The main hepatic lesion induced by preoperative FU/oxaliplatin chemotherapy in patients with CLM is vascular and not steatosis. Detailed pathologic analysis determined that the most severe vascular lesions are associated with increased intraoperative transfusions. The risk for other postoperative complications is related to the duration of preoperative chemotherapy administration.

An American Hepato-Pancreato-Biliary Association (AHPBA)-sponsored consensus meeting of expert panellists was convened on 15 January 2014 to review current evidence on the management of gallbladder carcinoma in order to establish practice guidelines. In summary, within high incidence areas, the assessment of routine gallbladder specimens should include the microscopic evaluation of a minimum of three sections and the cystic duct margin; specimens with dysplasia or proven cancer should be extensively sampled. Provided the patient is medically fit for surgery, data support the resection of all gallbladder polyps of >1.0 cm in diameter and those with imaging evidence of vascular stalks. The minimum staging evaluation of patients with suspected or proven gallbladder cancer includes contrasted cross-sectional imaging and diagnostic laparoscopy. Adequate lymphadenectomy includes assessment of any suspicious regional nodes, evaluation of the aortocaval nodal basin, and a goal recovery of at least six nodes. Patients with confirmed metastases to N2 nodal stations do not benefit from radical resection and should receive systemic and/or palliative treatments. Primary resection of patients with early T-stage (T1b-2) disease should include en bloc resection of adjacent liver parenchyma. Patients with T1b, T2 or T3 disease that is incidentally identified in a cholecystectomy specimen should undergo re-resection unless this is contraindicated by advanced disease or poor performance status. Re-resection should include complete portal lymphadenectomy and bile duct resection only when needed to achieve a negative margin (R0) resection. Patients with preoperatively staged T3 or T4 N1 disease should be considered for clinical trials of neoadjuvant chemotherapy. Following R0 resection of T2-4 disease in N1 gallbladder cancer, patients should be considered for adjuvant systemic chemotherapy and/or chemoradiotherapy.

The American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) staging system for liver cancer is based on data exclusively derived from hepatocellular carcinoma (HCC) patients and thus may be inappropriate for patients with intrahepatic cholangiocarcinoma (ICC). We sought to empirically derive an ICC staging system from population-based data on patients with ICC. The Surveillance, Epidemiology, and End Results (SEER) database was used to identify 598 patients who underwent surgery for ICC between 1988 and 2004. The discriminative abilities of the AJCC/UICC liver cancer and two Japanese ICC staging systems were evaluated. Independent predictors of survival were identified using Cox proportional hazards models. A staging system for ICC was then derived based on these analyses. The AJCC/UICC T classification system failed to adequately stratify the T2 and T3 cohorts due to tumor size >5 cm not being a relevant prognostic factor [hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.72-1.30]. In contrast, presence of multiple lesions (HR 1.42, 95% CI 1.01-2.01) or vascular invasion (HR 1.53, 95% CI 1.10-2.12) predicted adverse prognosis. Based on these findings, an ICC staging system was developed that omits tumor size. This system showed no loss of prognostic discrimination compared with the AJCC/UICC system and significant superiority over the Japanese systems. We conclude that the AJCC/UICC liver cancer staging system fails to stratify ICC patients adequately and inappropriately includes tumor size. We propose a staging system specifically developed for ICC based on number of tumors, vascular invasion, lymph node status, and presence of metastatic disease.

Objective To determine the impact of RAS mutation status on survival and patterns of recurrence in patients undergoing curative resection of colorectal liver metastases (CLM) after preoperative modern chemotherapy. Summary Background Data RAS mutation has been reported to be associated with aggressive tumor biology. However, the effect of RAS mutation on survival and patterns of recurrence after resection of CLM remains unclear. Methods Somatic mutations were analyzed using mass spectroscopy in 193 patients who underwent single-regimen modern chemotherapy before resection of CLM. The relationship between RAS mutation status and survival outcomes was investigated. Results Detected somatic mutations included RAS (KRAS/NRAS) in 34 patients (18%), PIK3CA in 13 (7%), and BRAF in 2 (1%). At a median follow-up of 33 months, 3-year overall survival (OS) rates were 81% in patients with wild-type vs 52.2% in patients with mutant RAS (P=0.002); 3-year recurrence-free survival (RFS) rates were 33.5% with wild-type vs 13.5% with mutant RAS (P=0.001). Liver and lung recurrences were observed in 89 and 83 patients, respectively. Patients with RAS mutation had a lower 3-year lung RFS rate (34.6% vs 59.3%, P<0.001), but not a lower 3-year liver RFS rate (43.8% vs 50.2%, P=0.181). In multivariate analyses, RAS mutation predicted worse OS (hazard ratio [HR] 2.3, P=0.002), overall RFS (HR 1.9, P=0.005), and lung RFS (HR 2.0, P=0.01), but not liver RFS (P=0.181). Conclusions RAS mutation predicts early lung recurrence and worse survival after curative resection of CLM. This information may be used to individualize systemic and local tumor-directed therapies and follow-up strategies.

Background: Hepatic resection (HR) and radiofrequency ablation (RFA) have been proposed as equivalent treatments for colorectal liver metastasis. Hypothesis: Recurrence patterns after HR and RFA for solitary liver metastasis are similar. Design: Analysis of a prospective database at a tertiary care center with systematic review of follow-up imaging in all of the patients. Patients and Methods: Patients with solitary liver metastasis as the first site of metastasis treated for cure by HR or RFA were studied (patients received no prior liverdirected therapy). Prognostic factors, recurrence patterns, and survival rates were analyzed. Results: Of the 180 patients who were studied, 150 underwent HR and 30 underwent RFA. Radiofrequency ablation was used when resection would leave an inadequate liver remnant (20 patients) or comorbidity precluded safe HR (10 patients). Tumor size and treatment determined recurrence and survival. The local recurrence (LR) rate was markedly lower after HR (5%) than

An American Hepato-Pancreato-Biliary Association (AHPBA)-sponsored consensus meeting of expert panellists met on 15 January 2014 to review current evidence on the management of hilar cholangiocarcinoma in order to establish practice guidelines and to agree consensus statements. It was established that the treatment of patients with hilar cholangiocarcinoma requires a coordinated, multidisciplinary approach to optimize the chances for both durable survival and effective palliation. An adequate diagnostic and staging work-up includes high-quality cross-sectional imaging; however, pathologic confirmation is not required prior to resection or initiation of a liver transplant trimodal treatment protocol. The ideal treatment for suitable patients with resectable hilar malignancy is resection of the intra- and extrahepatic bile ducts, as well as resection of the involved ipsilateral liver. Preoperative biliary drainage is best achieved with percutaneous transhepatic approaches and may be indicated for patients with cholangitis, malnutrition or hepatic insufficiency. Portal vein embolization is a safe and effective strategy for increasing the future liver remnant (FLR) and is particularly useful for patients with an FLR of <30%. Selected patients with unresectable hilar cholangiocarcinoma should be evaluated for a standard trimodal protocol incorporating external beam and endoluminal radiation therapy, systemic chemotherapy and liver transplantation. Post-resection chemoradiation should be offered to patients who show high-risk features on surgical pathology. Chemoradiation is also recommended for patients with locally advanced, unresectable hilar cancers. For patients with locally recurrent or metastatic hilar cholangiocarcinoma, first-line chemotherapy with gemcitabine and cisplatin is recommended based on multiple Phase II trials and a large randomized controlled trial including a heterogeneous population of patients with biliary cancers.

Purpose Standard therapies for localized inoperable intrahepatic cholangiocarcinoma (IHCC) are ineffective. Advances in radiotherapy (RT) techniques and image guidance have enabled ablative doses to be delivered to large liver tumors. This study evaluated the effects of RT dose escalation in the treatment of IHCC. Patients and Methods Seventy-nine consecutive patients with inoperable IHCC were identified and treated with definitive RT from 2002 to 2014. At diagnosis, the median tumor size was 7.9 cm (range, 2.2 to 17 cm). Seventy patients (89%) received systemic chemotherapy before RT. RT doses were 35 to 100 Gy (median, 58.05 Gy) in three to 30 fractions for a median biologic equivalent dose (BED) of 80.5 Gy (range, 43.75 to 180 Gy). Results Median follow-up time for patients alive at time of analysis was 33 months (range, 11 to 93 months). Median overall survival (OS) time after diagnosis was 30 months; 3-year OS rate was 44%. Radiation dose was the single most important prognostic factor; higher doses correlated with an improved local control (LC) rate and OS. The 3-year OS rate for patients receiving BED greater than 80.5 Gy was 73% versus 38% for those receiving lower doses (P = .017); 3-year LC rate was significantly higher (78%) after a BED greater than 80.5 Gy than after lower doses (45%, P = .04). BED as a continuous variable significantly affected LC (P = .009) and OS (P = .004). There were no significant treatment-related toxicities. Conclusion Delivery of higher doses of RT improves LC and OS in inoperable IHCC. A BED greater than 80.5 Gy seems to be an ablative dose of RT for large IHCCs, with long-term survival rates that compare favorably with resection.

For patients with BCLM, HR is safe and may provide a significant survival benefit over medical therapy alone. Response to preoperative chemotherapy, resection margin, and rehepatectomy for intrahepatic recurrence are key prognostic factors. Importantly, favorable outcomes can be achieved even in patients with medically controlled or surgically resectable extrahepatic disease, indicating that surgery should be considered more frequently in the multidisciplinary care of patients with BCLM.