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Background: Hepatic artery infusion (HAI) chemotherapy is associated with overall survival (OS) in patients with resected colon cancer liver metastases (CLM). The prognostic impact of primary tumor location in CLM following hepatic resection in patients receiving regional HAI is unknown. This study seeks to investigate the prognostic impact of HAI in relation to laterality in this patient population., Methods: Consecutive patients with resected CLM, with known primary tumor site treated with and without HAI, were reviewed from a prospective institutional database. Correlations between HAI, laterality, other clinicopathological factors, and survival were analyzed, and Cox proportional hazard regression was used to determine whether laterality was an independent prognostic factor., Results: From 1993 to 2012, 487 patients [182 with right colon cancer (RCC), 305 with left colon cancer (LCC)] were evaluated with a median follow-up of 6.5 years. Fifty-seven percent (n = 275) received adjuvant HAI. Patients with RCC had inferior 5-year OS compared with LCC (56% vs. 67%, P = 0.01). HAI was associated with improved 5-year OS in both RCC (68% vs. 45%; P < 0.01) and LCC (73% vs. 55%; P < 0.01). On multivariable analysis, HAI remained associated with improved OS (HR 0.52; 95% CI 0.39-0.70; P < 0.01) but primary tumor site did not (HR 0.83; 95% CI 0.63-1.11; P = 0.21). Additional significant prognostic factors on multivariable analysis included age, number of tumors, node-positive primary, positive margins, RAS mutation, two-stage hepatectomy, and extrahepatic disease. Cox proportional hazard regression determined no significant interaction between HAI and laterality on OS [parameter estimate (SEM), 0.12 (0.28); P = 0.67]., Conclusions: Our data show an association of adjuvant HAI and increased OS in patients who underwent curative hepatectomy, irrespective of primary tumor location. Laterality should therefore not impact decision-making when offering adjuvant HAI.

Background: The role of carcinoembryonic antigen (CEA) in surveillance and follow-up of patients with colorectal cancer continues to be debated. The objective of this study was to assess the utility of postoperative CEA as a predictor of recurrence for patients with resected colorectal liver metastases (CLM)., Methods: Patients were identified from a prospectively maintained CLM database, and were studied retrospectively. Patients with extrahepatic disease or initially unresectable CLM were excluded. All patients in this study received adjuvant systemic chemotherapy after resection., Results: Between 1997 and 2007, a total of 318 consecutive patients were studied, with 168 patients (53 %) experiencing recurrence within 2 years. Various postoperative CEA cutoffs were tested as independent predictors of recurrence. A postoperative CEA ≥15 ng/ml obtained the highest hazard ratio (1.87; 95 % CI 1.09-3.2; p = 0.023) and was chosen to be included in the survival analysis in the multivariate model. A postoperative CEA ≥15 ng/ml had a specificity of 96 % and positive predictive value of 82 % for recurrence. On multivariate analysis, age ≥70 years, the presence of positive lymph node at primary tumor resection, disease-free interval ≤12 months, number of lesions >1, largest lesion ≥5 cm, presence of positive margins, and postoperative CEA ≥15 ng/ml were independent predictors of recurrence within 2 years., Conclusion: This study demonstrates a postoperative CEA ≥15 ng/ml to be a predictive test for recurrence.

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.

Background: Surgical approach is an accepted approach for metastatic neuroendocrine tumors (NET), but the safety and effectiveness of synchronous liver metastases resection with primary and/or locally recurrent NET is unclear., Methods: From 1992 to 2009, a total of 36 patients underwent synchronous resection of primary NET or local recurrence and liver metastases. Patients and tumor characteristics, surgical procedures, and postoperative and long-term outcome were reviewed., Results: Primary lesions were solitary in 28 patients (80 %), with a median size of 25 mm. Liver metastases were multiple in 32 cases (89 %), with a bilobar distribution in 29 patients (81 %) and a median size of 62 mm. Resections included gastroduodenal (n = 5), ileocolonic (n = 18), pancreatic resection (n = 13), and major hepatectomy (n = 15). Resections were R0, R1, and R2 in 13, 11, and 12 cases, respectively, and tumors were classified as G1 in 20 (56 %) and G2 in 15 (42 %). There was 1 postoperative death after a Whipple/right trisectionectomy, and postoperative complication occurred in 16 patients (44 %). With a median follow-up of 56 months, 31 patients (89 %) experienced recurrence, which was confined to the liver in 90 %. Reduction of disease to liver only allowed subsequent liver-directed therapy, such as arterial embolization or percutaneous ablation, in 25 patients (71 %). Five-year symptom-free survival and overall survival were 60 %, and 69 %, respectively., Conclusions: In highly selected patients, an initial surgical approach combining simultaneous resection of liver metastases and primary/recurrent tumors can be performed with low mortality. Most patients develop liver-confined recurrence, which is usually amenable to ablative therapies that offer ongoing disease and symptom control.

Background: Epidemiologic studies have reported a positive correlation between body mass index (BMI) and pancreatic cancer risk, but clinical relevance of obesity and/or body fat distribution on tumor characteristics and cancer-related outcome remain controversial. We sought to assess the influence of obesity and body fat distribution on pathologic characteristics and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma., Methods: Demographic and biometric data were collected on 328 patients undergoing pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. In a subset of patients, pancreatic fatty infiltration and fibrosis were assessed pathologically, and visceral fat area (VFA) was evaluated. Influence of BMI and body fat distribution on tumor characteristics and survival were evaluated., Results: A significant positive correlation between BMI and VFA was observed, with a wide range of VFA value within each BMI class. According to BMI or VFA distribution, there were no significant differences in patient characteristics, intraoperative or perioperative outcome, or pathologic characteristics, with the exception of significantly higher blood loss in patients with an increased body weight or VFA. Unadjusted overall and disease-free survival between BMI class and VFA quartile were not significantly different., Conclusions: In this study, obesity and body fat distribution were not correlated with specific tumor characteristics or cancer-related outcome.

Background: While tumor infiltrating lymphocytes (TIL) have been shown to independently predict survival in primary colorectal cancer, the prognostic implications of TIL in resectable colorectal cancer liver metastases (CRCLM) have not been previously defined. This study examines the correlation between TIL numbers and survival following hepatic resection., Methods: We studied patients who survived or=10 years following CRCLM resection. Immunohistochemistry was performed on tissue microarrays (TMAs) to determine the number of T cells within CRCLM. Correlation between TIL frequency and or=10 year survival was determined while controlling for established prognostic factors., Results: Of 162 patients, 104 survived or=10 years. Independent correlates of 10-year survival following CRCLM resection included a high number of CD8 T cells, a low number of CD4 T cells, and a clinical risk score of

Background: Surgical resection for patients with hepatic and extrahepatic (EHD) colorectal metastases is controversial. We analyzed our experience with hepatic resection in patients with concomitant EHD. The aims were to characterize survival, recurrence rates, and factors associated with outcome., Methods: From 1992 to 2007, 1,369 patients underwent resection of hepatic colorectal metastases, of whom 127 (9%) had concurrent resection of EHD. Survival and recurrence were compared between patients with and without EHD. Survival data were stratified by site of metastatic involvement. Variables potentially associated with survival were analyzed in univariate and multivariate analyses., Results: Median follow-up was 24 months (range 3-152 months). The 3- and 5-year survival for patients with concomitant EHD were 47% and 26%, respectively, compared with 67% and 49%, for those without EHD (P < 0.001). Among the patients with EHD, multivariate analysis identified higher clinical risk score, incomplete resection of all EHD, EHD detected intraoperatively, and having received neoadjuvant chemotherapy to be independently associated with a worse survival. Patients with portal lymph node metastases had worse survival than those with lung or ovarian metastases. Among patients who had a complete resection of all disease, 95% recurred., Conclusion: Concurrent resection of hepatic and EHD in well-selected patients is associated with a possibility of long-term survival. The presence of limited and resectable EHD should not be an absolute contraindication to resection. The site of EHD and the nearly universal recurrence rate must be taken into consideration.

Background: Patients with potentially resectable hepatobiliary malignancy are frequently found to have unresectable tumors at laparotomy. We prospectively evaluated staging laparoscopy in patients with resectable disease on preoperative imaging., Methods: Staging laparoscopy was performed on 410 patients with potentially resectable hepatobiliary malignancy. The preoperative likelihood of resectability was recorded. Data on preoperative imaging, operative findings, and hospital course were analyzed., Results: Laparoscopic inspection was complete in 291 (73%) patients. In total, 153 patients (38%) had unresectable disease, 84 of whom were identified laparoscopically, increasing resectability from 62% to 78%. On multivariate analysis, a complete examination, preoperative likelihood of resection, and primary diagnosis were significant predictors of identifying unresectable disease at laparoscopy. The highest yield was for biliary cancers, and the lowest was for metastatic colorectal cancer. In patients with unresectable disease identified at laparoscopy, the mean hospital stay was 3 days, and postoperative morbidity was 9%, compared with 8 days and 27%, respectively, in patients found to have unresectable disease at laparotomy., Conclusions: Laparoscopy spared one in five patients a laparotomy while reducing hospital stay and morbidity. Targeting laparoscopy to patients at high risk for unresectable disease requires consideration of disease-specific factors; however, the surgeons' preoperative impression of resectability is also important.

Background: Carefully selected patients with noncolorectal, nonneuroendocrine (NCNN) liver metastases may benefit from hepatic resection. The incidence of occult unresectable disease and the possible benefits of staging laparoscopy in these patients are not known., Methods: From December 1997 to July 2000, staging laparoscopy was performed in 30 consecutive patients with NCNN metastases before planned open exploration and resection. Demographics, extent of preoperative imaging, operative and postoperative findings, and factors associated with laparoscopic identification of unresectable disease were analyzed., Results: Twenty-four patients (80%) had a complete laparoscopic examination, and 23 had laparoscopic ultrasonography. All patients underwent preoperative computed tomography or magnetic resonance imaging, and 21 (70%) patients had 2 or more preoperative radiological studies. Overall, nine patients had unresectable disease, six of whom were identified by laparoscopy. Of the remaining 24 patients believed to have resectable disease at laparoscopy, 21 went on to a potentially curative procedure. Laparoscopy did not identify irresectability because of vascular involvement in three patients. Laparoscopy added a median of 30 minutes of operative time to those patients going on to laparotomy., Conclusions: Laparoscopy identified the majority of patients with occult unresectable disease, improved resectability, and should be routine in patients being considered for potentially curative hepatic resection.

Background: Hepatic resection is potentially curative in selected patients with colorectal metastases. It is a widely held practice that multiple colorectal hepatic metastases are not resected, although outcome after removal of four or more metastases is not well defined., Methods: Patients with four or more colorectal hepatic metastases who submitted to resection were identified from a prospective database. Number of metastases was determined by serial sectioning of the gross specimen at the time of resection. Demographic data, tumor characteristics, complications, and survival were analyzed., Results: From August 1985 to September 1998, 155 patients with four or more metastatic tumors (range 4-20) underwent potentially curative resection by extended hepatectomy (39%), lobectomy (42%), or multiple segmental resections (19%). Operative morbidity and mortality were 26% and 1%, respectively. Actuarial 5-year survival was 23% for the entire group (median = 32 months) and there were 12 actual 5-year survivors. On multivariate analysis, only number of hepatic tumors (P = .005) and the presence of a positive margin (P = .003) were independent predictors of poor survival., Conclusions: Hepatic resection in patients with four or more colorectal metastases can achieve long-term survival although the results are less favorable as the number of tumors increases. Number of hepatic metastases alone should not be used as a sole contraindication to resection, but it is clear that the majority of patients will not be cured after resection of multiple lesions.