopathology Sep 2022Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is a recently recognized pancreatic tumor entity. Here we aimed to determine the most important features with... (Review)
Review
AIMS
Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is a recently recognized pancreatic tumor entity. Here we aimed to determine the most important features with a systematic review coupled with an integrated statistical approach.
METHODS AND RESULTS
PubMed, SCOPUS, and Embase were searched for studies reporting data on pancreatic ITPN. The clinicopathological, immunohistochemical, and molecular data were summarized. Then a comprehensive survival analysis and a comparative analysis of the molecular alterations of ITPN with those of pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) from reference cohorts (including the International Cancer Genome Consortium- ICGC dataset and The Cancer Genome Atlas, TCGA program) were conducted. The core findings of 128 patients were as follows: (i) Clinicopathological parameters: pancreatic head is the most common site; presence of an associated adenocarcinoma was reported in 60% of cases, but with rare nodal metastasis. (ii) Immunohistochemistry: MUC1 (>90%) and MUC6 (70%) were the most frequently expressed mucins. ITPN lacked the intestinal marker MUC2; unlike IPMN, it did not express MUC5AC. (iii) Molecular landscape: Compared with PDAC/IPMN, the classic pancreatic drivers KRAS, TP53, CDKN2A, SMAD4, GNAS, and RNF43 were less altered in ITPN (P < 0.001), whereas MCL amplifications, FGFR2 fusions, and PI3KCA mutations were commonly altered (P < 0.001). (iv) Survival analysis: ITPN with a "pure" branch duct involvement showed the lowest risk of recurrence.
CONCLUSION
ITPN is a distinct pancreatic neoplasm with specific clinicopathological and molecular characteristics. Its recognition is fundamental for its clinical/prognostic implications and for the enrichment of potential targets for precision oncology.
Topics: Carcinoma, Pancreatic Ductal; Carcinoma, Papillary; Humans; Pancreas; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms; Precision Medicine
PubMed: 35583805
DOI: 10.1111/his.14698 -
BJS Open Sep 2023Groove pancreatitis is a focal form of chronic pancreatitis affecting the area of the paraduodenal groove. The aim of this systematic review was to assess the clinical...
BACKGROUND
Groove pancreatitis is a focal form of chronic pancreatitis affecting the area of the paraduodenal groove. The aim of this systematic review was to assess the clinical presentation, diagnosis and treatment of patients with groove pancreatitis.
METHODS
Medical literature databases (Embase, Medline via PubMed and Cochrane Central Register of Controlled Trials) were systematically searched for data recorded between 1 January 1990 and 31 August 2022 regarding patient characteristics, diagnosis, surgical treatment and outcomes. The following inclusion criteria were applied: RCTs, observational studies (cohort and case-control studies) and case studies with >3 cases including patients with groove pancreatitis undergoing medical, endoscopic or surgical treatment with available clinical and diagnostic data. Fisher's exact test for binary data and Mann-Whitney U test or Student t-test for continuous data were adopted for statistical analysis.
RESULTS
Of 649 studies, 44 were included, involving reports on 1404 patients with a mean age of 49 years. In 41 of the 44 studies in which patient gender was described, 86 per cent (N = 1023) of patients were male. Information on the risk factors of alcohol and nicotine was available in 37 and 23 studies, respectively. Seventy-nine per cent (N = 886) of patients had a history of excessive alcohol consumption and 83 per cent (N = 595) were smokers. Information on clinical symptoms was available in 37 of the 44 included studies and 78.5 per cent (N = 870) presented with abdominal pain. Some 27 studies comprising 920 groove pancreatitis patients were treatment oriented. Seventy-four per cent (N = 682) of patients were treated conservatively, 26.4 per cent (N = 134) underwent endoscopic treatment and 54.7 per cent (N = 503) required surgery. There was complete relief of symptoms in 35.6 per cent (N = 243) after conservative treatment, 55.2 per cent (N = 74) after endoscopic treatment and 69.6 per cent (N = 350) after surgical treatment. The median follow-up time was 42 months (range, 1-161 months).
CONCLUSION
Groove pancreatitis shows on imaging a typical triad: cystic lesions in the pancreatic duct or duodenal wall, calcifications, and thickenings of the duodenal wall. Surgery appears to be the most effective treatment modality.
Topics: Humans; Male; Middle Aged; Female; Rare Diseases; Abdominal Pain; Case-Control Studies; Conservative Treatment; Pancreatitis
PubMed: 37749756
DOI: 10.1093/bjsopen/zrad094 -
World Journal of Radiology Feb 2023Paraduodenal pancreatitis (PP) represents a diagnostic challenge, especially in non-referral centers, given its potential imaging overlap with pancreatic cancer. There...
BACKGROUND
Paraduodenal pancreatitis (PP) represents a diagnostic challenge, especially in non-referral centers, given its potential imaging overlap with pancreatic cancer. There are two main histological variants of PP, the cystic and the solid, with slightly different imaging appearances. Moreover, imaging findings in PP may change over time because of disease progression and/or as an effect of its risk factors exposition, namely alcohol intake and smoking.
AIM
To describe multimodality imaging findings in patients affected by PP to help clinicians in the differential diagnosis with pancreatic cancer.
METHODS
The systematic review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-analyses 2009 guidelines. A Literature search was performed on PubMed, Embase and Cochrane Library using (groove pancreatitis [Title/Abstract]) OR (PP [Title/Abstract]) as key words. A total of 593 articles were considered for inclusion. After eliminating duplicates, and title and abstract screening, 53 full-text articles were assessed for eligibility. Eligibility criteria were: Original studies including 8 or more patients, fully written in English, describing imaging findings in PP, with pathological confirmation or clinical-radiological follow-up as the gold standard. Finally, 14 studies were included in our systematic review.
RESULTS
Computed tomography (CT) findings were described in 292 patients, magnetic resonance imaging (MRI) findings in 231 and endoscopic ultrasound (EUS) findings in 115. Duodenal wall thickening was observed in 88.8% of the cases: Detection rate was 96.5% at EUS, 91.0% at MRI and 84.1% at CT. Second duodenal portion increased enhancement was recognizable in 76.3% of the cases: Detection rate was 84.4% at MRI and 72.1% at CT. Cysts within the duodenal wall were detected in 82.6% of the cases: Detection rate was 94.4% at EUS, 81.9% at MRI and 75.7% at CT. A solid mass in the groove region was described in 40.9% of the cases; in 78.3% of the cases, it showed patchy enhancement in the portal venous phase, and in 100% appeared iso/hyperintense during delayed phase imaging. Only 3.6% of the lesions showed restricted diffusion. The prevalence of radiological signs of chronic obstructive pancreatitis, namely main pancreatic duct dilatation, pancreatic calcifications, and pancreatic cysts, was extremely variable in the different articles.
CONCLUSION
PP has peculiar imaging findings. MRI is the best radiological imaging modality for diagnosing PP, but EUS is more accurate than MRI in depicting duodenal wall alterations.
PubMed: 36874260
DOI: 10.4329/wjr.v15.i2.42 -
World Journal of Gastroenterology Nov 2015To review applications of confocal laser endomicroscopy (CLE) in pancreatobiliary lesions and studies that assessed training and interpretation of images. (Review)
Review
AIM
To review applications of confocal laser endomicroscopy (CLE) in pancreatobiliary lesions and studies that assessed training and interpretation of images.
METHODS
A computerized literature search was performed using OVID MEDLINE, EMBASE, Cochrane library, and the ISI Web of Knowledge from 1980 to October 2014. We also searched abstracts from major meetings that included the Digestive Disease Week, Canadian Digestive Disease Week and the United European Gastroenterology Week using a combination of controlled vocabulary and text words related to pCLE, confocal, endomicroscopy, probe-based confocal laser endomicroscopy, and bile duct to identify reports of trials. In addition, recursive searches and cross-referencing was performed, and manual searches of articles identified after the initial search was also completed. We included fully published articles and those in abstract form. Given the relatively recent introduction of CLE we included randomized trials and cohort studies.
RESULTS
In the evaluation of indeterminate pancreatobiliary strictures CLE with ERCP compared to ERCP alone can increase the detection of cancerous strictures with a sensitivity of (98% vs 45%) and has a negative predictive value (97% vs 69%), but decreased the specificity (67% vs 100%) and the positive predictive value (71% vs 100%) when compared to index pathology. Modifications in the classification systems in indeterminate biliary strictures have increased the specificity of pCLE from 67% to 73%. In pancreatic cystic lesions there is a need to develop similar systems to interpret and characterize lesions based on CLE images obtained. The presence of superficial vascular network predicts serous cystadenomas accurately. Also training in acquiring and interpretation of images is feasible in those without any prior knowledge in CLE in a relatively simple manner and computer-aided diagnosis software is a promising innovation.
CONCLUSION
The role of pCLE in the evaluation of pancreatobiliary disorders might be better suited for those with an intermediate and low probability.
Topics: Bile Ducts; Biliary Tract Diseases; Biopsy; Cholangiopancreatography, Endoscopic Retrograde; Contrast Media; Endoscopy, Gastrointestinal; Humans; Microscopy, Confocal; Pancreas; Pancreatic Diseases; Patient Selection; Predictive Value of Tests; Reproducibility of Results
PubMed: 26640347
DOI: 10.3748/wjg.v21.i44.12696