Definition of large bowel obstruction by primary colorectal cancer:A systematic review

Aim: Controversies on therapeutic strategy for large bowel obstruction by primary colorectal cancer mainly concern acute conditions, being essentially different from subacute obstruction. Clearly defining acute obstruction is important for design and interpretation of studies as well as for guidelines and daily practice. This systematic review aimed to evaluate definitions of obstruction by colorectal cancer in prospective studies. Method: A systematic search was performed in PubMed, Embase and the Cochrane Library. Eligibility criteria included randomized or prospective observational design, publication between 2000 and 2019, and the inclusion of patients with an obstruction caused by colorectal cancer. Provided definitions of obstruction were extracted with assessment of common elements. Results: A total of 16 randomized controlled trials (RCTs) and 99 prospective observational studies were included. Obstruction was specified as acute in 28 studies, complete/emergency in five, (sub)acute or similar terms in four and unspecified in 78. Five of 16 RCTs (31%) and 37 of 99 cohort studies (37%) provided a definition. The definitions included any combination of clinical symptoms, physical signs, endoscopic features and radiological imaging findings in 25 studies. The definition was only based on clinical symptoms in 11 and radiological imaging in six studies. Definitions included a radiological component in 100% of evaluable RCTs (5/5) vs. 54% of prospective observational studies (20/37, P = 0.07). Conclusion: In this systematic review, the majority of prospective studies did not define obstruction by colorectal cancer and its urgency, whereas provided definitions varied hugely. Radiological confirmation seems to be an essential component in defining acute obstruction

Sex Differences in Neoplastic Progression in Barrett's Esophagus:A Multicenter Prospective Cohort Study

Recommendations in Barrett’s esophagus (BE) guidelines are mainly based on male patients. We aimed to evaluate sex differences in BE patients in (1) probability of and (2) time to neoplastic progression, and (3) differences in the stage distribution of neoplasia. We conducted a multicenter prospective cohort study including 868 BE patients. Cox regression modeling and accelerated failure time modeling were used to estimate the sex differences. Neoplastic progression was defined as highgrade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC). Among the 639 (74%) males and 229 females that were included (median follow-up 7.1 years), 61 (7.0%) developed HGD/EAC. Neoplastic progression risk was estimated to be twice as high among males (HR 2.26, 95% CI 1.11–4.62) than females. The risk of HGD was found to be higher in males (HR 3.76, 95% CI 1.33–10.6). Time to HGD/EAC (AR 0.52, 95% CI 0.29–0.95) and HGD (AR 0.40, 95% CI 0.19–0.86) was shorter in males. Females had proportionally more EAC than HGD and tended to have higher stages of neoplasia at diagnosis. In conclusion, both the risk of and time to neoplastic progression were higher in males. However, females were proportionally more often diagnosed with (advanced) EAC. We should strive for improved neoplastic risk stratification per individual BE patient, incorporating sex disparities into new prediction models

Decompressing Stoma as Bridge to Elective Surgery is an Effective Strategy for Left-sided Obstructive Colon Cancer:A National, Propensity-score Matched Study

OBJECTIVE: The purpose of this population-based study was to compare decompressing stoma (DS) as bridge to surgery (BTS) with emergency resection (ER) for left-sided obstructive colon cancer (LSOCC) using propensity-score matching. SUMMARY BACKGROUND DATA: Recently, an increased use of DS as BTS for LSOCC has been observed in the Netherlands. Unfortunately, good quality comparative analyses with ER are scarce. METHODS: Patients diagnosed with nonlocally advanced LSOCC between 2009 and 2016 in 75 Dutch hospitals, who underwent DS or ER in the curative setting, were propensity-score matched in a 1:2 ratio. The primary outcome measure was 90-day mortality, and main secondary outcomes were 3-year overall survival and permanent stoma rate. RESULTS: Of 2048 eligible patients, 236 patients who underwent DS were matched with 472 patients undergoing ER. After DS, more laparoscopic resections were performed (56.8% vs 9.2%, P < 0.001) and more primary anastomoses were constructed (88.5% vs 40.7%, P < 0.001). DS resulted in significantly lower 90-day mortality compared to ER (1.7% vs 7.2%, P = 0.006), and this effect could be mainly attributed to the subgroup of patients over 70 years (3.5% vs 13.7%, P = 0.027). Patients treated with DS as BTS had better 3-year overall survival (79.4% vs 73.3%, hazard ratio 0.36, 95% confidence interval 0.20-0.65) and fewer permanent stomas (23.4% vs 42.4%, P < 0.001). CONCLUSIONS: In this nationwide propensity-score matched study, DS as a BTS for LSOCC was associated with lower 90-day mortality and better 3-year overall survival compared to ER, especially in patients over 70 years of age

Fluvoxamine for fatigue in primary biliary cirrhosis and primary sclerosing cholangitis: a randomised controlled trial [ISRCTN88246634]

BACKGROUND: Fatigue is a major clinical problem in many patients with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). An effective treatment has not been defined. Recently, a large proportion of patients with these diseases was found to have symptoms of depression. Because fatigue is a frequent symptom of depression and there is some evidence that treatment with an antidepressant improves fatigue in patients with fibromyalgia, we hypothesised that the antidepressant fluvoxamine might improve fatigue related to PBC and PSC. METHODS: Fatigued patients were randomised to receive fluvoxamine (75 mg BID) or placebo for a six-week period. Fatigue and quality of life were quantified using a visual analogue scale, the Fisk Fatigue Severity Scale, the Multidimensional Fatigue Inventory and the SF-36. RESULTS: Seventeen and 16 patients were allocated to fluvoxamine and placebo, respectively. There was no statistically significant beneficial effect of fluvoxamine on fatigue or quality of life. The median VAS scores in the fluvoxamine and placebo groups were 7.40 and 7.45 at day 0, 6.9 and 7.15 at day 14, 7.45 and 7.65 at day 42 and 7.8 and 8.0 four weeks after treatment discontinuation. CONCLUSION: We found no evidence for a beneficial effect of fluvoxamine on fatigue in these patients with cholestatic liver disease and severe chronic fatigue

Health outcomes of 1000 children born to mothers with inflammatory bowel disease in their first 5 years of life

OBJECTIVE: The aim of this study was to describe the long-term health outcomes of children born to mothers with inflammatory bowel disease (IBD) and to assess the impact of maternal IBD medication use on these outcomes. DESIGN: We performed a multicentre retrospective study in The Netherlands. Women with IBD who gave birth between 1999 and 2018 were enrolled from 20 participating hospitals. Information regarding disease characteristics, medication use, lifestyle, pregnancy outcomes and long-term health outcomes of children was retrieved from mothers and medical charts. After consent of both parents, outcomes until 5 years were also collected from general practitioners. Our primary aim was to assess infection rate and our secondary aims were to assess adverse reactions to vaccinations, growth, autoimmune diseases and malignancies. RESULTS: We included 1000 children born to 626 mothers (381 (61%) Crohn's disease, 225 (36%) ulcerative colitis and 20 (3%) IBD unclassified). In total, 196 (20%) had intrauterine exposure to anti-tumour necrosis factor-α (anti-TNF-α) (60 with concomitant thiopurine) and 240 (24%) were exposed to thiopurine monotherapy. The 564 children (56%) not exposed to anti-TNF-α and/or thiopurine served as control group. There was no association between adverse long-term health outcomes and in utero exposure to IBD treatment. We did find an increased rate of intrahepatic cholestasis of pregnancy (ICP) in case thiopurine was used during the pregnancy without affecting birth outcomes and long-term health outcomes of children. All outcomes correspond with the general age-adjusted population. CONCLUSION: In our study, we found no association between in utero exposure to anti-TNF-α and/or thiopurine and the long-term outcomes antibiotic-treated infections, severe infections needing hospital admission, adverse reactions to vaccinations, growth failure, autoimmune diseases and malignancies

A Prediction Model for Successful Increase of Adalimumab Dose Intervals in Patients with Crohn’s Disease:Secondary Analysis of the Pragmatic Open-Label Randomised Controlled Non-inferiority LADI Trial

Background: In the pragmatic open-label randomised controlled non-inferiority LADI trial we showed that increasing adalimumab (ADA) dose intervals was non-inferior to conventional dosing for persistent flares in patients with Crohn’s disease (CD) in clinical and biochemical remission. Aims: To develop a prediction model to identify patients who can successfully increase their ADA dose interval based on secondary analysis of trial data. Methods: Patients in the intervention group of the LADI trial increased ADA intervals to 3 and then to 4 weeks. The dose interval increase was defined as successful when patients had no persistent flare (&gt; 8 weeks), no intervention-related severe adverse events, no rescue medication use during the study, and were on an increased dose interval while in clinical and biochemical remission at week 48. Prediction models were based on logistic regression with relaxed LASSO. Models were internally validated using bootstrap optimism correction. Results: We included 109 patients, of which 60.6% successfully increased their dose interval. Patients that were active smokers (odds ratio [OR] 0.90), had previous CD-related intra-abdominal surgeries (OR 0.85), proximal small bowel disease (OR 0.92), an increased Harvey-Bradshaw Index (OR 0.99) or increased faecal calprotectin (OR 0.997) were less likely to successfully increase their dose interval. The model had fair discriminative ability (AUC = 0.63) and net benefit analysis showed that the model could be used to select patients who could increase their dose interval. Conclusion: The final prediction model seems promising to select patients who could successfully increase their ADA dose interval. The model should be validated externally before it may be applied in clinical practice. Clinical Trial Registration Number: ClinicalTrials.gov, number NCT03172377.</p

Different perceptions of the burden of upper GI endoscopy: an empirical study in three patient groups

Background: Few studies have evaluated patients' perceived burden of cancer surveillance tests. Cancer screening and surveillance, however, require a large number of patients to undergo potentially burdensome tests with only some experiencing health gains from it. We investigated the determinants of patients' reported burden of upper gastrointestinal (GI) endoscopy by comparing data from three patient groups. Patients and methods: A total of 476 patients were included: 180 patients under regular surveillance for Barrett esophagus (BE), a premalignant disorder; 214 patients with non-specific upper GI symptoms (NS), and 82 patients recently diagnosed with upper GI cancer (CA). We assessed pain, discomfort and overall burden experienced during endoscopy, symptoms in the week afterwards and psychological distress over time (Hospital Anxiety and Depression scale and Impact of Event Scale). Results: Two-thirds (66%) of patients reported discomfort and overall burden of upper GI endoscopy. Only 23% reported any pain. BE patients reported significantly less discomfort, pain and overall burden than the other patients: those with NS reported more discomfort, CA patients more pain, and both more overall burden. These differences could be statistically explained by the number of previous endoscopies and whether sedation was provided or not, but not by patient characteristics. Conclusion: The perception of upper GI endoscopy varies by patient group, due to potential adaptation after multiple endoscopies and aspects of th