Onco-Surgical Management of Liver Metastases from Colorectal Cancer

Metastatic disease is the main cause of death in patients with colorectal cancer and the most frequent location of metastases is in the liver. The treatment of liver metastases of colorectal origin is multimodal and should be based on a multidisciplinary team decision. A systematic review of the literature revealed that the number of liver metastases, their maximum size, CEA level, advanced age of the patients, and presence of extrahepatic disease are no longer contraindications to liver resection. The resectability rate of colorectal liver metastases increased from 10 to almost 40%, enabling 5-year overall survival rates higher than 30%. Short-term and long-term results achieved by simultaneous resection (SR) are similar to those achieved by staged resections in patients with synchronous colorectal liver metastases. Whenever possible, major hepatectomies should be replaced by ultrasound-guided limited liver resections, and primary tumor should be approached in a minimally invasive manner. Even initially unresectable colorectal liver metastases could be rendered resectable by an aggressive multimodal approach (“two-stage” hepatectomies, hepatectomy after portal vein embolization/ligation, resection after conversion chemotherapy, and hepatectomy associated with ablation). The presence of extrahepatic metastases is no longer a contraindication to liver resection, when extrahepatic disease is resectable. Repeat hepatectomy improves survival in patients with recurrent liver metastases

The Impact of Hepatic Arterial Variations and Reconstructions on Arterial Complications in Liver Transplantation

Background: The purposes of the study were to determine the variations in hepatic arterial supply, to delineate the optimal methods of arterial anastomoses and reconstructions in liver transplantation and to analyse the incidence of arterial complications. Methods: The surgical anatomy of the extrahepatic arterial vascularization was investigated retrospectively in 209 donors and patients who underwent liver transplantation at Fundeni Clinical Institute (Bucharest, Romania) from January 1, 2015 to December 31, 2017. The vascular anatomy of the hepatic grafts was classified according to Michels’ description and other rare variations. Results: Anatomical variants of the classical pattern were detected in 26.3% of the livers (n = 55). The most common variant was a replaced right hepatic artery arising from the superior mesenteric artery (n = 17; 8.13%), followed by a common hepatic artery from superior mesenteric artery (n = 6; 2.87%). Arterial reconstructions were reported in 97 cases (45.5%). In recipients, used sites were intermediate: common hepatic artery (CHA) in 73.8% (n = 158), distal: proper hepatic artery (PHA) or common hepatic artery/gastro-duodenal artery bifurcation (CHA/GDA bifurcation) in 16.4% (n = 35) and proximal: coeliac trunk-splenic artery-aorta (CT–SA–A) in 9.3% (n = 20) of patients. Most common reconstructions were short graft artery (CT) on the recipient CHA (n = 33, 34.02%) and long graft artery: complex reconstruction between CT and superior mesenteric artery (SMA) - accessory right hepatic artery (RHA) from SMA on CHA (n = 12, 12.37%) and right hepatic graft artery on PHA or CHA/GDA bifurcation (n = 16, 16.49%). Conclusion: The information about the different hepatic arterial patterns, as well as establishing specific methods for arterial anastomoses and reconstructions is important in the determination of better outcomes

Diagnostic Challenges and Multimodal Treatment in Primary Peritoneal Cancer: a Case Report

Peritoneal cancer (PPC), a rare and aggressive malignancy, can develop from the peritoneal lining or as a secondary peritoneal cancer caused by metastases from neighbouring organs such as the ovaries, gastrointestinal tract, or breast. Early identification is still difficult due to its ambiguous signs, ranging from bloating, distension, and stomach pain. Due to their comparable histological and clinical characteristics, PPC and ovarian cancer are frequently misdiagnosed. Advanced imaging, histological investigation, and immunohistochemical markers are essential for accurate diagnosis. In order to control any remaining disease and enhance results, treatment usually encompasses an assortment of therapeutic approaches, such as hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgical procedure (CRS). We present a 69-year-old woman who got diagnosed with PPC after first being suspected of having ovarian cancer. The current instance emphasizes how crucial a thorough diagnostic process is to differentiating PPC from related cancers

Upfront surgery for intrahepatic cholangiocarcinoma:Prediction of futility using artificial intelligence

Objective: We sought to identify patients at risk of “futile” surgery for intrahepatic cholangiocarcinoma using an artificial intelligence (AI)–based model based on preoperative variables. Methods: Intrahepatic cholangiocarcinoma patients who underwent resection between 1990 and 2020 were identified from a multi-institutional database. Futility was defined either as mortality or recurrence within 12 months of surgery. Various machine learning and deep learning techniques were used to develop prediction models for futile surgery. Results: Overall, 827 intrahepatic cholangiocarcinoma patients were included. Among 378 patients (45.7%) who had futile surgery, 297 patients (78.6%) developed intrahepatic cholangiocarcinoma recurrence and 81 patients (21.4%) died within 12 months of surgical resection. An ensemble model consisting of multilayer perceptron and gradient boosting classifiers that used 10 preoperative factors demonstrated the highest accuracy, with areas under receiver operating characteristic curves of 0.830 (95% confidence interval 0.798–0.861) and 0.781 (95% confidence interval 0.707–0.853) in the training and testing cohorts, respectively. The model displayed sensitivity and specificity of 64.5% and 80.0%, respectively, with positive and negative predictive values of 73.1% and 72.7%, respectively. Radiologic tumor burden score, serum carbohydrate antigen 19-9, and direct bilirubin levels were the factors most strongly predictive of futile surgery. The artificial intelligence–based model was made available online for ease of use and clinical applicability (https://altaf-pawlik-icc-futilityofsurgery-calculator.streamlit.app/). Conclusion: The artificial intelligence ensemble model demonstrated high accuracy to identify patients preoperatively at high risk of undergoing futile surgery for intrahepatic cholangiocarcinoma. Artificial intelligence–based prediction models can provide clinicians with reliable preoperative guidance and aid in avoiding futile surgical procedures that are unlikely to provide patients long-term benefits.</p

Benchmarks in Liver Resection for Intrahepatic Cholangiocarcinoma

Introduction: Benchmarking in surgery has been proposed as a means to compare results across institutions to establish best practices. We sought to define benchmark values for hepatectomy for intrahepatic cholangiocarcinoma (ICC) across an international population. Methods: Patients who underwent liver resection for ICC between 1990 and 2020 were identified from an international database, including 14 Eastern and Western institutions. Patients operated on at high-volume centers who had no preoperative jaundice, ASA class &lt;3, body mass index &lt;35 km/m2, without need for bile duct or vascular resection were chosen as the benchmark group. Results: Among 1193 patients who underwent curative-intent hepatectomy for ICC, 600 (50.3%) were included in the benchmark group. Among benchmark patients, median age was 58.0 years (interquartile range [IQR] 49.0–67.0), only 28 (4.7%) patients received neoadjuvant therapy, and most patients had a minor resection (n = 499, 83.2%). Benchmark values included ≥3 lymph nodes retrieved when lymphadenectomy was performed, blood loss ≤600 mL, perioperative blood transfusion rate ≤42.9%, and operative time ≤339 min. The postoperative benchmark values included TOO achievement ≥59.3%, positive resection margin ≤27.5%, 30-day readmission ≤3.6%, Clavien-Dindo III or more complications ≤14.3%, and 90-day mortality ≤4.8%, as well as hospital stay ≤14 days. Conclusions: Benchmark cutoffs targeting short-term perioperative outcomes can help to facilitate comparisons across hospitals performing liver resection for ICC, assess inter-institutional variation, and identify the highest-performing centers to improve surgical and oncologic outcomes.</p

Development and Validation of a Predictive Risk Score for Blood Transfusion in Patients Undergoing Curative-Intent Surgery for Intrahepatic Cholangiocarcinoma

Background and Objectives: Among patients undergoing liver resection for intrahepatic cholangiocarcinoma (ICC), perioperative bleeding requiring blood transfusion is a common complication, yet preoperative identification of patients at risk for transfusion remains challenging. The objective of this study was to develop a preoperative risk score for blood transfusion requirement during surgery for ICC. Methods: Patients undergoing curative-intent liver surgery for ICC (1990–2020) were identified from a multi-institutional database. A predictive model was developed and validated. An easy-to-use risk calculator was made available online. Results: Among 1420 patients, 300 (21.1%) received an intraoperative transfusion. Independent predictors of transfusion included severe preoperative anemia (OR = 1.65, 95% CI 1.10–2.47), T2 category or higher (OR = 2.00, 95% CI 1.36–3.02), positive lymph nodes (OR = 1.75, 95% CI 1.32–2.32) and major resection (OR = 2.56, 95%CI 1.85–3.58). Receipt of blood transfusion significantly correlated with worse outcomes. The model showed good discriminative ability in both training (AUC = 0.68, 95% CI 0.66–0.72) and bootstrapping validation (C-index = 0.67, 95% CI 0.65–0.70) cohorts. An online risk calculator of blood transfusion requirement was developed (https://catalano-giovanni.shinyapps.io/TransfusionRisk). Conclusions: Intraoperative blood transfusion was significantly associated with poor postoperative outcomes among patients undergoing surgery for ICC. The identification of patients at high risk of transfusion could improve perioperative patient care and blood resources allocation.</p

Benchmarks in Liver Resection for Intrahepatic Cholangiocarcinoma

Introduction: Benchmarking in surgery has been proposed as a means to compare results across institutions to establish best practices. We sought to define benchmark values for hepatectomy for intrahepatic cholangiocarcinoma (ICC) across an international population. Methods: Patients who underwent liver resection for ICC between 1990 and 2020 were identified from an international database, including 14 Eastern and Western institutions. Patients operated on at high-volume centers who had no preoperative jaundice, ASA class &lt;3, body mass index &lt;35 km/m2, without need for bile duct or vascular resection were chosen as the benchmark group. Results: Among 1193 patients who underwent curative-intent hepatectomy for ICC, 600 (50.3%) were included in the benchmark group. Among benchmark patients, median age was 58.0 years (interquartile range [IQR] 49.0–67.0), only 28 (4.7%) patients received neoadjuvant therapy, and most patients had a minor resection (n = 499, 83.2%). Benchmark values included ≥3 lymph nodes retrieved when lymphadenectomy was performed, blood loss ≤600 mL, perioperative blood transfusion rate ≤42.9%, and operative time ≤339 min. The postoperative benchmark values included TOO achievement ≥59.3%, positive resection margin ≤27.5%, 30-day readmission ≤3.6%, Clavien-Dindo III or more complications ≤14.3%, and 90-day mortality ≤4.8%, as well as hospital stay ≤14 days. Conclusions: Benchmark cutoffs targeting short-term perioperative outcomes can help to facilitate comparisons across hospitals performing liver resection for ICC, assess inter-institutional variation, and identify the highest-performing centers to improve surgical and oncologic outcomes.</p

Early Onset Intrahepatic Cholangiocarcinoma:Clinical Characteristics, Oncological Outcomes, and Genomic/Transcriptomic Features

Introduction: Data on clinical characteristics and disease-specific prognosis among patients with early onset intrahepatic cholangiocarcinoma (ICC) are currently limited. Methods: Patients undergoing hepatectomy for ICC between 2000 and 2020 were identified by using a multi-institutional database. The association of early (≤50 years) versus typical onset (&gt;50 years) ICC with recurrence-free (RFS) and disease-specific survival (DSS) was assessed in the multi-institutional database and validated in an external cohort. The genomic and transcriptomic profiles of early versus late onset ICC were analyzed by using the Total Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center databases. Results: Among 971 patients undergoing resection for ICC, 22.7% (n = 220) had early-onset ICC. Patients with early-onset ICC had worse 5-year RFS (24.1% vs. 29.7%, p &lt; 0.05) and DSS (36.5% vs. 48.9%, p = 0.03) compared with patients with typical onset ICC despite having earlier T-stage tumors and lower rates of microvascular invasion. In the validation cohort, patients with early-onset ICC had worse 5-year RFS (7.4% vs. 20.5%, p = 0.002) compared with individuals with typical onset ICC. Using the TCGA cohort, 652 and 266 genes were found to be upregulated (including ATP8A2) and downregulated (including UTY and KDM5D) in early versus typical onset ICC, respectively. Genes frequently implicated as oncogenic drivers, including CDKN2A, IDH1, BRAF, and FGFR2 were infrequently mutated in the early-onset ICC patients. Conclusions: Early-onset ICC has distinct clinical and genomic/transcriptomic features. Morphologic and clinicopathologic characteristics were unable to fully explain differences in outcomes among early versus typical onset ICC patients. The current study offers a preliminary landscape of the molecular features of early-onset ICC.</p

Machine learning based prediction model for bile leak following hepatectomy for liver cancer

Objective: We sought to develop a machine learning (ML) preoperative model to predict bile leak following hepatectomy for primary and secondary liver cancer. Methods: An eXtreme Gradient Boosting (XGBoost) model was developed to predict post-hepatectomy bile leak using data from the ACS-NSQIP database. The model was externally validated using data from hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) multi-institutional databases. Results: Overall, 20,570 and 2253 patients were identified from the ACS-NSQIP and multi-institutional databases, respectively. The incidence rates of bile leak were 7.0 %, 6.3 % and 10.2 % in the ACS-NSQIP, HCC and ICC databases, respectively. The XGBoost model achieved areas under receiver operating characteristic curves (AUROC) of 0.748, 0.719 and 0.711 in the training, testing and external validation cohorts, respectively. The SHAP algorithm demonstrated that the factors most strongly predictive of postoperative bile leak were serum alkaline phosphatase, surgical approach and cancer diagnosis. An online tool was developed for ease-of-use and clinical applicability (https://altaf-pawlik-bileleak-calculator.streamlit.app/). Conclusion: A novel ML model demonstrated strong discrimination power to preoperatively identify patients at high risk of developing bile leak post-hepatectomy. The online calculator may be used as a clinical tool to inform preoperative surgical planning, intraoperative decision-making, and postoperative recovery protocols for patients undergoing hepatectomy.</p