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.

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.

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.

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.

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.

Relationship between intraoperative fluid administration and perioperative outcome after pancreaticoduodenectomy: results of a prospective randomized trial of acute normovolemic hemodilution compared with standard intraoperative management.

BACKGROUND: Pancreaticoduodenectomy (PD) can be associated with significant blood loss and transfusion requirements, with potential adverse short- and long-term consequences. The aim of this study was to determine whether acute normovolemic hemodilution (ANH), an established blood conservation technique, reduces perioperative allogeneic transfusions in patients undergoing PD. METHODS: One hundred thirty patients undergoing PD were randomized to ANH or standard management (STDM). In the ANH group, intraoperative blood collection was performed to a target hemoglobin of 8.0 g/dL; crystalloid and colloid were used for volume replacement. Strict transfusion triggers were applied during and after operation. Perioperative complications were prospectively assessed and graded for severity. RESULTS: From July 2005 to May 2009, 209 patients were registered, 79 excluded, 65 were randomized to ANH, and 65 to STD. The groups were well matched for demographic, operative, and histopathologic variables. Patients undergoing ANH received over 2 L more fluid intraoperatively (6250 mL, range 2000-11850) compared with patients undergoing STD (3900 mL, range 2000-9000) (P < 0.001). Transfusion rates were similar (ANH = 16.9%, 30 units vs STD = 18.5%, 33 units; P = 0.82), as was overall perioperative morbidity (ANH = 49.2% vs STD = 47%, P = 0.86). There was, however, a trend toward more grade-3 complications in patients undergoing ANH (32% vs 23.1% STD, P = 0.17), and complications related to the pancreatic anastomosis (leak/fistula/abscess) were significantly higher in the ANH group (21.5% vs 7.7%, P = 0.045). The intraoperative fluid volume was higher for all patients with pancreatic anastomotic complications (n = 19), regardless of randomization arm (ANH 6000 mL, range 2800-11350 mL vs STD 5000 mL, range 2000-11850 mL, P < 0.042). CONCLUSION: In this randomized trial of patients undergoing PD, ANH did not reduce allogeneic transfusions and resulted in more pancreatic anastomotic complications, likely related to greater intraoperative fluid administration. The benefits of ANH do not necessarily extend to all procedures, and restrictive intravenous fluid management during PD may help improve postoperative outcome.

Survival after hepatic resection for metastatic colorectal cancer: trends in outcomes for 1,600 patients during two decades at a single institution.

BACKGROUND: This study analyzes factors associated with differences in long-term outcomes after hepatic resection for metastatic colorectal cancer over time. STUDY DESIGN: Sixteen-hundred consecutive patients undergoing hepatic resection for metastatic colorectal cancer between 1985 and 2004 were analyzed retrospectively. Patients were grouped into 2 eras according to changes in availability of systemic chemotherapy: era I, 1985 to 1998; era II, 1999 to 2004. RESULTS: There were 1,037 patients in era I and 563 in era II. Operative mortality decreased from 2.5% in era I to 1% in era II (p = 0.04). There were no differences in age, Clinical Risk Score, or number of hepatic metastases between the 2 groups; however, more recently treated patients (era II) had more lymph node-positive primary tumors, shorter disease-free intervals, more extrahepatic disease, and smaller tumors. Median follow-up was 36 months for all patients and 63 months for survivors. Median and 5-year disease-specific survival (DSS) were better in era II (64 months and 51% versus 43 months and 37%, respectively; p < 0.001); but median and 5-year recurrence-free survival (RFS) for all patients were not different (23 months and 33% era II versus 22 months and 27% era I; p = 0.16). There was no difference in RFS or DSS for high-risk (Clinical Risk Score >2, n = 506) patients in either era. There was a marked improvement in both RFS and DSS for low risk (Clinical Risk Score < or =2, n = 1,094) patients. CONCLUSIONS: Despite worse clinical and pathologic characteristics, survival but not recurrence rates after hepatic resection for colorectal metastases have improved over time and might be attributable to improvements in patient selection, operative management, and chemotherapy. The improvement in survival over time is largely accounted for by low-risk patients.

Adequate lymph node assessment for extrahepatic bile duct adenocarcinoma.

OBJECTIVE: To examine the importance of adequate lymph node sampling in staging of extrahepatic bile duct cancer (EHBDCA). SUMMARY OF BACKGROUND DATA: The American Joint Committee on Cancer staging manual (sixth edition) states that histologic examination of at least 3 lymph nodes is required for adequate N stage determination for EHBDCA. This recommendation has not been validated; however, there has been no comparative assessment of the proximal versus distal bile duct cancer. METHODS: A total of 257 patients (144 hilar cholangiocarcinoma [HCCA] and 113 distal bile duct adenocarcinoma [DBDCA]) who underwent curative intent resection (1987-2007) were analyzed; patients with gallbladder cancer were excluded. Final disease staging, including lymph node status and total number of nodes examined (total lymph node count), was obtained from the final pathology report. Differences in disease-specific survival, according to nodal status, were compared using the log-rank test. R1 resections (n = 51) were excluded from this analysis. RESULTS: Metastasis to regional lymph nodes was noted in 89 patients (34.6%) and was an independent prognostic factor of poor survival (median disease-specific survival N0 vs. N1: 53.5 vs. 19.3 months, P < 0.0001, hazard ratio = 2.1 [95% CI: 1.4-3.2]). The median total lymph node count was 6 (range: 0-42), and was significantly lower for HCCA compared with DBDCA (median = 3 [range: 0-16] vs. 12 [range: 1-42], P < 0.001, respectively). For the entire cohort, patients who underwent R0 resection and were classified as N0, based on total lymph node count <11, had a disease-specific survival that was significantly worse than that of patients classified as N0 based on total lymph node count >or=11 (52.6 +/- 9.8 months vs. not reached, P = 0.008). The estimated optimal total lymph node count for HCCA differed from that of DBDCA (n = 7 vs. n = 11, respectively). CONCLUSIONS: Adequate lymph nodes assessment of EHBDCA, based on the current AJCC recommendations, results in understaging of these tumors. With respect to the optimal total lymph node count, HCCA, and DBDCA should be considered separately.

Predictors of a true complete response among disappearing liver metastases from colorectal cancer after chemotherapy.

BACKGROUND: During chemotherapy, some colorectal liver metastases (LMs) disappear on serial imaging. This disappearance may represent a complete response (CR) or a reduction in the sensitivity of imaging during chemotherapy. The objective of the current study was to determine the fate of disappearing LMs (DLMs) and the factors that predict a true CR. METHODS: Between 2000 and 2003, 435 patients who were evaluated by hepatobiliary surgeons received chemotherapy before they were considered for resection. Inclusion criteria were <12 LMs before chemotherapy, at least 1 DLM on a computed tomography (CT) scan, and either surgical resection or 1 year of clinical follow-up after the disappearance of LMs. A true CR was defined as either a pathologic CR (no tumor detected in the resection specimen) or a durable clinical CR (did not reappear on follow-up imaging). Clinical and pathologic factors were analyzed to identify those associated with a true CR. RESULTS: During chemotherapy, 39 patients (9%) had a total of 118 DLMs on follow-up CT scans. Sixty-eight DLMs were resected, and 50 were followed clinically. Overall, 75 DLMs (64%) were true CRs, including 44 pathologic CRs and 31 durable clinical CRs. On multivariate analysis, the use of hepatic arterial infusion (HAI) chemotherapy (odds ratio [OR], 6.2; P = .02), the inability to observe the DLM on a magnetic resonance image (OR, 4.7; P = .005), and normalization of serum carcinoembryonic antigen levels (OR, 4.6; P = .006) were associated independently with a true CR. CONCLUSIONS: Approximately 66% of DLMs represented a true CR according to assessment by resection or radiologic follow-up. Predictive factors may help to stratify patients who are likely to harbor residual disease.