Patient-reported outcomes after oesophagectomy in the multicentre LASER study.

BACKGROUND: Data on the long-term symptom burden in patients surviving oesophageal cancer surgery are scarce. The aim of this study was to identify the most prevalent symptoms and their interactions with health-related quality of life. METHODS: This was a cross-sectional cohort study of patients who underwent oesophageal cancer surgery in 20 European centres between 2010 and 2016. Patients had to be disease-free for at least 1 year. They were asked to complete a 28-symptom questionnaire at a single time point, at least 1 year after surgery. Principal component analysis was used to assess for clustering and association of symptoms. Risk factors associated with the development of severe symptoms were identified by multivariable logistic regression models. RESULTS: Of 1081 invited patients, 876 (81.0 per cent) responded. Symptoms in the preceding 6 months associated with previous surgery were experienced by 586 patients (66.9 per cent). The most common severe symptoms included reduced energy or activity tolerance (30.7 per cent), feeling of early fullness after eating (30.0 per cent), tiredness (28.7 per cent), and heartburn/acid or bile regurgitation (19.6 per cent). Clustering analysis showed that symptoms clustered into six domains: lethargy, musculoskeletal pain, dumping, lower gastrointestinal symptoms, regurgitation/reflux, and swallowing/conduit problems; the latter two were the most closely associated. Surgical approach, neoadjuvant therapy, patient age, and sex were factors associated with severe symptoms. CONCLUSION: A long-term symptom burden is common after oesophageal cancer surgery.

Treatment and Outcome of Synchronous Colorectal Carcinomas: A Nationwide Study.

BACKGROUND: Synchronous colorectal carcinomas (CRC) occur in 1-8% of patients diagnosed with CRC. This study evaluated treatment patterns and patient outcomes in synchronous CRCs compared with solitary CRC patients. METHODS: All patients diagnosed with primary CRC between 2008 and 2013, who underwent elective surgery, were selected from the Netherlands Cancer Registry. Using multivariable regressions, the effects of synchronous CRC were assessed for both short-term outcomes (prolonged postoperative hospital admission, anastomotic leakage, postoperative 30-day mortality, administration of neoadjuvant or adjuvant treatment), and 5-year relative survival (RS). RESULTS: Of 41,060 CRC patients, 1969 patients (5%) had synchronous CRC. Patients with synchronous CRC were older (mean age 71 ± 10.6 vs. 69 ± 11.4 years), more often male (61 vs. 54%), and diagnosed with more advanced tumour stage (stage III-IV 54 vs. 49%) compared with solitary CRC (all p < 0.0001). In 50% of the synchronous CRCs, an extended surgery was conducted (n = 934). Synchronous CRCs with at least one stage II-III rectal tumour less likely received neoadjuvant (chemo)radiation [78 vs. 86%; adjusted OR 0.6 (0.48-0.84)], and synchronous CRCs with at least one stage III colon tumour less likely received adjuvant chemotherapy [49 vs. 63%; adjusted OR 0.7 (0.55-0.89)]. Synchronous CRCs were independently associated with decreased survival [RS 77 vs. 71%; adjusted RER 1.1 (1.01-1.23)]. CONCLUSIONS: The incidence of synchronous CRCs in the Dutch population is 5%. Synchronous CRCs were associated with decreased survival compared with solitary CRC. The results emphasize the importance of identifying synchronous tumours, preferably before surgery to provide optimal treatment.

Mannose-binding lectin null alleles are associated with preserved epithelial cell integrity following intestinal ischemia reperfusion in man.

Mannose-binding lectin (MBL) deficiency is associated with reduced intestinal ischemia-reperfusion (IR) damage in rodents. We set out to investigate an association between frequently observed MBL deficiency and IR associated intestinal cell damage in man. Using a newly developed IR model of the human small intestine 29 patients were consecutively included. Part of the jejunum was subjected to 30 min of ischemia and reperfusion. The MBL genotype was assessed by means of quantitative-PCR analysis. Enterocyte loss was explored by measuring plasma intestinal-fatty acid binding protein (I-FABP) levels. Arterial and venous MBL plasma levels were measured to assess MBL consumption, MBL deposition was analyzed by immunofluorescence. Ethical approval and informed consent were obtained. The amount of epithelial cell damage varied significantly between the carriers of different mbl2 genotypes (ANOVA, p=0.02). I-FABP release, representing disintegration of differentiated enterocytes, observed in homozygous wildtype individuals was twice (p=0.03) that measured in heterozygous and ten times (p=0.04) that observed in homozygous variant individuals. No MBL deposition was observed over the course of reperfusion. The data indicate that MBL influences intestinal epithelial cell integrity in an immediate and non-complement dependent manner during ischemia and reperfusion.

Some effects of ORG GC 94, a potential anti-migraine drug, on human platelets.

Some effects of Org GC 94 (1,3,4,14b-tetrahydro-2,7-dimethyl-2H-dibenzo[b,f]pyrazino[1,2-d][1,4]oxazepine maleate) on human platelets have been investigated. Without pretreatment with ADP, 5-HT-induced aggregation of humam platets was completely inhibited by 2.5 x 10(-8) M of Org GC 94. Aggregation triggered by noradrenaline (2.5 x 10(-5) M) and uptake of 5-HT by human platelets were inhibited only at the high concentrations of 10(-5) and 10(-4) M of Org GC 94 respectively. Up to millimolar concentrations, Org GC 94 did not liberate lactate dehydrogenase from human platelets. Org GC 94 did not block the oxidative deamination of benzylamine by human platelet rich plasma up to 2.5 x 10(-4) M.