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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 -
International Journal of Surgery... 2014Postoperative pancreatic fistula formation (POPF) remains one of the most common and detrimental complications following pancreaticojejunostomy (PJ). The aim of this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postoperative pancreatic fistula formation (POPF) remains one of the most common and detrimental complications following pancreaticojejunostomy (PJ). The aim of this meta-analysis is to analyze the efficacy of external pancreatic duct stent placement in preventing POPF formation following PJ.
METHODS
The primary end-point was the incidence of POPF formation following pancreaticoduodenectomy (PD) in the presence and absence of external stent placement. Secondary outcomes examined were the incidence of perioperative mortality, delayed gastric emptying, postoperative wound infection, operative time, blood loss, and length of hospital stay.
RESULTS
Four trials were included comprising 416 patients. External pancreatic duct stenting was found to reduce the incidence of both any grade POPF formation (OR 0.37, 95% CI = 0.23 to 0.58, p = 0.0001) and clinically significant (grade B or C) POPF formation (OR 0.50, 95% CI = 0.30 to 0.84, p = 0.0009) following PD. The use of an external stent was also found to significantly lessen length of hospital stay (SMD -0.39, 95% CI = -0.63 to -0.15, p = 0.001).
CONCLUSIONS
This analysis has shown that external pancreatic duct stenting is indeed efficacious in the incidence of both any grade as well as clinically significant POPF formation following PD. Length of hospital stay was also found to be significantly less by external duct stenting.
Topics: Female; Humans; Length of Stay; Male; Operative Time; Pancreatic Ducts; Pancreatic Fistula; Pancreaticoduodenectomy; Pancreaticojejunostomy; Postoperative Period; Stents; Surgical Wound Infection
PubMed: 25003575
DOI: 10.1016/j.ijsu.2014.06.008 -
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 -
BMJ Clinical Evidence May 2010Pancreatic cancer is the fourth most common cause of cancer death in higher-income countries, with 5-year survival only 10% even in people presenting with early-stage... (Review)
Review
INTRODUCTION
Pancreatic cancer is the fourth most common cause of cancer death in higher-income countries, with 5-year survival only 10% even in people presenting with early-stage cancer. Risk factors include smoking, high alcohol intake, and dietary factors, while diabetes mellitus and previous pancreatitis may also increase the risk.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of surgical treatments in people with pancreatic cancer considered suitable for complete tumour resection? What are the effects of interventions to prevent pancreatic leak after pancreaticoduodenectomy in people with pancreatic cancer considered suitable for complete tumour resection? What are the effects of adjuvant treatments in people with completely resected pancreatic cancer? What are the effects of interventions in people with non-resectable (locally advanced or advanced) pancreatic cancer? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 46 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: chemoradiotherapy; chemoradiotherapy for non-resectable pancreatic cancer; chemoradiotherapy for resected pancreatic cancer; fibrin glue; fluorouracil-based chemotherapy (adjuvant) for resected pancreatic cancer (with or without surgery); fluorouracil-based chemotherapy for non-resectable pancreatic cancer; fluorouracil-based chemotherapy (systemic); fluorouracil-based combination chemotherapy; fluorouracil-based monotherapy for non-resectable pancreatic cancer; gemcitabine-based chemotherapy (adjuvant) for resected pancreatic cancer; gemcitabine-based chemotherapy (systemic); gemcitabine-based combination chemotherapy; gemcitabine-based monotherapy for non-resectable pancreatic cancer; lymphadenectomy (extended [radical], or standard) in people having pancreaticoduodenectomy; pancreatic duct occlusion; pancreaticoduodenectomy (pylorus-preserving); pancreaticoduodenectomy (Whipple's procedure); pancreaticogastrostomy reconstruction; pancreaticojejunostomy; and somatostatin and somatostatin analogues.
Topics: Fluorouracil; Humans; Pancreatectomy; Pancreatic Neoplasms; Pancreaticoduodenectomy; Pylorus
PubMed: 21729338
DOI: No ID Found -
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 -
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 -
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 -
HPB : the Official Journal of the... Sep 2022Pancreatoduodenectomy is burdened by elevated postoperative morbidity. Pancreatic duct ligation or occlusion have been experimented as an alternative to reduce the... (Meta-Analysis)
Meta-Analysis Review
Postoperative morbidity and mortality after pancreatoduodenectomy with pancreatic duct occlusion compared to pancreatic anastomosis: a systematic review and meta-analysis.
BACKGROUND
Pancreatoduodenectomy is burdened by elevated postoperative morbidity. Pancreatic duct ligation or occlusion have been experimented as an alternative to reduce the insurgence of postoperative pancreatic fistula. The aim of this systematic review and meta-analysis was to compare postoperative mortality and morbidity (pancreatic fistula, postoperative hemorrhage, delayed gastric emptying, pancreatic exocrine insufficiency and diabetes mellitus) between patients undergoing pancreatic anastomosis or pancreatic duct ligation/occlusion after pancreatoduodenectomy.
METHODS
A systematic review and meta-analysis of 13 studies was conducted following the PRISMA guidelines and the Cochrane protocol (PROSPERO ID: CRD42021249232).
RESULTS
No difference in postoperative mortality was highlighted. Pancreatic anastomosis was found to be protective considering all-grades pancreatic fistula (RR: 2.38, p = 0.0005), but pancreatic duct occlusion presented a 3-folded reduced risk to develop "grade C" pancreatic fistula (RR: 0.36, p = 0.1186), although not significant. Diabetes mellitus was more often diagnosed after duct occlusion (RR: 1.61, p < 0.0001); no difference was found in terms of pancreatic exocrine insufficiency (RR: 1.19, p = 0.151).
CONCLUSION
Postoperative mortality is not influenced by the pancreatic reconstruction technique. Pancreatic anastomosis is associated with a reduction in all-grades pancreatic fistula. More high-quality studies are needed to clarify if duct sealing could reduce the prevalence of "grade C" fistula.
Topics: Anastomosis, Surgical; Exocrine Pancreatic Insufficiency; Humans; Morbidity; Pancreatic Diseases; Pancreatic Ducts; Pancreatic Fistula; Pancreaticoduodenectomy; Pancreaticojejunostomy; Postoperative Complications
PubMed: 35450800
DOI: 10.1016/j.hpb.2022.03.015 -
HPB : the Official Journal of the... Aug 2020Pancreatic duct occlusion (PDO) without anastomosis is a technique proposed to mitigate the clinical consequences of postoperative pancreatic fistulas (POPF) after... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatic duct occlusion (PDO) without anastomosis is a technique proposed to mitigate the clinical consequences of postoperative pancreatic fistulas (POPF) after pancreaticoduodenectomy. The aim of this study was to appraise the morbidity following PDO through a systematic review and meta-analysis.
METHODS
A systematic search of MEDLINE, Embase, and Web Of Science identified studies reporting outcomes of PDO following pancreaticoduodenectomy. Pooled prevalence rates of postoperative complications and mortality were computed using random-effect modeling. Meta-regression analyses were performed to examine the impact of moderators on the overall estimates.
RESULTS
Sixteen studies involving 1000 patients were included. Pooled postoperative mortality was 2.7%. A POPF was reported in 29.7% of the patients. Clinically relevant POPFs occurred in 13.5% of the patients, while intra-abdominal abscess and haemorrhages occurred in 6.7% and 5.5% of the patients, respectively. Re-operation was necessary in 7.6% of the patients. Postoperatively new onset diabetes occurred in 15.8% of patients, more frequently after the use of chemical substances for PDO (p = 0.003).
CONCLUSIONS
PDO is associated with significant morbidity including new onset of post-operative diabetes. The risk of new onset post-operative diabetes is associated with the use of chemical substance for PDO. Further evidence is needed to evaluate the potential benefits of PDO in patients at high risk of POPF.
Topics: Anastomosis, Surgical; Humans; Morbidity; Pancreatic Ducts; Pancreatic Fistula; Pancreaticoduodenectomy; Pancreaticojejunostomy; Postoperative Complications
PubMed: 32471694
DOI: 10.1016/j.hpb.2020.04.014 -
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