The Hellenic emergency laparotomy study (HELAS): a prospective multicentre study on the outcomes of emergency laparotomy in Greece

Background Emergency laparotomy (EL) is accompanied by high post-operative morbidity and mortality which varies significantly between countries and populations. The aim of this study is to report outcomes of emergency laparotomy in Greece and to compare them with the results of the National Emergency Laparotomy Audit (NELA). Methods This is a multicentre prospective cohort study undertaken between 01.2019 and 05.2020 including consecutive patients subjected to EL in 11 Greek hospitals. EL was defined according to NELA criteria. Demographics, clinical variables, and post-operative outcomes were prospectively registered in an online database. Multivariable logistic regression analysis was used to identify independent predictors of post-operative mortality. Results There were 633 patients, 53.9% males, ASA class III/IV 43.6%, older than 65 years 58.6%. The most common operations were small bowel resection (20.5%), peptic ulcer repair (12.0%), adhesiolysis (11.8%) and Hartmann’s procedure (11.5%). 30-day post-operative mortality reached 16.3% and serious complications occurred in 10.9%. Factors associated with post-operative mortality were increasing age and ASA class, dependent functional status, ascites, severe sepsis, septic shock, and diabetes. HELAS cohort showed similarities with NELA patients in terms of demographics and preoperative risk. Post-operative utilisation of ICU was significantly lower in the Greek cohort (25.8% vs 56.8%) whereas 30-day post-operative mortality was significantly higher (16.3% vs 8.7%). Conclusion In this study, Greek patients experienced markedly worse mortality after emergency laparotomy compared with their British counterparts. This can be at least partly explained by underutilisation of critical care by surgical patients who are at high risk for death

Development and internal validation of a clinical prediction model for serious complications after emergency laparotomy

Purpose Emergency laparotomy (EL) is a common operation with high risk for postoperative complications, thereby requiring accurate risk stratification to manage vulnerable patients optimally. We developed and internally validated a predictive model of serious complications after EL. Methods Data for eleven carefully selected candidate predictors of 30-day postoperative complications (Clavien-Dindo grade >  = 3) were extracted from the HELAS cohort of EL patients in 11 centres in Greece and Cyprus. Logistic regression with Least Absolute Shrinkage and Selection Operator (LASSO) was applied for model development. Discrimination and calibration measures were estimated and clinical utility was explored with decision curve analysis (DCA). Reproducibility and heterogeneity were examined with Bootstrap-based internal validation and Internal–External Cross-Validation. The American College of Surgeons National Surgical Quality Improvement Program’s (ACS-NSQIP) model was applied to the same cohort to establish a benchmark for the new model. Results From data on 633 eligible patients (175 complication events), the SErious complications After Laparotomy (SEAL) model was developed with 6 predictors (preoperative albumin, blood urea nitrogen, American Society of Anaesthesiology score, sepsis or septic shock, dependent functional status, and ascites). SEAL had good discriminative ability (optimism-corrected c-statistic: 0.80, 95% confidence interval [CI] 0.79–0.81), calibration (optimism-corrected calibration slope: 1.01, 95% CI 0.99–1.03) and overall fit (scaled Brier score: 25.1%, 95% CI 24.1–26.1%). SEAL compared favourably with ACS-NSQIP in all metrics, including DCA across multiple risk thresholds. Conclusion SEAL is a simple and promising model for individualized risk predictions of serious complications after EL. Future external validations should appraise SEAL’s transportability across diverse settings

Mutation of genes of the PI3K/AKT pathway in breast cancer supports their potential importance as biomarker for breast cancer aggressiveness

Deregulation of phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is closely associated with cancer development and cancer progression. PIK3CA, AKT1, and PTEN are the fundamental molecules of the PI3K/AKT pathway with increased mutation rates in cancer cases leading to aberrant regulation of the pathway. Even though molecular alterations of the PI3K/AKT pathway have been studied in breast cancer, correlations between specific molecular alterations and clinicopathological features remain contradictory. In this study, we examined mutations of the PI3K/AKT pathway in 75 breast carcinomas using high-resolution melting analysis and pyrosequencing, in parallel with analysis of relative expression of PIK3CA and AKT2 genes. Mutations of PIK3CA were found in our cohort in 21 cases (28 %), 10 (13 %) in exon 9 and 11(15 %) in exon 20. Mutation frequency of AKT1 and PTEN genes was 4 and 3 %, respectively. Overall, alterations in the PI3K/AKT signaling cascade were detected in 35 % of the cases. Furthermore, comparison of 50 breast carcinomas with adjacent normal tissues showed elevated PIK3CA messenger RNA (mRNA) levels in 18 % of tumor cases and elevated AKT2 mRNA levels in 14 %. Our findings, along with those of previous studies, underline the importance of the PI3K/AKT pathway components as potential biomarkers for breast carcinogenesis. © 2016, Springer-Verlag Berlin Heidelberg

Effects of caspase-9 and survivin gene polymorphisms in pancreatic cancer risk and tumor characteristics

Objectives: This case-control study was performed to evaluate the association between a specific caspase-9 polymorphism as well as the genetic polymorphism -31G/C located in the cycle-dependent elements/cell cycle homology regions repressor element of the human survivin promoter and the risk of pancreatic cancer. Methods: Eighty patients with pancreatic cancer and 160 healthy controls were investigated for genotype and allelic frequencies of caspase-9 1263A/G and survivin -31G/C polymorphisms by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism. Results: The G carrier group of patients and the G allele of caspase-9 1263A/G were overrepresented among the pancreatic cancer cases. With regard to tumor characteristics, a statistically significant association was detected between the survivin C carrier group of patients and the advanced T stage as well as the presence of lymph node metastasis. Conclusions: The caspase-9 G allele confers increased susceptibility to pancreatic cancer development, and the survivin C carriage status may be related to aggressive features of this malignancy. Copyright © 2010 by Lippincott Williams & Wilkins

Concurrent Wnt pathway component expression in breast and colorectal cancer

Wnt signaling pathway regulates important cell functions such as proliferation and migration and is frequently deregulated in colorectal and breast cancer. Thus, it constitutes an attractive therapeutic target with many drugs being investigated in clinical trials. Eighty-two breast and 102 colorectal carcinomas were analyzed for: relative mRNA expression levels of Wnt pathway components namely Wnt3 ligand, Frizzled 7 receptor and LEF1 transcriptional factor, their concurrent expression patterns and their correlation with clinicopathological features. Regarding breast carcinomas, increased relative mRNA expression levels of WNT3 were found in 54 % of cases whereas decreased relative mRNA expression levels were observed in FZD7 and LEF1 in 82 % and 43 % of cases, respectively. Expression levels of WNT3 were significantly correlated with tumour grade (p = 0.021) in breast cancer. As far as colorectal carcinomas are concerned, increased relative mRNA expression levels of WNT3, FZD7 and LEF1 were found in 60 %, 37 % and 48 % of cases respectively. A statistically significant correlation emerged between LEF1expression levels and pT-category (p = 0.027), suggesting a possible association with tumour aggressiveness in colorectal carcinomas. Statistically significant linear correlations were observed between the expression of WNT3/LEF1 (R = 0.233, p = 0.035) and FZD7/LEF1 (R = 0.359, p = 0.001) in breast carcinomas as well as in colorectal carcinomas (R = 0.536, p < 0.01 and R = 0.210, p = 0.034) respectively. Our results demonstrate a possible clinical significance of Wnt pathway gene expression levels in both tumour types. The distinct expression patterns and simultaneous expression of the investigated genes underscore the complexity of this pathway in breast and colorectal carcinogenesis and highlights the necessity of patient selection with regard to the effectiveness of Wnt pathway inhibitors. © 2020 Elsevier Gmb