Role of bariatric surgery in reducing the risk of colorectal cancer: a meta-analysis.

BACKGROUND: Obesity increases the risk of multiple co-morbidities such as type 2 diabetes, cardiovascular disease and most cancers, including colorectal cancer. Currently, the literature presents conflicting results regarding the protective effects of bariatric surgery on the incidence of colorectal cancer. This meta-analysis was conducted to investigate the effect of bariatric surgery on the risk of developing colorectal cancer in obese individuals. METHODS: Ovid Embase, Ovid MEDLINE, Cochrane CENTRAL and Web of Science were searched for relevant articles. Articles published by the end of December 2018 were retrieved; data were extracted according to evidence-based PICO (population, intervention, control, outcome) model and analysed using a random-effects model to estimate the pooled relative risk (RR) and its 95 per cent confidence interval. The heterogeneity of studies was tested and quantified using Cochran's Q and I2 statistics. Meta-regression was used to investigate the association of year of study, region, mean length of follow-up and sample size with RR. RESULTS: Seven articles, involving a total of 1 213 727 patients, were included in the meta-analysis. The pooled estimate of the RR was 0·64 (95 per cent c.i. 0·42 to 0·98). The test of asymmetry found no significant publication bias. Meta-regression showed that sample size was a statistically significant factor (P = 0·037), but year of publication, region and mean duration of follow-up were not significant. CONCLUSION: Patients who underwent bariatric surgery had a greater than 35 per cent reduction in the risk of developing colorectal cancer compared with obese individuals who had no surgery.

ANTECEDENTES: La obesidad aumenta el riesgo de múltiples comorbilidades, como la diabetes tipo II, las enfermedades cardiovasculares y la mayoría de los cánceres, entre los que se incluye el cáncer colorrectal. En la actualidad, la literatura presenta resultados contradictorios sobre el efecto protector de la cirugía bariátrica en la incidencia del cáncer colorrectal. Este metaanálisis se llevó a cabo para investigar el efecto de la cirugía bariátrica sobre el riesgo de desarrollar un cáncer colorrectal en individuos obesos. MÉTODOS: Se realizó una búsqueda de artículos relevantes en Ovid Embase, Ovid Medline, Cochrane CENTRAL y Web of Science. Se recuperaron los artículos publicados hasta diciembre 2018 y los datos se extrajeron de acuerdo con el modelo PICO que se utiliza en la práctica de la medicina basada en la evidencia (población, intervención, control, resultado). Asimismo, los datos se analizaron mediante un modelo de efectos aleatorios para estimar el riesgo relativo combinado y su intervalo de confianza del 95%. La heterogeneidad de los estudios se comprobó y se cuantificó utilizando los estadísticos de Cochran Q y I2 . Se utilizó un análisis de metarregresión para investigar la asociación del año del estudio, región, tiempo de seguimiento medio (años), y tamaño de la muestra con el riesgo relativo. RESULTADOS: Para este estudio se incluyeron siete artículos en el metaanálisis final lo que representa un total de 108.070 pacientes. Los resultados mostraron que la estimación combinada del riesgo relativo fue de 0,64 con un intervalo de confianza 95% (i.c. 0,42- 0,98). De acuerdo con la prueba de asimetría, no hubo sesgo significativo de publicación. La metarregresión mostró que el año de publicación, región, y la media de seguimiento no fueron significativas, mientras que el tamaño de la muestra sí lo fue. CONCLUSIÓN: Los pacientes sometidos a cirugía bariátrica tuvieron más del 35% de reducción del riesgo de desarrollar cáncer colorrectal en comparación con individuos obesos no operados.

Modified frailty index predicts early outcomes after colorectal surgery: an ACS-NSQIP study.

AIM: Frailty is defined as a decrease in physiological reserve with increased risk of morbidity following significant physiological stressors. This study examines the predictive power of the five-item modified frailty index (5-mFI) in predicting outcomes in colorectal surgery patients. METHODS: The American College of Surgeons National Surgical Quality Improvement Program Database was queried from 2011 to 2016 to determine the predictive power of 5-mFI in patients who had colorectal surgery. RESULTS: Of 295 490 patients, 45.8% had a score of 0, 36.2% had a score of 1 and 18% had a score of ≥ 2. On univariate analysis, frailer patients had significantly greater incidences for overall morbidity, serious morbidity, mortality, prolonged length of hospital stay, discharge to a facility other than home, reoperation and unplanned readmission. These findings were consistent on multivariate analysis where the frailest patients had greater odds of postoperative overall morbidity (OR 1.39; 95% CI 1.35-1.43), serious morbidity (OR 1.39; 95% CI 1.33-1.45), mortality (OR 2.00; 95% CI 1.87-2.14), prolonged length of hospital stay (OR 1.24; 95% CI 1.20-1.27), discharge destination to a facility other than home (OR 2.80; 95% CI 2.70-2.90), reoperation (OR 1.17; 95% CI 1.11-1.23) and unplanned readmission (OR 1.31; 95% CI 1.26-1.36). Weighted kappa statistics showed strong agreement between the 5-mFI and 11-mFI (kappa = 0.987, P < 0.001). CONCLUSIONS: The 5-mFI is a valid and easy to use predictor of 30-day postoperative outcomes after colorectal surgery. This tool may guide the surgeon to proactively recognize frail patients to instigate interventions to optimize them preoperatively.

Conserved regulation of mesenchymal gene expression by Fgf-8 in face and limb development.

Clim-2 (NLI, Lbd1) is one of two related mouse proteins that interact with Lim-domain homeoproteins. In the mouse, embryonic expression of Clim-2 is particularly pronounced in facial ectomesenchyme and limb bud mesenchyme in association with Lim genes, Lhx-6 and Lmx-1 respectively. We show that in common with both these Lim genes, Clim-2 expression is regulated by signals from overlying epithelium. In both the developing face and the limb buds we identify Fgf-8 as the likely candidate signalling molecule that regulates Clim-2 expression. We show that in the mandibular arch, as in the limb, Fgf-8 functions in combination with CD44, a cell surface binding protein, and that blocking CD44 binding results in inhibition of Fgf8-induced expression of Clim-2 and Lhx-6. Regulation of gene expression by Fgf8 in association with CD44 is thus conserved between limb and mandibular arch development.

Interactions between Bmp-4 and Msx-1 act to restrict gene expression to odontogenic mesenchyme.

Tooth development is regulated by a reciprocal series of epithelial-mesenchymal interactions. Bmp4 has been identified as a candidate signalling molecule in these interactions, initially as an epithelial signal and then later at the bud stage as a mesenchymal signal (Vainio et al. [1993] Cell 75:45-58). A target gene for Bmp4 signalling is the homeobox gene Msx-1, identified by the ability of recombinant Bmp4 protein to induce expression in mesenchyme. There is, however, no evidence that Bmp4 is the endogenous inducer of Msx-1 expression. Msx-1 and Bmp-4 show dynamic, interactive patterns of expression in oral epithelium and ectomesenchyme during the early stages of tooth development. In this study, we compare the temporal and spatial expression of these two genes to determine whether the changing expression patterns of these genes are consistent with interactions between the two molecules. We show that changes in Bmp-4 expression precede changes in Msx-1 expression. At embryonic day (E)10.5-E11.0, expression patterns are consistent with BMP4 from the epithelium, inducing or maintaining Msx-1 in underlying mesenchyme. At E11.5, Bmp-4 expression shifts from epithelium to mesenchyme and is rapidly followed by localised up-regulation of Msx-1 expression at the sites of Bmp-4 expression. Using cultured explants of developing mandibles, we confirm that exogenous BMP4 is capable of replacing the endogenous source in epithelium and inducing Msx-1 gene expression in mesenchyme. By using noggin, a BMP inhibitor, we show that endogenous Msx-1 expression can be inhibited at E10.5 and E11.5, providing the first evidence that endogenous Bmp-4 from the epithelium is responsible for regulating the early spatial expression of Msx-1. We also show that the mesenchymal shift in Bmp-4 is responsible for up-regulating Msx-1 specifically at the sites of future tooth formation. Thus, we establish that a reciprocal series of interactions act to restrict expression of both genes to future sites of tooth formation, creating a positive feedback loop that maintains expression of both genes in tooth mesenchymal cells.

Critical flicker fusion frequency in early chloroquine retinopathy.

Since increasing numbers of patients with connective tissue diseases are taking chloroquine and its derivatives, there is an urgent need for a simple, reasonably fast method of screening for toxic effects on the retina. Measurement of the critical flicker fusion frequency is one technique for assessing retinal function. Its screening value was assessed in a study of nine patients with bilateral visual field defects and visual acuity of 6/12 or better after various periods of chloroquine therapy and nine healthy subjects matched for age and sex who had never taken chloroquine. The control subjects' eyes consistently demonstrated the normal pattern previously described, whereas 16 of the 17 eyes tested in the patients showed one of two abnormal patterns of response.