Background: The treatment options for patients with therapy refractory metastatic colorectal cancer (mCRC) are sparse. TAS-102 (FTD/TPI) is a new oral anti-tumour agent composed of a nucleoside analogue, trifluridine, and a thymidine phosphorylase inhibitor, tipiracil, indicated for patients with mCRC who are refractory to standard therapies. This study summarizes published and unpublished experience with FTD/TPI in clinical practice settings. Patients and methods: The Medline/PubMed, Embase and Cochrane Library databases were searched to identify observational studies on FTD/TPI monotherapy for mCRC. Papers describing use of FTD/TPI monotherapy outside clinical trials in series of patients evaluable for effectiveness were eligible. The outcomes of interest were median progression free survival (mPFS), median overall survival (mOS) as well as mean PFS time restricted to six months (PFS 6m ) and mean OS time restricted to one year (OS 1y ). Results of the pooled analyses of observational studies were compared to the results of the Japanese phase II trial and the two phase III trials, RECOURSE and TERRA. Results: Seven published and two unpublished studies with 1008 patients from 64 centres were included for analysis. The pooled mPFS was 2.2 months (95% CI 2.1 to 2.3 months), and the pooled mOS was 6.6 months (95% CI 6.1 to 7.1 months). PFS 6m was 2.9 months (95% CI 2.6 to 3.1 months) and OS 1y was 6.8 (95% CI 6.0 to 7.5) months. While these results all reflect RECOURSE, the pooled mOS is lower than in the phase II trial and the OS 1y is inferior to both the phase II trial and TERRA. Conclusion: This systematic review and a meta-analysis indicates that in real life settings, the survival benefit of FTD/TPI monotherapy in patients with therapy refractory mCRC reflects the outcomes in RECOURSE but is inferior to outcomes in the two Asian efficacy trials. WHAT IS ALREADY KNOWNTAS 102 (Lonsurf) is an oral fixed dose combination of trifluridine (FTD) and tipiracil (TPI) indicated as salvage-line treatment in patients with therapy refractory metastatic colorectal cancer (mCRC). A Japanese phase II trial and two phase III trials, RECOURSE and TERRA, demonstrated that FTD/TPI prolonged overall survival. WHAT THIS STUDY ADDSThis systematic review and meta-analysis of real life data from 64 sites indicates that the effectiveness in daily clinical practice settings of FTD/TPI monotherapy in late stage mCRC reflects the outcomes in RECOURCE but is inferior to the outcomes in the Japanese phase II trial and TERRA.

Helicobacter pyloni infection is associated with increased meal stimulated gastrin secretion, but the reason for this is unknown. Sequence specific radioimmunoassays were used to measure the concentration of ot-amidated gastrin, the total progastrin product, and somatostatin in biopsy specimens of human antral mucosa. The antral concentrations of ct-amidated gastrin and of total progastrin products were significantly higher in H pyloni infected patients than in those not infected by this organism. In contrast, the antral somatostatin concentration was significantly decreased in infected patients. Progastrin processing, determined by gel chromatography, seemed unaffected by H pyloni infection. The results suggest that the finding of increased gastrin secretion from the antral G cells in H pyloni infected patients may be a result of reduced inhibition of G-cell secretion by somatostatin.

Aim To assess the metabolic effects of dopamine agonists compared with placebo in randomized controlled trials (RCTs) including adults with type 2 diabetes. Materials and methods Eligible trials were identified by searching PubMed, Embase and CENTRAL. The primary outcomes were HbA1c and serious adverse events (SAEs) assessed at longest available follow‐up. Secondary outcomes were fasting plasma glucose, adverse events, body weight, hypoglycaemia and triglycerides. We assessed risk of bias and evaluated the certainty of the evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results Nine RCTs enrolling 3456 participants were included, six of which assessed the effect of bromocriptine, and the other three the effect of cabergoline. Dopamine agonists reduced HbA1c with 0.69 standardized mean difference (95% CI = 0.28 to 1.09; P = .0008; I2 = 80%; GRADE: low) compared with placebo. There was no difference in the effect between bromocriptine and cabergoline. Heterogeneity was partly explained by dosage and study duration, both of which were inversely associated with effect size. Only one large trial reported SAEs and no difference was reported for the risk of an SAE (RR = 0.89; 95% CI = 0.70 to 1.12; P = .32) between active intervention and placebo. Secondary outcomes suggested a decrease in fasting plasma glucose and triglycerides and no effect on the remaining outcomes. Conclusion Dopamine agonists reduce HbA1c as well as fasting plasma glucose and triglycerides in patients with type 2 diabetes without causing SAEs. These data are based on moderate to low quality evidence thus our confidence in the effect estimates is limited.

Objective To estimate the proportion of patients with persistent normoprolactinaemia following dopamine agonist (DA) withdrawal and to identify predictors of successful withdrawal in patients with hyperprolactinaemia. Design, patients, and measurements A systematic review of observational eligible studies were identified by searching PubMed and Embase. The primary outcome was the proportion of patients with normoprolactinaemia after cessation of DA treatment. Secondary outcome included the proportion of patients with normoprolactinaemia after DA withdrawal using individual patient data. Risk of bias was assessed by using Newcastle‐Ottawa Scale. Pooled proportions were estimated using a random effects model in case I2 ≤ 75% or by reporting range of effects if I2 > 75%. Results Thirty‐two observational studies enroling 1563 patients were included. The proportion of patients with persistent normoprolactinaemia ranged from 0% to 75% (I2 = 84%). Heterogeneity was partly explained by age with more successful withdrawal in patients of higher age. Individual patient data analyses suggested that the proportion of patients with persistent normoprolactinaemia 6 months after DA withdrawal with a low maintenance dose and full regression of the prolactinoma was 87.7% (95% confidence interval [CI] = 60.7–97.1; I2 = 0%) and 58.4% (95% CI = 23.8–86.3; I2 = 75%) for microadenomas and macroadenomas, respectively. Conclusions The proportion of patients with persistent normoprolactinaemia following DA withdrawal treatment varied greatly, partly explained by the mean age of participants of the individual studies. Individual patient data analysis suggested that successful withdrawal was likely in patients with full regression of prolactinomas using a low maintenance dose before cessation.