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

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

Sentinel Node Navigation in Gastric Cancer: Where Do We Stand?

Background: Early gastric cancer (EGC) is more common nowadays and is related a to low percentage of lymph node metastasis. For this reason, there is enormous interest to implicate minimally invasive approaches. Recently, special efforts have been made towards a potential intraoperative (real-time) lymph node metastasis (LNM) assessment, as nodal disease status could not be identified with precision before or during surgery. In this direction, accurate prediction of the LNM status through sentinel LN mapping has been attempted, as an approach to the intraoperative detection of sentinel lymph nodes (SLNs). A careful literature search was conducted in order to clarify the potential clinical application of SN biopsy in the gastric cancer field. Conclusion: The real clinical application of SN biopsy in gastric cancer treatment has been more than challenging due to the “complicated” nature of gastric lymphatic drainage and the high possibility of “skip” metastasis phenomenon. Notably, sophisticated technical aspects, such as the preferred tracer used and the potential “ideal” method to verify the presence of metastases in the resected SLNs, made SN biopsy application in gastric cancer field extremely demanding. Assessing the potential role of SN navigation for gastric cancer treatment in the era of advanced technology, where the minimally invasive surgical approaches are in the top of the scientific interest, it has to be highlighted that SN navigation for gastric cancer is a topic that remains highly controversial, and the need for future clinical trials on this topic is obvious. © 2019, Springer Science+Business Media, LLC, part of Springer Nature

Primary liver cancer genome sequencing: Translational implications and challenges

Introduction: The prognosis of primary liver cancer (PLC) remains poor and is explained by the slow progress in understanding the molecular pathways driving tumorigenesis, therapeutic resistance and relapse. For early PLCs, complete surgical resection is the only effective treatment, with sorafenib and, more recently, regorafenib prolonging overall survival by a few months. Areas covered: Application of next-generation sequencing (NGS), including targeted NGS (tNGS), whole-exome sequencing (WES), whole-genome sequencing (WGS) and RNA sequencing (RNAseq), on clinical samples from patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) could aid in comprehending tumorigenesis, genetic and genomic heterogeneity, as well as developing molecular classifications for specialized targeted therapy. Expert commentary: Despite the many overenthusiastic original and opinion reports, we have critically reviewed available NGS studies, with focus on the challenges to achieve clinical implications. Based on the recommendations for valid identification of clinically crucial genomic alterations (GAs) by NGS, we propose NGS integration into appropriately designed clinical trials. Furthermore, valid detection of genomic heterogeneity enables the conduction of clinical trials investigating the efficacy both of GAs as prognostic and predictive tools, as well as the discovery of novel oncotargets, on the basis of an early drug development strategy. © 2017 Informa UK Limited, trading as Taylor & Francis Group

Clinical heterogeneity in patients with non-alcoholic fatty liver disease-associated hepatocellular carcinoma

Introduction: The indisputable increase in nonalcoholic Fatty Liver Disease (NAFLD) prevalence (25% of population) has consequently led to an increase in Hepatocellular Carcinoma (HCC) and liver-related mortality worldwide. The characteristics of patients with HCC, secondary to NAFLD, are older age, large tumors due to late diagnosis, often without cirrhosis and high prevalence of the metabolic syndrome components, leading to an increased mortality rate. Although the mechanisms of disease remain partially obscure, insulin resistance, oxidative stress, apoptosis, iron overload, and excessive local and systemic inflammation are identified as culprits for hepatocarcinogenesis in the presence of NAFLD. Area covered: In this review, the authors report that there are no uniform guidelines for surveillance and early diagnosis in this patient group. Barcelona Clinic Liver Cancer staging is generally applicable to HCC due to NAFLD and management depends on liver function, tumor characteristics, and cardiovascular comorbidity. Evidence suggests that HCC due to NAFLD can be associated with worse survival due to late diagnosis. Expert opinion: The need for effective early diagnosis and management of NAFLD is urgent, considering the galloping incidence of the obesity and the fact that liver cirrhosis and HCC due to NAFLD will become the first indication for liver transplantation in foreseeable future. © 2020 Informa UK Limited, trading as Taylor & Francis Group

Colour Duplex and/or Contrast-Enhanced Ultrasound Compared with Computed Tomography Angiography for Endoleak Detection after Endovascular Abdominal Aortic Aneurysm Repair: A Systematic Review and Meta-Analysis

This study aims to assess the role of Color Duplex Ultrasound with or without contrast media for surveillance following endovascular aortic aneurysm repair (EVAR). A systematic search of the literature published until April 2022 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The pooled rates of en-doleak detection through Contrast-Enhanced or Color Duplex Ultrasound (CEUS or CDUS) and Computed Tomography Angiography (CTA) with 95% confidence intervals (CIs) were estimated using random-effect analysis. Thirty-eight studies were considered eligible for inclusion. The total number of patients in the included studies was 5214 between 1997 and 2021. The overall pooled rate of endoleak detection using CDUS and CTA was 82.59% and 97.22%, while the rates for CEUS and CTA were 96.67% and 92.82%, respectively. The findings of the present study support the use of the CEUS for endoleak detection. However, it should be integrated into institutional protocols for EVAR surveillance to further evaluate its clinical utility in the post-EVAR period before it can be recommended as the sole imaging modality after EVAR. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

The role of liver resection in the management of intermediate and advanced stage hepatocellular carcinoma. A systematic review

Background: The ideal management for patients with intermediate and advanced stage hepatocellular carcinoma (HCC) is controversial. The main purpose of this systematic review is to examine the role of liver resection in patients with intermediate stage HCC (multinodular HCCs) and in advanced stage HCC [mainly patients with portal vein tumor thrombosis (PVTT)]. Methods: A systematic search of the literature was performed in Pud Med and the Cochrane Library from 01.01.2000 to 30.06.2016. Results: Twenty-three articles with 2412 patients with multinodular HCCs were selected. Also, 29 studies with 3659 patients with HCCs with macrovascular invasion were selected. In patients with multinodular HCCs the median post-operative morbidity was 25% and the 90-day mortality was 2.7%. The median survival was 37 months and the 5-year survival 35%. The 5-year survival was much better for patients with a number of HCCs ≤3 vs. HCCs >3 (49% vs. 23%). In patients with macrovascular invasion, who underwent hepatic resection, the median post-operative morbidity was 33% and the in-hospital mortality 2.7%. The median survival was 15 months. The 3 and 5year survival was 33% and 20% respectively. Moreover a significant difference in survival was noted according to PVTT stage: 5- year survival for distal PVTT, PVTT of the main intrahepatic PV branch and PVTT extending to the main PV was 45%, 19% and 14.5% respectively. Conclusions: Liver resection in patients with multinodular HCCs and HCCs with PVTT offers satisfactory long-term survival and should be considered in selected patients. © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncolog

From clinical standards to translating next-generation sequencing research into patient care improvement for hepatobiliary and pancreatic cancers

Hepatobiliary and pancreatic (HBP) cancers are associated with high cancer-related death rates. Surgery aiming for complete tumor resection (R0) remains the cornerstone of the treatment for HBP cancers. The current progress in the adjuvant treatment is quite slow, with gemcitabine chemotherapy available only for pancreatic ductal adenocarcinoma (PDA). In the advanced and metastatic setting, only two targeted drugs have been approved by the Food & Drug Administration (FDA), which are sorafenib for hepatocellular carcinoma and erlotinib for PDA. It is a pity that multiple Phase III randomized control trials testing the efficacy of targeted agents have negative results. Failure in the development of effective drugs probably reflects the poor understanding of genome-wide alterations and molecular mechanisms orchestrating therapeutic resistance and recurrence. In the post-ENCODE (Encyclopedia of DNA Elements) era, cancer is referred to as a highly heterogeneous and systemic disease of the genome. The unprecedented potential of next-generation sequencing (NGS) technologies to accurately identify genetic and genomic variations has attracted major research and clinical interest. The applications of NGS include targeted NGS with potential clinical implications, while whole-exome and whole-genome sequencing focus on the discovery of both novel cancer driver genes and therapeutic targets. These advances dictate new designs for clinical trials to validate biomarkers and drugs. This review discusses the findings of available NGS studies on HBP cancers and the limitations of genome sequencing analysis to translate genome-based biomarkers and drugs into patient care in the clinic. © 2017 by the authors; licensee MDPI, Basel, Switzerland

Update on surgical management of small bowel neuroendocrine tumors

The widespread use of endoscopy and imaging in combination with the continuous update of the staging systems for neuroendocrine tumors has led to an increase in the incidence of small intestinal neuroendocrine tumors (si-NENs) globally. Despite high survival rates, severe complications may occur even in early stages due to the anatomic location of the primary site and the desmoplastic reaction. Surgery plays a central role in the management of patients with si-NENs. Excision of locoregional disease along with extensive lymph node dissection should be performed in fit patients, even in the presence of metastases. Multimodality treatment of liver metastases includes hepatectomy, ablative techniques and liver transplantation. Hormone therapy with somatostatine analogs is of high importance for symptomatic control; special caution should be exercised both pre- and intra-operatively. A multidisciplinary approach is essential in order to provide personalized therapeutics for patients with si-NENs. Clinical research and specialization in this field should be further encouraged. © 2018 International Institute of Anticancer Research. All rights reserved

Prognostic significance of tumor genotypes and CD8+ infiltrates in stage I-III colorectal cancer

Background: We explored the clinical significance of tumor genotypes and immunophenotypes in non-metastatic colorectal cancer (CRC). Methods: In primary tumors (paraffin blocks) from 412 CRC patients treated with adjuvant chemotherapy, we examined pathogenic mutations (panel NGS; 347 informative); mismatch repair (MMR) immunophenotype (360 informative); and CD8+ lymphocyte density (high - low; 412 informative). The primary outcome measure was disease-free survival (DFS). Results: We evaluated 1713 pathogenic mutations (median: 3 per tumor; range 0-49); 118/412 (28.6%) tumors exhibited high CD8+ density; and, 40/360 (11.1%) were MMR-deficient. Compared to MMR-proficient, MMR-deficient tumors exhibitedhigher CD8+ density (chi-square, p<0.001) and higher pathogenic mutation numbers (p=0.003). High CD8+ density was an independent favorable prognosticator (HR=0.49, 95%CI 0.29-0.84, Wald's p=0.010). Pathogenic BRCA1 and ARID1A mutations were inversely associated with each other (p<0.001), were not associated with MMR-deficiency or CD8+ density, but both independently predicted for unfavorable DFS (HR=1.98, 95%CI 1.12-3.48, p=0.018 and HR=1.99, 95%CI 1.11-3.54, p=0.020, respectively). Conclusion: In non-metastatic CRC, high CD8+ lymphocyte density confers a favorable prognosis and may be developed as a single marker in routine diagnostics. The unfavorable prognostic effect of pathogenic BRCA1 and ARID1A mutations is a novel observation that, if further validated, may improve treatment selection. © 2018 Impact Journals LLC. All rights reserved