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The Lancet. Gastroenterology &... Sep 2016There is a lack of robust estimates of the worldwide incidence and mortality of acute pancreatitis, chronic pancreatitis, pancreatic cysts, and pancreatic cancer in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is a lack of robust estimates of the worldwide incidence and mortality of acute pancreatitis, chronic pancreatitis, pancreatic cysts, and pancreatic cancer in the general population. Our aim was to quantitate and compare the incidence and mortality of major pancreatic diseases in high-quality population-based cohort studies.
METHODS
Three databases (PubMed, Embase, and Scopus) were searched independently by two reviewers. Data from eligible studies were subject to meta-analysis to obtain global estimates. A number of prespecified subgroup analyses and meta-regression analyses were also done.
FINDINGS
48 population-based cohort studies (35 on pancreatic cancer, ten on acute pancreatitis, three on chronic pancreatitis, and none on pancreatic cysts) were identified, with a total study population of 296 million individuals and 119 000 patients with pancreatic diseases. Global estimates of incidence and mortality were 8·14 cases (95% CI 6·63-9·98) per 100 000 person-years and 6·92 deaths (95% CI 3·72-12·89) per 100 000 person-years for pancreatic cancer, 33·74 cases (95% CI 23·33-48·81) per 100 000 person-years and 1·60 deaths (95% CI 0·85-1·58) per 100 000 person-years for acute pancreatitis, and 9·62 cases (95% CI 7·86-11·78) per 100 000 person-years and 0·09 deaths (95% CI 0·02-0·47) per 100 000 person-years for chronic pancreatitis. Subgroup analysis based on the WHO regions showed that the incidences of both pancreatic cancer and acute pancreatitis, and mortality from pancreatic cancer, were significantly higher in the American region than in the European and Western Pacific regions, while the incidence of chronic pancreatitis was significantly higher in the European region than in the American region. Mortality from pancreatic cancer was lowest in the Southeast Asian region. The incidence of chronic pancreatitis was twice as high in men as in women, although there was no difference between sexes for pancreatic cancer or acute pancreatitis.
INTERPRETATION
Globally, acute pancreatitis is the most common pancreatic disease whilst pancreatic cancer is the most lethal. However, their burden is not equal across the globe. The epidemiological estimates reported in this study could inform future high-quality studies.
FUNDING
None.
Topics: Cohort Studies; Global Health; Humans; Incidence; Pancreatic Diseases; Regression Analysis
PubMed: 28404111
DOI: 10.1016/S2468-1253(16)30004-8 -
Gut Aug 2017The benefits of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis (CP) are inadequately defined. We have undertaken a systematic review and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The benefits of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis (CP) are inadequately defined. We have undertaken a systematic review and meta-analysis of randomised controlled trials of PERT to determine the efficacy of PERT in exocrine pancreatic insufficiency (EPI) from CP.
DESIGN
Major databases were searched from 1966 to 2015 inclusive. The primary outcome was coefficient of fat absorption (CFA). Effects of PERT versus baseline and versus placebo, and of different doses, formulations and schedules were determined.
RESULTS
A total of 17 studies (511 patients with CP) were included and assessed qualitatively (Jadad score). Quantitative data were synthesised from 14 studies. PERT improved CFA compared with baseline (83.7±6.0 vs 63.1±15.0, p<0.00001; I=89%) and placebo (83.2±5.5 vs 67.4±7.0, p=0.0001; I=86%). PERT improved coefficient of nitrogen absorption, reduced faecal fat excretion, faecal nitrogen excretion, faecal weight and abdominal pain, without significant adverse events. Follow-up studies demonstrated that PERT increased serum nutritional parameters, improved GI symptoms and quality of life without significant adverse events. High-dose or enteric-coated enzymes showed a trend to greater effectiveness than low-dose or non-coated comparisons, respectively. Subgroup, sensitive and meta-regression analyses revealed that sample size, CP diagnostic criteria, study design and enzyme dose contributed to heterogeneity; data on health inequalities were lacking.
CONCLUSIONS
PERT is indicated to correct EPI and malnutrition in CP and may be improved by higher doses, enteric coating, administration during food and acid suppression. Further studies are required to determine optimal regimens, the impact of health inequalities and long-term effects on nutrition.
Topics: Dietary Fats; Enzyme Therapy; Enzymes; Exocrine Pancreatic Insufficiency; Feces; Humans; Nutritional Status; Pancreas; Pancreatitis, Chronic; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 27941156
DOI: 10.1136/gutjnl-2016-312529 -
Signal Transduction and Targeted Therapy Mar 2023Research on obesity- and diabetes mellitus (DM)-related carcinogenesis has expanded exponentially since these two diseases were recognized as important risk factors for...
Research on obesity- and diabetes mellitus (DM)-related carcinogenesis has expanded exponentially since these two diseases were recognized as important risk factors for cancers. The growing interest in this area is prominently actuated by the increasing obesity and DM prevalence, which is partially responsible for the slight but constant increase in pancreatic cancer (PC) occurrence. PC is a highly lethal malignancy characterized by its insidious symptoms, delayed diagnosis, and devastating prognosis. The intricate process of obesity and DM promoting pancreatic carcinogenesis involves their local impact on the pancreas and concurrent whole-body systemic changes that are suitable for cancer initiation. The main mechanisms involved in this process include the excessive accumulation of various nutrients and metabolites promoting carcinogenesis directly while also aggravating mutagenic and carcinogenic metabolic disorders by affecting multiple pathways. Detrimental alterations in gastrointestinal and sex hormone levels and microbiome dysfunction further compromise immunometabolic regulation and contribute to the establishment of an immunosuppressive tumor microenvironment (TME) for carcinogenesis, which can be exacerbated by several crucial pathophysiological processes and TME components, such as autophagy, endoplasmic reticulum stress, oxidative stress, epithelial-mesenchymal transition, and exosome secretion. This review provides a comprehensive and critical analysis of the immunometabolic mechanisms of obesity- and DM-related pancreatic carcinogenesis and dissects how metabolic disorders impair anticancer immunity and influence pathophysiological processes to favor cancer initiation.
Topics: Humans; Carcinogenesis; Diabetes Mellitus; Obesity; Pancreas; Pancreatic Neoplasms; Tumor Microenvironment
PubMed: 36964133
DOI: 10.1038/s41392-023-01376-w -
Annals of Surgical Oncology Jul 2023Pancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is... (Meta-Analysis)
Meta-Analysis Review
FOLFIRINOX or Gemcitabine-based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-institutional, Patient-Level, Meta-analysis and Systematic Review.
BACKGROUND
Pancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC.
METHODS
We performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based.
RESULTS
A total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC.
CONCLUSIONS
In patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.
Topics: Humans; Gemcitabine; Antineoplastic Combined Chemotherapy Protocols; Oxaliplatin; Pancreatic Neoplasms; Fluorouracil; Leucovorin; Neoadjuvant Therapy; Paclitaxel; Multicenter Studies as Topic
PubMed: 37020094
DOI: 10.1245/s10434-023-13353-2 -
Deutsches Arzteblatt International Jul 2022Acute pancreatitis (AP) is among the commonest non-malignant admission diagnoses in gastroenterology. Its incidence in Germany lies between 13 and 43 per 100 000...
BACKGROUND
Acute pancreatitis (AP) is among the commonest non-malignant admission diagnoses in gastroenterology. Its incidence in Germany lies between 13 and 43 per 100 000 inhabitants and is increasing. In 2017, 24 per 100 000 inhabitants were hospitalized for chronic pancreatitis.
METHODS
From October 2018 to January 2019, we systematically searched the literature for original articles, meta-analyses, and evidence-based guidelines that were published in German or English between 1960 and 2018.
RESULTS
30-50% of cases of acute pancreatitis are caused by gallstone disease, and another 30-50% are due to alcohol abuse. The diagnosis is made when at least two of the following three criteria are met: typical abdominal pain, elevation of serum lipase, and characteristic imaging findings. If those criteria are ambiguous, transabdominal sonography is indicated. The early initiation of food intake lowers the rate of infected pancreatic necrosis, organ failure, or death (odds ratio 0.44; 95% confidence interval [0.2; 0.96]). In AP, Ringer's lactate solution should be preferred for fluid resuscitation, at 200-250 mL/hr for 24 hours. Severe pain should be treated with opiates.
CONCLUSION
The current German clinical practice guideline reflects the developments in the diagnosis and treatment of pancreatitis that have taken place over the past few years. The long-term care and monitoring of patients with complication-free pancreatitis is the responsibility of primary care physicians and gastroenterologists.
Topics: Humans; Acute Disease; Fluid Therapy; Pancreatitis, Acute Necrotizing; Pancreatitis, Chronic; Meta-Analysis as Topic
PubMed: 35945698
DOI: 10.3238/arztebl.m2022.0223 -
The American Journal of Medicine Jun 2022Severe gestational hypertriglyceridemia can lead to acute pancreatitis, with maternal mortality rate of approximately 20%. The recent National Lipid Association part 2... (Review)
Review
Severe gestational hypertriglyceridemia can lead to acute pancreatitis, with maternal mortality rate of approximately 20%. The recent National Lipid Association part 2 expert panel recommendations provide guidance on monitoring pregnant women at high risk for hyperlipidemia. We suggest that high-risk women have triglyceride levels checked once every trimester. Fasting triglycerides >250 mg/dL should prompt monthly triglyceride levels, screening for gestational diabetes, and implementing a strict low-carbohydrate, low-fat diet, exercise. Fasting triglycerides >500 mg/dL, despite a strict dietary and lifestyle modifications, should prompt treatment with omega-3-fatty acids and continue a fat-restricted diet (<20 g total fat/d or <15% total calories) under the guidance of a registered dietician. The use of fibrates should be considered as a second-line therapy due to their unclear risk versus benefit and potential teratogenic effects. Plasmapheresis should be considered early in asymptomatic pregnant women with fasting triglyceride levels >1000 mg/dL or in pregnant women with clinical signs and symptoms of pancreatitis and triglyceride levels >500 mg/dL despite maximal lifestyle changes and pharmacologic therapy.
Topics: Acute Disease; Female; Humans; Hypertriglyceridemia; Pancreatitis; Plasmapheresis; Pregnancy; Triglycerides
PubMed: 35081380
DOI: 10.1016/j.amjmed.2021.12.006 -
HPB : the Official Journal of the... Nov 2021Adequate fluid resuscitation is paramount in the management of acute pancreatitis (AP). The aim of this study is to assess benefits and harms of fluid therapy protocols... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Adequate fluid resuscitation is paramount in the management of acute pancreatitis (AP). The aim of this study is to assess benefits and harms of fluid therapy protocols in patients with AP.
METHODS
MEDLINE, Embase, Science Citation Index and clinical trial registries were searched for randomised clinical trials published before May 2020, assessing types of fluids, routes and rates of administration.
RESULTS
A total 15 trials (1073 participants) were included. Age ranged from 38 to 73 years; follow-up period ranged from 0.5 to 6 months. Ringer lactate (RL) showed a reduced number of severe adverse events (SAE) when compared to normal saline (NS) (OR 0.48; 95%CI 0.29-0.81, p = 0.006); additionally, NS showed reduced SAE (RR 0.38; 95%IC 0.27-0.54, p < 0.001) and organ failure (RR 0.30; 95%CI 0.21-0.44, p < 0.001) in comparison with hydroxyethyl starch (HES). High fluid rate fluid infusion showed increased mortality (OR 2.88; 95%CI 1.41-5.88, p = 0.004), increased number of SAE (RR 1.42; 95%CI 1.04-1.93, p = 0.030) and higher incidence of sepsis (RR 2.80; 95%CI 1.51-5.19, p = 0.001) compared to moderate fluid rate infusion.
CONCLUSIONS
In patients with AP, RL should be preferred over NS and HES should not be recommended. Based on low-certainty evidence, moderate-rate fluid infusion should be preferred over high-rate infusion.
Topics: Child; Child, Preschool; Humans; Acute Disease; Fluid Therapy; Pancreatitis; Sepsis; Clinical Protocols
PubMed: 34325967
DOI: 10.1016/j.hpb.2021.06.426 -
Correlation between pancreatic cancer and metabolic syndrome: A systematic review and meta-analysis.Frontiers in Endocrinology 2023Pancreatic cancer is a globally frequent cause of death, which can be caused by many factors. This meta-analysis was performed to assess the correlation between... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Pancreatic cancer is a globally frequent cause of death, which can be caused by many factors. This meta-analysis was performed to assess the correlation between pancreatic cancer and metabolic syndrome (MetS).
METHODS
Publications were identified by searching PubMed, EMBASE, and the Cochrane Library for studies published until November 2022. Case-control and cohort studies published in English that provided information on the odds ratio (OR), relative risk (RR), or hazard ratio (HR) of metabolic syndrome and pancreatic cancer were included in the meta-analysis. Two researchers separately retrieved the core data from the included Random effects meta-analysis was conducted to summarize the findings. Results were presented as relative risk (RR) and 95% confidence interval (CI).
RESULTS
MetS showed a strong association with an increased risk of developing pancreatic cancer (RR1.34, 95% CI1.23-1.46, <0.001), and gender differences were also observed (men: RR 1.26, 95% CI 1.03-1.54, =0.022; women: RR 1.64, 95% CI 1.41-1.90, < 0.001). Moreover, an increased risk of developing pancreatic cancer was strongly linked to hypertension, poor high-density lipoprotein cholesterol, and hyperglycemia (hypertension: RR 1.10 CI 1.01-1.19, =0.027; low high-density lipoprotein cholesterol: RR 1.24 CI 1.11-1.38, <0.001; hyperglycemia: RR 1.55, CI 1.42-1.70, < 0.001). However, pancreatic cancer was independent of obesity and hypertriglyceridemia (obesity: RR 1.13 CI 0.96-1.32, =0.151, hypertriglyceridemia: RR 0.96, CI 0.87-1.07, =0.486).
CONCLUSIONS
Although further prospective studies are required for confirmation, this meta-analysis indicated a strong relationship between MetS and pancreatic cancer. Regardless of gender, a greater risk of pancreatic cancer existed in people with MetS. Patients with MetS were more likely to develop pancreatic cancer, regardless of gender. Hypertension, hyperglycemia, and low HDL-c levels may largely account for this association. Further, the prevalence of pancreatic cancer was independent of obesity and hypertriglyceridemia.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022368980.
Topics: Male; Humans; Female; Metabolic Syndrome; Obesity; Hyperglycemia; Hypertension; Hyperlipidemias; Hypertriglyceridemia; Pancreatic Neoplasms; Lipoproteins, HDL; Cholesterol
PubMed: 37113491
DOI: 10.3389/fendo.2023.1116582 -
JAMA Surgery Jun 2023The incidence of chronic pancreatitis is 5 to 12 per 100 000 adults in industrialized countries, and the incidence is increasing. Treatment is multimodal, and involves...
IMPORTANCE
The incidence of chronic pancreatitis is 5 to 12 per 100 000 adults in industrialized countries, and the incidence is increasing. Treatment is multimodal, and involves nutrition optimization, pain management, and when indicated, endoscopic and surgical intervention.
OBJECTIVES
To summarize the most current published evidence on etiology, diagnosis, and management of chronic pancreatitis and its associated complications.
EVIDENCE REVIEW
A literature search of Web of Science, Embase, Cochrane Library, and PubMed was conducted for publications between January 1, 1997, and July 30, 2022. Excluded from review were the following: case reports, editorials, study protocols, nonsystematic reviews, nonsurgical technical publications, studies pertaining to pharmacokinetics, drug efficacy, pilot studies, historical papers, correspondence, errata, animal and in vitro studies, and publications focused on pancreatic diseases other than chronic pancreatitis. Ultimately, the highest-level evidence publications were chosen for inclusion after analysis by 2 independent reviewers.
FINDINGS
A total of 75 publications were chosen for review. First-line imaging modalities for diagnosis of chronic pancreatitis included computed tomography and magnetic resonance imaging. More invasive techniques such as endoscopic ultrasonography allowed for tissue analysis, and endoscopic retrograde cholangiopancreatography provided access for dilation, sphincterotomy, and stenting. Nonsurgical options for pain control included behavior modification (smoking cessation, alcohol abstinence), celiac plexus block, splanchnicectomy, nonopioid pain medication, and opioids. Supplemental enzymes should be given to patients with exocrine insufficiency to avoid malnutrition. Surgery was superior to endoscopic interventions for long-term pain control, and early surgery (<3 years from symptom onset) had more superior outcomes than late surgery. Duodenal preserving strategies were preferred unless there was suspicion of cancer.
CONCLUSIONS AND RELEVANCE
Results of this systematic review suggest that patients with chronic pancreatitis had high rates of disability. Strategies to improve pain control through behavioral modification, endoscopic measures, and surgery must also accompany management of the sequalae of complications that arise from endocrine and exocrine insufficiency.
Topics: Humans; Pancreatitis, Chronic; Cholangiopancreatography, Endoscopic Retrograde; Pain; Pain Management; Endosonography
PubMed: 37074693
DOI: 10.1001/jamasurg.2023.0367 -
Pancreatology : Official Journal of the... Nov 2023Mucinous pancreatic cysts harbor the potential to progress to highly lethal pancreatic ductal adenocarcinoma (PDAC). Since these precursor cysts require cancer... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mucinous pancreatic cysts harbor the potential to progress to highly lethal pancreatic ductal adenocarcinoma (PDAC). Since these precursor cysts require cancer surveillance or surgical resection, they need to be reliably distinguished from harmless pancreatic cysts. Current clinical and radiographic assessment is imperfect and the value of cyst fluid analysis for differential diagnosis is unclear. Therefore, we set out to investigate the value of cyst fluid biomarkers in distinguishing pancreatic cysts.
METHODS
We performed a systematic review of the current literature to identify articles that evaluated the diagnostic performance of clinically relevant and promising candidate cyst fluid biomarkers, with a particular emphasis on DNA-based biomarkers. Meta-analysis was performed for biomarkers targeted at identifying cyst type and presence of high-grade dysplasia or PDAC.
RESULTS
Data from a total of 42 studies was analyzed. Mutations in KRAS and/or GNAS allowed identification of mucinous cysts with a sensitivity of 79% and specificity of 98%. This exceeded the performance of the traditional biomarker carcinoembryonic antigen (CEA; sensitivity 58%, specificity 87%). Mutations in VHL were specific for serous cystadenomas (SCAs; sensitivity 56%, specificity 99%) and help to exclude mucinous cysts. Mutations in CDKN2A, PIK3CA, SMAD4, and TP53 each had high specificities of 97%, 97%, 98%, and 95%, respectively, to identify high-grade dysplasia or PDAC in mucinous cysts.
CONCLUSIONS
Cyst fluid analysis can be a valuable tool in the characterization of pancreatic cysts, with relevant clinical implications. Our results support the use of DNA-based cyst fluid biomarkers in the multidisciplinary diagnostic work-up of pancreatic cysts.
Topics: Humans; Cyst Fluid; Pancreatic Neoplasms; Carcinoembryonic Antigen; Carcinoma, Pancreatic Ductal; Pancreatic Cyst; DNA; Biomarkers, Tumor
PubMed: 37230894
DOI: 10.1016/j.pan.2023.05.005