Y.S. Chun

Prognostic factors after resection of colorectal liver metastases following preoperative second-line chemotherapy: Impact of RAS mutations.

BACKGROUNDnAfter resection of colorectal liver metastases (CLM), RAS mutations are associated with modest survival benefit and second-line chemotherapy confers limited hope for cure.nnnOBJECTIVEnTo evaluate the impact of RAS mutation after second-line chemotherapy for patients undergoing potentially curative liver resection for CLM.nnnMETHODSnAmong 1357 patients operated for CLM between January 2005 and November 2014, patients with known RAS mutational status were identified. Outcomes after second-line chemotherapy were analyzed by RAS status.nnnRESULTSnAmong 635 patients undergoing resection of CLM, 46 received second-line chemotherapy before resection, including 14 patients (30%) with RAS mutations. Patients who received second-line chemotherapy had significantly larger and greater number of liver metastases and were more likely to undergo major hepatectomy. Median overall (OS) and recurrence free survival (RFS) were significantly worse among patients requiring second-line chemotherapy (OS: 44.4 vs. 61.1 months, pxa0=xa00.021; RFS: 7.3 vs. 12.0 months, pxa0=xa00.001). Among patients undergoing liver resection after second-line chemotherapy, RAS mutations were associated with worse median OS and RFS (OS: 35.2 vs. 60.7 months, pxa0=xa00.038; RFS: 3.6 vs. 8.3 months, pxa0=xa00.015). RAS mutation was the only independent factor associated with OS and RFS. All patients with RAS mutations recurred within 18 months. Among patients with RAS wild-type tumors, the receipt of second-line chemotherapy did not affect OS (pxa0=xa00.493).nnnCONCLUSIONnAmong patients undergoing resection of CLM after second-line chemotherapy, RAS mutational status is an independent predictor of survival and outweighs other factors to select patients for liver resection.

Biomarkers in colorectal liver metastases

Despite a 5‐year overall survival rate of 58 per cent after liver resection for colorectal liver metastases (CLMs), more than half of patients develop recurrence, highlighting the need for accurate risk stratification and prognostication. Traditional prognostic factors have been superseded by newer outcome predictors, including those defined by the molecular origin of the primary tumour.

Prognostic value of carbohydrate antigen 19-9 in patients undergoing resection of biliary tract cancer

The clinical significance of abnormally high levels of carbohydrate antigen (CA) 19‐9 after resection of biliary tract cancer (BTC) is not well established. The aim of this study was to determine the prognostic value of CA19‐9 normalization in patients undergoing resection of BTC with curative intent.

Embryonic origin of primary colon cancer predicts survival in patients undergoing ablation for colorectal liver metastases

BACKGROUNDnIn patients with primary colorectal cancer (CRC) or unresectable metastatic CRC, midgut embryonic origin is associated with worse prognosis. The impact of embryonic origin on survival after ablation of colorectal liver metastases (CLM) is unclear.nnnMETHODSnWe identified 74 patients with CLM who underwent percutaneous ablation during 2004-2015. Survival and recurrence after ablation of CLM from midgut origin (n = 18) and hindgut origin (n = 56) were analyzed. Prognostic value of embryonic origin was evaluated.nnnRESULTSnRecurrence-free survival (RFS) and overall survival (OS) after percutaneous ablation were worse in patients from midgut origin (3-year RFS: 5.6% vs. 24%, P = 0.004; 3-year OS: 25% vs. 70%, P 0.001). In multivariable analysis, factors associated with worse OS were midgut origin (hazard ratio [HR] 4.87, 95% CI 2.14-10.9, P 0.001), multiple CLM (HR 2.35, 95% CI 1.02-5.39, P = 0.044), and RAS mutation (HR 2.78, 95% CI 1.25-6.36, P = 0.013). At a median follow-up of 25 months, 56 patients (76%) had developed recurrence, 16 (89%) with midgut origin and 40 (71%) with hindgut origin (P = 0.133). Recurrent disease was treated with local therapy in 20 patients (36%), 2 (13%) with midgut origin and 18 (45%) with hindgut origin (P = 0.022).nnnCONCLUSIONnCompared to CLM from hindgut origin tumors, CLM from midgut origin tumors were associated with worse survival after ablation, which was partly attributable to the fact that patients with hindgut origin were more frequently candidates for local therapy at recurrence.

Validation of American Joint Committee on Cancer eighth staging system for gallbladder cancer and its lymphadenectomy guidelines

BACKGROUNDnFor gallbladder cancer (GBC), the American Joint Committee on Cancer eighth edition (AJCC 8) staging system classifies lymph node (LN) stage by the number of positive LN and recommends sampling of ≥6 LNs. We evaluated the prognostic capability of the AJCC 8 for patients undergoing resection and the current national trends in LN staging in the context of these new recommendations for nodal (N) sampling.nnnMETHODSnUtilizing the National Cancer Data Base, we identified all gallbladder adenocarcinoma patients treated with surgical resection in 2004-2014. Cox regression modeling was used to calculate the concordance index of AJCC 8 in predicting overall survival. N sampling and positivity rates were analyzed over the study period.nnnRESULTSnIn our cohort, predicted 5-year overall survival by AJCC 8 was: stage I, 62.5%; II, 50.2%; IIIA, 25.7%; IIIB, 22.1%; IVA, 15.7%; IVB, 6.7% (Pxa0<xa00.01). The concordance index for the staging system was 0.832. Only 50.7% of the patients had any LN sampling to determine the N stage. LN sampling rates improved from 45.6% in 2004 to 55.1% in 2013 (Pxa0<xa00.001). However, only 24.5% of patients with any LN sampling had ≥6 LNs resected (12.4% of eligible cohort), with a median LN sample of two.nnnCONCLUSIONSnAJCC 8 offers adequate discrimination for GBC staging, especially for node-positive patients. With actual GBC LN sampling rates at 50.7%, and far short of the ≥6 LN threshold, quality improvement measures may need to focus on requiring any LN sampling before raising the minimum to six LNs.

Loss of muscle mass during preoperative chemotherapy predicts worse recurrence-free survival in patients with resectable colorectal liver metastases

MTA and 9.7% in the RFA group (p = 0.85). There was no mortality. Median hospital stay was 1 day for both groups. For the RFA vs MTA groups, local recurrence (LR) rate per lesion was 20.3% and 8.5%, respectively (p = 0.01). On Cox Proportion Hazards model, ablation modality was an independent predictor of LR following risk adjustment. Conclusion: To our knowledge, this is the first comparison of RFA and MTA in the treatment of CRLM. Our results demonstrates MTA achieves better local tumor control with shorter operative and ablation time.

Long-term survival after post-hepatectomy liver failure for colorectal liver metastases

BACKGROUNDnWhile post-hepatectomy liver failure (PHLF) accurately predicts short-term mortality, its role in prognosticating long-term overall survival (OS) remains unclear.nnnMETHODSnPatients who underwent hepatectomy for colorectal liver metastases (CRLM) after portal vein embolization during 1999-2015 were evaluated retrospectively. PHLF was defined per International Study Group of Liver Surgery (ISGLS) criteria and as PeakBil >7xa0mg/dl. Survival was analyzed using log-rank statistic and Cox regression; patient mortality within 90 days was excluded.nnnRESULTSnOf 175 patients, 68 (39%) had PHLF according to ISGLS criteria, including 40 (23%) with ISGLS grade B/C, and 14 (8%) had PeakBil >7xa0mg/dl. Patients with PeakBil >7xa0mg/dl had significantly worse OS than patients without PHLF (median OS, 16 vs 58 months, pxa0=xa00.001). Patients with ISGLS defined PHLF (pxa0=xa00.251) and patients with ISGLS grade B/C PHLF (pxa0=xa00.220) did not have worse OS than patients without PHLF.nnnCONCLUSIONnPeak bilirubin >7xa0mg/dl impacts on long-term survival after hepatectomy for CRLM and is a better predictor of long-term survival than ISGLS-defined PHLF.

Minimally invasive management of the entire treatment sequence in patients with stage IV colorectal cancer: a propensity-score weighting analysis

BACKGROUNDnIn patients with stage IV colorectal cancer (CRC), minimally invasive surgery (MIS) may offer optimal oncologic outcome with low morbidity. However, the relative benefit of MIS compared to open surgery in patients requiring multistage resections has not been evaluated.nnnMETHODSnPatients who underwent totally minimally invasive (TMI) or totally open (TO) resections of CRC primary and liver metastases (CLM) in 2009-2016 were analyzed. Inverse probability of weighted adjustment by propensity score was performed before analyzing risk factors for complications and survival.nnnRESULTSnThe study included 43 TMI and 121 TO patients. Before and after adjustment, TMI patients had significantly less cumulated postoperative complications (41% vs. 59%, p = 0.001), blood loss (median 100 vs. 200 ml, p = 0.001) and shorter length of hospital stay (median 4.5 vs. 6.0 days, p < 0.001). Multivariate analysis identified TO approach vs. MIS (OR = 2.4, p < 0.001), major liver resection (OR = 4.4, p < 0.001), and multiple CLM (OR = 2.3, p = 0.001) as independent risk factors for complications. 5-year overall survival was comparable (81% vs 68%, p = 0.59).nnnCONCLUSIONnIn patients with CRC undergoing multistage surgical treatment, MIS resection contributes to optimal perioperative outcomes without compromise in oncologic outcomes.

Prognostic impact of perihepatic lymph node metastases in patients with resectable colorectal liver metastases

Although perihepatic lymph node metastases (PLNMs) are known to be a poor prognosticator for patients with colorectal liver metastases (CRLMs), optimal management remains unclear. This study aimed to determine the risk factors for PLNMs, and the survival impact of their number and location in patients with resectable CRLMs.