Actual 10-year survival after hepatic resection of colorectal liver metastases: what factors preclude cure?

BACKGROUND: Hepatic resection of colorectal liver metastases is associated with long-term survival. This study analyzes actual 10-year survivors after resection of colorectal liver metastases, reports the observed rate of cure, and identifies factors that preclude cure. METHODS: A single-institution, prospectively maintained database was queried for all initial resections for colorectal liver metastases for the years 1992-2004. Observed cure was defined as actual 10-year survival with either no recurrence or resected recurrence with at least 3 years of disease-free follow-up. Clinical risk score was dichotomized into low (0-2) and high (3-5). Semiparametric proportional hazards mixture cure model was utilized to estimate probability of cure. RESULTS: We included 1,211 patients with a median follow-up for survivors of 11 years. Median disease-specific survival was 4.9 years (95% CI: 4.4-5.3). 295 patients (24.4%) were actual 10-year survivors. The observed cure rate was 20.6% (n = 250). Among 250 cured patients, 192 (76.8%) had no recurrence and 58 (23.2%) had a resected recurrence with at least 3 years of disease-free follow-up. Extrahepatic disease (n = 88), carcinoembryonic antigen >200 ng/mL (n = 119), positive margin (n = 109), and >10 tumors (n = 31) had observed cure rates less than 10%. In cure model analysis, patients with both extrahepatic disease and high clinical risk score (n = 31) had an estimated probability of cure of 3.5%. CONCLUSION: Actual 10-year survival after resection of colorectal liver metastases is 24% with an observed 20% cure rate. Patients with both high clinical risk score and extrahepatic disease have an estimated probability of cure less than 5%. When such factors are identified, strong consideration may be given to preoperative strategies, such as neoadjuvant chemotherapy, to help select patients for surgical therapy.

Recurrence Rate and Pattern of Perihilar Cholangiocarcinoma after Curative Intent Resection.

BACKGROUND: The aim of this study was to investigate the rate and pattern of recurrence after curative intent resection of perihilar cholangiocarcinoma (PHC). STUDY DESIGN: Patients were included from 2 prospectively maintained databases. Recurrences were categorized by site. Time to recurrence and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method. Cox proportional hazards modeling was used to identify independent poor prognostic factors. RESULTS: Between 1991 and 2012, 306 consecutive patients met inclusion criteria. Median overall survival was 40 months. A recurrence was diagnosed in 177 patients (58%). An initial local recurrence was found in 26% of patients: liver hilum (11%), hepaticojejunostomy (8%), liver resection margin (8%), or distal bile duct remnant (2%). An initial distant recurrence was observed in 40% of patients: retroperitoneal lymph nodes (14%), intrahepatic away from the resection margin (13%), peritoneum (12%), and lungs (8%). Only 18% of patients had an isolated initial local recurrence. The estimated overall recurrence rate was 76% at 8 years. After a recurrence-free period of 5 years, 28% of patients developed a recurrence in the next 3 years. Median RFS was 26 months. Independent prognostic factors for RFS were resection margin, lymph node status, and tumor differentiation. Only node-positive PHC precluded RFS beyond 7 years. CONCLUSIONS: Perihilar cholangiocarcinoma will recur in most patients (76%) after resection, emphasizing the need for better adjuvant strategies. The high recurrence rate of up to 8 years justifies prolonged surveillance. Only patients with an isolated initial local recurrence (18%) may have benefited from a more extensive resection or liver transplantation. Node-positive PHC appears incurable.

Resection margin and survival in 2368 patients undergoing hepatic resection for metastatic colorectal cancer: surgical technique or biologic surrogate?

OBJECTIVES: The impact of margin width on overall survival (OS) in the context of other prognostic factors after resection for colorectal liver metastases is unclear. We evaluated the relationship between resection margin and OS utilizing high-resolution histologic distance measurements. METHODS: A single-institution prospectively maintained database was queried for all patients who underwent an initial complete resection of colorectal liver metastases between 1992 and 2012. R1 resection was defined as tumor cells at the resection margin (0 mm). R0 resection was further divided into 3 groups: 0.1 to 0.9 mm, 1 to 9 mm, and 10 mm or greater. RESULTS: A total of 4915 liver resections were performed at Memorial Sloan Kettering Cancer Center between 1992 and 2012, from which 2368 patients were included in the current study. Half of the patients presented with synchronous disease, 43% had solitary metastasis, and the median tumor size was 3.4 cm. With a median follow-up for survivors of 55 months, the median OS of the R1, 0.1 to 0.9 mm, 1 to 9 mm, and 10 mm or more groups was 32, 40, 53, and 56 months, respectively (P < 0.001). Compared with R1 resection, all margin widths, including submillimeter margins correlated with prolonged OS (P < 0.05). The association between the margin width and OS remained significant when adjusted for all other clinicopathologic prognostic factors. CONCLUSIONS: Resection margin width is independently associated with OS. Wide margins should be attempted whenever possible. However, resection should not be precluded if narrow margins are anticipated, as submillimeter margin clearance is associated with improved survival. The prolonged OS observed with submillimeter margins is likely a microscopic surrogate for the biologic behavior of a tumor rather than the result of surgical technique.

Hepatic parenchymal preservation surgery: decreasing morbidity and mortality rates in 4,152 resections for malignancy.

BACKGROUND: Liver resection is used to treat primary and secondary malignancies. Historically, these procedures were associated with significant complications, which may affect cancer-specific outcomes. This study analyzed the changes in morbidity and mortality after hepatic resection over time. STUDY DESIGN: Records of all patients undergoing liver resection for a malignant diagnosis from 1993 to 2012 at Memorial Sloan Kettering were analyzed. Patients were divided into early (1993 to 1999), middle (2000 to 2006), and recent (2007 to 2012) eras. Major hepatectomy was defined as resection of 3 or more segments. Univariate and multivariate analyses were made with t-tests or Mann-Whitney tests. RESULTS: There were 3,875 patients who underwent 4,152 resections for malignancy. The most common diagnosis was metastatic colorectal cancer (n = 2,476, 64% of patients). Over the study period, 90-day mortality rate decreased from 5% to 1.6% (p < 0.001). Perioperative morbidity decreased from 53% to 20% (p < 0.001). The percentage of major hepatectomies decreased from 66% to 36% (p < 0.001). The rate of perioperative transfusion decreased from 51% to 21% (p < 0.001). The spectrum of perioperative morbidity changed markedly over time, with abdominal infections (43% of complications) overtaking cardiopulmonary complications (22% of complications). Peak postoperative bilirubin (odds ratio [OR] 1.1, p < 0.001), blood loss (OR 1.5, p = 0.001), major hepatectomy (OR 1.3, p = 0.031), and concurrent partial colectomy (OR 2.4, p < 0.001) were independent predictors of perioperative morbidity. The mortality associated with trisectionectomy (6%) and right hepatectomy (3%) remained unchanged over time. CONCLUSIONS: Morbidity and mortality rates after partial hepatectomy for cancer have decreased substantially as the major hepatectomy rate has dropped. Encouraging parenchymal preservation and preventing abdominal infections are vital for continued improvement of liver resection outcomes.

Genetic evidence that intratumoral T-cell proliferation and activation are associated with recurrence and survival in patients with resected colorectal liver metastases.

Though immune responses correlate with prognosis in primary colorectal cancer, the role of tumor immunity in metastatic disease is less clear. We hypothesized that patient survival and tumor recurrence correlate with transcriptional evidence of lymphocyte proliferation/activation in resected colorectal cancer liver metastases (CRLM). Microarray gene analysis was performed on liver tumor specimens from 96 patients who underwent resection for CRLM. A Cox proportional hazards model identified genes associated with overall survival (OS) and recurrence-free survival (RFS). Conventional gene ontology (GO) enrichment analysis ranked biologically relevant processes. Survival probabilities of prioritized processes were assessed. Protein expression was validated with immunohistochemistry in an independent set of patients. GO analysis identified and ranked unique biologic processes that correlated with survival. Genes that specifically functioned in the biologic process of "T-cell proliferation" were significant predictors of OS (P = 0.01), and both "T-cell proliferation" and "activation" were highly associated with RFS (P ≤ 0.01). Analysis of genes in these GO categories identified increased TNFSF14/LIGHT expression to be most associated with improved OS and RFS (P ≤ 0.0006). Immunohistochemistry of an independent validation set of CRLM confirmed that both increased tumor-infiltrating lymphocytes (TIL) and higher LIGHT expression on TILs were associated with improved OS and RFS. Differential expression of genes involved in T-cell proliferation/activation was associated with survival outcomes in a large number of surgical patients who underwent resection of CRLM. These biologic functions determined by GO analysis of the tumor microenvironment have identified specific immune-related genes that may be involved in an antitumor immune response.

Timing of elective surgery as a perioperative outcome variable: analysis of pancreaticoduodenectomy.

OBJECTIVES: The timing of major elective operations is a potentially important but rarely examined outcome variable. This study examined elective pancreaticoduodenectomy (PD) timing as a perioperative outcome variable. METHODS: Consecutive patients submitted to PD were identified. Determinants of 90-day morbidity (prospectively graded and tracked), anastomotic leak or fistula, and mortality, including operation start time (time of day), day of week and month, were assessed in univariate and multivariate analyses. Operation start time was analysed as a continuous and a categorical variable. RESULTS: Of the 819 patients identified, 405 (49.5%) experienced one or more complications (total number of events = 684); 90-day mortality was 3.5%. On multivariate analysis, predictors of any morbidity included male gender (P = 0.009) and estimated blood loss (P = 0.017). Male gender (P = 0.002), benign diagnosis (P = 0.002), presence of comorbidities (P = 0.002), American Society of Anesthesiologists (ASA) score (P = 0.025), larger tumour size (P = 0.013) and positive resection margin status (P = 0.005) were associated with the occurrence of anastomotic leak or fistula. Cardiac and pulmonary comorbidities were the only variables associated with 90-day mortality. Variables pertaining to procedure scheduling were not associated with perioperative morbidity or mortality. Operation start time was not significant when analysed as a continuous or a categorical variable, or when stratified by surgeon. CONCLUSIONS: Perioperative outcome after PD is determined by patient, disease and operative factors and does not appear to be influenced by procedure timing.

Comparison between perioperative and postoperative chemotherapy after potentially curative hepatic resection for metastatic colorectal cancer.

BACKGROUND: Additional chemotherapy in patients with resectable colorectal liver metastases (CRLM) likely improves outcomes. Whether to administer chemotherapy as perioperative or adjuvant therapy remains controversial. We analyzed outcomes between these two treatment strategies. METHODS: Patients were identified from a prospective CRLM database and studied retrospectively. Patients with extrahepatic disease or initially unresectable CRLM were excluded. Only patients receiving oxaliplatin- and/or irinotecan-containing chemotherapy regimens were included. Univariate and Cox regression models were developed for recurrence and death. RESULTS: Between 1998 and 2007, 236 patients (57.4 %) in the adjuvant group and 175 patients (42.6 %) in the perioperative group were compared. The perioperative group was younger and had more tumors, shorter disease-free intervals, and higher clinical risk scores (CRS), but had smaller tumors. The overall survival was similar between the groups (perioperative 72.9 months vs. adjuvant 71.5 months; p = 0.48). When the comparison was adjusted for other clinicopathologic factors and CRS, the differences remained insignificant. On univariate analysis, there was a significant difference in recurrence-free survival between the groups (perioperative 17.2 months vs. adjuvant 27.4 months, p = 0.036). However, when the recurrence-free survival was adjusted for other clinicopathologic factors and the CRS, differences were not significant. CONCLUSIONS: The timing of additional chemotherapy for resectable CRLM is not associated with outcomes. Trials comparing adjuvant and perioperative chemotherapy would have to be powered for small differences in outcome.

Vascular inflow control during hemi-hepatectomy: a comparison between intrahepatic pedicle ligation and extrahepatic vascular ligation.

BACKGROUND: Intrahepatic pedicle ligation (IPL) is an alternative to extrahepatic portal dissection (EPD). Although IPL has been well described, concern has arisen over a possible association with increased complication rates. METHODS: Patients who underwent hemi-hepatectomy during January 1995 to December 2010 were reviewed and the inflow control technique (IPL versus EPD) documented. Patient, tumour, treatment and outcome variables were compared. RESULTS: A total of 798 patients underwent hemi-hepatectomy, 568 (71.2%) of the right and 230 (28.8%) of the left liver. In univariate analysis, factors associated with the choice of IPL included surgeon, right hepatectomy, preoperative portal vein embolization, diagnosis of colorectal cancer liver metastasis, and smaller tumour size (P < 0.011). In multivariate analysis, right hepatectomy [versus left: hazard ratio (HR) 3.878, 95% confidence interval (CI) 1.15-13.14; P = 0.029] and smaller tumour size (median of 4.5 cm versus 5.5 cm: HR 0.72, 95% CI 0.59-0.88; P = 0.002) were associated with IPL. Pringle manoeuvre time was longer in IPL procedures (40 min versus 29 min; P < 0.001). Complication rates (49.8% in IPL versus 48.4% in EPD; P = 0.706) were similar in both groups, as was the severity of complications; 17.6% of EPD and 22.3% of IPL patients experienced complications of grade ≥3 (P = 0.225). CONCLUSIONS: Patients with small tumours undergoing right hepatectomy were more likely to undergo IPL. In selected patients, IPL was not associated with an increased complication rate and thus it should be considered a safe approach.

Hepatic pedicle clamping during hepatic resection for colorectal liver metastases: no impact on survival or hepatic recurrence.

BACKGROUND: Hepatic pedicle clamping is often used during liver resection. While its use reduces blood loss and transfusion requirements, the long-term effect on survival and recurrence has been debated. This study evaluates the effect of hepatic pedicle clamping [i.e., Pringle maneuver (PM)] on survival and recurrence following hepatic resection for colorectal liver metastasis (CRLM). METHODS: Patients who underwent R0 resection for CRLM from 1991 to 2004 were identified from a prospectively maintained database. Operative, perioperative, and clinicopathological variables were analyzed. The primary outcomes were disease-free survival (DFS) and liver recurrence (LR). Disease extent was categorized using a well-defined clinical risk score (CRS). Subgroup analysis was performed for patients given preoperative systemic chemotherapy and postoperative pump chemotherapy. RESULTS: This study included 928 consecutive patients with median follow-up of 8.9 years. PM was utilized in 874 (94%) patients, with median time of 35 min (range 1-181 min). On univariate analysis, only resection type (p<0.001) and tumor number (p=0.002) were associated with use of PM. Younger age (p=0.006), longer operative time (p<0.001), and multiple tumors (p=0.006) were associated with prolonged PM (>60 min). There was no association between DFS, overall survival (OS) or LR and Pringle time. Neither the CRS nor use of neoadjuvant therapy stratified disease-related outcome with respect to use of PM. CONCLUSIONS: PM was used in most patients undergoing resection for CRLM and did not adversely influence intrahepatic recurrence, DFS, or OS.

Resection of adrenocortical carcinoma liver metastasis: is it justified?

BACKGROUND: Adrenocortical carcinoma (ACC) liver metastases (LM) represent a therapeutic challenge, and it is unclear whether resection is justified. This study assesses long-term outcome and prognostic factors after liver resection for metastatic ACC. METHODS: Patients who underwent resection of ACC LM were identified from institutional databases. Recurrence, survival, and tumor characteristics, including ß-catenin and TP53 status based on immunohistochemistry and sequencing, were reviewed. The prognostic value of variables was assessed with log-rank test for univariate analysis and Cox proportional hazard models for multivariate analysis. RESULTS: From 1978 to 2009, 28 patients (20 females; median age, 45 years), including 11 with synchronous metastasis and 3 with extrahepatic metastasis, underwent resection for ACC LM (major hepatectomy in 61%). Postoperative mortality was nil and morbidity 55%. On pathological examination, tumors were multiple in 68%, with a median size of 43 mm, and resections were R0, 1, and 2 in 59%, 33%, and 7%, respectively. All 28 patients developed recurrent disease, which was treated surgically in 11, including repeat hepatectomy in 4. Of the 15 patients with adequate tissue for analysis, ß-catenin immunostaining was positive in 7, with 4 corresponding CTNNB1 mutations associated with decreased survival; p53 staining was positive in 5 (4 with corresponding TP53 mutations). The median disease-free and overall survival after hepatectomy was 7 and 31.5 months, respectively, with a 5-year survival of 39%. In multivariate analysis, nonfunctional tumor and surgical treatment of recurrence were independent predictors of good outcome. CONCLUSIONS: In selected patients with ACC LM, resection is associated with long-term survival and is, therefore, justified but rarely curative.

Improving the clinical risk score: an analysis of molecular biomarkers in the era of modern chemotherapy for resectable hepatic colorectal cancer metastases.

BACKGROUND: The prognostic relevance of variations in expression of specific tumor genes in colorectal cancer liver metastases (CRCLMs) in patients treated with resection and modern chemotherapy is not known. METHODS: Patients submitted to liver resection for CRCLM between January 2000 and October 2007 were studied. A clinical risk score (CRS; range, 0-5) was calculated for each patient. RNA was extracted from histologically confirmed tumor isolates, and using real-time polymerase chain reaction (PCR) studies, we assessed the quantitative expression of 12 genes with potential importance in chemotherapy resistance and tumor progression, including thymidylate synthase (TS; 5-fluorouracil), excision repair cross complementing gene-1, and xeroderma pigmentosum groups A through G (oxaliplatin), topoisomerase-I (irinotecan), c-met, and hepatocyte growth factor. Primary outcomes were recurrence-free survival (RFS) and disease-specific survival (DSS) after hepatic resection. RESULTS: One-hundred fifty-five patients with good quality tumor mRNA were identified. Median follow-up was 32 months for survivors, and the median CRS was 2. Eighty-seven patients (56%) received preoperative chemotherapy, and 124 (80%) received postoperative chemotherapy. Median RFS for all patients was 13 months, and 3-year DSS was 69%. Median RFS and 3-year DSS for patients with an increased CRS (3-5) was lower (7 vs 18 months [P < .0001] and 50% vs. 80% [P < .0001], respectively). Of the 12 genes studied, only increased TS expression was associated with a lower RFS (hazard ratio, 1.16; 95% confidence interval, 1.0-1.3; P = .03) and DSS (hazard ratio, 1.25; 95% confidence interval, 1.0-1.5; P = .03). Median RFS and 3-year DSS for patients with increased TS expression was decreased (9 vs. 15 months [P = .03] and 48% vs. 82% [P = .001], respectively). TS expression had prognostic value that was independent of CRS on multivariate analysis. CONCLUSION: In patients with hepatic CRCLM treated with resection and modern chemotherapy, increased expression of TS improves outcome stratification and appears to be a useful biomarker.

Biliary sclerosis after hepatic arterial infusion pump chemotherapy for patients with colorectal cancer liver metastasis: incidence, clinical features, and risk factors.

BACKGROUND: Hepatic arterial infusion pump chemotherapy (HAIPC) contributes to the prolonged survival of selected patients with colorectal cancer liver metastases (CRCLM). The most clinically important adverse event after HAIPC with floxuridine (FUDR) is biliary sclerosis (BS). Little is known about the etiology of BS. METHODS: HAIPC was administered to 475 consecutive patients who received HAIPC on prospective protocols from 1991 to 2008. The incidence, clinical features, variables related to demographics, comorbidity, medical history, CRCLM, surgery, chemotherapy, and laboratory data were reviewed. An analysis of factors potentially associated with BS, defined as a biliary stricture related to HAIPC requiring stent placement, was performed. RESULTS: The incidence of BS was 5.5% (16 of 293) in patients receiving HAIPC as an adjuvant therapy after hepatectomy, and 2% (2 of 100) in patients receiving HAIPC with FUDR for unresectable disease. The common hepatic duct was the site most frequently affected (87.5%). In patients receiving adjuvant HAIPC, BS was associated with abnormal postoperative flow scans (18.8% vs. 1.8%, P = 0.006), postoperative infectious complications (50.0% vs. 14.8%, P = 0.002), and larger dose/cycle/weight of FUDR (2.6 vs. 2.0 mg/cycle/kg, P = 0.025) than patients without BS. No patient died directly of BS. Median survival was not compromised by the development of BS (BS vs. non-BS: 61.0 months [range 6.2-171.6 months] vs. 47.2 months [range 2.4-200.8 months], P = 0.316, respectively). CONCLUSIONS: BS is an uncommon complication after HAIPC and does not compromise survival if adequately salvaged by stenting or dilatation. Surgical complications as well as type and dose of intra-arterial chemotherapy may contribute to the development of BS.

Comparison of adjuvant systemic chemotherapy with or without hepatic arterial infusional chemotherapy after hepatic resection for metastatic colorectal cancer.

BACKGROUND: The potential benefit of adjuvant hepatic arterial infusional floxuridine (HAI-FUDR) in addition to modern systemic chemotherapy using oxaliplatin or irinotecan remains unknown for patients with resected liver-confined colorectal metastases (CRLM). The principle aim of this study was to compare outcomes in patients receiving modern systemic chemotherapy with or without HAI-FUDR. METHODS: Between 2000 and 2005, 125 patients underwent resection of CRLM followed by adjuvant HAI-FUDR plus dexamethasone (Dex) and concurrent systemic chemotherapy including oxaliplatin or irinotecan. These patients were compared retrospectively to 125 consecutive patients who received modern systemic chemotherapy alone after liver resection. RESULTS: The median follow-up for all patients was 43 months. There were no differences in clinical risk score, disease-free interval, size of largest CRLM, number of CRLM, or prehepatectomy CEA level between the 2 groups. Adjuvant HAI-FUDR was associated with an improved overall and liver recurrence-free survival (liver RFS) and disease-specific survival (DSS). For the adjuvant HAI-FUDR group, the 5-year liver RFS, overall RFS, and DSS were 75%, 48%, and 79%, respectively, compared to 55%, 25%, and 55% for the systemic alone group (P < 0.01). On multivariate analysis, adjuvant treatment including HAI-FUDR was independently associated with improved liver RFS (HR = 0.34), overall RFS (HR = 0.65), and DSS (HR = 0.39), P < 0.01. CONCLUSIONS: Adjuvant HAI-FUDR combined with modern systemic chemotherapy is independently associated with improved survival compared to adjuvant systemic chemotherapy alone. A randomized clinical trial between these 2 regimens is justified.

The role of laparoscopic staging in patients with incidental gallbladder cancer.

BACKGROUND: The role of staging laparoscopy (SL) in patients with incidental gallbladder cancer (IGBC) is ill defined. This study evaluates the utility of SL with the aim of identifying variables associated with disseminated disease (DD). METHODS: Consecutive patients with IGBC who underwent re-exploration between 1998 and 2009 were identified from a prospective database. The yield and accuracy of SL were calculated. Demographics, tumour- and treatment-related variables were correlated with findings of DD. RESULTS: Of the 136 patients submitted to re-exploration for possible definitive resection, 19 (14.0%) had DD. Staging laparoscopy was carried out in 46 (33.8%) patients, of whom 10 (21.8%) had DD (peritoneal disease [n = 6], liver metastases [n = 3], retroperitoneal disease [n = 1]). Disseminated disease was identified by SL in two patients (yield = 4.3%), whereas eight were diagnosed after conversion to laparotomy (accuracy = 20.0%). The likelihood of DD correlated closely with T-stage (T1b, n = 0; T2, n = 5 [7.0%], T3, n = 14 [26.0%]; P = 0.004). A positive margin at initial cholecystectomy (odds ratio [OR] 5.44, 95% confidence interval [CI] 1.51-24.37; P = 0.004) and tumour differentiation (OR 7.64, 95% CI 1.1-NA; P= 0.006) were independent predictors of DD on multivariate analysis. DISCUSSION: Disseminated disease is relatively uncommon in patients with IGBC and SL provides a very low yield. However, patients with poorly differentiated, T3 or positive-margin gallbladder tumours are at high risk for DD and targeting these patients may increase the yield of SL.

Accurate staging for gallbladder cancer: implications for surgical therapy and pathological assessment.

BACKGROUND: This study evaluates the significance of tumor involvement of the liver in early T-stage tumors and lymph node (LN) metastases on outcome after R0 resection of gallbladder cancer (GBCA). METHODS: A prospectively maintained database, supplemented with review of the medical record, was used to identify patients who underwent a complete (R0) resection for GBCA. All patients underwent definitive surgical treatment at the initial operation (1 stage) or after initial noncurative cholecystectomy (incidental tumors, 2 stage), including partial hepatectomy and portal LN dissection, with or without bile duct and/or adjacent organ resection. Clinicopathological variables, including TNM stage, histologic tumor involvement of liver (residual or direct extension in the GB fossa or discontiguous disease), and the total number of regional LNs assessed were analyzed for their association with outcome. RESULTS: One hundred twenty-two patients were identified and analyzed. The median follow up period was 23 months. Liver and nodal involvement by GBCA were observed in 61 (50%) and 41(34%) patients, respectively. Among patients with T2 tumors (n = 53), 48 (91%) were incidental. Liver involvement was present in 26%, and this factor was associated with decreased recurrence-free (RFS) and disease-specific survival (DSS) compared with patients with T2 tumors without liver involvement (median RFS, 12 months vs. not reached, P = 0.004, median DSS 25 months versus not reached, P = 0.003); T1b tumors (n = 10) were not associated with liver involvement. The median total lymph node count (TLNC) was 3 (range 0-20). For the entire cohort, survival of patients classified as N0 based on TLNC < 6 was significantly worse than that of N0 patients based on TLNC ≥ 6 (median RFS, 22 months versus not reached, P < 0.001, median DSS 41 months versus not reached, P < 0.001). Liver involvement and TLNC remained significant prognostic factors in a multivariate model that included TNM stage. CONCLUSION: Resection and histologic evaluation of at least 6 lymph nodes improves risk-stratification after resection of GBCA. Incidental T2 tumors are often associated with residual liver disease and should be reclassified to reflect the adverse outcome. The data suggests a need for standardized minimum requirements for adequate surgical treatment and pathological examination.

Use of intraoperative ablation as an adjunct to surgical resection in the treatment of recurrent colorectal liver metastases.

OBJECTIVE: To evaluate the role of intraoperative ablation as an adjunct to resection in patients with recurrent colorectal liver metastases (rCLM). METHODS: All patients undergoing curative-intent reoperative surgery for rCLM from 1992 to 2009 at a tertiary cancer center were included. Overall survival (OS) and recurrence-free survival (RFS) were compared between patients treated with resection alone or in combination with ablation. RESULTS: A total of 112 reoperative hepatectomies were performed, of which 16 were combined with ablation. The proportion of patients treated with resection and ablation increased from 0% to 41%. Patients undergoing resection and ablation had a greater tumor burden (median, 4 vs. 1, p < 0.0001) and higher baseline clinical risk scores (median, 3 vs. 2, p = 0.065) than patients undergoing resection alone. Patients undergoing resection and ablation had lower intraoperative blood loss than patients undergoing resection alone (344 vs. 877 ml, p = 0.018). Five-year OS from the time of surgery was 48.6%. In multivariable analysis, there was no significant difference in OS or RFS based on the treatment modality. CONCLUSION: In patients with rCLM, the use of intraoperative ablation can extend the limits of surgical resection in patients with disease that might otherwise not be amenable to complete resection.

Comparative analysis of outcome in patients with hepatocellular carcinoma exceeding the milan criteria treated with liver transplantation versus partial hepatectomy.

INTRODUCTION: Proponents of orthotopic liver transplantation (TXP) for the treatment of hepatocellular carcinoma (HCC) advocate expanding the Milan criteria. We performed a matched analysis comparing patients treated with TXP to patients treated with partial hepatectomy (PHX) for HCC exceeding the Milan criteria. METHODS: From the United Network for Organ Sharing registry, we identified 92 US patients with HCC exceeding the Milan criteria who underwent TXP between 2002 and 2005. During the same period, 94 patients with similar tumor size criteria underwent PHX at a single center. Data were analyzed using χ(2), parametric, nonparametric, and Kaplan-Meier methods. RESULTS: TXP patients were more commonly male (82% vs. 65%, P=0.01) and had a higher Model for End Stage Liver Disease score (median 11 vs. 7, P<0.001). Pathologic cirrhosis (79% TXP vs. 38% PHX, P<0.001), particularly secondary to hepatitis C virus (29% TXP vs. 5% PHX, P<0.001), was more common among TXP patients. Mean cumulative tumor size was 10.0 cm (63% exceeding University of California at San Francisco criteria) among PHX patients compared with 6.4 cm (20% exceeding University of California at San Francisco criteria) for TXP patients (P<0.001). With a median follow-up of 34 months (range, 1-86), 3-year survival was similar between the cohorts (66%±10% for TXP vs. 66%±10% for PHX, P=0.97). Cancer deaths (26/37, 70%) were more prevalent among PHX patients, whereas noncancer deaths (25/37, 68%) were common in TXP patients (P<0.001). CONCLUSIONS: Among heterogeneous patients with HCC who exceed the Milan criteria, TXP and PHX achieve similar overall survival. Further study is needed to ensure appropriate patient selection for these disparate therapies.

Effect on outcome of recurrence patterns after hepatectomy for colorectal metastases.

BACKGROUND: Despite improvements in surgery and chemotherapy, most patients develop recurrence after hepatectomy for metastatic colorectal cancer. Data are lacking on the effect of these patterns on outcome. METHODS: A retrospective review of a prospectively maintained hepatobiliary database was performed. Pattern and timing of recurrence and outcome after recurrence were analyzed. Univariate and multivariate analyses of factors associated with outcome after recurrence were carried out. RESULTS: From January 1997 through May 2003, a total of 733 patients underwent hepatectomy for colorectal metastases. Of these, 637 patients (87%) were included in the analysis, and in 393 patients (62%), recurrence was documented at the time of last follow-up. Initial recurrence patterns included the following: liver only in 120 patients (31%), lung only in 107 (27%), other single sites in 49 (12%), and multiple sites in 117 (30%). Recurrence occurred within 2 years of hepatectomy in 75% of patients and after 3 years in 11%. Margins at hepatectomy, recurrence pattern, resected recurrence, and disease-free interval from time of colectomy to hepatic metastasis and from time of hepatectomy to recurrence were independently associated with survival as measured from the time of recurrence. Recurrence in the lung, resected recurrence, and time to recurrence after hepatectomy were associated with prolonged survival as measured from the time of hepatectomy and the time of recurrence. CONCLUSIONS: The timing and pattern of recurrence after hepatic resection for metastatic colorectal cancer are important predictors of long-term survival.