Effects of an aqueous extract of processed bidi tobacco on the growth of hamster tracheal epithelial cells

Inhalation of tobacco dust is responsible for elevated genotoxicity and pulmonary ailments in workers engaged in processing tobacco for the manufacture of bidis, the Indian version of cigarettes. Tracheal tissue being the major site of interaction with tobacco dust, the effects of different concentrations of an aqueous extract of bidi tobacco (ATE) on the growth of a hamster tracheal epithelial cell line (HTE) were investigated. Colony forming efficiency assay revealed that ATE was cytotoxic only at the highest concentration of 5.0 mg/ml. In cultures treated with 1.25 mg/ml ATE, the cell doubling time and growth rate were similar to that of the controls, while a significant increase in cell doubling time (29.4±0.3 h vs 14.0±3.75 h, P<0.001) was observed at 2.5 mg/ml ATE concentration. Exposure of HTE cells to the non-toxic ATE concentration of 2.5 mg/ml was found to stimulate ornithine decarboxylase (ODC) activity, incorporation of [3H] methyl thymidine into DNA and increase in the S phase fraction was seen by flow cytometry. However, a 56% reduction in the growth rate of cultures treated with 2.5 mg/ml ATE was related to the prolongation of the traverse of cells through S phase. ATE-induced growth suppression was reversed when cultures were grown in ATE-free medium or upon repeated exposure to ATE. The findings suggest that increased tracheal cell proliferation induced by chronic inhalation of tobacco dust may contribute to the development of pulmonary disorders and possibly neoplasia in exposed individuals

A nomogram for predicting complications in patients with solid tumours and seemingly stable febrile neutropenia

Background: We sought to develop and externally validate a nomogram and web-based calculator to individually predict the development of serious complications in seemingly stable adult patients with solid tumours and episodes of febrile neutropenia (FN). Patients and methods: The data from the FINITE study (n ¼ 1133) and University of Salamanca Hospital (USH) FN registry (n ¼ 296) were used to develop and validate this tool. The main eligibility criterion was the presence of apparent clinical stability, defined as events without acute organ dysfunction, abnormal vital signs, or major infections. Discriminatory ability was measured as the concordance index and stratification into risk groups. Results: The rate of infection-related complications in the FINITE and USH series was 13.4% and 18.6%, respectively. The nomogram used the following covariates: Eastern Cooperative Group (ECOG) Performance Status X2, chronic obstructive pulmonary disease, chronic cardiovascular disease, mucositis of grade X2 (National Cancer Institute Common Toxicity Criteria), monocytes o200/mm3 , and stress-induced hyperglycaemia. The nomogram predictions appeared to be well calibrated in both data sets (Hosmer–Lemeshow test, P40.1). The concordance index was 0.855 and 0.831 in each series. Risk group stratification revealed a significant distinction in the proportion of complications. With a X116-point cutoff, the nomogram yielded the following prognostic indices in the USH registry validation series: 66% sensitivity, 83% specificity, 3.88 positive likelihood ratio, 48% positive predictive value, and 91% negative predictive value. Conclusions: We have developed and externally validated a nomogram and web calculator to predict serious complications that can potentially impact decision-making in patients with seemingly stable FN

Nomogram-based prediction of survival in patients with advanced oesophagogastric adenocarcinoma receiving first-line chemotherapy: a multicenter prospective study in the era of trastuzumab

Background: To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination chemotherapy. Methods: Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrell's c-index was used to evaluate discrimination. Results: The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5–6.6), 9.4 (95% CI, 8.5–10.6), and 14 months (95% CI, 11.8–16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3–8.1), 12.7 (95% CI, 11.3–14.3), and 18.3 months (95% CI, 14.6–24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591–0.631) and 0.673 (95% CI, 0.636–0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351). Conclusions: We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design

Publicación: Prognostic significance of performing universal HER2 testing in cases of advanced gastric cancer

Trastuzumab significantly improves overall survival (OS) when added to cisplatin and fluoropyrimidine as a treatment for HER2-positive advanced gastric cancers (AGC). The aim of this study was to evaluate the impact of the gradual implementation of HER2 testing on patient prognosis in a national registry of AGC. This Spanish National Cancer Registry includes cases who were consecutively recruited at 28 centers from January 2008 to January 2016. The effect of missing HER2 status was assessed using stratified Cox proportional hazards (PH) regression. The rate of HER2 testing increased steadily over time, from 58.3 % in 2008 to 92.9 % in 2016. HER2 was positive in 194 tumors (21.3 %). In the stratified Cox PH regression, each 1 % increase in patients who were not tested for HER2 at the institutions was associated with an approximately 0.3 % increase in the risk of death: hazard ratio, 1.0035 (CI 95 %, 1.001-1.005), P = 0.0019. Median OS was significantly lower at institutions with the highest proportions of patients who were not tested for HER2. Patients treated at centers that took longer to implement HER2 testing exhibited worse clinical outcomes. The speed of implementation behaves as a quality-of-care indicator. Reviewed guidelines on HER2 testing should be used to achieve this goal in a timely manner