Portal vein reconstruction during surgery for cholangiocarcinoma.

PURPOSE OF REVIEW: Complete surgical resection is the only curative-intent therapy for patients with hilar cholangiocarcinoma, and obtaining negative pathologic margins is crucial to allow for prolonged disease-free survival. Macrovascular tumor invasion adds technical complexity to surgical extirpation, but can be achieved with en bloc vessel resection. This tumor extension adversely affects overall prognosis, but is nonetheless technically feasible. RECENT FINDINGS: Several recent meta-analyses have studied the short and long-term results of concomitant vascular resection during surgery for hilar cholangiocarcinoma. There is little doubt that vascular resection (particularly arterial resection) has been associated with vascular complications and increased mortality. Although R0 rates are lower when vascular abutment is present, achieving an R0 resection consistently is correlated with improved survival. When portal vein resection is necessary, there does not appear to be a difference in disease-free outcome when tumor simply abuts the vein compared to when there is microscopic evidence of pathologic invasion. SUMMARY: When R0 resection of hilar cholangiocarcinoma demands en bloc removal and reconstruction of hilar vessels, perioperative risk may increase, but prognosis is improved. Heterogeneity in published reports still limits our knowledge in this area, and a proposal is made to clarify the extent of vascular reconstruction necessary in these operations for future study.

Implications of CA19-9 elevation for survival, staging, and treatment sequencing in intrahepatic cholangiocarcinoma: A national cohort analysis.

BACKGROUND: Optimal management of patients with intrahepatic cholangiocarcinoma (ICCA) and elevated CA19-9 remains undefined. We hypothesized CA19-9 elevation above normal indicates aggressive biology and that inclusion of CA19-9 would improve staging discrimination. METHODS: The National Cancer Data Base (NCDB-2010-2012) was reviewed for patients with ICCA and reported CA19-9. Patients were stratified by CA19-9 above/below normal reference range. Unadjusted Kaplan-Meier and adjusted Cox-proportional-hazards analysis of overall survival (OS) were performed. RESULTS: A total of 2,816 patients were included: 938 (33.3%) normal; 1,878 (66.7%) elevated CA19-9 levels. Demographic/pathologic and chemotherapy/radiation were similar between groups, but patients with elevated CA19-9 had more nodal metastases and less likely to undergo resection. Among elevated-CA19-9 patients, stage-specific survival was decreased in all stages. Resected patients with CA19-9 elevation had similar peri-operative outcomes but decreased long-term survival. In adjusted analysis, CA19-9 elevation independently predicted increased mortality with impact similar to node-positivity, positive-margin resection, and non-receipt of chemotherapy. Proposed staging system including CA19-9 improved survival discrimination over AJCC 7th edition. CONCLUSION: Elevated CA19-9 is an independent risk factor for mortality in ICCA similar in impact to nodal metastases and positive resection margins. Inclusion of CA19-9 in a proposed staging system increases discrimination. Multi-disciplinary therapy should be considered in patients with ICCA and CA19-9 elevation. J. Surg. Oncol. 2016;114:475-482. © 2016 Wiley Periodicals, Inc.

Mixed hepatocellular and cholangiocarcinoma: a rare tumor with a mix of parent phenotypic characteristics.

BACKGROUND: Intrahepatic lesions of mixed hepatocellular (HCC) and intrahepatic cholangiocellular carcinoma (ICC) histology are rare. The aim was to describe the natural history of these tumors relative to monomorphic ICC or HCC utilizing the National Cancer Data Base (NCDB). METHODS: Patients with ICC, HCC, and mixed histology (cHCC-CCA) were identified in the NCDB (2004-2012). Inter-group comparisons were made. Kaplan-Meier and multivariable Cox Proportional Hazards analyzed overall survival. RESULTS: The query identified 90,499 patients with HCC; 14,463 with ICC; and 1141 with cHCC-CCA histology. Patients with cHCC-CCA histology were relatively young (61 vs. 62 (HCC, p = 0.877) and 67 (ICC, p < 0.001) years) and more likely to have poorly differentiated tumor (29.2% vs. 10.3% (HCC) and 17.2% (ICC) p < 0.001). Median overall survival for cHCC-CCA was 7.9 months vs. 10.8 (HCC) and 8.2 (ICC, all p < 0.001). Stage-specific survival for mixed histology tumors was most similar to that of HCC for all stages. cHCC-CCA were transplanted at a relatively high rate, and transplant outcomes for mixed tumors were substantially worse than for HCC lesions. DISCUSSION: cHCC-CCA demonstrate stage-specific survival similar to HCC, but post-surgical survival more consistent with ICC. Patients with a pre-operative diagnosis of cHCC-CCA should undergo resection when appropriate.

Management of biliary cystic tumors: a multi-institutional analysis of a rare liver tumor.

OBJECTIVE: To characterize clinical and radiological features associated with biliary cystic tumors (BCTs) of the liver, and to define recurrence-free and overall survival. BACKGROUND: Biliary cystadenoma (BCA) and biliary cystadenocarcinoma (BCAC) are rare tumors that arise in the liver. METHODS: Between 1984 and 2013, 248 patients who underwent surgical resection of BCA or BCAC were identified. Clinical and outcome data were analyzed. RESULTS: Median total bilirubin, CA19-9, and carcinoembryonic antigen (CEA) levels were 0.6 mg/dL, 15.0 U/mL, and 2.7 ng/mL, respectively. Preoperative imaging included computed tomography only (62.5%), magnetic resonance imaging only (6.9%), or CT + MRI (18.5%). Features on cross-sectional imaging included multiloculation (56.9%), mural nodularity (16.5%), and biliary ductal dilatation (17.7%). The presence of these factors did not reliably predict BCAC versus BCA (sensitivity, 81%; specificity, 21%). Median biliary cyst size was 10.0 cm (interquartile range, 7-13 cm). Operative interventions included unroofing/partial excision of the lesion (14.1%), less than hemihepatectomy (48.8%), or hemi-/extended hepatectomy (36.3%). On pathology most lesions were BCA (89.1%), whereas 27 (10.9%) were BCAC. At last follow-up, there were 46 (18.3%) recurrences; 2 patients who initially had BCA recurred with BCAC. Median overall survival was 18.1 years; 1-year, 3-year, and 5-year survival was 95.0%, 86.8%, and 84.2%, respectively. Long-term outcomes were associated with BCAC versus BCA, as well as the presence of spindle cell/ovarian stroma (both P < 0.05). CONCLUSIONS: Among patients undergoing surgery for BCT, associated malignancy was uncommon (10%) and no preoperative findings reliably predicted underlying BCAC. After excision of BCA, long-term outcomes were good; however, patients with BCAC had a worse long-term prognosis.

Diagnostic laparoscopy should be performed before definitive resection for pancreatic cancer: a financial argument.

OBJECTIVES: Laparoscopy is recommended to detect radiographically occult metastases in patients with pancreatic cancer before curative resection. This study was conducted to test the hypothesis that diagnostic laparoscopy (DL) is cost-effective in patients undergoing curative resection with or without neoadjuvant therapy (NAT). METHODS: Decision tree modelling compared routine DL with exploratory laparotomy (ExLap) at the time of curative resection in resectable cancer treated with surgery first, (SF) and borderline resectable cancer treated with NAT. Costs (US$) from the payer's perspective, quality-adjusted life months (QALMs) and incremental cost-effectiveness ratios (ICERs) were calculated. Base case estimates and multi-way sensitivity analyses were performed. Willingness to pay (WtP) was US$4166/QALM (or US$50,000/quality-adjusted life year). RESULTS: Base case costs were US$34,921 for ExLap and US$33,442 for DL in SF patients, and US$39,633 for ExLap and US$39,713 for DL in NAT patients. Routine DL is the dominant (preferred) strategy in both treatment types: it allows for cost reductions of US$10,695/QALM in SF and US$4158/QALM in NAT patients. CONCLUSIONS: The present analysis supports the cost-effectiveness of routine DL before curative resection in pancreatic cancer patients treated with either SF or NAT.

Microwave ablation for hepatic malignancies: a multiinstitutional analysis.

OBJECTIVE: This study hypothesized that tumor size, number of tumors, surgical approach, and tumor histology significantly affected microwave ablation (MWA) success and recurrence-free survival. BACKGROUND: Although many hepatobiliary centers have adopted MWA, the factors that influence local control are not well described. METHODS: Consecutive patients with hepatic malignancy treated by MWA were included from 4 high-volume institutions (2003-2011) and grouped by histology: hepatocellular carcinoma (HCC), colorectal liver metastases, neuroendocrine liver metastases, and other cancers. Independent significance of outcome variables was established with logistic regression and Cox proportional hazards models. RESULTS: Four hundred fifty patients were treated with 473 procedures (139 HCC, 198 colorectal liver metastases, 61 neuroendocrine liver metastases, and 75 other) for a total of 875 tumors. Median follow-up was 18 months. Concurrent hepatectomy was performed in 178 patients (38%), and when performed was associated with greater morbidity. Complete ablation was confirmed for 839 of 865 tumors (97.0%) on follow-up cross-sectional imaging (10 were unevaluable). A surgical approach (open, laparoscopic, or percutaneous) had no significant impact on complication rates, recurrence, or survival. The local recurrence rate was 6.0% overall and was highest for HCC (10.1%, P = 0.045) and percutaneously treated lesions (14.1%, P = 0.014). In adjusted models, tumor size 3 cm or more predicted poorer recurrence-free survival (hazard ratio: 1.60, 95% CI: 1.02-2.50, P = 0.039). CONCLUSIONS: In this large data set, patients with 3 cm or more tumors showed a propensity for early recurrence, regardless of histology. Higher rates of local recurrence were noted in HCC patients, which may reflect underlying liver disease. There were no significant differences in morbidity or survival based on the surgical approach; however, local recurrence rates were highest for percutaneously ablated tumors.

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.

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.

Genomic profiling of intrahepatic cholangiocarcinoma: refining prognosis and identifying therapeutic targets.

BACKGROUND: The molecular alterations that drive tumorigenesis in intrahepatic cholangiocarcinoma (ICC) remain poorly defined. We sought to determine the incidence and prognostic significance of mutations associated with ICC among patients undergoing surgical resection. METHODS: Multiplexed mutational profiling was performed using nucleic acids that were extracted from 200 resected ICC tumor specimens from 7 centers. The frequency of mutations was ascertained and the effect on outcome was determined. RESULTS: The majority of patients (61.5 %) had no genetic mutation identified. Among the 77 patients (38.5 %) with a genetic mutation, only a small number of gene mutations were identified with a frequency of >5 %: IDH1 (15.5 %) and KRAS (8.6 %). Other genetic mutations were identified in very low frequency: BRAF (4.9 %), IDH2 (4.5 %), PIK3CA (4.3 %), NRAS (3.1 %), TP53 (2.5 %), MAP2K1 (1.9 %), CTNNB1 (0.6 %), and PTEN (0.6 %). Among patients with an IDH1-mutant tumor, approximately 7 % were associated with a concurrent PIK3CA gene mutation or a mutation in MAP2K1 (4 %). No concurrent mutations in IDH1 and KRAS were noted. Compared with ICC tumors that had no identified mutation, IDH1-mutant tumors were more often bilateral (odds ratio 2.75), while KRAS-mutant tumors were more likely to be associated with R1 margin (odds ratio 6.51) (both P < 0.05). Although clinicopathological features such as tumor number and nodal status were associated with survival, no specific mutation was associated with prognosis. CONCLUSIONS: Most somatic mutations in resected ICC tissue are found at low frequency, supporting a need for broad-based mutational profiling in these patients. IDH1 and KRAS were the most common mutations noted. Although certain mutations were associated with ICC clinicopathological features, mutational status did not seemingly affect long-term prognosis.

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.

Does histology predict outcome for malignant vascular tumors of the liver?

BACKGROUND AND OBJECTIVES: Malignant vascular tumors (MVT) of the liver are uncommon and poorly understood. We hypothesized that tumor histology is a predominant factor associated with survival in these tumors. METHODS: Patients with malignant histopathologic diagnoses of hepatic angiosarcoma (AS), hemangioendothelioma (HE) and its epithelioid variant (EHE), or hemangiopericytoma (HP) were identified using the SEER database (1973-2007). Overall survival (OS) was studied with Kaplan-Meier curves. RESULTS: We included 297 patients with MVT (207 AS, 28 HE, 56 EHE, 6 HP). All tumors demonstrated metastatic potential, although EHE and AS had the highest rate of regional or distant metastases (75% each). Patients with AS had the shortest median OS (1 month), however, those undergoing surgery had improved survival (6 months). Three patients with AS underwent liver transplant and lived for 11, 21, and 91 months each. Patients with EHE had the longest overall median survival of 75 months (30-183, P < 0.001). Surgical resection and transplant did not demonstrate an improvement in OS of patients with EHE in multivariable models. CONCLUSIONS: Histology is an important factor in determining survival for patients with hepatic MVT. Patients with EHE have the longest OS, whereas patients with AS have shorter survival but may benefit from surgery.

Multi-institutional analysis of recurrence and survival after hepatectomy for fibrolamellar carcinoma.

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.

Neutrophil-to-lymphocyte ratio as a predictor of outcomes for patients with hepatocellular carcinoma: a Western perspective.

BACKGROUND AND OBJECTIVES: Neutrophil-to-lymphocyte ratio (NLR) is simple, inexpensive, and has been proposed to be predictive in hepatocellular carcinoma (HCC) in Europe and Asia. We aimed to evaluate whether NLR at presentation in a Western center provides any prognostic value compared to other common prognostic scores. METHODS: NLR was calculated for 75 consecutive patients at presentation with HCC and regression models were used to analyze its value for predicting treatment strategy and short-term survival with Child-Pugh and Model for End Stage Liver Disease (MELD). RESULTS: NLR was not predictive of future treatment regimens with hepatectomy, liver transplant, or transarterial chemoembolization (TACE; odds ratio [OR]: 0.85, 95% confidence interval [CI]: 0.71-1.02, P = 0.079) as compared the predictive value of MELD (OR: 0.81, CI: 0.72-0.93, P = 0.002) or Child-Pugh (OR: 0.48, CI: 0.34-0.69, P < 0.001). Adding additional adjustment for treatment, NLR did not correlate with short-term overall survival (hazard ratio [HR]: 1.09, CI: 0.95-1.24, P = 0.227). MELD also did not correlate with overall survival (HR: 1.04, CI: 0.96-1.13, P = 0.357) whereas Child-Pugh (HR: 1.56, CI: 1.10-2.19, P = 0.011) was predictive. CONCLUSIONS: This study does not support the prognostic value of NLR to guide therapy for HCC in a Western center, whereas MELD and Child-Pugh score were more predictive.

Management of acute cholecystitis in cancer patients: a comparative effectiveness approach.

BACKGROUND: Host factors and therapy characteristics predispose cancer patients to a high risk of acute cholecystitis. Management of cholecystitis is often difficult given complex decision making involving the underlying cancer, possible interruption of treatment, and surgical fitness of the patient. METHODS: A management pathway was developed for cholecystitis in cancer patients which incorporated patient-specific survival and risks of recurrence. Estimates were obtained from a multistage systematic review. A decision tree with a lifetime horizon was constructed to compare conventional strategies [conservative treatment (CT), percutaneous cholecystostomy (PC) and definitive cholecystectomy (DC)] with the new pathway (NP). The decision tree was optimized for highest estimated survival. Sensitivity analyses were performed. RESULTS: In low surgical risk patients with cancer-specific survival of 12 months, the NP yielded estimated survivals of 11.9 versus 11.8 (CT) versus 11.8 (PC) versus 11.9 months for the DC arm. For high-risk patients, the estimated survival was 11.6 (NP), 9.9 (DC), 11.4 (PC), and 11 (CT) months, respectively. The decision to perform a DC at 6 weeks after a PC was optimum in patients expected to survive 24 months (23.2 months from the NP) or with a shorter expected survival but a high recurrence risk (>20 %). Model estimates were robust in sensitivity analyses. CONCLUSIONS: Incorporation of the surgical risk and the risk of recurrent cholecystitis, while balancing the patient-specific survival and the impact of antineoplastic therapy in the management of cholecystitis yields improved survival. This work provides measures to evaluate surgical judgment, and can augment the physician-patient decision making.

Hepatectomy for hemangioma; safe, but is it successful?

BACKGROUND/AIMS: Large hepatic hemangiomata may give rise to abdominal discomfort, prompting consultation with a hepatobiliary surgeon. The effectiveness of liver resection to treat such symptoms has varied in previously published reports. We sought to examine outcomes related to resection of hepatic hemangioma at a high-volume HPB center. METHODOLOGY: Consecutive patients between 1995-2011 undergoing resection for a hepatic hemangioma were identified. Demographic, operative, imaging, and complication-related data were collected. RESULTS: Fifty-four patients (41 female, 76%) underwent liver resection for hemangioma. Median age was 48 years (range: 25-80), and median lesion size was 8.0 cm (range: 1.6-25). Indications for resection included pain (28 patients, 52%), increasing size (9, 17%), patient anxiety (5, 9%), and inability to exclude malignancy (12, 22%). There were no perioperative deaths, and 16 patients (30%) had Clavien grade ≥II complications. Of the 28 patients with preoperative pain, 8 (28%) continued to report similar abdominal discomfort at a median follow-up of 10 months. CONCLUSIONS: Liver resection for hemangiomata can be performed safely, albeit with significant morbidity. The majority of patients,but not all, have pain relief following hepatic resection.A cautious approach should be taken when evaluating patients for hemangioma resection.

Ablation for hepatocellular carcinoma: validating the 3-cm breakpoint.

BACKGROUND: Although many previous studies on local ablation outcomes for hepatocellular carcinoma (HCC) have dichotomized tumor size with a 3-cm cutoff to determine prognostic significance, a growing number of reports describe excellent outcomes for larger tumors. To address the logic of this 3-cm cutoff beyond small single-center experiences, we stratified patients by 1-cm tumor size intervals and hypothesized that disease-specific survival (DSS) would not vary significantly between adjacent groups. METHODS: Patients treated with local ablation for T1 HCC (≤8 cm) were identified from the surveillance, epidemiology, and end results database (2004-2008). Log-rank tests and multivariable Cox proportional hazards models were used to compare DSS curves of adjacent study groups. RESULTS: There were 1,083 patients included in the study (26 % female, median age: 62 years). The 3-year DSS was significantly lower in patients with 3- to 4-cm tumors compared to 2- to 3-cm tumors (58 vs. 72 %, p = 0.002). In adjusted models, DSS did not vary significantly between any size intervals up to 3 cm. Patients with 3- to 4-cm tumors, however, had a poorer prognosis compared with patients with 2- to 3-cm tumors (hazard ratio: 1.6, 95 % confidence interval: 1.18-2.18, p = 0.002). DSS also fell when tumor size increased from 5-6 to 6-7 cm (53 vs. 21 %, 0.006). CONCLUSIONS: This study emphasizes the 3-cm size, and possibly the 6-cm size, as informative predictive thresholds when ablating HCC, because variability of DSS occurred specifically at these tumor sizes. Future research in this field should either adopt a 3-cm breakpoint or provide evidence for alternative thresholds.

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.

Transplantation versus resection for patients with combined hepatocellular carcinoma-cholangiocarcinoma.

BACKGROUND AND OBJECTIVES: Although transplantation has demonstrated survival benefit for patients with hepatocellular carcinoma (HCC), there is limited data to support or refute transplantation for combined hepatocellular-cholangiocarcinoma (cHCC-CC). We hypothesized that cHCC-CC patients had poorer overall survival (OS) than HCC patients after liver transplantation. METHODS: Patients with localized HCC and cHCC-CC treated with surgical resection or transplant were identified using the Surveillance, Epidemiology, and End Results (SEER) Database (1973-2007). Cox proportional hazards models were used to examine survival. RESULTS: We identified 3,378 (1,447 [43%] transplant, 1,931 [57%] resection) patients with HCC, and 54 (19 [35%] transplant, 35 [65%] resection) patients with cHCC-CC. Patients undergoing resection of HCC and cHCC-CC had similar 3-year OS (55% vs. 46%, P = 0.4). Three-year OS of patients undergoing transplant was significantly greater for HCC (78%) than for cHCC-CC (48%, P = 0.01). In adjusted models, patients transplanted for cHCC-CC had higher hazard of death compared to HCC patients (HR 2.5, 95% CI: 1.2-5.1, P = 0.01). CONCLUSIONS: Transplantation for localized cHCC-CC confers a survival benefit similar to liver resection for cHCC-CC, but inferior to transplantation for HCC. With survival data that mimics historic reports of transplant for intrahepatic cholangiocarcinoma, this study questions the benefit of transplantation for patients with cHCC-CC.

Management of primary hepatopancreatobiliary small cell carcinoma.

BACKGROUND AND OBJECTIVES: Primary small cell carcinomas (SCC) of the pancreas, liver, gallbladder, and bile ducts have only been described in case reports. We hypothesized that surgical treatment was associated with improved overall survival (OS) for patients with localized hepatopancreatobiliary SCC. METHODS: The Surveillance, Epidemiology, and End-Results (SEER) database was queried for patients with SCC from 1998 to 2008. Survival was analyzed with Cox proportional hazards models. RESULTS: Eighty-five patients had nonmetastatic hepatopancreatobiliary SCC and operative treatment data. Hepatic SCC was associated with a 2 month median OS, and no patient underwent surgery. Stage-adjusted median OS for pancreatobiliary SCC patients undergoing resection (19 months, 95% confidence interval [CI]: 10-42 months) was greater than those who were not resected (8 months, 95% CI: 4-12 months, P = 0.0052). Both surgical resection (hazard ratio [HR]: 0.42, 95% CI: 0.29-0.63, P < 0.001) and administration of radiation therapy (HR: 0.50, 95% CI: 0.35-0.71, P < 0.001) independently predicted prolonged OS in adjusted models. CONCLUSION: Surgical resection was associated with prolonged survival for patients with localized pancreatic, gallbladder, and biliary primaries. While we recognize several biases inherent in a population-based study, these results provide insight into the survival that can be achieved with surgical resection of SCC in these specific locations.

Key factors influencing prognosis in relation to gallbladder cancer.

INTRODUCTION: The 5-year survival of patients with gallbladder cancer remains low. However, patients can be stratified into prognostic categories based on established factors such as T, N, and R status. New concepts regarding prognostic significance of lymph node disease, the importance of residual gallbladder fossa disease, and the gravity of presentation with jaundice are reviewed. In addition, a number of new prognostic factors proposed in recent years are considered. METHODS: PubMed was searched for "gallbladder cancer" with builder "date-completion" 2008 to present. A total of 1,490 articles were screened from which 168 were retrieved. From this, 40 articles specifically related to prognosis form the basis for this review. DISCUSSION: Key factors of prognostic significance remain T and N stage and R0 resection. Residual disease either in the gallbladder fossa, lymph nodes, or cystic duct margin dictates hepatectomy, lymphadenectomy and bile duct resection, respectively. Adequate lymphadenectomy requires removal of six nodes, and hepatectomy must be sufficient to achieve R0. Subtleties regarding lymph node ratio, significance of pathological features such as dedifferentiation, and budding may hold value for stratifying patients with early stage disease, but require further investigation.