Purpose: Mutations within the KRAS proto-oncogene have predictive value but are of uncertain prognostic value in the treatment of advanced colorectal cancer. We took advantage of PETACC-3, an adjuvant trial with 3,278 patients with stage II to III colon cancer, to evaluate the prognostic value of KRAS and BRAF tumor mutation status in this setting. Patients and Methods: Formalin-fixed paraffin-embedded tissue blocks (n = 1,564) were prospectively collected and DNA was extracted from tissue sections from 1,404 cases. Planned analysis of KRAS exon 2 and BRAF exon 15 mutations was performed by allele-specific real-time polymerase chain reaction. Survival analyses were based on univariate and multivariate proportional hazard regression models. Results: KRAS and BRAF tumor mutation rates were 37.0% and 7.9%, respectively, and were not significantly different according to tumor stage. In a multivariate analysis containing stage, tumor site, nodal status, sex, age, grade, and microsatellite instability (MSI) status, KRAS mutation was associated with grade (P = .0016), while BRAF mutation was significantly associated with female sex (P = .017), and highly significantly associated with right-sided tumors, older age, high grade, and MSI-high tumors (all P < 10⁻⁴). In univariate and multivariate analysis, KRAS mutations did not have a major prognostic value regarding relapse-free survival (RFS) or overall survival (OS). BRAF mutation was not prognostic for RFS, but was for OS, particularly in patients with MSI-low (MSI-L) and stable (MSI-S) tumors (hazard ratio, 2.2; 95% CI, 1.4 to 3.4; P = .0003). Conclusion: In stage II-III colon cancer, the KRAS mutation status does not have major prognostic value. BRAF is prognostic for OS in MS-L/S tumors.

To determine the potential efficacy of radio-frequency (RF) ablation of liver metastases during long-term follow-up. Sixteen patients with 31 hepatic metastases were treated with percutaneous, ultrasound-guided RF ablation. RF was applied to monopolar electrodes (2-3-cm tip exposure) either individually or within a multiprobe array (two to four probes) for 6 minutes at 90 degrees C over one to four treatment sessions per metastasis. In only one of 75 sessions, a moderate complication, self-limited intraperitoneal hemorrhage, was observed. Four patients (four lesions) underwent surgical resection 15-60 days after RF treatment. Residual, viable tumor was seen in all of these patients. The remaining 12 patients were followed up for 9-29 months (mean, 18.1 months). In these patients, 18 of 27 lesions remained stable or decreased in size and showed no enhancement at computed tomography and/or magnetic resonance imaging for at least 9 months. Two patients died of disseminated disease at 13 months and one at 16 months. Disease-free survival was achieved in eight patients. RF ablation appears to be a simple, safe, and potentially effective treatment for selected patients with liver metastases and may become a less invasive alternative to surgical therapy.

Research from JAMA — Laparoscopic Antireflux Surgery vs Esomeprazole Treatment for Chronic GERD — The LOTUS Randomized Clinical Trial

Objective: Existing endoscopy-based data on gastro-oesophageal reflux disease (GORD) in the general population are scarce. This study aimed to evaluate typical symptoms and complications of GORD, and their associated risk factors, in a representative sample of the Italian population. Methods: 1533 adults from two Italian villages were approached to undergo symptom assessment using a validated questionnaire and upper gastrointestinal endoscopy. Data were obtained from 1033 individuals (67.4% response rate). Results: The prevalence of reflux symptoms was 44.3%; 23.7% of the population experienced such symptoms on at least 2 days per week (frequent symptoms). The prevalence rates of oesophagitis and Barrett’s oesophagus in the population were 11.8% and 1.3%, respectively. Both frequent (relative risk (RR) 2.6; 95% confidence interval (CI) 1.7 to 3.9) and infrequent (RR 1.9; 95% CI 1.2 to 3.0) reflux symptoms were associated with the presence of oesophagitis. No reflux symptoms were reported by 32.8% of individuals with oesophagitis and 46.2% of those with Barrett’s oesophagus. Hiatus hernia was associated with frequent reflux symptoms and oesophagitis, and was present in 76.9% of those with Barrett’s oesophagus. We found no association between body mass index and reflux symptoms or oesophagitis. Conclusions: GORD is common in Italy, but the prevalence of Barrett’s oesophagus in the community is lower than has been reported in selected populations. Both frequent and infrequent reflux symptoms are associated with an increased risk of oesophagitis. Individuals with oesophagitis and Barrett’s oesophagus often have no reflux symptoms.

Summary: Background and aims : Considerable difficulties persist amongst pathologists in agreeing on the presence and severity of gastric atrophy. An international group of pathologists pursued the following aims: (i) to generate an acceptable definition and a simple reproducible classification of gastric atrophy; and (ii) to develop guidelines for the recognition of atrophy useful for increasing agreement among observers.Methods : After redefining atrophy as the ‘loss of appropriate glands’ and examining histological samples from different gastric compartments, three categories were identified: (i) negative; (ii) indefinite; (iii) atrophy, with and without intestinalization. Atrophy was graded on a three‐level scale. Interobserver reproducibility of the classification was tested by κ statistics (general and weighted) in a series of 48 cases.Results : The medians of the general agreement and weighted κ values were 0.78 and 0.73, respectively. The weighted κ coefficients, obtained by cross‐tabulating the evaluation of each pathologist against all others, were, with only one exception, > 0.4 (moderate to excellent agreement).Conclusions : By using the definition of atrophy as the loss of appropriate glands and distinguishing the two main morphological entities of metaplastic and non‐metaplastic types, a high level of agreement was achieved by a group of gastrointestinal pathologists trained in different cultural contexts.