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Objective: To test the degree of agreement in selecting therapeutic options for patients suffering from colorectal liver metastasis (CRLM) among surgical experts around the globe., Summary/background: Only few areas in medicine have seen so many novel therapeutic options over the past decades as for liver tumors. Significant variations may therefore exist regarding the choices of treatment, even among experts, which may confuse both the medical community and patients., Methods: Ten cases of CRLM with different levels of complexity were presented to 43 expert liver surgeons from 23 countries and 4 continents. Experts were defined as experienced surgeons with academic contributions to the field of liver tumors. Experts provided information on their medical education and current practice in liver surgery and transplantation. Using an online platform, they chose their strategy in treating each case from defined multiple choices with added comments. Inter-rater agreement among experts and cases was calculated using free-marginal multirater kappa methodology. A similar, but adjusted survey was presented to 60 general surgeons from Asia, Europe, and North America to test their attitude in treating or referring complex patients to expert centers., Results: Thirty-eight (88%) experts completed the evaluation. Most of them are in leading positions (92%) with a median clinical experience of 25 years. Agreement on therapeutic strategies among them was none to minimal in more than half of the cases with kappa varying from 0.00 to 0.39. Many general surgeons may not refer the complex cases to expert centers, including in Europe, where they also engage in complex liver surgeries., Conclusions: Considerable inconsistencies of decision-making exist among expert surgeons when choosing a therapeutic strategy for CRLM. This might confuse both patients and referring physicians and indicate that an international high-level consensus statements and widely accepted guidelines are needed.

Background and Objectives: Delineation of adequate tumor margins is critical in oncologic surgery, particularly in resection of metastatic lesions. Surgeons are limited in visualization with bright-light surgery, but fluorescence-guided surgery (FGS) has been efficacious in helping the surgeon achieve negative margins., Methods: The present study uses FGS in a mouse model that has undergone surgical orthotopic implantation (SOI) of colorectal liver metastasis tagged with green fluorescent protein (GFP). An anti-CEA antibody conjugated to DyLight 650 was used to highlight the tumor., Results: The fluorescent antibody clearly demarcated the lesion at deeper tissue depth compared to GFP. Fluorescence of the anti-CEA-DyLight650 showed maximal tumor-to-liver contrast at 72 hr. Fifteen mice underwent bright-light surgery (BLS) versus FGS with GFP versus FGS with anti-CEA-DyLight650. Mice that underwent FGS had a significantly smaller area of residual tumor (P < 0.001) and significantly longer overall survival (P < 0.001) and disease-free survival (P < 0.001). Within the two FGS groups, mice undergoing surgery with anti-CEA-DyLight650 improved survival compared to only GFP labeling., Conclusions: In the present report, we demonstrate that an anti-CEA antibody conjugated to a DyLight 650 nm dye clearly labeled colon cancer liver metastases, thereby enabling successful FGS. J. Surg. Oncol. 2016;114:951-958. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: At a recently concluded Americas Hepato-Pancreato-Biliary Association Annual Meeting, a Clinical Practice Guidelines Conference Series was convened with the topic focusing on Venous Thromboembolism (VTE) Prophylaxis in Liver Surgery. The symposium brought together hepatobiliary surgeons from three continents as well as medical experts in hematology and coagulation., Methods: The content of the discussion included literature reviews, evaluation of multi-institutional VTE outcome data, and examination of practice patterns at multiple high-volume centers., Results: Literature review demonstrated that, within gastrointestinal surgery, liver resection patients are at particularly high-risk for VTE. Recent evidence clearly indicates a direct relationship between the magnitude of hepatectomy and postoperative VTE rates, however, the PT/INR does not accurately reflect the coagulation status of the post-hepatectomy patient. Evaluation of available data and practice patterns regarding the utilization and timing of anticoagulant VTE prophylaxis led to recommendations regarding preoperative and postoperative thromboprophylaxis for liver surgery patients., Conclusions: This conference was effective in consolidating our knowledge of coagulation abnormalities after liver resection. Based on the expert review of the available data and practice patterns, a number of recommendations were developed.

Introduction: The drive to improve outcomes and the inevitability of mandated public reporting necessitate uniform documentation and accurate databases. The reporting of wound classification in patients undergoing hepato-pancreatico-biliary (HPB) surgery and the impact of inconsistencies on quality metrics were investigated., Methods: The 2005-2011 National Surgical Quality Improvement Program (NSQIP) participant use file was interrogated to identify patients undergoing HPB resections. The effect of wound classification on post-operative surgical site infection (SSI) rates was determined through logistic regression. The impact of variations in wound classification reporting on perceived outcomes was modelled by simulating observed-to-expected (O/E) ratios for SSI., Results: In total, 27,376 patients were identified with significant heterogeneity in wound classification. In spite of clear guidelines prompting at least 'clean-contaminated' designation for HPB resections, 8% of all cases were coded as 'clean'. Contaminated [adjusted odds ratio (AOR): 1.39, P = 0.001] and dirty (AOR: 1.42, P = 0.02] cases were associated with higher odds of SSI, whereas clean-contaminated were not (P = 0.99). O/E ratios were highly sensitive to modest changes in wound classification., Conclusions: Perceived performance is affected by heterogeneous reporting of wound classification. As institutions work to improve outcomes and prepare for public reporting, it is imperative that all adhere to consistent reporting practices to provide accurate and reproducible outcomes., (© 2014 International Hepato-Pancreato-Biliary Association.)

Background: Hepatic and pancreatic surgery is rarely performed in patients with end-stage renal disease (ESRD). The present authors used a national clinical database to characterize outcomes and perioperative risk in ESRD patients who require hepatic or pancreatic resection., Methods: The 2005-2011 National Surgical Quality Improvement Program database was queried for all patients undergoing hepatic or pancreatic resection. Patients were classified by the presence or absence of ESRD. The independent effects of ESRD on outcomes were assessed after propensity score adjustment and multivariable logistic regression., Results: Of the 27 376 patients submitted to hepatic or pancreatic procedures identified in the database, 101 patients were found to have preoperative ESRD. Patients with ESRD experienced perioperative mortality at a rate similar to that in those without ESRD (5.0% versus 2.3%; P = 0.08). After risk adjustment, the presence of ESRD was associated with three-fold higher odds of postoperative sepsis (adjusted odds ratio: 2.98, P = 0.014), but no significant differences in mortality or major complication rates., Conclusions: Hepatic and pancreatic resections can be performed safely in selected patients with ESRD. These patients may have an increased risk for the development of postoperative sepsis. Further study is needed to characterize modifiable risk factors that impact outcomes in patients with ESRD who require hepatic or pancreatic resection., (© 2014 International Hepato-Pancreato-Biliary Association.)

Background and Objectives: Fibrolamellar carcinoma (FLC) presents in young, otherwise-healthy individuals. This study examined recurrence and survival characteristics after surgical resection for FLC by utilizing an international multi-institutional database., Methods: Consecutive patients undergoing hepatectomy for FLC from six institutions (1993-2010) were reviewed retrospectively. Survival was studied with life tables and Cox regression models., Results: Thirty-five patients (13 female, 37%) were included (median age: 32 years). R0 resection was achieved in all curative-intent operations (n = 30), and palliative operations were performed for five patients. Crude 30-day morbidity and mortality rates were 22% and 3%, respectively. For curative-intent surgery, overall and recurrence-free survivals at 5 years were 62% and 45%, respectively. In patients who achieved a 4-year disease-free interval after surgery, none subsequently developed recurrence. In multivariate models, presence of extrahepatic disease was the only factor that independently predicted overall (hazard ratio [HR]: 5.58, 95% confidence interval [CI]: 1.38-22.55, P = 0.016) and recurrence-free survival (HR: 5.64, 95% CI: 1.48-21.49, P = 0.011)., Conclusions: Patients with surgically amenable FLC had encouraging long-term survival. Recurrence-free survival to 4 years suggested possible freedom from disease thereafter. Recurrent resectable disease was associated with an excellent prognosis, and repeat surgery should be strongly considered., (© 2014 Wiley Periodicals, Inc.)

Introduction: Coronary artery disease (CAD) is often considered a contraindication to hepatectomy despite a lack of data to support this practice. The purpose of this study is to evaluate the impact of CAD on postoperative outcomes in patients undergoing hepatectomy., Material and Methods: A total of 1,206 consecutive patients undergoing hepatectomy from August 1995 to June 2009 were included. Propensity matching was performed to identify differences in morbidity and mortality between patients with and without CAD. Subgroup analyses were performed to stratify patients based on the severity of CAD and the interval between coronary intervention and hepatectomy., Results: Of all patients, 138 (11.4%) had a diagnosis of CAD and were more likely to have a malignant diagnosis and other comorbid conditions including renal insufficiency, COPD, and diabetes. Matched patients with CAD had no significant differences in complication rates, with 2.2 and 5.8% of CAD patients experiencing a postoperative myocardial infarction or arrhythmia, respectively. Propensity matching failed to identify differences in mortality or morbidity. Subgroup analysis revealed similar rates of mortality and complications regardless of the severity of CAD or the time interval between coronary intervention and hepatectomy., Conclusion: Despite the increased prevalence of major medical comorbidities, selected patients with CAD can safely undergo hepatectomy with acceptable rates of postoperative morbidity and mortality.

Background: Despite the rising incidence of hepatocellular carcinoma (HCC), challenges and controversy persist in optimizing treatment. As recent randomized trials suggest that ablation can have oncologic equivalence compared with resection for early HCC, the relative morbidity of the 2 approaches is a central issue in treatment decisions. Although excellent contemporary perioperative outcomes have been reported by a few hepatobiliary units, it is not clear that they can be replicated in broader practice. Our objective was to help inform this treatment dilemma by defining perioperative outcomes in a broader set of patients as represented in NSQIP-participating institutions., Study Design: Mortality and morbidity data were extracted from the 2005-2010 NSQIP Participant Use Data Files based on Current Procedural Terminology (hepatectomy and ablation) and ICD-9 (HCC). Perioperative outcomes were reviewed, and factors associated with morbidity and mortality were identified with multivariable logistic regression., Results: Eight hundred and thirty-seven (52%) underwent minor hepatectomy, 444 (28%) underwent major hepatectomy, and 323 (20%) underwent surgical ablation. Mortality rates were 3.4% for minor hepatectomy, 3.7% for ablation, and 8.3% for major hepatectomy (p < 0.01). Major complication rates were 21.3% for minor hepatectomy, 9.3% for ablation, and 35.1% for major hepatectomy (p < 0.01). When controlling for confounders, ablation was associated with decreased mortality (adjusted odds ratio = 0.20; 95% CI, 0.04-0.97; p = 0.046) and major complications (adjusted odds ratio = 0.34; 95% CI, 0.22-0.52; p < 0.001)., Conclusions: Exceedingly high complication rates after major hepatectomy for HCC exist in the broader NSQIP treatment environment. These data strongly support the use of parenchymal-sparing minor resections or ablation over major hepatectomy for early HCC when feasible., (Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Although the perioperative mortality from hepatic resection has improved considerably, this procedure is still associated with substantial morbidity and resource use. The goal of this investigation was to characterize the incidence, patterns, and risk factors for early reoperation and readmission after hepatectomy., Study Design: Perioperative outcomes of 1,281 patients undergoing hepatic resection at an academic center from 1996 to 2009 were analyzed. The indications for early reoperation and readmission (90 days) were reviewed. Multivariate logistic regression analysis was performed to determine variables associated with reoperation and readmission. A scoring system was generated to predict the need for readmission after hepatectomy., Results: Eighty-seven patients (6.8%) required reoperation. The perioperative mortality in patients requiring reoperation was significantly higher than for those not requiring reoperation (23.0% vs 3.4%; p < 0.001). Variables associated with reoperation included male sex, performance of concomitant major nonhepatic procedures, and greater intraoperative blood loss. One hundred and eighty-four patients (14.4%) required readmission. Variables associated with readmission included major hepatectomy, development of major postoperative complications, and index hospitalization >7 days. A Readmission Prediction Score ranging from 0 to 4 was generated and directly correlated with need for readmission., Conclusions: In the current era of hepatic surgery, early reoperation and readmission remain relatively frequent. As we care for patients who are increasingly receiving regionalized care far from home, we must be mindful of patients at increased risk for readmission. The development of strategies to minimize the complications that necessitate reoperation and readmission is critical to improving patient care., (Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Although a concomitant diaphragm resection might be required at the time of hepatectomy to achieve tumor-free surgical margins, studies addressing its effect on postoperative morbidity and mortality have been inconclusive. The objective of this study was to determine whether the need for diaphragm resection at the time of hepatectomy truly increases 30-day morbidity or mortality using data from the American College of Surgeons National Surgical Quality Improvement Program., Study Design: Data were obtained from the 2005-2010 American College of Surgeons National Surgical Quality Improvement Program Participant User Files based on CPT coding. All patients undergoing a simultaneous liver and diaphragm resection were propensity-matched to a subset of liver resection patients not undergoing a diaphragm resection. The main outcomes measures were 30-day mortality and morbidity., Results: One hundred and ninety-two patients who underwent combined liver and diaphragm resection were matched to 192 patients treated with liver resection alone. The need for concomitant diaphragm resection was associated with a higher overall complication rate (38.54% vs 28.65%; p = 0.048), major complication rate (33.33% vs 23.44%; p = 0.030), and respiratory complication rate (14.06% vs 7.81%; p = 0.058). Postoperative mortality was similar between groups. Combined diaphragm and liver resection was also associated with longer operative times (median 311 minutes vs 247.5 minutes; p < 0.001), higher rates of intraoperative packed RBC transfusion (33.33% vs 23.44%; p = 0.037), and a longer length of hospitalization (median 7 vs 6 days; p = 0.002)., Conclusions: The results of this study, when taken into account with those reported previously, suggest that the need for diaphragm resection at time of hepatectomy increases postoperative morbidity but not mortality., (Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: The optimal timing of primary and metastatic tumor management in patients with synchronous hepatic colorectal metastases remains controversial. We aimed to compare perioperative outcomes of simultaneous colorectal/liver resection (SCLR) with isolated resections utilizing a national clinical database., Methods: NSQIP data from 2005 to 2009 were examined to construct risk-adjusted generalized linear models and to calculate group-specific predicted estimates. These were used to compare 30-day perioperative outcomes among patients undergoing SCLR with colorectal (CR) and liver resections (LR) only in patients with metastatic colorectal cancer., Results: A total of 3,983 patients were identified, who underwent SCLR (192), LR (1,857), or CR (1,934). Rectal resection was performed in 45 (23.4 %) SCLR patients and 269 (13.9 %) CR patients (p < 0.001). Major hepatectomy was performed in 69 (35.9 %) SCLR patients and 774 (41.7 %) LR patients (p = 0.12). Median adjusted operation time (SCLR: 273 min, 95 % CI: 253-295; CR: 172, CI: 168-177; LR: 222, CI: 217-228; p < 0.001) and median adjusted length of hospital stay (SCLR: 9.5 days, CI: 8.8-10.4; CR: 8.1, CI: 7.9-8.3; LR: 6.4, CI: 6.3-6.6; p < 0.001) were longer for SCLR compared to CR and LR. Adjusted predicted risks for at least one postoperative complication were higher in SCLR (36.3 %) than in CR (26.6 %) and LR (19.8 %) (p < 0.003), mostly due to infectious/cardiopulmonary issues., Discussion: In SCLR patients, the risk of 30-day adverse outcomes is higher, and median operation time as well as length of hospital stay is longer compared to CR and LR patients. However, the expected combined morbidities of staged procedures though likely favor SCLR in carefully selected patients undergoing even complex hepatic and colorectal resections and should be considered.

Unlabelled: BACKGROUND. Surgical strategy for hilar cholangiocarcinoma often includes hepatectomy, but the role of portal vein resection (PVR) remains controversial. In this study, the authors sought to identify factors associated with outcome after surgical management of hilar cholangiocarcinoma and examined the impact of PVR on survival., Methods: Three hundred five patients who underwent curative-intent surgery for hilar cholangiocarcinoma between 1984 and 2010 were identified from an international, multi-institutional database. Clinicopathologic data were evaluated using univariate and multivariate analyses., Results: Most patients had hilar cholangiocarcinoma with tumors classified as T3/T4 (51.1%) and Bismuth-Corlette type II/III (60.9%). Resection involved extrahepatic bile duct resection (EHBR) alone (26.6%); or hepatectomy and EHBR without PVR (56.7%); or combined hepatectomy, EHBR, and PVR (16.7%). Negative resection (R0) margin status was higher among the patients who underwent hepatectomy plus EHBR (without PVR, 64.2%; with PVR, 66.7%) versus EHBR alone (54.3%; P < .001). The median number of lymph nodes assessed was higher among the patients who underwent hepatectomy plus EHBR (without PVR, 6 lymph nodes; with PVR, 4 lymph nodes) versus EHBR alone (2 lymph nodes; P < .001). The 90-day mortality rate was lower for patients who underwent EHBR alone (1.2%) compared with the rate for patients who underwent hepatectomy plus EHBR (without PVR, 10.6%, with PVR, 17.6%; P < .001). The overall 5-year survival rate was 20.2%. Factors that were associated with an adverse prognosis included lymph node metastasis (hazard ratio [HR], 1.79; P = .002) and R1 margin status (HR, 1.81; P < .001). Microscopic vascular invasion did not influence survival (HR, 1.23; P = .19). Among the patients who underwent hepatectomy plus EHBR, PVR was not associated with a worse long-term outcome (P = .76)., Conclusions: EHBR alone was associated with a greater risk of positive surgical margins and worse lymph node clearance. The current results indicated that hepatectomy should be considered the standard treatment for hilar cholangiocarcinoma, and PVR should be undertaken when necessary to extirpate all disease. Combined hepatectomy, EHBR, and PVR can offer long-term survival in some patients with advanced hilar cholangiocarcinoma., (Copyright © 2012 American Cancer Society.)

Objective: The routine use of venous thromboembolism (VTE) chemoprophylaxis after hepatic surgery remains controversial due to the relatively low incidence of this complication and the significant risk of perioperative bleeding. The objective of our analysis was to identify perioperative predictors of postoperative VTE in patients undergoing resection., Methods: All patients from the American College of Surgeons National Surgical Quality Improvement Program Participant User File from 2005 to 2009 who underwent hepatic resection were included for analysis. Forward stepwise multivariate logistic regression models were used to determine perioperative variables that are significantly associated with VTE after hepatic surgery., Results: The overall incidence of VTE after hepatic resection was 2.9 %. Significant predictors of VTE after hepatic resection included preoperative mechanical ventilation, male gender, operative time > 3 h, age ≥ 70 years, intraoperative transfusion, and extended hepatectomy. Several non-VTE postoperative complications were also associated with subsequent VTE, including prolonged mechanical ventilation, need for early reoperation, and postoperative bleeding., Conclusions: Many perioperative factors, including extended hepatectomy as well as several postoperative non-VTE complications, are associated with an increased risk of VTE after hepatic resection. Knowledge of these factors may assist surgeons in deciding which patients merit more aggressive prophylaxis against this complication.

Introduction: For colorectal cancer patients with liver metastases involving the hepatic dome or invading the diaphragm, a concomitant diaphragm resection is often required to achieve negative surgical margins. The purpose of this study is to determine whether diaphragm resection during partial hepatectomy for metastatic colorectal cancer influences short-term perioperative outcomes and overall survival., Methods: Demographics, treatments, and outcomes of 442 patients who underwent hepatic resection for metastatic colorectal cancer from 1996 to 2010 at a high-volume center were reviewed. Recurrence and survival were measured from the date of metastectomy. Actuarial curves were generated using the Kaplan-Meier method and compared using log-ranks testing. Multivariate predictors of worse survival were compared using a Cox-proportional hazards model., Results: A total of 442 patients underwent hepatectomy for metastatic colorectal cancer. Of these, 34 required simultaneous diaphragm resection (DR) and 408 did not (LR). No significant differences existed in patient demographics or comorbidities. The DR group had longer median operative times (336 vs. 267 min, p = 0.0008) but had comparable rates of perioperative morbidity and mortality. Median overall survival was shorter in the DR group compared to the LR group (18.8 vs. 36 months, p = 0.0017). When controlling for potential cofounders, liver metastases size > 5 cm (HR 1.45 95 % CI (1.08-1.99), p = 0.015) and diaphragm resection (HR = 1.72 95 % CI (1.03-2.86), p = 0.038) predicted worse survival., Conclusions: Simultaneous diaphragm resection during partial hepatectomy does not significantly influence perioperative morbidity or mortality despite longer operative times. However, patients who require diaphragm resection have less favorable survival rates as compared to those who do not.

Background: Before the advent of tyrosine kinase inhibitors (TKIs), surgical resection was the primary treatment for hepatic gastrointestinal stromal tumor (GIST) metastases. Although TKIs have improved survival in the metastatic setting, outcomes after multimodal therapy comprised of hepatectomy and TKIs for GIST are unknown. The objective of this study was to determine whether combination therapy for hepatic GIST metastases is associated with improved overall survival compared with reported outcomes from surgery or TKI therapy alone., Methods: Demographics, clinicopathologic tumor characteristics, treatments, and outcomes of patients who underwent hepatic resection at 3 high-volume centers from 1995 to 2010 were reviewed., Results: In total, 39 patients underwent hepatectomy for metastatic GISTs, and 27 patients received postoperative TKI therapy. At a median follow-up of 39.7 months, 23 patients (59%) experienced recurrence at a median of 18 months. The 1-year, 2-year, and 3-year overall survival rates were 96.7%, 76.8%, and 67.9%, respectively. Median survival was not reached at 5 years. The rates of severe complication and mortality were 10.2% (4 patients) and 2.5% (1 patient), respectively. When controlling for confounders, postoperative TKI therapy was associated with improved survival (hazard ratio, 0.04; 95% confidence interval, 0.01-0.50; P = .006), and extrahepatic disease was associated with worse survival (hazard ratio, 9.51; 95% confidence interval, 1.63-55.7; P = .012)., Conclusions: Overall survival after combination therapy exceeded previous reports for the treatment of metastatic GIST with hepatic resection or TKI therapy alone and was significantly enhanced by postoperative TKI therapy. The results from this study support findings that combination therapy for GIST liver metastases comprised of surgical resection and TKI therapy is more effective than surgery or TKI therapy alone., (Copyright © 2011 American Cancer Society.)

Background: Although hepatic metastasectomy is well established for colorectal and neuroendocrine cancer, the approach to hepatic metastases from other sites is not well defined. We sought to examine the management of noncolorectal non-neuroendocrine liver metastases., Study Design: A retrospective review from 4 major liver centers identified patients who underwent liver resection for noncolorectal non-neuroendocrine metastases between 1990 and 2009. The Kaplan-Meier method was used to analyze survival, and Cox regression models were used to examine prognostic variables., Results: There were 420 patients available for analysis. Breast cancer (n = 115; 27%) was the most common primary malignancy, followed by sarcoma (n = 98; 23%), and genitourinary cancers (n = 92; 22%). Crude postoperative morbidity and mortality rates were 20% and 2%, respectively. Overall median survival was 49 months, and 1, 3, and 5-year Kaplan-Meier survival rates were 73%, 50%, and 31%. Survival was not significantly different between the various primary tumor types. Recurrent disease was found after hepatectomy in 66% of patients. In multivariable models, lymphovascular invasion (p = 0.05) and metastases ≥5 cm (p = 0.04) were independent predictors of poorer survival. Median survival was shorter for resections performed between 1990 and 1999 (n = 101, 32 months) when compared with resections between 2000 and 2009 (n = 319, 66 months; p = 0.003)., Conclusions: Hepatic metastasectomy for noncolorectal non-neuroendocrine cancers is safe and feasible in selected patients. Lymphovascular invasion and metastases ≥5 cm were found to be associated with poorer survival. Patients undergoing metastasectomy in more recent years appear to be surviving longer, however, the reasons for this are not conclusively determined., (Copyright © 2012 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Management of patients with neuroendocrine liver metastasis (NELM) remains controversial. We sought to examine the relative efficacy of surgical management versus intra-arterial therapy (IAT) for NELM and determine factors predictive of survival., Methods: A total of 753 patients who had surgery (n = 339) or IAT (n = 414) for NELM from 1985 to 2010 were identified from nine hepatobiliary centers. Clinicopathologic data were assessed with regression modeling and propensity score matching., Results: Most patients had a pancreatic (32%) or a small bowel (27%) primary tumor; 47% had a hormonally active tumor. There were statistically significant differences in characteristics between surgery versus IAT groups (hormonally active tumors: 28 vs. 48%; hepatic tumor burden >25%: 52% vs. 76%) (all P < 0.001). Among surgical patients, most underwent hepatic resection alone without ablation (78%). The median number of IAT treatments was 1 (range, 1-4). Median and 5-year survival of patients treated with surgery was 123 months and 74% vs. 34 months and 30% for IAT (P < 0.001). In the propensity-adjusted multivariate Cox model, asymptomatic disease (hazard ratio 2.6) was strongly associated with worse outcome (P = 0.001). Although surgical management provided a survival benefit over IAT among symptomatic patients with >25% hepatic tumor involvement, there was no difference in long-term outcome after surgery versus IAT among asymptomatic patients (P = 0.78)., Conclusions: Asymptomatic patients with a large (>25%) burden of liver disease benefited least from surgical management and IAT may be a more appropriate treatment strategy. Surgical management of NELM should be reserved for patients with low-volume disease or for those patients with symptomatic high-volume disease.

Background: Although standard of care after most abdominal surgeries, post-operative pharmacologic thromboprophylaxis after major hepatectomy is commonly withheld due to bleeding risks. The objective of this retrospective study is to evaluate the benefits and risks of post-operative pharmacologic thromboprophylaxis after major hepatectomy at two high volume academic centers., Methods: Demographics, clinicopathologic data, treatments, and post-operative outcomes from patients who underwent major hepatectomy were reviewed., Results: From 2005 to 2010, 419 patients underwent major hepatectomy; 275 (65.6%) were treated with pharmacologicthromboprophylaxis beginning a median of 1 day after resection. Post-operative symptomatic venous thromboembolism (VTE) occurred in 15 (3.6%) patients. Patients treated with pharmacologic thromboprophylaxis had lower rates of symptomatic VTE (2.2% vs. 6.3%, p = 0.03) and post-operative red blood cell (RBC) transfusion (16.7% vs. 26.4%, p = 0.02) with similar rates of overall RBC transfusion (35.0% vs. 30.6%, p = 0.36) compared to untreated patients. Specifically, isolated deep venous thrombosis (0% vs. 2.1%, p = 0.04) and pulmonary embolism (2.2% vs. 4.2%, p = 0.35) occurred less often in treated patients. Analysis of demographics, clinicopathologic data, and treatment factors revealed that pharmacologic thromboprophylaxis was the only variable associated with post-operative VTE., Conclusions: Post-operative pharmacologic thromboprophylaxis lowers the incidence of symptomatic VTE after major hepatectomy without increasing the rate of RBC transfusion.

Background: While commonly used to describe liver resections at risk for post-operative complications, no standard definition of 'major hepatectomy' exists. The objective of the present retrospective study is to specify the extent of hepatic resection that should describe a major hepatectomy., Methods: Demographics, diagnoses, surgical treatments and outcomes from patients who underwent a liver resection at two high-volume centres were reviewed., Results: From 2002 to 2009, 1670 patients underwent a hepatic resection. Post-operative mortality and severe, overall and hepatic-related morbidity occurred in 4.4%, 29.7%, 41.6% and 19.3% of all patients. Mortality (7.4% vs. 2.7% vs. 2.6%) and severe (36.7% vs. 24.7% vs. 24.1%), overall (49.3% vs. 40.6% vs. 35.9%) and hepatic-related (25.6% vs. 16.4% vs. 15.2%) morbidity were more common after resection of four or more liver segments compared with after three or after two or fewer segments (all P < 0.001). There were no significant differences in any post-operative outcome after resection of three and two or fewer segments (all P > 0.05). On multivariable analysis, resection of four or more liver segments was independently associated with post-operative mortality and severe, overall, and hepatic-related morbidity (all P < 0.01)., Conclusions: A major hepatectomy should be defined as resection of four or more liver segments., (© 2011 International Hepato-Pancreato-Biliary Association.)

Background: Because of the aging United States population, increase in overall life expectancy, and rising incidence of hepatobiliary tumors, more elderly patients are considered for hepatic resection. The objective of this study was to assess the influence of age on postoperative outcomes after major hepatectomy among a contemporary cohort from 2 high volume centers., Study Design: Demographics, diagnoses, surgical treatments, and postoperative outcomes of patients who underwent major hepatic resection were reviewed., Results: There were 856 patients who underwent major hepatectomy (resection of 3 or more segments) from 2002 to 2009. Postoperative mortality and morbidity occurred in 53 (6.2%) and 403 (47.1%) patients, respectively. Increasing age was independently associated with postoperative mortality (p = 0.0345). Each 1-year and 10-year increase in age resulted in an odds ratio of mortality after major hepatic resection of 1.036 (95% CI [1.003-1.071]) and 1.426 (95% CI [1.026-1.982]), respectively. This relationship was independent of American Society of Anesthesiology (ASA) score. Increasing age was associated with postoperative sepsis (p = 0.0224, odds ratio for each year 1.025 [range 1.003 to 1.048]) after major hepatic resection, but not overall postoperative morbidity., Conclusions: In the contemporary era, increasing age is independently associated with postoperative mortality after major hepatic resection at high volume academic centers., (Copyright © 2011 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

This review summarizes regional strategies for management of neuroendocrine liver metastases (NLM), including hepatic resection, ablation, liver transplantation, and hepatic arterial embolization/chemoembolization. Despite early disease recurrence and/or progression, resection of NLM with or without combined ablation provides long-term survival and symptom improvement. When complete resection of gross liver disease is not feasible, resection as a tumor debulking strategy should be considered in patients with extreme hormonal symptoms refractory to other treatments or with tumors in locations that would affect short-term quality of life. Hepatic arterial embolization with or without local instillation of chemotherapy may induce disease response, symptomatic improvement, and prolonged survival in patients with unresectable NLM. Early disease recurrence, high postoperative mortality, the absence of extensive experience, and lack of universal indications for organ allocation preclude orthotopic liver transplantation as an option for most patients with unresectable NLM., (Copyright 2010 Elsevier Inc. All rights reserved.)

The optimal timing of chemotherapy relative to resection of synchronous colorectal liver metastases (SCRLM) is not known. The objective of this retrospective multi-institutional study was to assess the influence of chemotherapy administered before and after hepatic resection on long-term outcomes among patients with initially resectable SCRLM treated from 1995 to 2005. Clinicopathologic data, treatments, and long-term outcomes from patients with initially resectable SCRLM who underwent partial hepatectomy at three hepatobiliary centers were reviewed. Four hundred ninety-nine consecutive patients underwent resection; 297 (59.5%) and 264 (52.9%) were treated with chemotherapy before and after resection. Chemotherapy strategies included pre-hepatectomy alone (n = 148, 24.7%), post-hepatectomy alone (n = 115, 23.0%), perioperative (n = 149, 29.0%), and no chemotherapy (n = 87, 17.4%). Male gender (p = 0.0029, HR = 1.41 [1.12-1.77]), node-positive primary tumor (p = 0.0046, HR = 1.40 [1.11-1.77]), four or more SCRLM (p = 0.0005, HR = 1.65 [1.24-2.18]), and post-hepatectomy chemotherapy treatment for 6 months or longer (p = 0.039, HR = 0.75 [0.57-0.99]) were associated with recurrence-free survival after discovery of SCRLM. Carcinoembryonic antigen >200 ng/ml (p = 0.0003, HR = 2.33 [1.48-3.69]), extrahepatic metastatic disease (p = 0.0025, HR = 2.34 [1.35-4.05]), four or more SCRLM (p = 0.033, HR = 1.43 [1.03-2.00]), and post-hepatectomy chemotherapy treatment for 2 months or longer (p < 0.0001, HR = 0.59 [0.45-0.76]) were associated with overall survival. Pre-hepatectomy chemotherapy was not associated with recurrence-free or overall survival. Patients treated with perioperative chemotherapy had similar outcomes as patients treated with post-hepatectomy chemotherapy only. We conclude that chemotherapy administered after but not before resection of SCRLM was associated with improved recurrence-free and overall survival. However, prospective randomized trials are needed to determine the optimal timing of chemotherapy.

Purpose: Extrahepatic cholangiocarcinoma is a rare malignancy. Despite radical resection, survival remains poor, with high rates of local and distant failure. To clarify the role of radiotherapy with chemotherapy, we performed a retrospective analysis of resected patients who had undergone chemoradiotherapy., Methods and Materials: A total of 45 patients (13 with proximal and 32 with distal disease) underwent resection plus radiotherapy (median dose, 50.4 Gy). All but 1 patient received concurrent fluoropyrimidine-based chemotherapy. The median follow-up was 30 months for all patients and 40 months for survivors., Results: Of the 45 patients, 33 underwent adjuvant radiotherapy, and 12 were treated neoadjuvantly. The 5-year actuarial overall survival, disease-free survival, metastasis-free survival, and locoregional control rates were 33%, 37%, 42%, and 78%, respectively. The median survival was 34 months. No patient died perioperatively. Patient age

Background: The goal of our study was to determine the temporal trends in provider volume for liver resection procedures., Study Design: The Nationwide Inpatient Sample database for 1988 through 2003 was used to determine temporal trends in hospital and surgeon volume of liver resection procedures. We also examined whether these trends in provider volume were associated with any changes in postoperative outcomes or in patients' access to high-volume providers., Results: Regionalization of liver resection procedures to high-volume surgeons and hospitals has been occurring since 1988 and, in the most recent time period assessed, 25.8% of patients underwent hepatic resection by high-volume surgeons (> or = 17 procedures per year) and 29.9% of patients underwent resection in high-volume hospitals (> or = 45 procedures per year). Unadjusted mortality data suggest that these trends might be associated with a strengthening of the inverse relationship between hospital volume of hepatic resection and postoperative mortality and with an increasing disparity for some patient populations in use of high-volume hospitals., Conclusions: Regionalization of liver resections is occurring at both the level of the individual surgeon and the hospitals where these procedures are performed. These trends in provider volume might be associated with increasing discrepancies in outcomes and patient demographics among different volume categories of hospitals.

Background: This retrospective study compares the safety and efficacy of hepatic parenchymal transection using vascular staplers (VS) and the crush-clamp (CC) technique., Methods: Demographics, clinicopathologic data, treatments, and postoperative outcomes from patients who underwent VS or CC hepatic parenchymal transection were compared., Results: From 1996-2006, 99 and 112 patients underwent hepatic transection with VS and CC, respectively. Compared to CC, VS transection was associated with less operative time (median 210 vs 275 minutes), blood loss (median 250 vs 500 mL), and postoperative red blood cell (RBC) transfusion (29% vs 44%), all P < .05. VS transection was not associated with RBC transfusion on multivariate analysis. There were no differences in rates of positive resection margins (9% vs 13%), postoperative mortality (2% vs 4%), overall morbidity (32% vs 29%), and severe morbidity (20% vs. 23%), all P > .05., Conclusion: Hepatic parenchymal transection with VS can be accomplished with similar safety and efficacy as CC transection.

Background: Although commonly used in combination with irinotecan or oxaliplatin (iri/oxal) for treatment of colorectal liver metastases before extirpation, the effects of preoperative bevacizumab on surgical outcomes are not established. The objective of this retrospective study was to determine if addition of bevacizumab to iri/oxal preoperative chemotherapy increases morbidity after hepatic resection., Study Design: We compared demographics, clinicopathologic data, treatments, and postoperative outcomes between patients given preoperative iri/oxal with and without bevacizumab and patients who underwent hepatic resection within and after 8 weeks from the last dose of bevacizumab., Results: From 1996 to 2006, 96 patients were treated with preoperative iri/oxal; 39 (40.6%) received concurrent bevacizumab. Preoperative bevacizumab treatment was associated with less blood loss (median 425 mL versus 600 mL, p=0.01) and lower RBC transfusion rates (43.9% versus 23.1%, p=0.06) after partial hepatectomy on univariable analysis. Only age>or=70 years (hazard ratio=8.52, 95% CI [2.00 to 36.45]) and concurrent extrahepatic procedures (hazard ratio=4.12, 95% CI [1.49 to 11.39]) independently predicted RBC transfusion and overall complications, respectively. There were no differences in overall (43.6% versus 38.6%), severe (28.2% versus 24.6%), hepatic (17.9% versus 26.3%), wound (10.3% versus 7%), or thromboembolic or bleeding (2.6% versus 5.3%) complications (all p > 0.05). For patients treated with iri/oxal and bevacizumab, overall complications were more common when resection was performed within 8 weeks after the last bevacizumab dose (62.5% versus 30.4%), but this difference was not statistically significant (p=0.06)., Conclusions: If discontinued at least 8 weeks before hepatic resection, addition of bevacizumab to preoperative iri/oxal does not increase morbidity after hepatic resection.

Background: The safety of simultaneous resections of colorectal cancer and synchronous liver metastases (SCRLM) is not established. This multi-institutional retrospective study compared postoperative outcomes after simultaneous and staged colorectal and hepatic resections., Methods: Clinicopathologic data, treatments, and postoperative outcomes from patients who underwent simultaneous or staged colorectal and hepatic resections at three hepatobiliary centers from 1985-2006 were reviewed., Results: 610 patients underwent simultaneous (n = 135) or staged (n = 475) resections of colorectal cancer and SCRLM. Seventy staged patients underwent colorectal and hepatic resections at the same institution. Simultaneous patients had fewer (median 1 versus 2) and smaller (median 2.5 versus 3.5 cm) metastases and less often underwent major (> or = three segments) hepatectomy (26.7% versus 61.3%, p < 0.05). Combined hospital stay was lower after simultaneous resections (median 8.5 versus 14 days, p < 0.0001). Mortality (1.0% versus 0.5%) and severe morbidity (14.1% versus 12.5%) were similar after simultaneous colorectal resection and minor hepatectomy compared with isolated minor hepatectomy (both p > 0.05). For major hepatectomy, simultaneous colorectal resection increased mortality (8.3% versus 1.4%, p < 0.05) and severe morbidity (36.1% versus 15.1%, p < 0.05). Combined severe morbidity after staged resections was lower compared to simultaneous resections (36.1% versus 17.6%, p = 0.05) for major hepatectomy but similar for minor hepatectomy (14.1% versus 10.5%, p > 0.05). Major hepatectomy independently predicted severe morbidity after simultaneous resections [hazard ratio (HR) = 3.4, p = 0.008]., Conclusions: Simultaneous colorectal and minor hepatic resections are safe and should be performed for most patients with SCRLM. Due to increased risk of severe morbidity, caution should be exercised before performing simultaneous colorectal and major hepatic resections.

Background: The role of hepatic resection for metastatic squamous cell carcinoma (SCC) remains unknown. The current study evaluates the role of hepatic resection in patients with metastatic SCC to the liver., Methods: Between 1988 and 2006, 52 patients underwent hepatic resection of metastatic SCC at eight major cancer centers. Clinicopathologic factors were analyzed with regard to disease-free survival (DFS) and overall survival (OS)., Results: Primary SCC site was anal (n = 27), head/neck (n = 12), lung (n = 4), esophagus (n = 2), and other (n = 7). Treatment of primary SCC was chemotherapy +/- radiotherapy alone (n = 29), chemotherapy +/- radiotherapy + surgery (n = 15), or surgery alone (n = 8). Forty-seven patients underwent resection alone, 2 resection + radiofrequency ablation (RFA), and 3 RFA only. At last follow-up, 33 (63.5%) patients had recurred. The median time to recurrence was 9.8 months, and 5-year DFS was 18.6%. Factors associated with reduced DFS were liver tumor size > 5 cm (hazard ratio (HR) = 2.02) and positive surgical margin (HR = 2.33). The overall median survival after hepatic resection was 22.3 months and 5-year actuarial OS was 20.5%. Risk factors associated with worse overall survival included synchronous disease (HR = 4.09), hepatic metastasis > 5 cm (HR = 1.71) and positive surgical resection margin (HR = 1.83)., Conclusions: The majority of patients will recur following hepatic resection of SCC. Long-term survival, however, can be achieved following surgical resection of SCC liver metastasis, especially in patients who present with limited metachronous disease amenable to margin negative resection.

Background: Although radical cholecystectomy is the standard of care for gallbladder cancers that invade perimuscular connective tissue or perforate visceral peritoneum, the role of extended right hepatectomy in achieving negative resection margins is not clear., Methods: Clinicopathologic, perioperative, and long-term outcome data were reviewed from patients who underwent hepatic resection for gallbladder cancer., Results: From 1995 to 2005, 22 consecutive patients underwent hepatic resection for gallbladder cancer, and 11 underwent extended hepatectomy. Negative resection margins were achieved in all patients. There were no significant differences in postoperative morbidity, mortality, and long-term survival after extended and minor hepatectomy. T3 tumors negatively predicted overall and recurrence-free survival., Comments: Extended hepatectomy achieves negative resection margins for patients with gallbladder cancer and is associated with acceptable morbidity and long-term survival.

Background: To establish a reliable definition of postoperative hepatic insufficiency (PHI) in noncirrhotic patients undergoing major hepatectomy. No standard definition of PHI has been established, but one is essential for meaningful comparison of outcomes data across studies., Methods: Data from 1,059 noncirrhotic patients who underwent major hepatectomy (3 or more liver segments) at 3 centers from 1995 to 2005 were analyzed. Receiver operating characteristics (ROC) analysis of peak postoperative bilirubin ((Peak)Bil) and international normalized ratio ((Peak)INR) were used to define PHI., Results: A total of 669 patients (63%) underwent resection of 3 to 4 liver segments; 390 (37%) underwent resection of 5 or more segments. Complications occurred in 453 (43%). The 90-day all-cause mortality rate was 4.7%, which is 47% higher than the 30-day rate (3.2%). Twenty (1.9%) patients died of causes unrelated to the liver. Of the remaining 1,039 patients, 30 (2.8%) died a median 36 days from liver-related causes (liver failure with or without multiorgan failure). ROC analysis revealed cut-offs that predict liver-related death are (Peak)Bil 7.0 mg/dL (area under the curve 0.982; sensitivity 93.3%; specificity 94.3%) and (Peak)INR 2.0 (area under the curve 0.846; sensitivity 76.7%; specificity 82.0%). (Peak)Bil > 7.0 mg/dL was the most powerful predictor of any (odds ratio [OR] = 83.3) or major complication (OR = 10.0), 90-day mortality (OR = 10.8), and 90-day liver-related mortality (OR = 250) (all p < 0.0001)., Conclusions: PHI defined as (Peak)Bil > 7.0 mg/dL accurately predicts liver-related death and worse outcomes after major hepatectomy. Standardized reporting of complications, PHI, and 90-day mortality is essential to accurately determine the risk of major hepatectomy and to compare outcomes data.

Background: Although established for metastatic colorectal (CR) and neuroendocrine (NE) malignancies, the role of partial hepatectomy in management of metastases from other primaries (NCRNE) is not well-defined., Study Design: The objective of this retrospective study is to compare outcomes after partial hepatectomy for NCRNE, NE, and CR metastases and to identify factors associated with longterm survival for patients with NCRNE diseases. Tumor characteristics, treatments, and outcomes of 360 consecutive patients undergoing resection of NCRNE (n = 82), CR (n = 245), and NE (n = 33) hepatic metastases from 1995 to 2005 were analyzed. NCRNE tumors included breast (n = 20), sarcomas (n = 19), genitourinary (n = 18), melanoma (n = 11), and other (n = 14) cancers. The start date for follow-up and survival analyses was the date of partial hepatectomy., Results: For patients with NCRNE, CR, and NE tumors, there were no marked differences in postoperative mortality (4%, 4%, and 9%) or complication (30%, 42%, and 42%) rates. Median overall survival was longest for NE patients (not yet reached) versus NCRNE and CR (both 44 months) patients (p < 0.05, log-rank test). NCRNE patients had shorter disease-free survival than CR counterparts (13 versus 16 months), p < 0.05 (log-rank test). After median followup of 59 months for NCRNE patients, actuarial 5-year overall and disease-free survival was 37% and 16%, respectively, with 15 5-year survivors. Multivariable analysis suggests that interval from discovery of liver metastases to resection > 6 months (p = 0.08) and administration of chemoradiotherapy after resection (p = 0.06) might be associated with improved overall survival., Conclusions: In selected patients, resection of NCRNE liver metastases can be done safely with survival similar to CR metastases. Delay of liver resection for at least 6 months and treatment with chemoradiotherapy after resection might be associated with improved longterm survival after partial hepatectomy.