-
Alimentary Pharmacology & Therapeutics Jun 2022Inflammatory bowel disease (IBD) is a chronic inflammatory immune-mediated disorder of the gut with frequent extra-intestinal complications. Pancreatic involvement in... (Review)
Review
BACKGROUND
Inflammatory bowel disease (IBD) is a chronic inflammatory immune-mediated disorder of the gut with frequent extra-intestinal complications. Pancreatic involvement in IBD is not uncommon and comprises a heterogeneous group of conditions, including acute pancreatitis (AP), chronic pancreatitis (CP), autoimmune pancreatitis (AIP) and pancreatic exocrine insufficiency (PEI); however, data on such an association remain sparse and heterogeneous.
METHOD
PubMed/MEDLINE and EMBASE databases were searched for studies investigating pancreatic involvement in patients with IBD.
RESULTS
Four thousand one hundred and twenty-one records were identified and 547 screened; finally, 124 studies were included in the review. AP is the most frequent pancreatic manifestation in IBD; the majority of AP cases in IBD are due to gallstones and drugs but cases of idiopathic AP are increasingly reported. AIP is a rare disease, but a strong association with IBD has been demonstrated, especially for type 2 and ulcerative colitis. The pathogenetic link between IBD and AIP remains unclear, but an immune-mediated pathway seems plausible. An association between CP and PEI with IBD has also been suggested, but data are to date scarce and conflicting.
CONCLUSION
This is the first systematic review of the association between IBD and pancreatic diseases. Gallstones and drugs should be considered the most probable causes of AP in IBD, with type 2 AIP also being possible.
Topics: Acute Disease; Autoimmune Diseases; Chronic Disease; Colitis, Ulcerative; Exocrine Pancreatic Insufficiency; Gallstones; Humans; Inflammatory Bowel Diseases; Pancreatitis, Chronic
PubMed: 35505465
DOI: 10.1111/apt.16949 -
PloS One 2020A current assessment of case reports of possible drug-induced pancreatitis is needed. We systematically reviewed the case report literature to identify drugs with...
OBJECTIVE
A current assessment of case reports of possible drug-induced pancreatitis is needed. We systematically reviewed the case report literature to identify drugs with potential associations with acute pancreatitis and the burden of evidence supporting these associations.
METHODS
A protocol was developed a priori (PROSPERO CRD42017060473). We searched MEDLINE, Embase, the Cochrane Library, and additional sources to identify cases of drug-induced pancreatitis that met accepted diagnostic criteria of acute pancreatitis. Cases caused by multiple drugs or combination therapy were excluded. Established systematic review methods were used for screening and data extraction. A classification system for associated drugs was developed a priori based upon the number of cases, re-challenge, exclusion of non-drug causes of acute pancreatitis, and consistency of latency.
RESULTS
Seven-hundred and thirteen cases of potential drug-induced pancreatitis were identified, implicating 213 unique drugs. The evidence base was poor: exclusion of non-drug causes of acute pancreatitis was incomplete or poorly reported in all cases, 47% had at least one underlying condition predisposing to acute pancreatitis, and causality assessment was not conducted in 81%. Forty-five drugs (21%) were classified as having the highest level of evidence regarding their association with acute pancreatitis; causality was deemed to be probable or definite for 19 of these drugs (42%). Fifty-seven drugs (27%) had the lowest level of evidence regarding an association with acute pancreatitis, being implicated in single case reports, without exclusion of other causes of acute pancreatitis.
DISCUSSION
Much of the case report evidence upon which drug-induced pancreatitis associations are based is tenuous. A greater emphasis on exclusion of all non-drug causes of acute pancreatitis and on quality reporting would improve the evidence base. It should be recognized that reviews of case reports, are valuable scoping tools but have limited strength to establish drug-induced pancreatitis associations.
REGISTRATION
CRD42017060473.
Topics: Acute Disease; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Humans; Pancreatitis; Pharmaceutical Preparations
PubMed: 32302358
DOI: 10.1371/journal.pone.0231883 -
The British Journal of Surgery Apr 2011Many studies have shown lower mortality and higher survival rates after pancreatic surgery with high-volume providers, suggesting that centralization of pancreatic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many studies have shown lower mortality and higher survival rates after pancreatic surgery with high-volume providers, suggesting that centralization of pancreatic surgery can improve outcomes. The methodological quality of these studies is open to question. This study involves a systematic review of the volume-outcome relationship for pancreatic surgery with a meta-analysis of studies considered to be of good quality.
METHODS
A systematic search of electronic databases up to February 2010 was performed to identify all primary studies examining the effects of hospital or surgeon volume on postoperative mortality and survival after pancreatic surgery. All articles were critically appraised with regard to methodological quality and risk of bias. After strict inclusion, meta-analysis assuming a random-effects model was done to estimate the effect of higher surgeon or hospital volume on patient outcome.
RESULTS
Fourteen studies were included in the meta-analysis. The results showed a significant association between hospital volume and postoperative mortality (odds ratio 0.32, 95 per cent confidence interval 0.16 to 0.64), and between hospital volume and survival (hazard ratio 0.79, 0.70 to 0.89).The effect of surgeon volume on postoperative mortality was not significant (odds ratio 0.46, 0.17 to 1.26). Significant heterogeneity was seen in the analysis of hospital volume and mortality. Sensitivity analysis showed no correlation with the extent of risk adjustment or study country; after removing one outlier study, the result was homogeneous. The data did not suggest publication bias.
CONCLUSION
There was a consistent association between high hospital volume and lower postoperative mortality rates with improved long-term survival.
Topics: Colorectal Surgery; Health Facility Size; Humans; Pancreas; Pancreatic Diseases; Postoperative Complications; Treatment Outcome; Workload
PubMed: 21500187
DOI: 10.1002/bjs.7413 -
Pharmacological Research Apr 2019Pancreatic diseases, such as acute pancreatitis, chronic pancreatitis, and pancreatic cancer, are common gastrointestinal diseases resulting in the development of local...
Pancreatic diseases, such as acute pancreatitis, chronic pancreatitis, and pancreatic cancer, are common gastrointestinal diseases resulting in the development of local and systemic complications with a high risk of death. Numerous studies have examined pancreatic diseases over the past few decades; however, the pathogenesis remains unclear, and there is a lack of effective treatment options. Recently, emerging evidence has suggested that transforming growth factor beta (TGF-β) exerts controversial functions in apoptosis, inflammatory responses, and carcinogenesis, indicating its complex role in the pathogenesis of pancreas-associated disease. Therefore, a further understanding of relevant TGF-β signalling will provide new ideas and potential therapeutic targets for preventing disease progression. This is the first systematic review of recent data from animal and human clinical studies focusing on TGF-β signalling in pancreas damage and diseases. This information may aid in the development of therapeutic agents for regulating TGF-β in this pathology to prevent or treat pancreatic diseases.
Topics: Animals; Humans; Pancreatic Diseases; Transforming Growth Factor beta
PubMed: 30682425
DOI: 10.1016/j.phrs.2019.01.038 -
European Radiology Dec 2023To determine informational CT findings for distinguishing autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC) and to review their diagnostic... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To determine informational CT findings for distinguishing autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC) and to review their diagnostic accuracy.
METHODS
A systematic and detailed literature review was performed through PubMed, EMBASE, and the Cochrane library. Similar descriptors to embody the identical image finding were labeled as a single CT characteristic. We calculated the pooled diagnostic odds ratios (DORs) of each CT characteristic using a bivariate random-effects model.
RESULTS
A total of 145 various descriptors from 15 studies (including 562 AIP and 869 PDAC patients) were categorized into 16 CT characteristics. According to the pooled DOR, 16 CT characteristics were classified into three groups (suggesting AIP, suggesting PDAC, and not informational). Seven characteristics suggesting AIP were diffuse pancreatic enlargement (DOR, 48), delayed homogeneous enhancement (DOR, 46), capsule-like rim (DOR, 34), multiple pancreatic masses (DOR, 16), renal involvement (DOR, 15), retroperitoneal fibrosis (DOR, 13), and bile duct involvement (DOR, 8). Delayed homogeneous enhancement showed a pooled sensitivity of 83% and specificity of 85%. The other six characteristics showed relatively low sensitivity (12-63%) but high specificity (93-99%). Four characteristics suggesting PDAC were discrete pancreatic mass (DOR, 23), pancreatic duct cutoff (DOR, 16), upstream main pancreatic duct dilatation (DOR, 8), and upstream parenchymal atrophy (DOR, 7).
CONCLUSION
Eleven CT characteristics were informational to distinguish AIP from PDAC. Diffuse pancreatic enlargement, delayed homogeneous enhancement, and capsule-like rim suggested AIP with the highest DORs, whereas discrete pancreatic mass suggested PDAC. However, pooled sensitivities of informational CT characteristics were moderate.
CLINICAL RELEVANCE STATEMENT
This meta-analysis underscores eleven distinctive CT characteristics that aid in differentiating autoimmune pancreatitis from pancreatic adenocarcinoma, potentially preventing misdiagnoses in patients presenting with focal/diffuse pancreatic enlargement.
KEY POINTS
• Diffuse pancreatic enlargement (pooled diagnostic odds ratio [DOR], 48), delayed homogeneous enhancement (46), and capsule-like rim (34) were CT characteristics suggesting autoimmune pancreatitis. • The CT characteristics suggesting autoimmune pancreatitis, except delayed homogeneous enhancement, had a general tendency to show relatively low sensitivity (12-63%) but high specificity (93-99%). • Discrete pancreatic mass (pooled diagnostic odds ratio, 23) was the CT characteristic suggesting pancreatic ductal adenocarcinoma with the highest pooled DORs.
Topics: Humans; Pancreatic Neoplasms; Autoimmune Pancreatitis; Pancreatitis; Adenocarcinoma; Tomography, X-Ray Computed; Autoimmune Diseases; Carcinoma, Pancreatic Ductal; Diagnosis, Differential
PubMed: 37466708
DOI: 10.1007/s00330-023-09959-5 -
Frontiers in Immunology 2023This review aims to determine the incidence and risk of pancreatic adverse events (AEs) associated with immune checkpoint inhibitors (ICIs) therapy for solid tumors. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This review aims to determine the incidence and risk of pancreatic adverse events (AEs) associated with immune checkpoint inhibitors (ICIs) therapy for solid tumors.
METHODS
We conducted a comprehensive systematic literature search in PubMed, Embase, and Cochrane Library up to March 15, 2023, to identify all randomized controlled trials comparing ICIs with standard treatment in solid tumors. We included studies that reported immune-related pancreatitis or elevation of serum amylase or lipase levels. Following protocol registration in PROSPERO, we conducted a systematic review and meta-analysis.
RESULTS
59 unique randomized controlled trials with at least one ICI-containing arm (41 757 patients) were retrieved. The incidences for all-grade pancreatitis, amylase elevation and lipase elevation were 0.93% (95% CI 0.77-1.13), 2.57% (95% CI 1.83-3.60) and 2.78% (95% CI 1.83-4.19), respectively. The incidences for grade ≥3 pancreatitis, amylase elevation and lipase elevation were 0.68% (95% CI 0.54-0.85), 1.17% (95% CI 0.83-1.64) and 1.71% (95% CI 1.18-2.49), respectively. The use of ICIs was associated with an increased risk of all-grade pancreatic immune-related AEs (irAEs) including pancreatitis (OR=2.04, 95% CI 1.42-2.94, P =0.0001), amylase elevation (OR=1.91, 95% CI 1.47-2.49, P < 0.0001) and lipase elevation (OR=1.77, 95% CI 1.37-2.29, P < 0.0001). In addition to these, the analysis found that PD-1 inhibitors had a significant higher risk of pancreatic AEs compared with PD-L1 inhibitors and the patients undergoing dual ICI therapy were at a significantly higher risk of pancreatic AEs than the patients receiving single ICI therapy.
CONCLUSION
Our study provides an overview of the incidence and risk of ICI-associated pancreatitis and pancreatic enzyme elevations in the treatment of solid tumors. Our findings may help raise awareness among clinicians of the potential for ICI-associated pancreatic AEs in clinical practice.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier 345350.
Topics: Humans; Immune Checkpoint Inhibitors; Pancreatitis; Neoplasms; Amylases; Lipase
PubMed: 37359551
DOI: 10.3389/fimmu.2023.1166299 -
Translational Research : the Journal of... Jun 2022Extensive research is focused on the role of liquid biopsy in pancreatic cancer since reliable diagnostic and follow-up biomarkers represent an unmet need for this... (Meta-Analysis)
Meta-Analysis Review
Extensive research is focused on the role of liquid biopsy in pancreatic cancer since reliable diagnostic and follow-up biomarkers represent an unmet need for this highly lethal malignancy. We performed a systematic review and meta-analysis on the prognostic value of exosomal biomarkers in pancreatic ductal adenocarcinoma (PDAC). MEDLINE, Embase, Scopus, Web of Science, and CENTRAL were systematically searched on the 18th of January, 2021 for studies reporting on the differences in overall (OS) and progression-free survival (PFS) in PDAC patients with positive vs negative exosomal biomarkers isolated from blood. The random-effects model estimated pooled multivariate-adjusted (AHR) and univariate hazard ratios (UHRs) with 95% confidence intervals (CIs). Eleven studies comprising 634 patients were eligible for meta-analysis. Detection of positive exosomal biomarkers indicated increased risk of mortality (UHR = 2.81, CI:1.31-6,00, I = 88.7%, P < 0.001), and progression (UHR = 3.33, CI: 2.33-4.77, I = 0, P = 0.879) across various disease stages. Positive exosomal biomarkers identified preoperatively revealed a higher risk of mortality in resectable stages (UHR = 5.55, CI: 3.24-9.49, I = 0, P = 0.898). The risk of mortality in unresectable stages was not significantly increased with positive exosomal biomarkers (UHR = 2.51, CI: 0.55-11.43, I = 90.3%, P < 0.001). Detectable exosomal micro ribonucleic acids were associated with a decreased OS (UHR = 4.08, CI: 2.16-7.69, I = 46.9%, P = 0.152) across various stages. Our results reflect the potential of exosomal biomarkers for prognosis evaluation in PDAC. The associated heterogeneity reflects the variability of study methods and need for their uniformization before transition to clinical use.
Topics: Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Exosomes; Humans; Pancreatic Neoplasms; Prognosis
PubMed: 35066189
DOI: 10.1016/j.trsl.2022.01.001 -
Cancer Medicine Jun 2017There is a strong rationale and many theoretical advantages for neoadjuvant therapy in pancreatic cancer (PC). However, study results have varied significantly. In this... (Meta-Analysis)
Meta-Analysis Review
There is a strong rationale and many theoretical advantages for neoadjuvant therapy in pancreatic cancer (PC). However, study results have varied significantly. In this study, a systematic review and meta-analysis of prospective studies were performed in order to evaluate safety and effectiveness of neoadjuvant therapy in PC. Thirty-nine studies were selected (n = 1458 patients), with 14 studies focusing on patients with resectable disease (group 1), and 19 studies focusing on patients with borderline resectable and locally advanced disease (group 2). Neoadjuvant chemotherapy was administered in 97.4% of the studies, in which 76.9% was given radiotherapy and 74.4% administered with chemoradiation. The complete and partial response rate was 3.8% and 20.9%. The incidence of grade 3/4 toxicity was 11.3%. The overall resection rate after neoadjuvant therapy was 57.7% (group 1: 73.0%, group 2: 40.2%). The R0 resection rate was 84.2% (group 1: 88.2%, group 2: 79.4%). The overall survival for all patients was 16.79 months (resected 24.24, unresected 9.81; group 1: 17.76, group 2: 16.20). Our results demonstrate that neoadjuvant therapy has not been proven to be beneficial and should be considered with caution in patients with resectable PC. Patients with borderline resectable or locally advanced disease may benefit from neoadjuvant therapy, but further research is needed.
Topics: Antineoplastic Agents; Humans; Morbidity; Neoadjuvant Therapy; Pancreatic Neoplasms; Prospective Studies; Treatment Outcome
PubMed: 28544758
DOI: 10.1002/cam4.1071 -
Journal of Gastrointestinal Surgery :... Jul 2012von Hippel-Lindau (vHL) disease is a rare condition that leads to characteristic lesions within many different body systems. Pancreatic manifestations of vHL cover a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
von Hippel-Lindau (vHL) disease is a rare condition that leads to characteristic lesions within many different body systems. Pancreatic manifestations of vHL cover a wide spectrum of pathologies, and thus, accurate characterization and management is critical.
METHODS
A comprehensive and systematic text word and MeSH search of the medical literature was performed to identify studies where information regarding the prevalence, clinical characteristics, and management recommendations could be extracted.
RESULTS
Eleven studies were identified but 2 studies utilized the same data set. Of the 10 remaining studies, a total of 1,442 patients with vHL were available for analysis. Four hundred and twenty patients were examined for any type of pancreatic lesion, 362 for simple cysts or serous cystadenomas (SCAs), and 1,442 for neuroendocrine tumors (NETs). Of the 420 assessed for any pancreatic manifestation of vHL, 252 (60%) had a pancreatic lesion identified. Simple cysts that present as the sole manifestation of pancreatic disease were common and found in 169 of 362 (47%) patients. These are usually asymptomatic and do not normally require intervention. SCAs were reported in 39 of 362 (11%) patients and followed a similar benign course; resection is acceptable in symptomatic patients. NETs were identified in 211 of 1,442 (15%) patients, and 27 of 1,442 (2%) lesions behaved malignantly. Management of NETs depends on size, doubling time, and underlying genetics. Renal cell carcinoma is a characteristic in vHL, but there were no cases of pancreatic metastases identified from the included studies. Adenocarcinomas of the pancreas are not pathogenically linked to vHL.
CONCLUSIONS
This review highlights the wide spectrum and high prevalence of pancreatic lesions in vHL. Simple cysts and SCAs are benign, but NETs require careful observation due to their malignant potential.
Topics: Cystadenoma, Serous; Humans; Neuroendocrine Tumors; Pancreatic Cyst; Pancreatic Neoplasms; Prevalence; von Hippel-Lindau Disease
PubMed: 22370733
DOI: 10.1007/s11605-012-1847-0 -
European Journal of Surgical Oncology :... Jan 2018Identification of factors associated with dismal survival after surgery in resectable pancreatic ductal adenocarcinoma is important to select patients for neoadjuvant... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Identification of factors associated with dismal survival after surgery in resectable pancreatic ductal adenocarcinoma is important to select patients for neoadjuvant treatment. The present meta-analysis aimed to compare the results of distal pancreatectomy for resectable adenocarcinoma of the pancreatic body-tail with and without splenic vessels infiltration.
METHODS
A systematic search was performed of PubMed, Embase and the Cochrane Library in accordance with PRISMA guidelines. The inclusion criteria were studies including patients who underwent distal pancreatectomy for pancreatic cancer with or without splenic vessels infiltration. 5-year overall survival (OS) was the primary outcomes. Meta-analysis was carried out applying time-to-event method.
RESULTS
Six articles with 423 patients were analysed. Patients with pathological splenic artery invasion had a worse survival compared with those without infiltration (Hazard ratio 1.76, 95% CI 1.36-2.28; P < 0.0001). A similar results was found when considering pathological splenic vessels infiltration, showing that survival was significantly poorer when splenic vein infiltration was present (Hazard ratio 1.51, 95% CI 1.19-1.93; P = 0.0009).
CONCLUSIONS
This meta-analysis showed worse survival for patients with splenic vessels infiltration undergoing distal pancreatectomy for pancreatic cancer. Splenic vessels infiltration represents the stigmata of a more aggressive disease, although resectable.
Topics: Carcinoma, Pancreatic Ductal; Humans; Neoplasm Invasiveness; Neoplasm Staging; Pancreatectomy; Pancreatic Neoplasms; Prognosis; Splenic Artery
PubMed: 29183639
DOI: 10.1016/j.ejso.2017.10.217