Natural history of undifferentiated pleomorphic sarcoma: Experience from the US Sarcoma Collaborative.

BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS) is a relatively rare but aggressive neoplasm. We sought to utilize a multi-institutional US cohort of sarcoma patients to examine predictors of survival and recurrence patterns after resection of UPS. METHODS: From 2000 to 2016, patients with primary UPS undergoing curative-intent surgical resection at seven academic institutions were retrospectively reviewed. Epidemiologic and clinicopathologic factors were reviewed by site of origin. Overall survival (OS), recurrence-free survival (RFS), time-to-locoregional (TTLR), time-to-distant recurrence (TTDR), and patterns of recurrence were analyzed. RESULTS: Of the 534 UPS patients identified, 53% were female, with a median age of 60 and median tumor size of 8.5 cm. The median OS, RFS, TTLR, and TTDR for the entire cohort were 109, 49, 86, and 46 months, respectively. There were no differences in these survival outcomes between extremity and truncal UPS. Compared with truncal, extremity UPS were more commonly amenable to R0 resection (87% vs. 75%, p = 0.017) and less commonly associated with lymph node metastasis (1% vs. 6%, p = 0.031). R0 resection and radiation treatment, but not site of origin (extremity vs. trunk) were independent predictors of OS and RFS. TTLR recurrence was shorter for UPS resected with a positive margin and for tumors not treated with radiation. CONCLUSION: For patients with resected extremity and truncal UPS, tumor size >5 cm and positive resection margin are associated with worse survival OS and RFS, irrespectively the site of origin. R0 surgical resection and radiation treatment may help improve these survival outcomes.

Molecular and Genetic Markers in Appendiceal Mucinous Tumors: A Systematic Review.

INTRODUCTION: The role of somatic mutation profiling in the management of appendiceal mucinous tumors (AMTs) is evolving. Using a systematic review, we identified somatic alterations (SAs) that comprise histopathologic types of AMTs and those associated with aggressive clinical phenotypes. METHODS: MEDLINE/PubMed was searched for studies on AMTs including molecular markers or genomic alterations, published between 1990 and 2018. Studies were grouped under low- and high-grade histological type for primary and metastatic tumors. RESULTS: Twenty-one studies involving 1099 tumors (primary/metastatic) were identified. Seven studies involving 101 primary low-grade AMTs identified KRAS (76.5%) as the predominant SA. Four studies noted GNAS in 45.2% of 42 low-grade appendiceal mucinous neoplasms, and KRAS was identified in 74.4% of 14 studies with 238 low-grade pseudomyxoma peritonei (PMP). GNAS was noted in 56% of 101 tumors and TP53 was noted in only 9.7% of 31 tumors. Primary high-grade tumors demonstrated lower SAs in KRAS (50.4% of 369 tumors) and GNAS (27.8% of 97 tumors), and higher SAs in TP53 (26.0% of 123 tumors). In high-grade PMP, SAs were noted in KRAS (55.0% of 200 tumors), GNAS (35.0% of 60 tumors), and TP53 (26.3% of 19 tumors). No clear association was noted between SAs and survival. CONCLUSIONS: KRAS and GNAS are frequently altered in low-grade AMTs, while TP53 is frequently altered in high-grade AMTs, with no apparent change in expression between primary and metastatic tumors. Although SAs may provide valuable insights into variability in tumor biology, larger studies utilizing clinically annotated genomic databases from multi-institutional consortiums are needed to improve their identification and clinical applicability.

Elective Regional Therapy Treatment for Hepatic Adenoma.

BACKGROUND: Locoregional therapy treatments for hepatic adenoma (HA) are typically limited to selective hepatic arterial embolization (HAE) to control acute hemorrhage. This systematic review sought to report the utilization of HAE and ablation for non-emergent treatment of HA. METHODS: A PubMed query identified studies reporting ablation or embolization for HA patients. Abstracts were screened to exclude studies with only patients managed for acute hemorrhage. Outcomes of interest included rate of success, complications, and repeat procedures. RESULTS: Of 209 initial search results, 33 full-text publications were reviewed, and 10 were selected after applying the exclusion criteria. All were published from 2005 to 2016. A total of 105 patients were included, of which 66 patients with 138 adenomas underwent elective locoregional therapy treatment. The mean size of treated adenomas was 2.9 (range 0.8-8.3) cm. HAE was utilized in 25 patients with 58 adenomas, whereas 35 patients with 68 adenomas underwent radiofrequency ablation. Six patients with 12 adenomas received microwave ablation. Most patients were female (89/105), and adenomas were associated with oral contraceptive use or hormonal therapies in 49 of 105 patients. Success was reported in 115 of 138 first-time procedures, and repeat procedures were needed after 18 of 138. Mean follow-up time was 36.4 months, with two complications. CONCLUSIONS: Reports of elective locoregional therapy for the treatment of HA are limited to case reports and small institutional series. In the select patients treated, outcomes are acceptable, with low rates of repeat procedures or complications. This systematic review warrants further discussion and broader consideration for the treatment of HA.

Antiproliferative and apoptotic effect of LY2090314, a GSK-3 inhibitor, in neuroblastoma in vitro.

BACKGROUND: Neuroblastoma (NB) is a devastating disease. Despite recent advances in the treatment of NB, about 60% of high-risk NB will have relapse and therefore long-term event free survival is very minimal. We have reported that targeting glycogen synthase kinase-3 (GSK-3) may be a potential strategy to treat NB. Consequently, investigating LY2090314, a clinically relevant GSK-3 inhibitor, on NB cellular proliferation and may be beneficial for NB treatment. METHODS: The effect of LY2090314 was compared with a previously studied GSK-3 inhibitor, Tideglusib. Colorimetric, clonogenic, and live-cell image confluency assays were used to study the proliferative effect of LY2090314 on NB cell lines (NGP, SK-N-AS, and SH-SY-5Y). Western blotting and caspase glo assay were performed to determine the mechanistic function of LY2090314 in NB cell lines. RESULTS: LY2090314 treatment exhibited significant growth reduction starting at a 20 nM concentration in NGP, SK-N-AS, and SH-SY-5Y cells. Western blot analysis indicated that growth suppression was due to apoptosis as evidenced by an increase in pro-apoptotic markers cleaved PARP and cleaved caspase-3 and a reduction in the anti-apoptotic protein, survivin. Further, treatment significantly reduced the level of cyclin D1, a key regulatory protein of the cell cycle and apoptosis. Functionally, this was confirmed by an increase in caspase activity. LY2090314 treatment reduced the expression levels of phosphorylated GSK-3 proteins and increased the stability of ß-catenin in these cells. CONCLUSIONS: LY2090314 effectively reduces growth of both human MYCN amplified and non-amplified NB cell lines in vitro. To our knowledge, this is the first study to look at the effect of LY2090314 in NB cell lines. These results indicate that GSK-3 may be a therapeutic target for NB and provide rationale for further preclinical analysis using LY2090314.

Minimally invasive hepatectomy conversions: an analysis of risk factors and outcomes.

BACKGROUND: Surgical approach may influence morbidity following hepatectomy. This study sought to compare outcomes in minimally invasive surgery (MIS), conversion from MIS to open, and planned open hepatectomy patients and analyze factors leading to conversion. METHODS: The 2014 National Surgical Quality Improvement Program dataset was queried for patients undergoing hepatectomy. Patients were divided into three cohorts: MIS, open, or conversion. Propensity matching was performed to compare MIS vs. conversion (3:1) and open vs. conversion (8:1). The logistic regression model was used to identify odds ratios for conversion. RESULTS: Patients undergoing conversion had a higher transfusion rate (26% vs. 9%, p < 0.001), longer length of stay (5 vs. 3 days, p < 0.001), and higher morbidity (38% vs. 18%, p < 0.001) than MIS patients. Patients who underwent conversion had similar short-term outcomes to those who had planned open procedures. Independent predictors of conversion included hypertension (OR 1.91; 95% CI 1.12-3.26) and right lobectomy (OR 20.23; 95% CI 3.74-109.35). CONCLUSION: Patients with hypertension and those undergoing right lobectomy had a higher risk of conversion to open procedure. Conversion resulted in higher morbidity and longer length of stay compared to MIS patients, but outcomes were similar to planned open procedures.

Conditional Survival as a Patient Centered Metric for Patients with Appendiceal Adenocarcinoma.

BACKGROUND: Prognosis of appendiceal adenocarcinoma patients is based on burden of disease, histology, and nature of therapy, which remains static despite time in follow-up. We hypothesized that conditional survival provides an informative metric that allows patients better understanding of their disease. METHODS: Using the Surveillance, Epidemiology and End Results database, patients with appendiceal adenocarcinoma from 1988 to 2012 were included. Actuarial Life table analyses and Kaplan-Meier curves were used for statistical inference. RESULTS: Of 5,952 patients, the median age was 60 years (IQR 50-72) and 52 % were female. Histologies included were adenocarcinoma (NOS 37 %), mucinous adenocarcinoma (MA 53 %), and signet ring cell (SRC 10 %). Five-year overall survival (OS) at diagnosis for patients with metastatic disease was 11 % (NOS), 45 % (MA), and 8 % (SRC), respectively. Annual conditional probability of survival from years 1-5 after diagnosis for patients with SRC with metastatic disease was 55, 60, 68, 55, and 82 % compared with 84, 86, 86, 88, and 92 % with MA. Probability of surviving the first year after extended surgery was 77 % (NOS), 85 % (MA), and 75 % (SRC). Those that survived 5 years after surgery had a 94 % (NOS), 93 % (MA), and 86 % (SRC) probability of surviving the sixth year. CONCLUSIONS: In the setting of dismal cumulative probability of survival (or overall survival), conditional probability is more informative in providing prognostication. This distinction might be important for patients especially with SRC who may live in constant fear of disease. Such data can be used to reassure patients and perhaps modify surveillance strategies for patients.

Age-based disparities in treatment and outcomes of retroperitoneal rhabdomyosarcoma.

BACKGROUND: Elderly patients (EPs) suffering from retroperitoneal rhabdomyosarcoma (RRMS) carry a considerably poorer prognosis compared to younger patients (YPs). We hypothesized that EPs received less aggressive and comprehensive treatment than YPs, resulting in poorer survival outcomes. MATERIALS AND METHODS: All patients diagnosed with RRMS since 1998 in the National Cancer Data Base (NCDB) were reviewed for patient demographics, tumor characteristics, treatment modalities and survival outcomes. RESULTS: Of the 100 patients identified, 35 % were ≥65 years of age. EPs (aged ≥65 years), when compared to YPs (aged <65), were less likely to receive systemic chemotherapy (20 % EPs vs 71 % YPs, p < 0.001) and treatment at an academic center (34 % EPs vs 60 % YPs, p = 0.05), although the frequency of radiation (23 % EPs vs 31 % YPs, p = 0.40) and radical surgery (26 % EPs vs 22 % YPs, p = 0.55) were similar. EPs received treatment more frequently at comprehensive community cancer programs (57 %) and had a shorter median distance of travel for care (6.4 vs 13 miles, p = 0.009). After adjusting for gender and tumor size, EPs had a hazard ratio of 3.6 (95 % CI 1.8-7.2, p < 0.001), with a median survival of 2 months (interquartile range [IQR] 1-8 months) versus 17 months for YPs (IQR 8-43 months). CONCLUSION: Altered practice patterns exist for EPs and include reduced use of systemic chemotherapy which may contribute to poorer outcomes for RRMS patients. Although regionalization of care poses challenges, this may offer benefit to the EP group.

Management and Outcomes of Patients with Recurrent Intrahepatic Cholangiocarcinoma Following Previous Curative-Intent Surgical Resection.

BACKGROUND: Management and outcomes of patients with recurrent intrahepatic cholangiocarcinoma (ICC) following curative-intent surgery are not well documented. We sought to characterize the treatment of patients with recurrent ICC and define therapy-specific outcomes. METHODS: Patients who underwent surgery for ICC from 1990 to 2013 were identified from an international database. Data on clinicopathological characteristics, operative details, recurrence, and recurrence-related management were recorded and analyzed. RESULTS: A total of 563 patients undergoing curative-intent hepatic resection for ICC who met the inclusion criteria were identified. With a median follow-up of 19 months, 400 (71.0 %) patients developed a recurrence. At initial surgery, treatment was resection only (98.8 %) or resection + ablation (1.2 %). Overall 5-year survival was 23.6 %; 400 (71.0 %) patients recurred with a median disease-free survival of 11.2 months. First recurrence site was intrahepatic only (59.8 %), extrahepatic only (14.5 %), or intra- and extrahepatic (25.7 %). Overall, 210 (52.5 %) patients received best supportive care (BSC), whereas 190 (47.5 %) patients received treatment, such as systemic chemotherapy-only (24.2 %) or repeat liver-directed therapy ± systemic chemotherapy (75.8 %). Repeat liver-directed therapy consisted of repeat hepatic resection ± ablation (28.5 %), ablation alone (18.7 %), and intra-arterial therapy (IAT) (52.8 %). Among patients who recurred, median survival from the time of the recurrence was 11.1 months (BSC 8.0 months, systemic chemotherapy-only 16.8 months, liver-directed therapy 18.0 months). The median survival of patients undergoing resection of recurrent ICC was 26.7 months versus 9.6 months for patients who had IAT (p < 0.001). CONCLUSIONS: Recurrence following resection of ICC was common, occurring in up to two-thirds of patients. When there is recurrence, prognosis is poor. Only 9 % of patients underwent repeat liver resection after recurrence, which offered a modest survival benefit.

Challenges to clinical utilization of hereditary cancer gene panel testing: perspectives from the front lines.

Next generation sequencing (NGS) technology is rapidly being implemented into clinical practice. Qualitative research was performed to gain an improved understanding of the landscape surrounding the use of NGS in cancer genetics. A focus group was conducted at the Wisconsin Cancer Risk Programs Network biannual meeting. Free flowing discussion with occasional open-ended questions provided insights into the use of NGS. 19 genetic counselors and medical professionals participated. Three major themes were identified with respect to NGS and its use in cancer genetics: knowledge gaps, the evolving clinician role, and uncertain utility. Several corresponding subthemes were identified. With respect to knowledge gaps, participants expressed concern regarding unexpected results and variants of unknown significance, lack of data about NGS findings, absence of standardization regarding use of NGS and guidelines for interpretation, and discomfort with new technology. Regarding the evolving clinician role, necessary changes to the roles of genetic counselors and physicians were noted, as was the resultant impact on care received by patients and their families. Finally, the clinical and economic utility of NGS was questioned. While a shift from traditional Sanger sequencing to NGS is occurring in molecular genetic testing for disease susceptibility, there are several obstacles that need to be overcome before widespread adoption of this technology can occur. Furthermore, key aspects of NGS and it utility remain unexplored. Continued investigation into these subjects is necessary before this technology will consistently be of benefit to patients and their families.

Chemotherapy for Surgically Resected Intrahepatic Cholangiocarcinoma.

BACKGROUND: The benefit of chemotherapy for surgically resected intrahepatic cholangiocarcinoma (ICC) remains poorly defined. The present study sought to determine the survival impact of chemotherapy for surgically resected ICC. METHODS: Patients with non-metastatic ICC who underwent surgery were identified from the National Cancer Database (1998-2011) and stratified by receipt of chemotherapy. Survival outcomes were analyzed following propensity score modeling using the greedy matching algorithm. RESULTS: A total of 2751 patients were identified (median age 64 years); 985 (35.8 %) received chemotherapy. Younger age, advanced tumor stage, R1/R2 surgical margins, and lymph node metastasis were all independently associated with receipt of chemotherapy (p < 0.05). Following propensity score matching, advanced tumor stage, lymph node metastasis, poorly differentiated tumors, and R1/R2 surgical margins were associated with poorer overall survival (OS) (p < 0.05). Median OS comparing patients who received chemotherapy compared with surgery alone was 23 versus 20 months (p = 0.09). However, when stratified by lymph node status, chemotherapy demonstrated a significant improvement in median OS among N1 patients (19.8 vs. 10.7 months; p < 0.001). In contrast, patients with N0 disease derived no benefit from chemotherapy (29.4 vs. 29 months; p = 0.33). Additional tumor characteristics associated with improved survival with chemotherapy included T3/T4 tumors (21.3 vs. 15.6 months; p < 0.001) and R1/R2 surgical margins (19.5 vs. 11.6 months; p = 0.006). CONCLUSION: The use of chemotherapy was associated with a survival benefit only for ICC patients with nodal metastasis, advanced tumor stage, or an inadequate surgical resection. Chemotherapy for resected ICC should be strongly considered for tumors harboring high-risk features.

Is Hepatic Resection for Large or Multifocal Intrahepatic Cholangiocarcinoma Justified? Results from a Multi-Institutional Collaboration.

BACKGROUND: The role of surgical resection for patients with large or multifocal intrahepatic cholangiocarcinoma (ICC) remains unclear. This study evaluated the long-term outcome of patients who underwent hepatic resection for large (≥7 cm) or multifocal (≥2) ICC. METHODS: Between 1990 and 2013, 557 patients who underwent liver resection for ICC were identified from a multi-institutional database. Clinicopathologic characteristics, operative details, and long-term survival data were evaluated. RESULTS: Of the 557 patients, 215 (38.6 %) had a small, solitary ICC (group A) and 342 (61.4 %) had a large or multifocal ICC (group B). The patients in group B underwent an extended hepatectomy more frequently (16.9 vs. 30.4 %; P < 0.001). At the final pathology exam, the patients in group B were more likely to show evidence of vascular invasion (22.5 vs. 38.5 %), direct invasion of contiguous organs (6.5 vs. 12.9 %), and nodal metastasis (13.3 vs. 21.0 %) (all P < 0.05). Interestingly, the incidences of postoperative complications (39.3 vs. 46.8 %) and hospital mortality (1.1 vs. 3.7 %) were similar between the two groups (both P > 0.05). The group A patients had better rates for 5-year overall survival (OS) (30.5 vs. 18.7 %; P < 0.05) and disease-free survival (DFS) (22.6 vs. 8.2 %; P < 0.05) than the group B patients. For the patients in group B, the factors associated with a worse OS included more than three tumor nodules [hazard ratio (HR), 1.56], nodal metastasis (HR, 1.47), and poor differentiation (HR, 1.48). CONCLUSIONS: Liver resection can be performed safely for patients with large or multifocal ICC. The long-term outcome for these patients can be stratified on the basis of a prognostic score that includes tumor number, nodal metastasis, and poor differentiation.

Palliative care training in surgical oncology and hepatobiliary fellowships: a national survey of the fellows.

BACKGROUND: Surgical oncologists (SO) and hepatobiliary (HPB) surgeons frequently care for patients with advanced diseases near the end of life, yet little is known about their training, comfort, and readiness in the provision of palliative care. This study sought to assess the quality, adequacy, and extent of palliative care training and the readiness of SO and HPB fellows in delivering palliative care. METHODS: A self-administered survey was distributed to all fellows enrolled in Society of Surgical Oncology (SSO) and HPB fellowships during the 2013-2014 academic year. The survey assessed attitudes, training, experience, and readiness of fellows in caring for patients at the end of life. Descriptive analysis was performed, and Chi square, Student's t test, and the Mann-Whitney U test were used to compare mean or median values as appropriate. RESULTS: The response rate was 47.2 %, and 50.9 % of the fellows reported exposure to a palliative care specialty service during their fellowship. Of the study participants, 75 % observed their faculty discussing the side effects of surgery compared with 54 % who observed faculty communication with patients regarding end-of-life goals (p < 0.01). On the other hand, 40 % of the fellows were never observed by faculty discussing symptoms management, goals of care, or hospice referral with patients, and 56.7 % never received feedback on their palliative skills. CONCLUSION: The fellows rated the quality of their palliative care education as poor compared with other aspects of their fellowship training, implying the lack and need of palliative care teaching. Surgical oncology and HPB fellows and ultimately patients may benefit from increased clinical and didactic palliative care training.

Open versus minimally invasive resection of gastric GIST: a multi-institutional analysis of short- and long-term outcomes.

BACKGROUND: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Overall surgical experience with minimally invasive surgery (MIS) has increased; however, published reports on MIS resection of GIST are limited to small, single-institution experiences. METHODS: A total of 397 patients who underwent open surgery (n = 230) or MIS (n = 167) for a gastric GIST between 1998 and 2012 were identified from a multicenter database. The impact of MIS approach on recurrence and survival was analyzed using propensity-score matching by comparing clinicopathologic factors between patients who underwent MIS versus open resection. RESULTS: There were 19 conversions (10 %) to open; the most common reasons for conversion were tumor more extensive than anticipated (26 %) and unclear anatomy (21 %). On multivariate analysis, smaller tumor size and higher body mass index (BMI) were associated with receipt of MIS. In the propensity-matched cohort (n = 248), MIS resection was associated with decreased length of stay (MIS, 3 days vs open, 8 days) and fewer ≥ grade 3 complications (MIS, 3 % vs open, 14 %) compared with open surgery. High rates of R0 resection and low rates of tumor rupture were seen in both groups. After propensity-score matching, there was no difference in recurrence-free or overall survival comparing the MIS and the open group (both p > 0.05). CONCLUSIONS: An MIS approach for gastric GIST was associated with low morbidity and a high rate of R0 resection. The long-term oncological outcome following MIS was excellent, and therefore the MIS approach should be considered the preferred approach for gastric GIST in well-selected patients.

Cost effectiveness of routine laparoscopic ultrasound for assessment of resectability of gallbladder cancer.

BACKGROUND: In addition to a diagnostic laparoscopy (DL), a routine laparoscopic ultrasound (LUS) has been proposed to identify undetected hepatic metastases and/or anatomically advanced disease in patients with T2 or higher gall bladder cancer (GBC) patients planned for surgical resection. It was hypothesized that a routine LUS is not a cost-effective strategy for these patients. METHODS: Decision tree modeling was undertaken to compare DL-LUS vs. DL at the time of definitive resection of GBC (with no prior cholecystectomy). Costs in US dollars (payer's perspective), quality-adjusted life weeks (QALWs), and incremental cost-effectiveness ratios (ICER) were calculated (horizon: 6 weeks, willingness-to-pay: $1,000/QALW or $50,000/QALY). RESULTS: DL-LUS was cost effective at the base case scenario (costs: $30,838 for DL vs. $30,791 for DL-LUS and effectiveness 3.81 QALWs DL vs. 3.82 QALW DL-LUS), resulting in a cost reduction of $9,220 per quality-adjusted life week gained (or $479,469 per QALY). DL-LUS became less cost effective as the cost of ultrasound increased or the probability of exclusion from resection decreased. CONCLUSIONS: Routine LUS with DL for the assessment of resectability and exclusion of metastases is cost effective for patients with GBC. Until improvements in preoperative imaging occur to decrease the probability of exclusion, this appears to be a feasible strategy.

Review of the impact of antineoplastic therapies on the risk for cholelithiasis and acute cholecystitis.

BACKGROUND: Development of cholecystitis in patients with malignancies can potentially disrupt their treatment and alter prognosis. This review aims to identify antineoplastic interventions associated with increased risk of cholecystitis in cancer patients. METHODS: A comprehensive search strategy was developed to identify articles pertaining to risk factors and complications of cholecystitis in cancer patients. FDA-issued labels of novel antineoplastic drugs released after 2010 were hand-searched to identify more therapies associated with cholecystitis in nonpublished studies. RESULTS: Of an initial 2,932 articles, 124 were reviewed in the study. Postgastrectomy patients have a high (5-30 %) incidence of gallstone disease, and 1-7 % develop symptomatic disease. One randomized trial addressing the role of cholecystectomy concurrent with gastrectomy is currently underway. Among other risk groups, patients with neuroendocrine tumors treated with somatostatin analogs have a 15 % risk of cholelithiasis, and most are symptomatic. Hepatic artery based therapies carry a risk of cholecystitis (0.02-24 %), although the risk is reduced with selective catheterization. Myelosuppression related to chemotherapeutic agents (0.4 %), bone marrow transplantation, and treatment with novel multikinase inhibitors are associated with high risk of cholecystitis. CONCLUSIONS: There are several risk factors for gallbladder-related surgical emergencies in patients with advanced malignancies. Incidental cholecystectomy at index operation should be considered in patients planned for gastrectomy, and candidates for regional therapies to the liver or somatostatin analogs. While prophylactic cholecystectomy is currently recommended for patients with cholelithiasis receiving myeloablative therapy, this strategy may have value in patients treated with multikinase inhibitors, immunotherapy, and oncolytic viral therapy based on evolving evidence.

Surgical resection in hepatocellular carcinoma patients with minimal background fibrosis: a strategy in the era of organ shortage.

BACKGROUND: Surgical therapies for hepatocellular carcinoma (HCC) represent the potentially curative approaches and provide patients the greatest survival advantage. We sought to examine the outcomes of patients with HCC treated with surgical resection, transplantation, and local ablation. METHODS: The Surveillance, Epidemiology, and End Results database was queried for all patients with nonmetastatic HCC from 2004 to 2007 who underwent local ablation (LA), segmental resection (SR), hemihepatectomy or extended resection (ER), or transplantation (TP). RESULTS: Of 16,209 patients with HCC, 3,989 (24.6 %) met criteria for inclusion and received therapies: 1,550 LA (39 %), 703 SR (18 %), 619 ER (16 %), and 1,117 TP (28 %). AFP was elevated in 69 % (2,026 of 2,921), and fibrosis grade 0-4 was noted in 32 % (368 of 1,156). The 3-year survival by procedure was 34 % (LA), 50 % (SR), 54 % (ER), and 74 % (TP), p = .001. In patients with minimal fibrosis, 1-year survival for patients undergoing resection was similar to TP (85 vs. 92 %, p = .346), but greater than LA (69 %, p = .001). DISCUSSION: Survival after surgical resection for HCC patients without extensive fibrosis appears to be superior to ablation and non-inferior to transplantation. In an era of organ shortage, transplantation may be better reserved for patients with cirrhosis and/or unresectable disease.

Surgery versus intra-arterial therapy for neuroendocrine liver metastasis: a multicenter international analysis.

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.