Koo Jeong Kang

In Brief Objective: To prospectively evaluate the survival benefit of dissection of the nerve plexus and lymphadenectomy in patients with pancreatic head cancer. Background: Despite randomized controlled trials on the extent of surgery in pancreatic cancer, attempts have been made to perform more extended resections. Methods: A total of 244 patients were enrolled; of these, 200 were randomized to undergo standard resection or extended resection, with the latter including the dissection of additional lymph nodes and the right half of the nerve plexus around the superior mesenteric artery and celiac axis. We evaluated 167 patients from 7 centers who fulfilled all of the required criteria. Result: Operation time was longer and estimated blood loss was higher in the extended resection group than in the standard resection group, but the R0 resection rate was comparable. The mean number of lymph nodes retrieved per patient was higher in the extended resection group than in the standard resection group (33.7 vs 17.3; P < 0.001). The morbidity rate was slightly higher in the extended resection group than in the standard resection group. Two patients in the extended resection group died in hospital. Median survival after R0 resection was similar in the extended resection and standard resection groups (18.0 vs 19.0 months; P = 0.239) regardless of lymph node metastasis. Adjuvant chemoradiation had a positive impact on overall survival. Conclusions: This study suggests that extended lymphadenectomy with dissection of the nerve plexus does not provide a significant survival benefit compared with standard resection in pancreatic head cancer. Standard resection can be performed safely and efficiently, without negatively affecting oncologic efficacy or long-term survival, when compared with extended pancreaticoduodenal resection. (NCT00679913)? This randomized controlled trial suggests that extended lymphadenectomy with dissection of the nerve plexus does not provide significant survival benefit compared with standard resection in patients with pancreatic head cancer. Standard resection can be performed safely and efficiently, without negatively affecting oncologic efficacy or long-term survival, compared with extended pancreaticoduodenal resection.

OBJECTIVE: The aim of this study was to define robust benchmark values for the surgical treatment of perihilar cholangiocarcinomas (PHC) to enable unbiased comparisons. BACKGROUND: Despite ongoing efforts, postoperative mortality and morbidity remains high after complex liver surgery for PHC. Benchmark data of best achievable results in surgical PHC treatment are however still lacking. METHODS: This study analyzed consecutive patients undergoing major liver surgery for PHC in 24 high-volume centers in 3 continents over the recent 5-year period (2014-2018) with a minimum follow-up of 1 year in each patient. Benchmark patients were those operated at high-volume centers (≥50 cases during the study period) without the need for vascular reconstruction due to tumor invasion, or the presence of significant co-morbidities such as severe obesity (body mass index ≥35), diabetes, or cardiovascular diseases. Benchmark cutoff values were derived from the 75th or 25th percentile of the median values of all benchmark centers. RESULTS: Seven hundred eight (39%) of a total of 1829 consecutive patients qualified as benchmark cases. Benchmark cut-offs included: R0 resection ≥57%, postoperative liver failure (International Study Group of Liver Surgery): ≤35%; in-hospital and 3-month mortality rates ≤8% and ≤13%, respectively; 3-month grade 3 complications and the CCI: ≤70% and ≤30.5, respectively; bile leak-rate: ≤47% and 5-year overall survival of ≥39.7%. Centers operating mostly on complex cases disclosed better outcome including lower post-operative liver failure rates (4% vs 13%; P = 0.002). Centers from Asia disclosed better outcomes. CONCLUSION: Surgery for PHC remains associated with high morbidity and mortality with now the availability of benchmark values covering 21 outcome parameters, which may serve as key references for comparison in any future analyses of individuals, group of patients or centers.

OBJECTIVE: To compare the oncologic outcomes of liver resection (LR) and local ablation therapies for HCC. SUMMARY OF BACKGROUND DATA: Although several studies have compared LR and local ablation therapies, the optimal treatment of choice for HCC within the Milan criteria remains controversial. METHODS: We systemically searched the MEDLINE, Embase, and Cochrane Library databases for randomized control trials (RCTs) and matched nonrandomized trials (NRTs) that compared LR and local ablation therapies for HCC within the Milan criteria. The primary outcome was overall survival (OS). Secondary outcomes were recurrence free survival (RFS) and recurrence pattern. RESULTS: A total of 7 RCTs and 18 matched NRTs, involving 2865 patients in the LR group and 2764 patients in the local ablation therapy group [RFA, MWA, RFA plus trans-arterial chemoembolization (TACE)], were included. Although there was no significant difference in OS between LR and RFA, LR showed a significantly better 5-year RFS than RFA in the analysis of RCTs (hazards ratio: 0.75; 95% confidence interval: 0.62-0.92; P = 0.006). The RFA group showed a significantly higher local recurrence than the LR group in both analyses of RCTs and NRTs. Additionally, the LR group showed better OS and RFS than the MWA or RFA plus TACE groups. CONCLUSION: Our meta-analysis showed that LR was superior to RFA in terms of RFS and incidence of local recurrence. Moreover, LR showed better oncologic outcomes than MWA or RFA plus TACE.

BACKGROUND: Typically observed at 2 y after surgical resection, late recurrence is a major challenge in the management of hepatocellular carcinoma (HCC). We aimed to develop a genomic predictor that can identify patients at high risk for late recurrence and assess its clinical implications. METHODS AND FINDINGS: Systematic analysis of gene expression data from human liver undergoing hepatic injury and regeneration revealed a 233-gene signature that was significantly associated with late recurrence of HCC. Using this signature, we developed a prognostic predictor that can identify patients at high risk of late recurrence, and tested and validated the robustness of the predictor in patients (n = 396) who underwent surgery between 1990 and 2011 at four centers (210 recurrences during a median of 3.7 y of follow-up). In multivariate analysis, this signature was the strongest risk factor for late recurrence (hazard ratio, 2.2; 95% confidence interval, 1.3-3.7; p = 0.002). In contrast, our previously developed tumor-derived 65-gene risk score was significantly associated with early recurrence (p = 0.005) but not with late recurrence (p = 0.7). In multivariate analysis, the 65-gene risk score was the strongest risk factor for very early recurrence (<1 y after surgical resection) (hazard ratio, 1.7; 95% confidence interval, 1.1-2.6; p = 0.01). The potential significance of STAT3 activation in late recurrence was predicted by gene network analysis and validated later. We also developed and validated 4- and 20-gene predictors from the full 233-gene predictor. The main limitation of the study is that most of the patients in our study were hepatitis B virus-positive. Further investigations are needed to test our prediction models in patients with different etiologies of HCC, such as hepatitis C virus. CONCLUSIONS: Two independently developed predictors reflected well the differences between early and late recurrence of HCC at the molecular level and provided new biomarkers for risk stratification. Please see later in the article for the Editors' Summary.

BACKGROUND/AIMS: Treating hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) remains controversial. We compared the outcomes of hepatic resection (HR), transarterial chemoembolization (TACE), and sorafenib therapy as treatments for HCC with PVTT. METHODS: Patients diagnosed as HCC with PVTT between January 2000 and December 2011 who received treatment with sorafenib, HR, or TACE were included. Patients with main PVTT, superior mesenteric vein tumor thrombosis, or Child-Turcotte-Pugh (CTP) class C were excluded. The records of 172 patients were analyzed retrospectively. HR, TACE, and sorafenib treatment were performed is 40, 80, and 52 patients respectively. PVTT was classified as either involving the segmental branch (type I) or extending to involve the right or left portal vein (type II). RESULTS: The median survival time was significantly longer in the HR group (19.9 months) than in the TACE and sorafenib groups (6.6 and 6.2 months, respectively; both p<0.001), and did not differ significantly between the latter two groups (p=0.698). Among patients with CTP class A, type I PVTT or unilobar-involved HCC, the median survival time was longer in the HR group than in the TACE and sorafenib groups (p=0.006). In univariate analyses, the initial treatment method, tumor size, PVTT type, involved lobe, CTP class, and presence of cirrhosis or ascites were correlated with overall survival. The significant prognostic factors for overall survival in Cox proportional-hazards regression analysis were initial treatment method (HR vs. TACE: hazard ratio=1.750, p=0.036; HR vs. sorafenib: hazard ratio=2.262, p=0.006), involved lobe (hazard ratio=1.705, p=0.008), PVTT type (hazard ratio=1.617, p=0.013), and CTP class (hazard ratio=1.712, p=0.012). CONCLUSIONS: Compared with TACE or sorafenib, HR may prolong the survival of patients with HCC in cases of CTP class A, type I PVTT or unilobar-involved HCC.