Guidelines from national and international professional societies on upper gastrointestinal bleeding highlight the important clinical issues but do not always identify specific management strategies ...pertaining to individual patients. Optimal treatment should consider the personal needs of an individual patient and the pertinent resources and experience available at the point of care. This article integrates international guidelines and consensus into three stages of management: pre-endoscopic assessment and treatment, endoscopic evaluation and haemostasis and postendoscopic management. We emphasise the need for personalised management strategies based on patient characteristics, nature of bleeding lesions and the clinical setting including available resources.
Gastroesophageal variceal bleeding in patients with cirrhosis is associated with significant morbidity and mortality, as well as a high rebleeding risk. Limited data are available on the role of ...transjugular intrahepatic portosystemic shunt (TIPS) with covered stents in patients receiving standard endoscopic, vasoactive, and antibiotic treatment. In this multicenter randomized trial, long‐term endoscopic variceal ligation (EVL) or glue injection + β‐blocker treatment was compared with TIPS placement in 72 patients with a first or second episode of gastric and/or esophageal variceal bleeding, after hemodynamic stabilization upon endoscopic, vasoactive, and antibiotic treatment. Randomization was stratified according to Child‐Pugh score. Kaplan‐Meier (event‐free) survival estimates were used for the endpoints rebleeding, death, treatment failure, and hepatic encephalopathy. During a median follow‐up of 23 months, 10 (29%) of 35 patients in the endoscopy + β‐blocker group, as compared to 0 of 37 (0%) patients in the TIPS group, developed variceal rebleeding (P = 0.001). Mortality (TIPS 32% vs. endoscopy 26%; P = 0.418) and treatment failure (TIPS 38% vs. endoscopy 34%; P = 0.685) did not differ between groups. Early hepatic encephalopathy (within 1 year) was significantly more frequent in the TIPS group (35% vs. 14%; P = 0.035), but during long‐term follow‐up this difference diminished (38% vs. 23%; P = 0.121). Conclusions: In unselected patients with cirrhosis, who underwent successful endoscopic hemostasis for variceal bleeding, covered TIPS was superior to EVL + β‐blocker for reduction of variceal rebleeding, but did not improve survival. TIPS was associated with higher rates of early hepatic encephalopathy. (Hepatology 2016;63:581–589)
Background Nausea and occasional vomiting in early pregnancy is common. Why some women experience severe nausea and occasional vomiting in early pregnancy is unknown. Causes are multifactorial and ...only symptomatic treatment options are available, although adverse birth outcomes have been described. Helicobacter pylori infection has been implicated in the cause of nausea and occasional vomiting in early pregnancy. Objective The purpose of this study was to investigate the association of H pylori with vomiting severity in pregnancy and its effect on birth outcome. Study Design We assembled a population-based prospective cohort of pregnant women in The Netherlands. Enrolment took place between 2002 and 2006. H pylori serology was determined in mid gestation. Women reported whether they experienced vomiting in early, mid, and late gestation. Maternal weight was measured in the same time periods. Birth outcomes were obtained from medical records. Main outcome measures were vomiting frequency (no, occasional, daily) and duration (early, mid, late gestation), maternal weight gain, birthweight, small for gestational age, and prematurity. Data were analyzed with the use of multivariate regression. Results We included 5549 Women, of whom 1932 (34.8%) reported occasional vomiting and 601 (10.8%) reported daily vomiting. Women who were H pylori- positive (n=2363) were more likely to report daily vomiting (adjusted odds ratio, 1.44; 95% confidence interval, 1.16−1.78). H pylori– positivity was associated with a reduction of total weight gain in women with daily vomiting (adjusted difference, –2.1 kg; 95% confidence interval, –2.7 to –1.5); infants born to women with H pylori and daily vomiting had slightly reduced birthweight (addjusted difference −60g; 95% confidence interval, −109 - −12) and an increased risk of being small for gestational age (adjusted odds ratio, 1.49; 95% confidence interval, 1.04−2.14). H pylori and daily vomiting did not significantly affect prematurity rate. Conclusion This study suggests that H pylori is an independent risk factor for vomiting in pregnancy. In women with daily vomiting, H pylori is also associated with low maternal weight gain, reduced birth weight, and small for gestational age. Because effective treatments for severe nausea and occasional vomiting in early pregnancy are currently lacking, the effect of H pylori eradication therapy on nausea and occasional vomiting in early pregnancy symptom severity should be the target of future studies.
Although endoscopic surveillance of patients with Barrett's oesophagus has been widely implemented, its effectiveness is debateable. The recently reported low annual oesophageal adenocarcinoma risk ...in population studies, the failure to identify most Barrett's patients at risk of disease progression, the poor adherence to surveillance and biopsy protocols, and the significant risk of misclassification of dysplasia all tend to undermine the effectiveness of current management, in particular, endoscopic surveillance programmes, to prevent or improve the outcomes of patients with oesophageal adenocarcinoma. The ongoing increase in incidence of Barrett's oesophagus and consequent growth of the surveillance population, together with the associated discomfort and costs of endoscopic surveillance, demand improved techniques for accurately determining individual risk of oesophageal adenocarcinoma. More accurate techniques are needed to run efficient surveillance programmes in the coming decades. In this review, we will discuss the current knowledge on the epidemiology of Barrett's oesophagus, and the challenging epidemiological dilemmas that need to be addressed when assessing the current screening and surveillance strategies.
Background & Aims We assessed the course of inflammatory bowel disease (IBD) among pregnant women who stopped taking anti–tumor necrosis factor (TNF) agents. We also analyzed levels of anti-TNF ...agents in cord blood samples. Methods We followed 31 pregnancies in 28 women with IBD between April 2006 and April 2011 who were treated with anti-TNF agents (18 received infliximab, and 13 received adalimumab) during pregnancy. We used enzyme-linked immunosorbent assays to measure levels of anti-TNF agents in cord blood collected from 18 newborns (12 whose mothers took infliximab, and 6 whose mothers took adalimumab). Results Among the patients taking infliximab, 12 (71%) discontinued treatment before gestational week 30; all patients remained in remission. All the patients taking adalimumab discontinued treatment before gestational week 30; two patients had relapses of IBD. There were 28 live births, 1 miscarriage among patients taking infliximab (at gestational week 6), and 2 miscarriages among patients taking adalimumab (at weeks 6 and 8); there were no congenital malformations. The mean cord blood level of infliximab was 6.4 ± 1.6 μg/mL; it was significantly lower among women who received the drug 10 weeks or less before delivery (2.8 ± 1.1 μg/mL) than those who received infliximab closer to delivery (10 ± 2.3 μg/mL; P = .02). Adalimumab was detected in 5 samples of cord blood (mean concentration, 1.7 ± 0.4 μg/mL); 1 cord blood sample from a woman who discontinued the treatment at gestational week 22 had an undetectable level of the drug. Conclusions Discontinuation of anti-TNF therapy appears to be safe for pregnant women with quiescent IBD. However, these drugs are still detected in cord blood samples.
Correspondence to Professor Ernst J Kuipers, Erasmus University Medical Center, Rotterdam 3015 GD, The Netherlands; e.j.kuipers@erasmusmc.nl Colorectal cancer (CRC) is among the most common causes of ...cancer-related mortality.1 For the purpose of population-based CRC screening, faecal immunochemical tests (FIT) have been widely accepted.2 FIT can both be used in a qualitative manner, leading to either a positive or negative result, or a quantitative manner resulting in the reporting of microgram faecal haemoglobin (Hb) per gram faeces. The results of this Italian study are also in line with the results from a Dutch CRC screening cohort.8 Though the threshold used in this study was much lower (10 µg/g faeces), screenees with a faecal Hb concentration just under the threshold had an eightfold increase of long-term risk of advanced neoplasia over four screening rounds.8 These results were based on a smaller cohort limiting additional subgroup analyses on interval cancers and CRC location. The Italian data published in Gut combined with the two previous similar studies from Spain and the Netherlands now firmly establish ground for development of personalised FIT screening strategies using individual actual faecal Hb data.5 7 8 These findings have the potential to help move risk stratification along and to aid public health decision makers in choosing the optimal screening strategy in FIT-based CRC screening.
The evidence for a strong correlation between the gut microbiota and colorectal carcinogenesis is quickly gathering pace. This correlation raises important questions, such as whether analysis of the ...microbiota can be used for screening purposes, and whether targeted intervention can influence the risk of development and progression of neoplasia. The recovery of several pathobionts-such as members of the different bacterial phyla Proteobacteria, Bacteroidetes and Fusobacteria-from the tumour microenvironment of patients with colorectal cancer (CRC) now provides a link between specific microbial colonization and cancer. However, other intestinal bacteria belonging to another major intestinal phylum, Firmicutes, might be effective in the treatment of pathogenic inflammation related to CRC. Future approaches based on the analysis of the gut microbiota of patients with CRC combined with large human cohort studies might open up new possibilities for further prophylactic, screening and treatment strategies.
Background Although colorectal cancer screening is cost-effective, it requires a considerable net investment by governments or insurance companies. If screening was cost saving, governments and ...insurance companies might be more inclined to invest in colorectal cancer screening programs. We examined whether colorectal cancer screening would become cost saving with the widespread use of the newer, more expensive chemotherapies. Methods We used the MISCAN-Colon microsimulation model to assess whether widespread use of new chemotherapies would affect the treatment savings of colorectal cancer screening in the general population. We considered three scenarios for chemotherapy use: the past, the present, and the near future. We assumed that survival improved and treatment costs for patients diagnosed with advanced stages of colorectal cancer increased over the scenarios. Screening strategies considered were annual guaiac fecal occult blood testing (FOBT), annual immunochemical FOBT, sigmoidoscopy every 5 years, colonoscopy every 10 years, and the combination of sigmoidoscopy every 5 years and annual guaiac FOBT. Analyses were conducted from the perspective of the health-care system for a cohort of 50-year-old individuals who were at average risk of colorectal cancer and were screened with 100% adherence from age 50 years to age 80 years and followed up until death. Results Compared with no screening, the treatment savings from preventing advanced colorectal cancer and colorectal cancer deaths by screening more than doubled with the widespread use of new chemotherapies. The lifetime average treatment savings were larger than the lifetime average screening costs for screening with Hemoccult II, immunochemical FOBT, sigmoidoscopy, and the combination of sigmoidoscopy and Hemoccult II (average savings vs costs per individual in the population: Hemoccult II, $1398 vs $859; immunochemical FOBT, $1756 vs $1565; sigmoidoscopy, $1706 vs $1575; sigmoidoscopy and Hemoccult II $1931 vs $1878). Colonoscopy did not become cost saving, but the total net costs of this strategy decreased from $1317 to $296 per individual in the population. Conclusions With the increase in chemotherapy costs for advanced colorectal cancer, most colorectal cancer screening strategies have become cost saving. As a consequence, screening is a desirable approach not only to reduce colorectal cancer incidence and mortality but also to control the costs of colorectal cancer treatment.
Background
Almost half of people with esophageal or gastroesophageal junction cancer have metastatic disease at the time of diagnosis. Chemotherapy and targeted therapies are increasingly used with a ...palliative intent to control tumor growth, improve quality of life, and prolong survival. To date, and with the exception of ramucirumab, evidence for the efficacy of palliative treatments for esophageal and gastroesophageal cancer is lacking.
Objectives
To assess the effects of cytostatic or targeted therapy for treating esophageal or gastroesophageal junction cancer with palliative intent.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Web of Science, PubMed Publisher, Google Scholar, and trial registries up to 13 May 2015, and we handsearched the reference lists of studies. We did not restrict the search to publications in English. Additional searches were run in September 2017 prior to publication, and they are listed in the 'Studies awaiting assessment' section.
Selection criteria
We included randomized controlled trials (RCTs) on palliative chemotherapy and/or targeted therapy versus best supportive care or control in people with esophageal or gastroesophageal junction cancer.
Data collection and analysis
Two authors independently extracted data. We assessed the quality and risk of bias of eligible studies according to the Cochrane Handbook for Systematic Reviews of Interventions. We calculated pooled estimates of effect using an inverse variance random‐effects model for meta‐analysis.
Main results
We identified 41 RCTs with 11,853 participants for inclusion in the review as well as 49 ongoing studies. For the main comparison of adding a cytostatic and/or targeted agent to a control arm, we included 11 studies with 1347 participants. This analysis demonstrated an increase in overall survival in favor of the arm with an additional cytostatic or targeted therapeutic agent with a hazard ratio (HR) of 0.75 (95% confidence interval (CI) 0.68 to 0.84, high‐quality evidence). The median increased survival time was one month. Five studies in 750 participants contributed data to the comparison of palliative therapy versus best supportive care. We found a benefit in overall survival in favor of the group receiving palliative chemotherapy and/or targeted therapy compared to best supportive care (HR 0.81, 95% CI 0.71 to 0.92, high‐quality evidence). Subcomparisons including only people receiving second‐line therapies, chemotherapies, targeted therapies, adenocarcinomas, and squamous cell carcinomas all showed a similar benefit. The only individual agent that more than one study found to improve both overall survival and progression‐free survival was ramucirumab. Palliative chemotherapy and/or targeted therapy increased the frequency of grade 3 or higher treatment‐related toxicity. However, treatment‐related deaths did not occur more frequently. Quality of life often improved in the arm with an additional agent.
Authors' conclusions
People who receive more chemotherapeutic or targeted therapeutic agents have an increased overall survival compared to people who receive less. These agents, administered as both first‐line or second‐line treatments, also led to better overall survival than best supportive care. With the exception of ramucirumab, it remains unclear which other individual agents cause the survival benefit. Although treatment‐associated toxicities of grade 3 or more occurred more frequently in arms with an additional chemotherapy or targeted therapy agent, there is no evidence that palliative chemotherapy and/or targeted therapy decrease quality of life. Based on this meta‐analysis, palliative chemotherapy and/or targeted therapy can be considered standard care for esophageal and gastroesophageal junction carcinoma.
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