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The American Journal of Gastroenterology Mar 2019Subtle histopathologic features such as eosinophilia and increased mast cells have been observed in functional gastrointestinal disorders (FGIDs), including functional...
BACKGROUND
Subtle histopathologic features such as eosinophilia and increased mast cells have been observed in functional gastrointestinal disorders (FGIDs), including functional dyspepsia (FD) and the irritable bowel syndrome (IBS). The mechanisms that drive recruitment of these cells to the gastrointestinal tract remain unexplained, largely due to the heterogeneity in phenotypes among patients diagnosed with such conditions. We aimed to systematically review the literature and collate the evidence for immune activation in FD and IBS, and where possible, detail the nature of activation.
METHODS
Seven literature databases were searched using the keywords: 'functional gastrointestinal disorder', FGID, 'functional dyspepsia', 'non-ulcer dyspepsia', 'idiopathic dyspepsia', 'irritable bowel syndrome', IBS and 'immun*'.
RESULTS
Fifty-one papers reporting discordant immune features met the selection criteria for this review. Changes in lymphocyte populations, including B and T lymphocyte numbers and activation status were reported in IBS and FD, in conjunction with duodenal eosinophilia in FD and increased colonic mast cells in IBS. Increases in circulating α4+β7+ gut-homing T cells appear to be linked to the pathophysiology of both FD and IBS. Studies in the area are complicated by poor phenotyping of patients into subgroups and the subtle nature of the immune activity involved in FD and IBS.
CONCLUSIONS
Alterations in proportions of gut-homing T lymphocytes in both FD and IBS indicate that a loss of mucosal homeostasis may drive the symptoms of FD and IBS. There is indirect evidence that Th17 responses may play a role in FGIDs, however the evidence for a Th2 immune phenotype in FD and IBS is limited. Although immune involvement is evident, large, well-characterised patient cohorts are required to elucidate the immune mechanisms driving the development of FGIDs.
Topics: B-Lymphocytes; Colon; Duodenum; Dyspepsia; Eosinophilia; Gastrointestinal Diseases; Humans; Irritable Bowel Syndrome; Lymphocyte Activation; Lymphocyte Count; Mast Cells; T-Lymphocytes; Th17 Cells; Th2 Cells
PubMed: 30839392
DOI: 10.1038/s41395-018-0377-0 -
Frontiers in Pharmacology 2018Short-term use of standard-dose proton pump inhibitors (PPIs) is the first-line initial non-eradication treatment for duodenal ulcer (DU), but the choice on individual...
Standard-Dose Proton Pump Inhibitors in the Initial Non-eradication Treatment of Duodenal Ulcer: Systematic Review, Network Meta-Analysis, and Cost-Effectiveness Analysis.
Short-term use of standard-dose proton pump inhibitors (PPIs) is the first-line initial non-eradication treatment for duodenal ulcer (DU), but the choice on individual PPI drug is still controversial. The purpose of this study is to compare the efficacy, safety, and cost-effectiveness of standard-dose PPI medications in the initial non-eradication treatment of DU. We searched PubMed, Embase, Cochrane Library, Clinicaltrials.gov, China National Knowledge Infrastructure, VIP database, and the Wanfang database from their earliest records to September 2017. Randomized controlled trials (RCTs) evaluating omeprazole (20 mg/day), pantoprazole (40 mg/day), lansoprazole (30 mg/day), rabeprazole (20 mg/day), ilaprazole (10 mg/day), ranitidine (300 mg/day), famotidine (40 mg/day), or placebo for DU were included. The outcomes were 4-week ulcer healing rate (4-UHR) and the incidence of adverse events (AEs). A network meta-analysis (NMA) using a Bayesian random effects model was conducted, and a cost-effectiveness analysis using a decision tree was performed from the payer's perspective over 1 year. A total of 62 RCTs involving 10,339 participants (eight interventions) were included. The NMA showed that all the PPIs significantly increased the 4-UHR compared to H receptor antagonists (HRA) and placebo, while there was no significant difference for 4-UHR among PPIs. As to the incidence of AEs, no significant difference was observed among PPIs, HRA, and placebo during 4-week follow-up. Based on the costs of both PPIs and management of AEs in China, the incremental cost-effectiveness ratio per quality-adjusted life year (in US dollars) for pantoprazole, lansoprazole, rabeprazole, and ilaprazole compared to omeprazole corresponded to $5134.67, $17801.67, $25488.31, and $44572.22, respectively. Although the efficacy and tolerance of different PPIs are similar in the initial non-eradication treatment of DU, pantoprazole (40 mg/day) seems to be the most cost-effective option in China.
PubMed: 30666204
DOI: 10.3389/fphar.2018.01512 -
Journal of Gastrointestinal Surgery :... Mar 2019Over the last 3 decades, laparoscopic procedures have emerged as the standard treatment for many elective and emergency surgical conditions. Despite the increased use of...
PURPOSE
Over the last 3 decades, laparoscopic procedures have emerged as the standard treatment for many elective and emergency surgical conditions. Despite the increased use of laparoscopic surgery, the role of laparoscopic repair for perforated peptic ulcer remains controversial among general surgeons. The aim of this study was to compare the outcomes of laparoscopic versus open repair for perforated peptic ulcer.
METHODS
A systemic literature review was conducted using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. A search was conducted using MEDLINE, EMBASE, PubMed and Cochrane Database of all randomised controlled trials (RCT) that compared laparoscopic (LR) with open repair (OR) for perforated peptic ulcer (PPU). Data was extracted using a standardised form and subsequently analysed.
RESULTS
The meta-analysis using data from 7 RCT showed that LR for PPU has decreased overall post-operative morbidity (LR = 8.9% vs. OR = 17.0%) (OR = 0.54, 95% CI 0.37 to 0.79, p < 0.01), wound infections, (LR = 2.2% vs. OR = 6.3%) (OR = 0.3, 95% CI 0.16 to 0.5, p < 0.01) and shorter duration of hospital stay (6.6 days vs. 8.2 days, p = 0.01). There were no significant differences in length of operation, leakage rate, incidence of intra-abdominal abscess, post-operative sepsis, respiratory complications, re-operation rate or mortality. There was no publication bias and the quality of the studies ranged from poor to good.
CONCLUSION
These results demonstrate that laparoscopic repair for perforated peptic ulcer has a reduced morbidity and total hospital stay compared with open approach. There are no significant differences in mortality, post-operative sepsis, abscess and re-operation rates. LR should be the preferred treatment option for patients with perforated peptic ulcer disease.
Topics: Duodenal Ulcer; Emergencies; Humans; Laparoscopy; Peptic Ulcer Perforation; Stomach Ulcer; Treatment Outcome
PubMed: 30465190
DOI: 10.1007/s11605-018-4047-8 -
Carcinogenesis Mar 2019Variants in the prostate stem cell antigen (PSCA) gene have been linked with risk of multiple cancers and other diseases. But results have been inconclusive and no... (Meta-Analysis)
Meta-Analysis
Variants in the prostate stem cell antigen (PSCA) gene have been linked with risk of multiple cancers and other diseases. But results have been inconclusive and no systematic research synopsis has been available. We did a comprehensive meta-analysis to investigate associations between variants in this gene and risk of nine cancers and four nonneoplastic diseases based on data from 55 publications including 81 961 cases and 442 932 controls. We graded levels of cumulative epidemiological evidence of a significant association using the Venice criteria and false-positive report probability tests. We performed functional annotation for these variants using data from the Encyclopedia of DNA Elements Project and other public databases. We found that six variants were nominally significantly associated with an increased or reduced risk of three cancers and three nonneoplastic diseases (P < 0.05). Cumulative evidence of an association was graded as strong for rs2294008 [odds ratio (OR) = 1.32, P = 5.1 × 10-33], rs2976392 (OR = 1.29, P = 1.8 × 10-8), rs9297976 (OR = 0.75, P = 1.4 × 10-7), rs2976391 (OR = 1.38, P = 6.1 × 10-5) and rs138377917 (OR = 0.53, P = 0.008) with gastric cancer, rs2294008 with bladder cancer (OR = 1.15, P = 8.0 × 10-19), gastritis (OR = 1.35, P = 1.2 × 10-5), duodenal ulcer (OR = 0.68, P = 2.4 × 10-57) and gastric ulcer (OR = 0.88, P = 1.7 × 10-7). Data from the Encyclopedia of DNA Elements Project and other databases showed that these variants and other variants correlated with them might fall in putative functional regions. In conclusion, this study provides summary evidence that variants in the PSCA gene are associated with risk of gastric and bladder cancer, gastritis, as well as duodenal and gastric ulcer and highlights the significant role of this gene in the pathogenesis of these diseases.
Topics: Antigens, Neoplasm; Duodenal Ulcer; GPI-Linked Proteins; Genetic Predisposition to Disease; Humans; Neoplasm Proteins; Neoplasms; Risk; Stomach Neoplasms; Stomach Ulcer; Urinary Bladder Neoplasms
PubMed: 30407486
DOI: 10.1093/carcin/bgy151 -
Journal of Pain Research 2018Locally advanced pancreatic carcinoma (LAPC) has a poor prognosis and the purpose of treatment is survival prolongation and symptom palliation. Radiotherapy has been... (Review)
Review
Locally advanced pancreatic carcinoma (LAPC) has a poor prognosis and the purpose of treatment is survival prolongation and symptom palliation. Radiotherapy has been reported to reduce pain in LAPC. Stereotactic RT (SBRT) is considered as an emerging radiotherapy technique able to achieve high local control rates with acceptable toxicity. However, its role in pain palliation is not clear. To review the impact on pain relief with SBRT in LAPC patients, a literature search was performed on PubMed, Scopus, and Embase (January 2000-December 2017) for prospective and retrospective articles published in English. Fourteen studies (479 patients) reporting the effect of SBRT on pain relief were finally included in this analysis. SBRT was delivered with both standard and/or robotic linear accelerators. The median prescribed SBRT doses ranged from 16.5 to 45 Gy (median: 27.8 Gy), and the number of fractions ranged from 1 to 6 (median: 3.5). Twelve of the 14 studies reported the percentage of pain relief (in patients with pain at presentation) with a global overall response rate (complete and partial response) of 84.9% (95% CI, 75.8%-91.5%), with high heterogeneity ( test: <0.001; 2=83.63%). All studies reported toxicity data. Acute and late toxicity (grade ≥3) rates were 3.3%-18.0% and 6.0%-8.2%, respectively. Reported gastrointestinal side effects were duodenal obstruction/ulcer, small bowel obstruction, duodenal bleeding, hemorrhage, and gastric perforation. SBRT achieves pain relief in most patients with pancreatic cancer with an acceptable gastrointestinal toxicity rate. Further prospective studies are needed to define optimal dose/fractionation and the best systemic therapies modality integration to reduce toxicity and improve the palliative outcome. Finally, the quality of life and, particularly, pain control should be considered as an endpoint in all future trials on this emerging treatment technique.
PubMed: 30323651
DOI: 10.2147/JPR.S167994 -
Strahlentherapie Und Onkologie : Organ... Feb 2019Non-surgical treatment including stereotactic body radiation therapy (SBRT) have been used practically as alternative modalities for unresectable or recurrent... (Meta-Analysis)
Meta-Analysis
PURPOSE
Non-surgical treatment including stereotactic body radiation therapy (SBRT) have been used practically as alternative modalities for unresectable or recurrent cholangiocarcinoma (CC). We performed a systematic review and meta-analysis to examine the efficacy of SBRT for such patients.
METHODS
Embase, PubMed, MEDLINE, and Cochrane library databases were searched systematically until October 2017. Primary endpoint was 1‑year local control (LC) rate; 1‑year overall survival (OS), response rates, and grade ≥3 toxicities were assessed as secondary endpoints.
RESULTS
Eleven studies (226 patients) were included. The prescribed median SBRT dose was 45 (range 30-55) Gy in 3-5 fractions. The pooled 1‑year LC rate was 81.8% (95% confidence interval [CI] 69.4-89.9%) in the studies using an equivalent dose in 2 Gy per fraction (EQD2) ≥71.3 Gy and 74.7% (95% CI 57.1-86.7%) in the studies using an EQD2 <71.3 Gy. The median OS was 13.6 (range 10-35.5) months. The pooled 1‑year OS rate was 53.8% (95% CI 44.9-62.5%) and the pooled 1‑year LC rate was 78.6% (95% CI 69.0-85.8%). Most common toxicity was duodenal ulcer and gastric ulcer in available studies, with the acute incidence of grade ≥3 of less than 10% and the late incidence of 10-20%.
CONCLUSIONS
SBRT was a feasible treatment option with respect to achieving a high LC for unresectable or recurrent CC. Gastrointestinal toxicity is acceptable, but remains an obstacle related to dose escalation.
Topics: Bile Duct Neoplasms; Cholangiocarcinoma; Feasibility Studies; Humans; Neoplasm Recurrence, Local; Radiosurgery; Radiotherapy Dosage; Survival Rate; Treatment Outcome
PubMed: 30206644
DOI: 10.1007/s00066-018-1367-2 -
The Journal of Trauma and Acute Care... Aug 2018Surgery is the treatment of choice for perforated peptic ulcer disease. The aim of the present review was to compare the perioperative outcomes of acute laparoscopic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Surgery is the treatment of choice for perforated peptic ulcer disease. The aim of the present review was to compare the perioperative outcomes of acute laparoscopic versus open repair for peptic ulcer disease.
METHODS
A systematic literature search was performed for randomized controlled trials (RCTs) published in PubMed, SCOPUS, and Web of Science.
RESULTS
The search included eight RCTs: 615 patients comparing laparoscopic (307 patients) versus open peptic perforated ulcer repair (308 patients). Only few studies reported the Boey score, the Acute Physiologic Assessment and Chronic Health Evaluation score, and the Mannheim Peritonitis Index. In the RCTs, there is a significant heterogeneity about the gastric or duodenal location of peptic ulcer and perforation size. All trials were with high risk of bias. This meta-analysis reported a significant advantage of laparoscopic repair only for postoperative pain in first 24 hours (-2.08; 95% confidence interval, -2.79 to -1.37) and for postoperative wound infection (risk ratio, 0.39; 95% confidence interval, 0.23-0.66). An equivalence of the other clinical outcomes (postoperative mortality rate, overall reoperation rate, overall leaks of the suture repair, intra-abdominal abscess rate, operative time of postoperative hospital stay, nasogastric aspiration time, and time to return to oral diet) was reported.
CONCLUSION
In this meta-analysis, there were no significant differences in most of the clinical outcomes between the two groups; there was less early postoperative pain and fewer wound infections after laparoscopic repair. The reported equivalence of clinical outcomes is an important finding. These results parallel the results of several other comparisons of open versus laparoscopic general surgery operations-equally efficacious with lower rates of wound infection and improvement in some measures of enhanced speed or comfort in recovery. Notably, the trials included have been published throughout a considerable time span during which several changes have occurred in most health care systems, not least a widespread use of laparoscopy and increase in the laparoscopic skills.
LEVEL OF EVIDENCE
Systematic review and meta-analysis, level III.
Topics: Emergency Treatment; Humans; Laparotomy; Operative Time; Peptic Ulcer Perforation; Perioperative Period; Postoperative Complications; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 29659470
DOI: 10.1097/TA.0000000000001925 -
European Journal of Radiology Mar 2018To evaluate the value of yttrium-90 (Y) microspheres in the management of unresectable liver metastases secondary to neuroendocrine tumors (NETs). (Review)
Review
OBJECTIVE
To evaluate the value of yttrium-90 (Y) microspheres in the management of unresectable liver metastases secondary to neuroendocrine tumors (NETs).
MATERIALS AND METHODS
PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and the "gray" literature (Google Scholar) were searched for all studies related to Y therapy for unresectable liver metastases of NETs.
RESULTS
A total of 11 studies and 7 abstracts involving 870 patients were included in the final analysis. In 11 of these studies, 19.8% (77/388) of patients had undergone transarterial bland embolization (TABE) or transarterial chemoembolization (TACE) before Y therapy. The median disease control rate among all patients was 86% at 3 months after Y therapy. The median survival was 28 months, with 1-, 2-, and 3-year survival rates of 72.5%, 57%, and 45%, respectively. The median survival values for patients who received resin- and glass-based Y treatment were 27.6 and 31.7 months, respectively. The survival values for patients with carcinoid, pancreatic, and unclassified origin of NETs were 56, 31, and 28 months, respectively; the survival values for patients with grade I, II, and III NETs were 71, 56, and 28 months, respectively. Carcinoid syndrome was reported in 52.4% (55/105) of patients, and 69.1% of those with clinical symptoms demonstrated improvement in symptoms after Y radioembolization. Complications were reported in 9 studies, including radiation gastritis (n = 4), duodenal ulcer (n = 2), death due to liver failure (n = 1), and radiation cholecystitis (n = 1). The most common side effects were abdominal pain (median, 32.6%), nausea/vomiting (median, 32.5%), and fatigue (median, 30.4%).
CONCLUSIONS
Y radioembolization can be used as an alternative therapy for unresectable liver metastases of NETs, with an improved survival rate and tumor response. This treatment is also effective for patients who have undergone unsuccessful TABE/TACE therapy and for the relief of symptoms in patients with carcinoid syndrome.
Topics: Aged; Brachytherapy; Female; Humans; Liver Neoplasms; Male; Middle Aged; Neuroendocrine Tumors; Survival Rate; Treatment Outcome; Young Adult; Yttrium Radioisotopes
PubMed: 29496075
DOI: 10.1016/j.ejrad.2018.01.012 -
Critical Care (London, England) Jan 2018Pharmacologic stress ulcer prophylaxis (SUP) is recommended in critically ill patients with high risk of stress-related gastrointestinal (GI) bleeding. However, as to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pharmacologic stress ulcer prophylaxis (SUP) is recommended in critically ill patients with high risk of stress-related gastrointestinal (GI) bleeding. However, as to patients receiving enteral feeding, the preventive effect of SUP is not well-known. Therefore, we performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of pharmacologic SUP in enterally fed patients on stress-related GI bleeding and other clinical outcomes.
METHODS
We searched PubMed, Embase, and the Cochrane database from inception through 30 Sep 2017. Eligible trials were RCTs comparing pharmacologic SUP to either placebo or no prophylaxis in enterally fed patients in the ICU. Results were expressed as risk ratio (RR) and mean difference (MD) with accompanying 95% confidence interval (CI). Heterogeneity, subgroup analysis, sensitivity analysis and publication bias were explored.
RESULTS
Seven studies (n = 889 patients) were included. There was no statistically significant difference in GI bleeding (RR 0.80; 95% CI, 0.49 to 1.31, p = 0.37) between groups. This finding was confirmed by further subgroup analyses and sensitivity analysis. In addition, SUP had no effect on overall mortality (RR 1.21; 95% CI, 0.94 to 1.56, p = 0.14), Clostridium difficile infection (RR 0.89; 95% CI, 0.25 to 3.19, p = 0.86), length of stay in the ICU (MD 0.04 days; 95% CI, -0.79 to 0.87, p = 0.92), duration of mechanical ventilation (MD -0.38 days; 95% CI, -1.48 to 0.72, p = 0.50), but was associated with an increased risk of hospital-acquired pneumonia (RR 1.53; 95% CI, 1.04 to 2.27; p = 0.03).
CONCLUSIONS
Our results suggested that in patients receiving enteral feeding, pharmacologic SUP is not beneficial and combined interventions may even increase the risk of nosocomial pneumonia.
Topics: Clostridium Infections; Critical Care; Duodenal Ulcer; Enteral Nutrition; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Hospital Mortality; Humans; Intensive Care Units; Length of Stay; Peptic Ulcer; Respiration, Artificial; Risk Management; Time Factors
PubMed: 29374489
DOI: 10.1186/s13054-017-1937-1 -
Critical Care (London, England) May 2016The relative efficacy and safety of proton pump inhibitors (PPIs) compared to histamine-2-receptor antagonists (H2RAs) should guide their use in reducing bleeding risk... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The relative efficacy and safety of proton pump inhibitors (PPIs) compared to histamine-2-receptor antagonists (H2RAs) should guide their use in reducing bleeding risk in the critically ill.
METHODS
We searched the Cochrane library, MEDLINE, EMBASE, ACPJC, clinical trials registries, and conference proceedings through November 2015 without language or publication date restrictions. Only randomized controlled trials (RCTs) of PPIs vs H2RAs for stress ulcer prophylaxis in critically ill adults for clinically important bleeding, overt gastrointestinal (GI) bleeding, nosocomial pneumonia, mortality, ICU length of stay and Clostridium difficile infection were included. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess our confidence in the evidence for each outcome.
RESULTS
In 19 trials enrolling 2117 patients, PPIs were more effective than H2RAs in reducing the risk of clinically important GI bleeding (RR 0.39; 95 % CI 0.21, 0.71; P = 0.002; I (2) = 0 %, moderate confidence) and overt GI bleeding (RR 0.48; 95 % CI 0.34, 0.66; P < 0.0001; I (2) = 3 %, moderate confidence). PPI use did not significantly affect risk of pneumonia (RR 1.12; 95 % CI 0.86, 1.46; P = 0.39; I (2) = 2 %, low confidence), mortality (RR 1.05; 95 % CI 0.87, 1.27; P = 0.61; I (2) = 0 %, moderate confidence), or ICU length of stay (mean difference (MD), -0.38 days; 95 % CI -1.49, 0.74; P = 0.51; I (2) = 30 %, low confidence). No RCT reported Clostridium difficile infection.
CONCLUSIONS
PPIs were superior to H2RAs in preventing clinically important and overt GI bleeding, without significantly increasing the risk of pneumonia or mortality. Their impact on Clostridium difficile infection is yet to be determined.
Topics: Duodenal Ulcer; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Peptic Ulcer; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Risk Assessment; Stomach Ulcer
PubMed: 27142116
DOI: 10.1186/s13054-016-1305-6