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The Cochrane Database of Systematic... Aug 2017Cystic fibrosis is an autosomal recessive inherited defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene resulting in abnormal regulation of... (Review)
Review
BACKGROUND
Cystic fibrosis is an autosomal recessive inherited defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene resulting in abnormal regulation of salt and water movement across the membranes. In the liver this leads to focal biliary fibrosis resulting in progressive portal hypertension and end-stage liver disease in some individuals. This can be asymptomatic, but may lead to splenomegaly and hypersplenism, development of varices and variceal bleeding, and ascites; it has negative impact on overall nutritional status and respiratory function in this population. Prognosis is poor once significant portal hypertension is established. The role and outcome of various interventions for managing advanced liver disease (non-malignant end stage disease) in people with cystic fibrosis is currently unidentified.
OBJECTIVES
To review and assess the efficacy of currently available treatment options for preventing and managing advanced liver disease in children and adults with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books.Date of last search: 06 April 2017.We also searched the reference lists of relevant articles and reviews and online trials registries. Date of last search: 04 January 2017.
SELECTION CRITERIA
Any published and unpublished randomised controlled trials and quasi-randomised controlled trials of advanced liver disease in cystic fibrosis with cirrhosis or liver failure, portal hypertension or variceal bleeding (or both).
DATA COLLECTION AND ANALYSIS
Authors independently examined titles and abstracts to identify potentially relevant trials, but none were eligible for inclusion in this review.
MAIN RESULTS
A comprehensive search of the literature did not identify any published eligible randomised controlled trials.
AUTHORS' CONCLUSIONS
In order to develop the best source of evidence, there is a need to undertake randomised controlled trials of interventions for preventing and managing advanced liver disease in adults and children with cystic fibrosis.
Topics: Cystic Fibrosis; Humans; Liver Diseases
PubMed: 28850173
DOI: 10.1002/14651858.CD012056.pub2 -
JCO Precision Oncology Jan 2023With the growing number of available targeted therapeutics and molecular biomarkers, the optimal care of patients with cancer now depends on a comprehensive...
PURPOSE
With the growing number of available targeted therapeutics and molecular biomarkers, the optimal care of patients with cancer now depends on a comprehensive understanding of the rapidly evolving landscape of precision oncology, which can be challenging for oncologists to navigate alone.
METHODS
We developed and implemented a precision oncology decision support system, GI TARGET, (Gastrointestinal Treatment Assistance Regarding Genomic Evaluation of Tumors) within the Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute. With a multidisciplinary team, we systematically reviewed tumor molecular profiling for GI tumors and provided molecularly informed clinical recommendations, which included identifying appropriate clinical trials aided by the computational matching platform MatchMiner, suggesting targeted therapy options on or off the US Food and Drug Administration-approved label, and consideration of additional or orthogonal molecular testing.
RESULTS
We reviewed genomic data and provided clinical recommendations for 506 patients with GI cancer who underwent tumor molecular profiling between January and June 2019 and determined follow-up using the electronic health record. Summary reports were provided to 19 medical oncologists for patients with colorectal (n = 198, 39%), pancreatic (n = 124, 24%), esophagogastric (n = 67, 13%), biliary (n = 40, 8%), and other GI cancers. We recommended ≥ 1 precision medicine clinical trial for 80% (406 of 506) of patients, leading to 24 enrollments. We recommended on-label and off-label targeted therapies for 6% (28 of 506) and 25% (125 of 506) of patients, respectively. Recommendations for additional or orthogonal testing were made for 42% (211 of 506) of patients.
CONCLUSION
The integration of precision medicine in routine cancer care through a dedicated multidisciplinary molecular tumor board is scalable and sustainable, and implementation of precision oncology recommendations has clinical utility for patients with cancer.
Topics: Humans; Precision Medicine; Medical Oncology; Gastrointestinal Neoplasms; Genomics; Molecular Diagnostic Techniques
PubMed: 36634297
DOI: 10.1200/PO.22.00342 -
Nutrients Nov 2022Prebiotic and probiotic supplementation and yogurt consumption (a probiotic food) alter gut microbial diversity, which may influence colorectal carcinogenesis. This... (Review)
Review
Prebiotic and probiotic supplementation and yogurt consumption (a probiotic food) alter gut microbial diversity, which may influence colorectal carcinogenesis. This systematic review evaluates the existing literature on the effect of these nutritional supplements and yogurt consumption on colorectal neoplasia incidence among adults. We systematically identified ten randomized controlled trials and observational studies in adults age ≥ 18 without baseline gastrointestinal disease. Prebiotics included inulin, fructooligosaccharides, galactooligosaccharides, xylooligosaccharides, isomaltooligosaccharides, and β-glucans. Probiotics included bacterial strains of Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, Bacillus, Pediococcus, Leuconostoc, and Escherichia coli. Synbiotic supplements, a mixture of both prebiotic and probiotic supplements, and yogurt, a commonly consumed dietary source of live microbes, were also included. We defined colorectal neoplasia as colorectal adenomas, sessile serrated polyps, and colorectal cancer (CRC). Overall, findings suggest a moderate decrease in risk of adenoma and CRC for high levels of yogurt consumption compared to low or no consumption. Prebiotic supplementation was not associated with colorectal neoplasia risk. There was some evidence that probiotic supplementation may be associated with lower risk of adenomas but not with CRC incidence. Higher yogurt consumption may be associated with lower incidence of colorectal neoplasia. We found little evidence to suggest that prebiotic or probiotic supplements are associated with significant decreases in CRC occurrence.
Topics: Humans; Prebiotics; Yogurt; Synbiotics; Probiotics; Colorectal Neoplasms
PubMed: 36432622
DOI: 10.3390/nu14224937 -
International Journal of Clinical... Feb 2018In exocrine pancreatic insufficiency (EPI), the quantity and/or activity of pancreatic digestive enzymes are below the levels required for normal digestion, leading to... (Review)
Review
AIMS
In exocrine pancreatic insufficiency (EPI), the quantity and/or activity of pancreatic digestive enzymes are below the levels required for normal digestion, leading to maldigestion and malabsorption. Diagnosis of EPI is often challenging because the characteristic signs and symptoms overlap with those of other gastrointestinal conditions. Additionally, there is no single convenient, or specific diagnostic test for EPI. The aim of this review is to provide a framework for differential diagnosis of EPI vs other malabsorptive conditions.
METHODS
This is a non-systematic narrative review summarising information pertaining to the aetiology, diagnosis and management of EPI.
RESULTS
Exocrine pancreatic insufficiency may be caused by pancreatic disorders, including chronic pancreatitis, cystic fibrosis, pancreatic resection and pancreatic cancer. EPI may also result from extra-pancreatic conditions, including coeliac disease, Zollinger-Ellison syndrome and gastric surgery. Timely and accurate diagnosis of EPI is important, as delays in treatment prolong maldigestion and malabsorption, with potentially serious consequences for malnutrition, overall health and quality of life. Symptoms of EPI are non-specific; therefore, a high index of clinical suspicion is required to make a correct diagnosis.
Topics: Diagnosis, Differential; Exocrine Pancreatic Insufficiency; Humans; Malabsorption Syndromes; Quality of Life
PubMed: 29405509
DOI: 10.1111/ijcp.13066 -
Archives of Osteoporosis Feb 2022Osteopenia typically presents low bone mineral density (BMD) and has recently been reported as a prognostic factor in various cancers. However, the prognostic value of... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Osteopenia typically presents low bone mineral density (BMD) and has recently been reported as a prognostic factor in various cancers. However, the prognostic value of osteopenia in digestive tract cancers remains to be defined. We aimed to review the prognostic value of preoperative osteopenia in patients with digestive cancers.
METHODS
Cohort studies evaluating the prognostic value of preoperative osteopenia in digestive cancers (colorectal, esophageal, hepatic, bile duct, and pancreatic cancer) were searched using electronic databases and trial registries. The exposure was defined as low BMD estimated by computed tomography at 11 thoracic vertebra, while comparator was normal BMD. The primary outcomes were overall survival and recurrence-free survival for osteopenia. Random effect meta-analyses were performed. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to assess the certainty of evidence.
RESULTS
A total of 11 studies (2230 patients) were included. Osteopenia was an independent risk factor for overall survival (hazard ratio [HR] = 2.02, 95% CI = 1.47 to 2.78; I = 74%), along with sarcopenia. Osteopenia also predicted poor recurrence-free survival (HR = 1.96, 95% CI = 1.36 to 2.81; I = 85%). In subgroup analyses, osteopenia predicted prognosis in colorectal, esophageal, hepatic, and bile duct cancers, but not in pancreatic cancer. The certainty of the evidence was low due to inconsistency and publication bias.
CONCLUSION
Osteopenia may be independently associated with poor prognosis in patients with digestive tract cancer. Further studies are needed to establish the relevance of osteopenia in the operative prognosis of these patients.
Topics: Bone Diseases, Metabolic; Humans; Pancreatic Neoplasms; Prognosis; Sarcopenia; Tomography, X-Ray Computed
PubMed: 35149903
DOI: 10.1007/s11657-022-01060-6 -
The Cochrane Database of Systematic... Feb 2016Cystic fibrosis is the most common, life-threatening, recessively inherited disease of Caucasian populations. It is a multisystem disorder caused by a mutation in the... (Review)
Review
BACKGROUND
Cystic fibrosis is the most common, life-threatening, recessively inherited disease of Caucasian populations. It is a multisystem disorder caused by a mutation in the gene encoding the cystic fibrosis transmembrane conductance regulator protein which is important in producing sweat, digestive juices and mucus.The impaired or absent function of this protein results in the production of viscous mucus within the lungs and an environment that is susceptible to chronic airway obstruction and pulmonary colonization by a range of pathogenic bacteria. Morbidity and mortality of cystic fibrosis is related to chronic pulmonary sepsis and its complications by these bacteria.Influenza can worsen the course of the disease in cystic fibrosis by increasing the risk of pneumonia and secondary respiratory complications. Antiviral agents form an important part of influenza management and include the neuraminidase inhibitors zanamivir and oseltamivir. These inhibitors can limit the infection and prevent the spread of the virus.
OBJECTIVES
To assess the effects of neuraminidase inhibitors for the treatment of influenza infection in people with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 02 November 2015.
SELECTION CRITERIA
Randomised controlled trials and quasi-randomised controlled trials comparing neuraminidase inhibitors with placebo or other antiviral drugs.
DATA COLLECTION AND ANALYSIS
Two review authors had planned to independently screen studies, extract data and assess risk of bias using standard Cochrane methodologies. No studies were identified for inclusion.
MAIN RESULTS
No relevant studies were retrieved after a comprehensive search of the literature.
AUTHORS' CONCLUSIONS
We were unable to identify any randomised controlled studies or quasi-randomised controlled studies on the efficacy of neuraminidase inhibitors for the treatment of influenza infection in people with cystic fibrosis. The absence of high level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately powered, randomised controlled clinical studies.
Topics: Cystic Fibrosis; Enzyme Inhibitors; Humans; Influenza, Human; Neuraminidase
PubMed: 26905631
DOI: 10.1002/14651858.CD008139.pub4 -
European Journal of Gastroenterology &... Dec 2023The effect of gallstones and cholecystectomy on the development of pancreatic cancer has recently prompted many population-based studies. However, the results are... (Meta-Analysis)
Meta-Analysis
The effect of gallstones and cholecystectomy on the development of pancreatic cancer has recently prompted many population-based studies. However, the results are controversial. We conducted an updated systematic review and meta-analysis to explore the causality among gallstones, cholecystectomy and pancreatic cancer. Cohort studies published in the PubMed, Web of Science, Embase, and Cochrane Library databases up to May 2023 were retrieved. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were analyzed using a random-effects model. We screened 1391 articles and included 16 studies. Gallstones were not associated with an increased risk of pancreatic cancer ( P = 0.082), with only the Asian population ( P = 0.011) showing an increased risk in the subgroup analysis. A markedly higher risk of pancreatic cancer was observed among patients with cholecystectomy (RR = 1.23; 95% CI, 1.07-1.41; P = 0.004; I 2 = 74.4%). The association remained significant in the Asian population ( P = 0.004), in the subgroup analyses stratified by sex, lag period, and time interval since cholecystectomy, and when the models were adjusted for diabetes, smoking, and BMI. Interestingly, cholecystectomy due to gallstones (RR = 1.30; 95% CI, 1.14-1.48; P < 0.001; I 2 = 30.8%), rather than for unspecified reasons ( P = 0.116), markedly increased the risk of pancreatic cancer. In conclusion, cholecystectomy due to gallstones, rather than gallstone formation, conferred an increased risk for pancreatic cancer. There was a higher risk for the Asian population for both gallstones and cholecystectomy.
Topics: Humans; Gallstones; Cholecystectomy; Cohort Studies; Risk; Pancreatic Neoplasms
PubMed: 37823406
DOI: 10.1097/MEG.0000000000002652 -
Nutrients Mar 2023Liver cirrhosis leads to clinically significant portal hypertension. Transjugular intrahepatic portosystemic shunt (TIPS) has been shown to effectively reduce the degree... (Review)
Review
BACKGROUND AND AIMS
Liver cirrhosis leads to clinically significant portal hypertension. Transjugular intrahepatic portosystemic shunt (TIPS) has been shown to effectively reduce the degree of portal hypertension and treat its complications. However, poor nutritional status has been shown to be associated with hepatic encephalopathy, acute on chronic liver failure, and mortality following TIPS placement. The purpose of this systematic review is to create another perspective and evaluate the effect of TIPS placement on the nutritional status of patients with liver cirrhosis.
METHODS
A comprehensive search of four major electronic databases was conducted to identify studies that assessed the nutritional status of cirrhotic patients before and after TIPS placement. The risk of bias was evaluated using ROBINS-I guidelines.
RESULTS
Fifteen studies were analyzed in this review. The results indicate that among the 11 studies that evaluated changes in ascites-free weight and body mass index or body cell mass, 10 reported an improvement in one or more measures. Furthermore, all seven studies that evaluated changes in muscle mass demonstrated an increase in muscle mass. Among the four studies that evaluated subcutaneous fat tissue, three showed a significant expansion, while two out of three studies evaluating visceral fat tissue reported a significant reduction.
CONCLUSIONS
The results of this systematic review suggest that TIPS placement is associated with improvement in the nutritional status of cirrhotic patients, indicated by an increase in ascites-free weight, body mass index, and muscle mass. Additionally, TIPS placement leads to a shift in the distribution of fat mass, with a preference for subcutaneous over visceral adipose tissue. Notably, sarcopenic patients seem to benefit the most from TIPS placement in terms of nutritional status.
Topics: Humans; Portasystemic Shunt, Transjugular Intrahepatic; Nutritional Status; Liver Cirrhosis; Hypertension, Portal; Hepatic Encephalopathy; Ascites
PubMed: 37049459
DOI: 10.3390/nu15071617 -
Hepatology Communications Jan 2024Primary sclerosing cholangitis (PSC) is an immune-mediated, chronic cholestatic liver disease. Currently, liver transplantation is the only established life-saving... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Primary sclerosing cholangitis (PSC) is an immune-mediated, chronic cholestatic liver disease. Currently, liver transplantation is the only established life-saving treatment. Several studies have evaluated the effect of different biologic therapies on PSC with inconclusive findings. We conducted a systematic review and meta-analysis to assess the effects of biologics in PSC and associated inflammatory bowel disease (IBD).
METHODS
MEDLINE, Scopus, and Embase were searched up to July 31, 2023, for studies reporting the effects of biologics in patients with PSC-IBD. Effects of biologic therapy on alkaline phosphatase, total bilirubin, ulcerative colitis response score, and adverse events were calculated and expressed as standardized difference of means (SMD), proportions, and 95% CI using a random-effects model.
RESULTS
Six studies, including 411 PSC-IBD patients who received biologics, were included. Biologic treatment was associated with no change in alkaline phosphatase (SMD: 0.1, 95% CI: -0.07 -0.17, p=0.43), but a small and statistically significant increase in total bilirubin (SMD: 0.2, 95% CI: 0.05-0.35, p<0.01). 31.2% (95% CI: 23.8-39.7) of patients with IBD achieved endoscopic response, and there was a significant improvement in ulcerative colitis response score (SMD: -0.6,95% CI: -0.88 to 0.36, p<0.01). Furthermore, 17.6% (95% CI: 13.0-23.5) of patients experienced adverse events severe enough to discontinue therapy, and 29.9% (95% CI: 25.2-34.8) had a loss of response to biologics.
CONCLUSIONS
Treatment of patients with PSC-IBD with biologics (vedolizumab, infliximab, and adalimumab) was not associated with improvement of biochemical markers of cholestasis. Biologics are effective in treating the colitis associated with PSC. Vedolizumab was associated with worsening liver enzymes in contrast to other biologics, a finding that warrants further study.
Topics: Humans; Colitis, Ulcerative; Alkaline Phosphatase; Cholangitis, Sclerosing; Inflammatory Bowel Diseases; Bilirubin; Cholestasis; Biological Products
PubMed: 38206197
DOI: 10.1097/HC9.0000000000000347 -
BMC Cancer Jul 2022Despite the understanding of the COP9 signalosome subunit 5 (CSN5) in tumor genesis, there is no conclusive evidence on its value to predict the survival and prognosis... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite the understanding of the COP9 signalosome subunit 5 (CSN5) in tumor genesis, there is no conclusive evidence on its value to predict the survival and prognosis of digestive system tumor patients. Hence this study aimed to evaluate the impact of CSN5 levels on the survival and clinicopathological parameters of digestive system neoplasm patients.
METHODS
First, a comprehensive search was conducted in four databases. We utilized the Hazard Ratio (HR) with a 95% confidence interval (CI) to evaluate the prognostic value of CSN5 for the overall survival (OS) and recurrence-free survival (RFS) of patients. Then, we estimated the connection between CSN5 and the clinicopathological parameters based on the Odds Ratio (OR) with the corresponding 95% CI.
RESULTS
This meta-analysis included 22 studies and 2193 patients diagnosed with digestive system tumors. High expression of CSN5 was correlated to poorer OS (HR = 2.28, 95% CI: 1.71-3.03; p < 0.00001). Additionally, high CSN5 levels were correlated with worse invasion depth (OR = 0.49, 95% CI: 0.25-0.96, p = 0.04), positive lymphatic metastasis (OR = 0.28, 95% CI: 0.16-0.47, p = 0.00001), positive distant metastasis (OR = 0.32, 95% CI: 0.13-0.76, p = 0.01) and poorer differentiation degree (OR = 0.34, 95% CI: 0.19-0.60, p = 0.0003). However, we did not detect a correlation between CSN5 expression and age, gender, tumor stage, tumor size or vascular invasion. Furthermore, no significant publication bias was detected.
CONCLUSION
This meta-analysis demonstrated that the overexpression of CSN5 level might foresee poorer OS in digestive system cancer patients. Additionally, CSN5 levels might be related to the prognosis of digestive system tumors.
Topics: Biomarkers, Tumor; Digestive System Neoplasms; Humans; Lymphatic Metastasis; Prognosis; Proportional Hazards Models
PubMed: 35870903
DOI: 10.1186/s12885-022-09867-9