Genetic Variants as Predictors of the Success of Colorectal Cancer Treatments.

BACKGROUND: Some genetic polymorphisms (SNPs) have been proposed as predictors for different colorectal cancer (CRC) outcomes. This work aims to assess their performance in our cohort and find new SNPs associated with them. METHODS: A total of 833 CRC cases were analyzed for seven outcomes, including the use of chemotherapy, and stratified by tumor location and stage. The performance of 63 SNPs was assessed using a generalized linear model and area under the receiver operating characteristic curve, and local SNPs were detected using logistic regressions. RESULTS: In total 26 of the SNPs showed an AUC > 0.6 and a significant association (p < 0.05) with one or more outcomes. However, clinical variables outperformed some of them, and the combination of genetic and clinical data showed better performance. In addition, 49 suggestive (p < 5 × 10-6) SNPs associated with one or more CRC outcomes were detected, and those SNPs were located at or near genes involved in biological mechanisms associated with CRC. CONCLUSIONS: Some SNPs with clinical data can be used in our population as predictors of some CRC outcomes, and the local SNPs detected in our study could be feasible markers that need further validation as predictors.

Functional Engagement of the PD-1/PD-L1 Complex But Not PD-L1 Expression Is Highly Predictive of Patient Response to Immunotherapy in Non-Small-Cell Lung Cancer.

PURPOSE: In many cancers, the expression of immunomodulatory ligands leads to immunoevasion, as exemplified by the interaction of PD-L1 with PD-1 on tumor-infiltrating lymphocytes. Profound advances in cancer treatments have come with the advent of immunotherapies directed at blocking these immuno-suppressive ligand-receptor interactions. However, although there has been success in the use of these immune checkpoint interventions, correct patient stratification for these therapies has been challenging. MATERIALS AND METHODS: To address this issue of patient stratification, we have quantified the intercellular PD-1/PD-L1 interaction in formalin-fixed paraffin-embedded tumor samples from patients with non-small cell lung carcinoma, using a high-throughput automated quantitative imaging platform (quantitative functional proteomics [QF-Pro]). RESULTS: The multisite blinded analysis across a cohort of 188 immune checkpoint inhibitor-treated patients demonstrated the intra- and intertumoral heterogeneity of PD-1/PD-L1 immune checkpoint engagement and notably showed no correlation between the extent of PD-1/PD-L1 interaction and PD-L1 expression. Importantly, PD-L1 expression scores used clinically to stratify patients correlated poorly with overall survival; by contrast, patients showing a high PD-1/PD-L1 interaction had significantly better responses to anti-PD-1/PD-L1 treatments, as evidenced by increased overall survival. This relationship was particularly strong in the setting of first-line treatments. CONCLUSION: The functional readout of PD-1/PD-L1 interaction as a predictive biomarker for the stratification of patients with non-small-cell lung carcinoma, combined with PD-L1 expression, should significantly improve the response rates to immunotherapy. This would both capture patients excluded from checkpoint immunotherapy (high PD-1/PD-L1 interaction but low PD-L1 expression, 24% of patients) and additionally avoid treating patients who despite their high PD-L1 expression do not respond and suffer from side effects.

IgA vasculitis (Henoch- Schönlein purpura) with gastrointestinal involvement.

We present the case of a patient who was admitted due to jejunitis in the context of an IgA vasculitis, previously known as Schönlein-Henoch vasculitis.

Performance of the Use of Genetic Information to Assess the Risk of Colorectal Cancer in the Basque Population.

Although the genetic contribution to colorectal cancer (CRC) has been studied in various populations, studies on the applicability of available genetic information in the Basque population are scarce. In total, 835 CRC cases and 940 controls from the Basque population were genotyped and genome-wide association studies were carried out. Mendelian Randomization analyses were used to discover the effect of modifiable risk factors and microbiota on CRC. In total, 25 polygenic risk score models were evaluated to assess their performance in CRC risk calculation. Moreover, 492 inflammatory bowel disease cases were used to assess whether that genetic information would not confuse both conditions. Five suggestive (p < 5 × 10−6) loci were associated with CRC risk, where genes previously associated with CRC were located (e.g., ABCA12, ATIC or ERBB4). Moreover, the analyses of CRC locations detected additional genes consistent with the biology of CRC. The possible contribution of cholesterol, BMI, Firmicutes and Cyanobacteria to CRC risk was detected by Mendelian Randomization. Finally, although polygenic risk score models showed variable performance, the best model performed correctly regardless of the location and did not misclassify inflammatory bowel disease cases. Our results are consistent with CRC biology and genetic risk models and could be applied to assess CRC risk in the Basque population.

Autoamputation of a polypoid carcinoma of the rectum / Autoamputación de un carcinoma polipoide en el recto

No disponible

Short article: Hormone therapy for severe gastrointestinal bleeding due to multiple angiodysplastic lesions.

OBJECTIVE: This study aims to assess the efficacy of hormone therapy in patients with severe gastrointestinal bleeding due to multiple angiodysplastic lesions. PATIENTS AND METHODS: Between May 2010 and July 2017, we included 12 consecutive patients with anaemia or recurrent bleeding due to angiodysplasia who had been started on hormone therapy. The therapy given was a combination of levonorgestrel (between 0.10 and 0.25 mg) and ethinylestradiol (between 0.02 and 0.05 mg). We determined the mean number of transfusions required in the 6 months before and after the start of the treatment, as well as the mean haemoglobin levels, number of admissions for anaemia due to gastrointestinal bleeding and length of hospital stay in these periods. RESULTS: The mean age of patients included was 77.83 years old and 75% were male. The follow-up period after treatment initiation was 6 months. Of the 12 patients included, only one stopped the treatment owing to it not being effective. Overall, 83.3% of the patients reported subjective improvement. Furthermore, we found significant differences comparing before and after starting treatment regarding the mean number of transfusions (7±4.8 vs. 3.4±4.6; P=0.005), the mean haemoglobin levels (9.5±1.2 vs. 10.8±2.6; P=0.034) and the mean number of admissions (1.6±1.6 vs. 0.2±0.4; P=0.024). On the contrary, differences between pretreatment and post-treatment length of hospital stay were not significant. CONCLUSION: Hormone therapy is a potentially useful therapeutic tool in patients with refractory bleeding and anaemia due to angiodysplasia.