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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 -
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 Sep 2020Pancreatic duct stones can lead to significant abdominal pain for patients. Per oral pancreatoscopy (POP)-guided intracorporal lithotripsy is being increasingly used for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pancreatic duct stones can lead to significant abdominal pain for patients. Per oral pancreatoscopy (POP)-guided intracorporal lithotripsy is being increasingly used for the management of main pancreatic duct calculi (PDC) in chronic pancreatitis. POP uses two techniques: Electrohydraulic lithotripsy (EHL) and laser lithotripsy (LL). Data on the safety and efficacy are limited for this procedure. We performed a systematic review and meta-analysis with a primary aim to calculate the pooled technical and clinical success rates of POP. The secondary aim was to assess pooled rates of technical success, clinical success for the two individual techniques, and adverse event rates.
AIM
To perform a systematic review and meta-analysis of POP, EHL and LL for management of PDC in chronic pancreatitis.
METHODS
We conducted a comprehensive search of multiple electronic databases and conference proceedings including PubMed, EMBASE, Cochrane, Google Scholar and Web of Science databases (from 1999 to October 2019) to identify studies with patient age greater than 17 and any gender that reported on outcomes of POP, EHL and LL. The primary outcome assessed involved the pooled technical success and clinical success rate of POP. The secondary outcome included the pooled technical success and clinical success rate for EHL and LL. We also assessed the pooled rate of adverse events for POP, EHL and LL including a subgroup analysis for the rate of adverse event subtypes for POP: Hemorrhage, post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP), perforation, abdominal pain, fever and infections. Technical success was defined as the rate of clearing pancreatic duct stones and clinical success as the improvement in pain. Random-effects model was used for analysis. Heterogeneity between study-specific estimates was calculated using the Cochran statistical test and statistics. Publication bias was ascertained, qualitatively by visual inspection of funnel plot and quantitatively by the Egger test.
RESULTS
A total of 16 studies including 383 patients met the inclusion criteria. The technical success rate of POP was 76.4% (95%CI: 65.9-84.5; = 64%) and clinical success rate was 76.8% (95%CI: 65.2-85.4; = 66%). The technical success rate of EHL was 70.3% (95%CI: 57.8-80.3; = 36%) and clinical success rate of EHL was 66.5% (95%CI: 55.2-76.2; = 19%). The technical success rate of LL was 89.3% (95%CI: 70.5-96.7; = 70%) and clinical success rate of LL was 88.2% (95%CI: 66.4-96.6; = 77%). The incidence of pooled adverse events for POP was 14.9% (95%CI: 9.2-23.2; = 49%), for EHL was 11.2% (95%CI: 5.9-20.3; = 15%) and for LL was 13.1% (95%CI: 6.3-25.4; = 31%). Subgroup analysis of adverse events showed rates of PEP at 7% (95%CI: 3.5-13.6; = 38%), fever at 3.7% (95%CI: 2-6.9; = 0), abdominal pain at 4.7% (95%CI: 2.7-7.8; = 0), perforation at 4.3% (95%CI: 2.1-8.4; = 0), hemorrhage at 3.4% (95%CI: 1.7-6.6; = 0) and no mortality. There was evidence of publication bias based on funnel plot analysis and Egger's test.
CONCLUSION
Our study highlights the high technical and clinical success rates for POP, EHL and LL. POP-guided lithotripsy could be a viable option for management of chronic pancreatitis with PDC.
Topics: Calculi; Cholangiopancreatography, Endoscopic Retrograde; Humans; Lithotripsy; Pancreatic Diseases; Pancreatic Ducts; Treatment Outcome
PubMed: 32982119
DOI: 10.3748/wjg.v26.i34.5207 -
Canadian Journal of Surgery. Journal... 2022Patients should be informed beforehand of the risk factors for exocrine pancreatic insufficiency (ExoPI) after pancreatic surgery; however, there are no clear identified... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients should be informed beforehand of the risk factors for exocrine pancreatic insufficiency (ExoPI) after pancreatic surgery; however, there are no clear identified risk factors for this condition. This study aimed to identify the preoperative, perioperative and postoperative risk factors for ExoPI after pancreatic surgery.
METHODS
We conducted a systematic search of PubMed, Scopus, SAGE, CINAHL Plus and Taylor & Francis from inception to Mar. 7, 2021, for full-text articles that included patients who had undergone pancreatic surgery. The primary outcome was the number of ExoPI events and any risk factors evaluated. We used the Newcastle-Ottawa Scale to assess study quality.
RESULTS
Twenty studies involving 4131 patients (2312 [52.3%] male, mean age 60.12 [standard deviation 14.07] yr) were included. Of the 4131 patients, 1651 (40.0%) had postoperative ExoPI. Among the 11 factors evaluated, the significant risk factors were preoperative main pancreatic duct (MPD) diameter greater than 3 mm (odds ratio [OR] 4.50, 95% confidence interval [CI] 1.06-19.05), pancreaticoduodenectomy (PD) as the surgical treatment procedure (OR 3.31, 95% CI 1.92-5.68), pancreaticogastrostomy (PG) as the anastomotic procedure (OR 3.13, 95% CI 1.83-5.35), hard pancreatic texture (OR 2.93, 95% CI 1.99-4.32) and adjuvant chemotherapy (OR 2.50, 95% CI 1.54-4.04). Gender, history of diabetes mellitus or endocrine pancreatic insufficiency (EndoPI), underlying diseases, de novo diabetes or EndoPI, pylorus-preserving PD and postoperative pancreatic fistula were not risk factors for ExoPI after pancreatic surgery.
CONCLUSION
Preoperative MPD diameter greater than 3 mm, PD, PG reconstruction, hard pancreatic texture and adjuvant chemotherapy were risk factors for the development of ExoPI after pancreatic surgery. The findings should provide useful information for patients to reduce postoperative dissatisfaction and improve quality of life.
Topics: Humans; Male; Middle Aged; Female; Quality of Life; Exocrine Pancreatic Insufficiency; Pancreaticoduodenectomy; Pancreatectomy; Pancreas; Postoperative Complications; Pancreatic Diseases
PubMed: 36384688
DOI: 10.1503/cjs.010621 -
Endoscopy International Open Oct 2020Per-oral pancreatoscopy (POP) with intraductal lithotripsy via electrohydraulic lithotripsy (EHL) or laser lithotripsy (LL) facilitates optically-guided stone... (Review)
Review
Per-oral pancreatoscopy (POP) with intraductal lithotripsy via electrohydraulic lithotripsy (EHL) or laser lithotripsy (LL) facilitates optically-guided stone fragmentation of difficult pancreatic stones refractory to conventional endoscopic therapy. The aim of this study was to perform a systematic review and meta-analysis to evaluate the efficacy and safety of POP with intraductal lithotripsy for difficult pancreatic duct stones. Individualized search strategies were developed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology guidelines. This was a cumulative meta-analysis performed by calculating pooled proportions with rates estimated using random effects models. Measured outcomes included pooled technical success, complete or partial stone fragmentation success, complete duct clearance after initial lithotripsy session, and adverse events (AEs). Ten studies (n = 302 patients; 67.72 % male; mean age 55.10 ± 3.22 years) were included with mean stone size of 10.66 ± 2.19 mm. The most common stone location was in the pancreatic head (66.17 %). Pooled technical success was 91.18 % with an overall fragmentation success of 85.77 %. Single lithotripsy session stone fragmentation and pancreatic duct clearance occurred in 62.05 % of cases. Overall, adverse events were reported in 14.09 % of patients with post-procedure pancreatitis developing in 8.73 %. Of these adverse events, 4.84 % were classified as serious. Comparing POP-EHL vs POP-LL, there was no significant difference in technical success, fragmentation success, single session duct clearance, or AEs ( > 0.0500). Based on this systematic review and meta-analysis, POP with intraductal lithotripsy appears to be an effective and relatively safe procedure for patients with difficult to remove pancreatic duct stones.
PubMed: 33043115
DOI: 10.1055/a-1236-3187