Background
Several investigators have advocated for extending the Barcelona Clinic Liver Cancer (BCLC) resection criteria to select patients with BCLC-B and even BCLC-C hepatocellular carcinoma ...(HCC). The objective of the current study was to define the outcomes and recurrence patterns after resection within and beyond the current resection criteria.
Patients and Methods
Patients who underwent resection for HCC within (i.e., BCLC 0/A) and beyond (i.e. BCLC B/C) the current resection criteria between 2005 and 2017 were identified from an international multi-institutional database. Overall survival (OS), disease-free survival (DFS), as well as patterns of recurrence of patients undergoing HCC resection within and beyond the BCLC guidelines were examined.
Results
Among 756 patients, 602 (79.6%) patients were BCLC 0/A and 154 (20.4%) were BCLC B/C. Recurrences were mostly intrahepatic (within BCLC: 74.3% versus beyond BCLC: 70.8%,
p
= 0.80), with BCLC B/C patients more often having multiple tumors at relapse (69.6% versus 49.4%,
p
= 0.001) and higher rates of early (< 2 years) recurrence (88.0% versus 75.5%,
p
= 0.011). During the first postoperative year, annual recurrence was 38.3% and 21.3% among BCLC B/C and BCLC 0/A patients, respectively; 5-year OS among BCLC 0/A and BCLC B/C patients was 76.9% versus 51.6% (
p
= 0.003). On multivariable analysis, only a-fetoprotein (AFP) > 400 ng/mL (HR = 1.84, 95% CI 1.07–3.15) and R1 resection (HR = 2.36, 95% CI 1.32–4.23) were associated with higher risk of recurrence among BCLC B/C patients.
Conclusions
Surgery can provide acceptable outcomes among select patients with BCLC B/C HCC. The data emphasize the need to further refine the BCLC treatment algorithm as well as highlight the need for surveillance protocols with a particular focus on the liver, especially for patients undergoing resection outside the BCLC criteria.
Background
The dissemination of robotic liver surgery is slow‐paced and must face the obstacle of demonstrating advantages over open and laparoscopic (LLS) approaches. Our objective was to show the ...current position of robotic liver surgery (RLS) worldwide and to identify if improved short‐term outcomes are observed, including secondary meta‐analyses for type of resection, etiology, and cost analysis.
Methods
A PRISMA‐based systematic review was performed to identify manuscripts comparing RLS vs open or LLS approaches. Quality analysis was performed using the Newcatle‐Ottawa score. Statistical analysis was performed after heterogeneity test and fixed‐ or random‐effect models were chosen accordingly.
Results
After removing duplications, 2728 RLS cases were identified from the final set of 150 manuscripts. More than 75% of the cases have been performed on malignancies. Meta‐analysis from the 38 comparative reports showed that RLS may offer improved short‐term outcomes compared to open procedures in most of the variables screened. Compared to LLS, some advantages may be observed in favour of RLS for major resections in terms of operative time, hospital stay and rate of complications. Cost analyses showed an increased cost per procedure of around US$5000.
Conclusions
The advantages of RLS still need to be demonstrated although early results are promising. Advantages vs open approach are demonstrated. Compared to laparoscopic surgery, minor perioperative advantages may be observed for major resections although cost analyses are still unfavorable to the robotic approach.
Highlight
Ciria and colleagues analyzed the impact of robotics in liver surgery. The largest systematic review and short‐term outcomes meta‐analysis performed to date was done on 2728 cases. Few initial advantages were observed for the robotic approach compared with laparoscopy, contrary to significant higher costs. However, a high potential was highlighted.
Aims
Immunotherapies represent a new alternative therapeutic approach for hepatocellular carcinomas (HCCs), and have shown promising results when used in combination therapy. The aim of this study ...was to evaluate the potential of transarterial chemoembolisation (TACE) to modulate programmed death‐1 (PD‐1) and programmed death‐ligand 1 (PD‐L1) expression profiles in a cohort of surgically treated HCCs.
Methods and results
A total of 82 surgically treated HCCs from patients who had undergone (n = 32) or not undergone (n = 50) preoperative TACE were included in the study. Immunohistochemical expression of PD‐1 and of PD‐L1 were analysed and compared according to TACE treatment. Pretreatment biopsies, which were available for 30 cases (20 with TACE and 10 without), were similarly analysed. Follow‐up data were retrieved from patients' charts. PD‐1 expression (≥1%) in intratumoral inflammatory cells (ICs) was observed in 46% of HCCs, and PD‐L1 expression (≥1%) in ICs and PD‐L1 expression in tumour cells (TCs) were observed in 46% and 16% of HCCs, respectively. A low level of PD‐1 expression (<1%) was associated with strong and diffuse glutamine synthetase overexpression (8% versus 27%, P = 0.024). HCCs from patients with TACE pretreatment showed significantly higher PD‐L1 expression in TCs than those from patients without TACE pretreatment (2% versus 0.4%, P = 0.027). PD‐1 expression in ICs and PD‐L1 expression in both ICs and TCs were higher in TACE‐resected tumours than in corresponding pre‐TACE biopsies (respectively: 1.8% versus 8.1%, P = 0.034; 0.8% versus 7.1%, P = 0.032; and 0% versus 2.4%, P = 0.043).
Conclusion
Our results, showing increases in PD‐1 expression and PD‐L1 expression in HCCs following TACE, support the use of TACE in combination with immunotherapy in selected cases to optimise tumour response.
An expert recommendation conference was conducted to identify factors associated with adverse events during laparoscopic cholecystectomy (LC) with the goal of deriving expert recommendations for the ...reduction of biliary and vascular injury. Nineteen hepato‐pancreato‐biliary (HPB) surgeons from high‐volume surgery centers in six countries comprised the Research Institute Against Cancer of the Digestive System (IRCAD) Recommendations Group. Systematic search of PubMed, Cochrane, and Embase was conducted. Using nominal group technique, structured group meetings were held to identify key items for safer LC. Consensus was achieved when 80% of respondents ranked an item as 1 or 2 (Likert scale 1–4). Seventy‐one IRCAD HPB course participants assessed the expert recommendations which were compared to responses of 37 general surgery course participants. The IRCAD recommendations were structured in seven statements. The key topics included exposure of the operative field, appropriate use of energy device and establishment of the critical view of safety (CVS), systematic preoperative imaging, cholangiogram and alternative techniques, role of partial and dome‐down (fundus‐first) cholecystectomy. Highest consensus was achieved on the importance of the CVS as well as dome‐down technique and partial cholecystectomy as alternative techniques. The put forward IRCAD recommendations may help to promote safe surgical practice of LC and initiate specific training to avoid adverse events.
HighlightAn international structured expert recommendation conference for safe laparoscopic cholecystectomy was conducted. Critical recommendations were divided into 7 statements. The highest consensus was achieved on the importance of the critical view of safety and alternative surgical techniques (dome‐down technique, and partial cholecystectomy).
Composite measures may be superior to individual measures for the analysis of hospital performance and quality of surgical care.
To determine the incidence of a so-called textbook outcome, a ...composite measure of the quality of surgical care, among patients undergoing curative-intent resection of intrahepatic cholangiocarcinoma.
This cohort study involved an analysis of a multinational, multi-institutional cohort of patient from 15 major hepatobiliary centers in North America, Europe, Australia, and Asia who underwent curative-intent resection of intrahepatic cholangiocarcinoma between 1993 and 2015. Data analysis was conducted from April 2018 to May 2018.
Hospital variation in the composite end point of textbook outcome, defined as negative margins, no perioperative transfusion, no postoperative surgical complications, no prolonged length of stay, no 30-day readmissions, and no 30-day mortality. Secondary end points were factors associated with achieving textbook outcomes.
Among 687 patients (of whom 370 53.9% were men; median patient age, 61 range, 18-86 years) undergoing curative-intent resection of intrahepatic cholangiocarcinoma, a textbook outcome was achieved in 175 patients (25.5%). Being 60 years or younger (odds ratio OR, 1.61 95% CI, 1.04-2.49; P = .03), absence of preoperative jaundice (OR, 4.40 95% CI, 1.28-15.15; P = .02), no neoadjuvant chemotherapy (OR, 2.57 95% CI, 1.05-6.29; P = .04), T1a/T1b-stage disease (OR, 1.58 95% CI, 1.01-2.49; P = .049), N0 status (OR, 3.89 95% CI, 1.77-8.54; P = .001), and no bile duct resection (OR, 2.46 95% CI, 1.25-4.84; P = .009) were independently associated with achieving a textbook outcome after resection. A prolonged length of stay had the greatest negative association with a textbook outcome. A nomogram to assess the probability of textbook outcome was developed and had good accuracy in both the training data set (area under the curve, 0.755) and validation data set (area under the curve, 0.763).
In this study, while hepatic resection for intrahepatic cholangiocarcinoma was performed with less than 5% mortality in specialized centers, a textbook outcome was achieved in only approximately 26% of patients. A textbook outcome may be useful for the reporting of patient-level hospital performance and hospital variation, leading to quality improvement efforts after resection of intrahepatic cholangiocarcinoma.
Lymphadenectomy ensures accurate staging for patients with intrahepatic cholangiocarcinoma, especially for those without preoperatively suspected positive lymph nodes (clinically node-negative); ...however, its prognostic value has been poorly documented. The aim of this study was to evaluate the prognostic value of lymphadenectomy on long-term outcomes in patients undergoing surgery for clinically node-negative intrahepatic cholangiocarcinoma.
Data from all patients who underwent liver resection with or without lymphadenectomy for preoperatively diagnosed intrahepatic cholangiocarcinoma between 2000 and 2016 at 3 tertiary hepatobiliary centers were analyzed retrospectively. Propensity score matching in a 1:1 ratio was conducted based on clinically relevant covariates between patients with clinically node-negative intrahepatic cholangiocarcinoma who underwent liver resection with (LND group) and without (NLND group) lymphadenectomy. Overall survival and disease-free survival were compared in the matched cohort.
Among 350 patients who underwent surgery during the study period, 192 (55%) with clinically node-negative intrahepatic cholangiocarcinoma met the inclusion criteria. After propensity score matching, 2 well-balanced groups of 56 patients each were analyzed. There was no significant difference regarding postoperative variables among these 112 matched patients. Patients who underwent a liver resection with lymphadenectomy achieved better 3- and 5-year overall survival (78% and 65% vs 52% and 46%, P = .017) and disease-free survival (46% and 34% vs 31% and 31%; P = .042) compared with patients who underwent liver resection without lymphadenectomy.
Lymphadenectomy can be associated with better long-term outcomes in patients with node-negative intrahepatic cholangiocarcinoma. Our data may support routine lymphadenectomy for node-negative intrahepatic cholangiocarcinoma with the objective of achieving better long-term outcomes.
Background Laparoscopic hepatectomy continues to be a challenging operation associated with a steep learning curve. This study aimed to evaluate the learning process during 15 years of experience ...with laparoscopic hepatectomy and to identify approaches to standardization of this procedure. Study Design Prospectively collected data of 317 consecutive laparoscopic hepatectomies performed from January 2000 to December 2014 were reviewed retrospectively. The operative procedures were classified into 4 categories (minor hepatectomy, left lateral sectionectomy LLS, left hepatectomy, and right hepatectomy), and indications were classified into 5 categories (benign-borderline tumor, living donor, metastatic liver tumor, biliary malignancy, and hepatocellular carcinoma). Results During the first 10 years, the procedures were limited mainly to minor hepatectomy and LLS, and the indications were limited to benign-borderline tumor and living donor. Implementation of major hepatectomy rapidly increased the proportion of malignant tumors, especially hepatocellular carcinoma, starting from 2011. Conversion rates decreased with experience for LLS (13.3% vs 3.4%; p = 0.054) and left hepatectomy (50.0% vs 15.0%; p = 0.012), but not for right hepatectomy (41.4% vs 35.7%; p = 0.661). Conclusions Our 15-year experience clearly demonstrates the stepwise procedural evolution from LLS through left hepatectomy to right hepatectomy, as well as the trend in indications from benign-borderline tumor/living donor to malignant tumors. In contrast to LLS and left hepatectomy, a learning curve was not observed for right hepatectomy. The ongoing development process can contribute to faster standardization necessary for future advances in laparoscopic hepatectomy.
Intrahepatic cholangiocarcinomas (iCCs) are primary tumors of the liver characterized by the presence of a desmoplastic stroma. While tumor stroma may have a protective or a pejorative value ...depending on the type of malignant disease, the precise role of the desmoplastic stroma in iCC remains poorly understood. The aim of the present study was to evaluate the prognostic value of stromal compartment in iCC through a multiparametric morphological analysis. Forty-nine surgically resected iCCs were included. For all cases, tumor paraffin blocks of iCCs were selected for stromal morphological characterization through quantitative and qualitative approaches using immunohistochemistry and second-harmonic generation imaging. Intratumor heterogeneity was also evaluated in regards with the different stromal features. High proportionated stromal area (PSA) (defined by stromal to tumor area ratio) was inversely correlated with vascular invasion (62.5% vs 95.7%, p = 0.006) and positively correlated with well-differentiated grade (60% vs 12.5%, p = 0.001). Patients with high PSA had a better disease-free survival (DFS) than patients with low stromal area (60% vs 10%, p = 0.077). Low activated stroma index (defined by cancer-associated fibroblasts number to stromal area ratio) was associated with a better DFS (60% vs 10%, p = 0.05). High collagen reticulation index (CRI), defined as the number of collagen fiber branches within the entire length of the collagen network, was associated with a poorer overall survival (42% vs NR, p = 0.026). Furthermore, we showed that CRI was also an homogeneous marker throughout the tumor. Based on morphological features, desmoplastic stroma seems to exert a protective effect in patients with iCC. Stromal collagen reticulation may provide additional clinically relevant information. In addition, these data support the potential value to evaluate CRI in biopsy specimen.
Background
Although the Barcelona Clinic Liver Cancer (BCLC) staging system has been largely adopted in clinical practice, recent studies have questioned the prognostic stratification of this ...classification schema, as well as the proposed treatment allocation of patients with a single large tumor.
Methods
Patients who underwent curative-intent hepatectomy for histologically proven hepatocellular carcinoma (HCC) between 1998 and 2017 were identified using an international multi-institutional database. Overall survival (OS) among patients with BCLC stage 0, A, and B was examined. Patients with a single large tumor were classified as BCLC stage A1 and were independently assessed.
Results
Among 814 patients, 68 (8.4%) were BCLC-0, 310 (38.1%) were BCLC-A, 279 (34.3%) were BCLC-A1, and 157 (19.3%) were BCLC-B. Five-year OS among patients with BCLC stage 0, A, A1, and B HCC was 86.2%, 69.0%, 56.9%, and 49.9%, respectively (
p
< 0.001). Among patients with very early- and early-stage HCC (BCLC 0, A, and A1), patients with BCLC stage A1 had the worst OS (
p
= 0.0016). No difference in survival was noted among patients undergoing surgery for BCLC stage A1 and B HCC (5-year OS: 56.9% vs. 49.9%;
p
= 0.259) even after adjusting for competing factors (hazard ratio 0.83, 95% confidence interval 0.54–1.28;
p
= 0.40).
Conclusion
Prognosis following liver resection among patients with BCLC-A1 HCC was similar to patients presenting with BCLC-B tumors. Surgery provided acceptable long-term outcomes among select patients with BCLC-B HCC. Designation into BCLC stage B should not be considered an a priori contraindication to surgery.
Background
The laparoscopic approach to liver resection has experienced exponential growth in recent years; however, its application is still under debate and objective, evidence-based guidelines for ...its safe future progression are needed.
Objective
The aim of this study was to perform a systematic review and meta-analysis comparing the short- and long-term outcomes of laparoscopic and open liver resections for hepatocellular carcinoma (HCC).
Methods
To identify all the comparative manuscripts reporting on laparoscopic and open liver resection for HCC, all published English-language studies with more than 10 cases were screened. In addition to the primary meta-analysis, four specific subgroup analyses were performed on patients with Child–Pugh A cirrhosis, resections for solitary tumors, and those undergoing minor and major resections. The quality of the studies was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) methodology and the Newcastle–Ottawa Scale.
Results
From the initial 361 manuscripts, 28 were included in the meta-analysis. Five of these 28 manuscripts were specific to patients with Child–Pugh A cirrhosis (321 cases), 11 focused on solitary tumors (1003 cases), 16 focused on minor resections (1286 cases), and 3 focused on major resections (164 cases). Three manuscripts compared 1079 cases but could not be assigned to any of the above subanalyses. In general terms, short-term outcomes were favorable when using a laparoscopic approach, especially in minor resections. The only advantage seen with an open approach was reduced operative time during major liver resections. No differences in long-term outcomes were observed between the approaches.
Conclusions
Laparoscopic liver resection for HCC is feasible and offers improved short-term outcomes, with comparable long-term outcomes as the open approach.
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