Prognostic value of specific KRAS mutations in patients with colorectal peritoneal metastases.

BACKGROUND: There is little evidence on KRAS mutational profiles in colorectal cancer (CRC) peritoneal metastases (PM). This study aims to determine the prevalence of specific KRAS mutations and their prognostic value in a homogeneous cohort of patients with isolated CRC PM treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. MATERIALS AND METHODS: Data were collected from 13 Italian centers, gathered in a collaborative group of the Italian Society of Surgical Oncology. KRAS mutation subtypes have been correlated with clinical and pathological characteristics and survival [overall survival (OS), local (peritoneal) disease-free survival (LDFS) and disease-free survival (DFS)]. RESULTS: KRAS mutations occurred in 172 patients (47.5%) out of the 362 analyzed. Two different prognostic groups of KRAS mutation subtypes were identified: KRASMUT1 (G12R, G13A, G13C, G13V, Q61H, K117N, A146V), median OS > 120 months and KRASMUT2 (G12A, G12C, G12D, G12S, G12V, G13D, A59E, A59V, A146T), OS: 31.2 months. KRASMUT2 mutations mainly occurred in the P-loop region (P < 0.001) with decreased guanosine triphosphate (GTP) hydrolysis activity (P < 0.001) and were more frequently related to size (P < 0.001) and polarity change (P < 0.001) of the substituted amino acid (AA). When KRASMUT1 and KRASMUT2 were combined with other known prognostic factors (peritoneal cancer index, completeness of cytoreduction score, grading, signet ring cell, N status) in multivariate analysis, KRASMUT1 showed a similar survival rate to KRASWT patients, whereas KRASMUT2 was independently associated with poorer prognosis (hazard ratios: OS 2.1, P < 0.001; DFS 1.9, P < 0.001; LDFS 2.5, P < 0.0001). CONCLUSIONS: In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.

Achievements and challenges in the health of Mexican women, 1990 and 2019: ecological analysis based on the global burden of disease data.

OBJECTIVES: To describe the burden and causes of disease in Mexican women in 1990 and 2019, based on the data disaggregation by age groups and states. Also, to evaluate the relationship of years of healthy life lost with the Socio-demographic Index (SDI) and with the Healthcare Access and Quality (HAQ) Index. STUDY DESIGN: This was an ecological descriptive study. METHODS: Based on the Global Burden of Disease, Injuries, and Risk Factors Study study, the age-standardized and age-specific rates for mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) were reported. RESULTS: At the national level, the all-cause age-standardized rates for Mexican women decreased in mortality -28.8%; YLLs -39.8%; YLDs -1.3%; and DALYs -26.2%. For 2019, the indicators analyzed had the worst performances in Chiapas and Chihuahua, while women in Sinaloa had the lowest age-standardized rates. In 1990, it is worth noting that there was a remarkable presence of CDs, mainly in YLLs. In all age groups, diabetes mellitus was the leading cause of DALYs in Mexico's 32 states, followed by CKD (in 24 states), and ischemic heart disease (in 18 states). In both 1990 and 2019, a negative and statistically significant correlation between DALYs and the HAQ Index was evident. The correlation between DALYs and the SDI was only significant in 1990. CONCLUSION: In the last 30 years, the burden of disease on Mexican women has undergone substantial changes that reflect progress in the improvement of their health conditions. However, the current scenario is complex because the convergence of communicable diseases, non-communicable diseases, and injuries is evident, which implies important challenges that must be addressed as soon as possible.

Hybrid minimally invasive esophagectomy for cancer: impact on postoperative inflammatory and nutritional status.

The purpose of this case-control study was to evaluate the impact of hybrid minimally invasive esophagectomy for cancer on surgical stress response and nutritional status. All 34 consecutive patients undergoing hybrid minimally invasive esophagectomy for cancer at our surgical unit between 2008 and 2013 were retrospectively compared with 34 patients undergoing esophagectomy with open gastric tubulization (open), matched for neoadjuvant therapy, pathological stage, gender and age. Demographic data, tumor features and postoperative course (including quality of life and systemic inflammatory and nutritional status) were compared. Postoperative course was similar in terms of complication rate. Length of stay in intensive care unit was shorter in patients undergoing hybrid minimally invasive esophagectomy (P = 0.002). In the first postoperative day, patients undergoing hybrid minimally invasive esophagectomy had lower C-reactive protein levels (P = 0.001) and white cell blood count (P = 0.05), and higher albumin serum level (P = 0.001). In this group, albumin remained higher also at third (P = 0.06) and seventh (P = 0.008) postoperative day, and C-reactive protein resulted lower at third post day (P = 0.04). Hybrid minimally invasive esophagectomy significantly improved the systemic inflammatory and catabolic response to surgical trauma, contributing to a shorter length of stay in intensive care unit.