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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 -
Medicine Aug 2018The contemporary demographics and prevalence of Meckel's diverticulum, clinical presentation and management is not well described. Thus, this article aims to review the... (Review)
Review
BACKGROUND
The contemporary demographics and prevalence of Meckel's diverticulum, clinical presentation and management is not well described. Thus, this article aims to review the recent literature concerning Meckel's diverticulum.
METHODS
A systematic PubMed/Medline database search using the terms "Meckel" and "Meckel's" combined with "diverticulum." English language articles published from January 1, 2000 to July 31, 2017 were considered. Studies reporting on the epidemiology of Meckel's diverticulum were included.
RESULTS
Of 857 articles meeting the initial search criteria, 92 articles were selected. Only 4 studies were prospective. The prevalence is reported between 0.3% and 2.9% in the general population. Meckels' diverticulum is located 7 to 200 cm proximal to the ileocecal valve (mean 52.4 cm), it is 0.4 to 11.0 cm long (mean 3.05 cm), 0.3 to 7.0 cm in diameter (mean 1.58 cm), and presents with symptoms in 4% to 9% of patients. The male-to-female (M:F 1.5-4:1) gender distribution is reported up to 4 times more frequent in men. Symptomatic patients are usually young. Of the pediatric symptomatic patients, 46.7% have obstruction, 25.3% have hemorrhage, and 19.5% have inflammation as presenting symptom. Corresponding values for adults are 35.6%, 27.3%, and 29.4%. Ectopic gastric tissue is present in 24.2% to 71.0% of symptomatic Meckel's diverticulum, is associated with hemorrhage and is the most common form of ectopic tissue, followed by ectopic pancreatic tissue present in 0% to 12.0%.
CONCLUSION
The epidemiological patterns and clinical presentation appears stable in the 21st century. A symptomatic Meckel's diverticulum is managed by resection. The issue of prophylactic in incidental Meckel's diverticulum resection remains controversial.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Choristoma; Disease Management; Female; Humans; Ileocecal Valve; Male; Meckel Diverticulum; Middle Aged; Pancreas; Prevalence; Sex Distribution; Stomach; Young Adult
PubMed: 30170459
DOI: 10.1097/MD.0000000000012154 -
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 -
Endocrine, Metabolic & Immune Disorders... 2021Type one diabetes mellitus (T1DM) is an autoimmune disease characterized by gradual destruction of beta cells in islets of Langerhans. Teplizumab is a humanized anti-... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Type one diabetes mellitus (T1DM) is an autoimmune disease characterized by gradual destruction of beta cells in islets of Langerhans. Teplizumab is a humanized anti- CD3 monoclonal antibody, which may have beneficial effects for T1DM patients.
OBJECTIVE
The aim of the study was to assess the safety and efficacy of teplizumab in T1DM patients.
METHODS
We searched electronic databases using related keywords for randomized clinical trials assessing the safety and efficacy of teplizumab. We evaluated the retrieved citations for eligibility, and we extracted the data and then analyzed it using Review Manager Software.
RESULTS
We included eight randomized clinical trials with 866 patients. Teplizumab was associated with lower insulin use than placebo at 6 months (MD = -0.17, 95% CI [-0.24, -0.09], P < 0.001), 12 months (MD = -0.12, 95% CI [-0.18, -0.06], P < 0.001), 18 months (MD = -0.22, 95% CI [-0.32, -0.11], P < 0.001) and 24 months (MD = -0.17, 95% CI [-0.28, -0.06], P = 0.003). The area under the curve of C-peptide was significantly increased in teplizumab group at 12 months (MD = 0.08, 95% CI [0.01, 0.15], P = 0.03), 18 months (MD = 0.13, 95% CI [0.01, 0.25], P = 0.03) and 24 months (MD = 0.13, 95% CI [0.01, 0.24], P = 0.03). No significant effect of teplizumab on HbA1c levels was observed at any time point. Teplizumab was found to be associated with some side effects such as lymphopenia, skin and subcutaneous tissue disorders.
CONCLUSION
Teplizumab is associated with lower insulin use and higher AUC of C-peptide in type 1 diabetic patients with no significant effect on Hb1c levels. Besides, teplizumab has shown some adverse effects.
Topics: Antibodies, Monoclonal, Humanized; Diabetes Mellitus, Type 1; Drug-Related Side Effects and Adverse Reactions; Glycated Hemoglobin; Humans; Insulin; Insulin-Secreting Cells; Treatment Outcome
PubMed: 33302842
DOI: 10.2174/1871530320999201209222921 -
World Journal of Gastroenterology Aug 2019Post endoscopic retrograde cholangiopancreatography (ERCP) is comparatively complex application. Researchers has been investigated prevention of post-ERCP pancreatitis...
BACKGROUND
Post endoscopic retrograde cholangiopancreatography (ERCP) is comparatively complex application. Researchers has been investigated prevention of post-ERCP pancreatitis (PEP), since it has been considered to be the most common complication of ERCP. Although ERCP can lead various complications, it can also be avoided.AIMSTo study the published evidence and systematically review the literature on the prevention and treatment for PEP.
METHODS
A systematic literature review on the prevention of PEP was conducted using the electronic databases of ISI Web of Science, PubMed and Cochrane Library for relevant articles. The electronic search for the review was performed by using the search terms "Post endoscopic retrograde cholangiopancreatography pancreatitis" AND "prevention" through different criteria. The search was restricted to randomized controlled trials (RCTs) performed between January 2009 and February 2019. Duplicate studies were detected by using EndNote and deleted by the author. PRISMA checklist and flow diagram were adopted for evaluation and reporting. The reference lists of the selected papers were also scanned to find other relevant studies.
RESULTS
726 studies meeting the search criteria and 4 relevant articles found in the edited books about ERCP were identified. Duplicates and irrelevant studies were excluded by screening titles and abstracts and assessing full texts. 54 studies were evaluated for full text review. Prevention methods were categorized into three groups as (1) assessment of patient related factors; (2) pharmacoprevention; and (3) procedural techniques for prevention. Most of studies in the literature showed that young age, female gender, absence of chronic pancreatitis, suspected Sphincter of Oddi dysfunction, recurrent pancreatitis and history of previous PEP played a crucial role in posing high risks for PEP. 37 studies designed to assess the impact of 24 different pharmacologic agents to reduce the development of PEP delivered through various administration methods were reviewed. Nonsteroidal anti-inflammatory drugs are widely used to reduce risks for PEP. Rectal administration of indomethacin immediately prior to or after ERCP in all patients is recommended by European Society for Gastrointestinal Endoscopy guidelines to prevent the development of PEP. The majority of the studies reviewed revealed that rectally administered indomethacin had efficacy to prevent PEP. Results of the other studies on the other pharmacological interventions had both controversial and promising results. Thirteen studies conducted to evaluate the efficacy of 4 distinct procedural techniques to prevent the development of PEP were reviewed. Pancreatic Stent Placement has been frequently used in this sense and has potent and promising benefits in the prevention of PEP. Studies on the other procedural techniques have had inconsistent results.
CONCLUSION
Prevention of PEP involves multifactorial aspects, including assessment of patients with high risk factors for alternative therapeutic and diagnostic techniques, administration of pharmacological agents and procedural techniques with highly precise results in the literature.
Topics: Administration, Rectal; Anti-Inflammatory Agents; Biliary Tract Diseases; Catheterization; Cholangiopancreatography, Endoscopic Retrograde; Drainage; Humans; Pancreas; Pancreatitis; Phosphodiesterase 5 Inhibitors; Postoperative Complications; Preoperative Care; Risk Assessment; Risk Factors; Somatostatin; Sphincter of Oddi; Stents
PubMed: 31413535
DOI: 10.3748/wjg.v25.i29.4019 -
Cancers Sep 2023Parenchymal-sparing approaches to pancreatectomy are technically challenging procedures but allow for preserving a normal pancreas and decreasing the rate of... (Review)
Review
BACKGROUND
Parenchymal-sparing approaches to pancreatectomy are technically challenging procedures but allow for preserving a normal pancreas and decreasing the rate of postoperative pancreatic insufficiency. The robotic platform is increasingly being used for these procedures. We sought to evaluate robotic parenchymal-sparing pancreatectomy and assess its complication profile and efficacy.
METHODS
This systematic review consisted of all studies on robotic parenchymal-sparing pancreatectomy (central pancreatectomy, duodenum-preserving partial pancreatic head resection, enucleation, and uncinate resection) published between January 2001 and December 2022 in PubMed and Embase.
RESULTS
A total of 23 studies were included in this review ( = 788). Robotic parenchymal-sparing pancreatectomy is being performed worldwide for benign or indolent pancreatic lesions. When compared to the open approach, robotic parenchymal-sparing pancreatectomies led to a longer average operative time, shorter length of stay, and higher estimated intraoperative blood loss. Postoperative pancreatic fistula is common, but severe complications requiring intervention are exceedingly rare. Long-term complications such as endocrine and exocrine insufficiency are nearly nonexistent.
CONCLUSIONS
Robotic parenchymal-sparing pancreatectomy appears to have a higher risk of postoperative pancreatic fistula but is rarely associated with severe or long-term complications. Careful patient selection is required to maximize benefits and minimize morbidity.
PubMed: 37686648
DOI: 10.3390/cancers15174369 -
Expert Review of Gastroenterology &... Aug 2018The pancreas plays a central role in metabolism and is involved in the pathogenesis of several diseases. Pancreas volume is a holistic quantitative measure of pancreas... (Meta-Analysis)
Meta-Analysis Review
The pancreas plays a central role in metabolism and is involved in the pathogenesis of several diseases. Pancreas volume is a holistic quantitative measure of pancreas size but the clinical relevance of pancreas volumetry is poorly understood. Areas covered: The aim was to systematically review studies in adults that used computed tomography or magnetic resonance imaging to measure pancreas volume in health and disease, to determine normal pancreas volume range, and to quantify changes in pancreas volume that are associated with disease. Expert commentary: The normal pancreas volume range in adults is 71-83 cm, with no statistically significant difference between men and women. Type 2 diabetes and type 1 diabetes are associated with a progressively reduced pancreas volume. Overweight and obesity are associated with a progressively increased pancreas volume. There is a paucity of studies on pancreas volume in the setting of diseases of the exocrine pancreas, which should become a research priority in the future.
Topics: Diabetes Complications; Healthy Volunteers; Humans; Magnetic Resonance Imaging; Organ Size; Overweight; Pancreas; Pancreatic Diseases; Reference Values; Tomography, X-Ray Computed
PubMed: 29972077
DOI: 10.1080/17474124.2018.1496015 -
Langenbeck's Archives of Surgery Aug 2023The systematic review is aimed to evaluate the cost-effectiveness of minimally invasive surgery (MIS) and open distal pancreatectomy and pancreaticoduodenectomy. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The systematic review is aimed to evaluate the cost-effectiveness of minimally invasive surgery (MIS) and open distal pancreatectomy and pancreaticoduodenectomy.
METHOD
The MEDLINE, CENTRAL, EMBASE, Centre for Reviews and Dissemination, and clinical trial registries were systematically searched using the PRISMA framework. Studies of adults aged ≥ 18 year comparing laparoscopic and/or robotic versus open DP and/or PD that reported cost of operation or index admission, and cost-effectiveness outcomes were included. The risk of bias of non-randomised studies was assessed using the Newcastle-Ottawa Scale, while the Cochrane Risk of Bias 2 (RoB2) tool was used for randomised studies. Standardised mean differences (SMDs) with 95% confidence intervals (CI) were calculated for continuous variables.
RESULTS
Twenty-two studies (152,651 patients) were included in the systematic review and 15 studies in the meta-analysis (3 RCTs; 3 case-controlled; 9 retrospective studies). Of these, 1845 patients underwent MIS (1686 laparoscopic and 159 robotic) and 150,806 patients open surgery. The cost of surgical procedure (SMD 0.89; 95% CI 0.35 to 1.43; I = 91%; P = 0.001), equipment (SMD 3.73; 95% CI 1.55 to 5.91; I = 98%; P = 0.0008), and operating room occupation (SMD 1.17, 95% CI 0.11 to 2.24; I = 95%; P = 0.03) was higher with MIS. However, overall index hospitalisation costs trended lower with MIS (SMD - 0.13; 95% CI - 0.35 to 0.06; I = 80%; P = 0.17). There was significant heterogeneity among the studies.
CONCLUSION
Minimally invasive major pancreatic surgery entailed higher intraoperative but similar overall index hospitalisation costs.
Topics: Adult; Humans; Pancreatectomy; Retrospective Studies; Cost-Benefit Analysis; Pancreas; Pancreaticoduodenectomy; Minimally Invasive Surgical Procedures; Laparoscopy
PubMed: 37572127
DOI: 10.1007/s00423-023-03017-w -
Cell Proliferation Oct 2023The liver is a common secondary metastasis site of many malignant tumours, such as the colorectum, pancreas, stomach, breast, prostate, and lung cancer. The clinical... (Review)
Review
The liver is a common secondary metastasis site of many malignant tumours, such as the colorectum, pancreas, stomach, breast, prostate, and lung cancer. The clinical management of liver metastases is challenging because of their strong heterogeneity, rapid progression, and poor prognosis. Now, exosomes, small membrane vesicles that are 40-160 nm in size, are released by tumour cells, namely, tumour-derived exosomes (TDEs), and are being increasingly studied because they can retain the original characteristics of tumour cells. Cell-cell communication via TDEs is pivotal for liver pre-metastatic niche (PMN) formation and liver metastasis; thus, TDEs can provide a theoretical basis to intensively study the potential mechanisms of liver metastasis and new insights into the diagnosis and treatment of liver metastasis. Here, we systematically review current research progress about the roles and possible regulatory mechanisms of TDE cargos in liver metastasis, focusing on the functions of TDEs in liver PMN formation. In addition, we discuss the clinical utility of TDEs in liver metastasis, including TDEs as potential biomarkers, and therapeutic approaches for future research reference in this field.
Topics: Humans; Exosomes; Liver Neoplasms; Cell Communication; Pancreas; Biomarkers, Tumor; Tumor Microenvironment; Neoplasm Metastasis
PubMed: 36941028
DOI: 10.1111/cpr.13452 -
HPB : the Official Journal of the... Feb 2022Central pancreatectomy is usually performed to excise lesions of the neck or proximal body of the pancreas. In the last decade, thanks to the advent of novel... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Central pancreatectomy is usually performed to excise lesions of the neck or proximal body of the pancreas. In the last decade, thanks to the advent of novel technologies, surgeons have started to perform this procedure robotically. This review aims to appraise the results and outcomes of robotic central pancreatectomies (RCP) through a systematic review and meta-analysis.
METHODS
A systematic search of MEDLINE, Embase, and Web Of Science identified studies reporting outcomes of RCP. Pooled prevalence rates of postoperative complications and mortality were computed using random-effect modelling.
RESULTS
Thirteen series involving 265 patients were included. In all cases but one, RCP was performed to excise benign or low-grade tumours. Clinically relevant post-operative pancreatic fistula (POPF) occurred in 42.3% of patients. While overall complications were reported in 57.5% of patients, only 9.4% had a Clavien-Dindo score ≥ III. Re-operation was necessary in 0.7% of the patients. New-onset diabetes occurred postoperatively in 0.3% of patients and negligible mortality and open conversion rates were observed.
CONCLUSION
RCP is safe and associated with low perioperative mortality and well preserved postoperative pancreatic function, although burdened by high overall morbidity and POPF rates.
Topics: Humans; Pancreas; Pancreatectomy; Pancreatic Fistula; Pancreatic Neoplasms; Postoperative Complications; Robotic Surgical Procedures
PubMed: 34625342
DOI: 10.1016/j.hpb.2021.09.014