Neutrophil-to-Lymphocyte Ratio as a Predictor of Invasive Carcinoma in Patients With Intraductal Papillary Mucinous Neoplasms of the Pancreas.

OBJECTIVES: Preoperative determination of the grade of dysplasia in intraductal papillary mucinous neoplasms (IPMNs) is necessary for optimal management. Previous data have suggested that serum neutrophil-to-lymphocyte ratio (NLR) can predict invasive disease in patients with IPMN. METHODS: A prospectively maintained database was queried for consecutive patients who underwent resection of IPMN. Exclusion criteria included recent diagnosis of cancer, immunosuppression, and infection or jaundice within 1 month of operation. A complete blood count with differential within 30 days of operation was used to calculate NLR. RESULTS: Within the study period, 446 patients underwent resection for IPMN, and 348 patients (78%) met the inclusion criteria. Low-grade dysplasia was present in 60 patients (17%), 137 patients (39%) had intermediate-grade dysplasia, 76 (22%) had high-grade dysplasia, and 75 (22%) had invasive carcinoma. A higher NLR was associated with invasive carcinoma as compared with noninvasive disease (3.00 vs 2.68, P = 0.039). There was no difference in NLR between patients with high-risk (invasive and high-grade) and low-risk (low-grade and intermediate-grade) lesions (2.80 vs 2.71, P > 0.95). CONCLUSIONS: Neutrophil-to-lymphocyte ratio was significantly higher in patients with IPMN-associated invasive carcinoma as compared with patients with noninvasive disease; however, NLR was not helpful in differentiating between high- and low-grade lesions.

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.

Phase II trial of hepatic artery infusional and systemic chemotherapy for patients with unresectable hepatic metastases from colorectal cancer: conversion to resection and long-term outcomes.

PURPOSE: Evaluate conversion rate of patients with unresectable colorectal-liver metastasis to complete resection with hepatic-arterial infusion plus systemic chemotherapy including bevacizumab (Bev). PATIENTS AND METHODS: Forty-nine patients with unresectable colorectal liver metastases (CRLM) were included in a single-institution phase II trial. Conversion to resection was the primary outcome. Secondary outcomes included overall survival (OS), progression-free survival, and response rates. Multivariate and landmark analyses were performed to evaluate survival differences between resected and nonresected patients. RESULTS: Median number of tumors was 14 and 65% were previously treated patients. A high biliary toxicity rate was found in the first 24 patients whose treatment included Bev. The remaining 25 patients were treated without Bev. Overall response rates were 76% (4 complete responses). Twenty-three patients (47%) achieved conversion to resection at a median of 6 months from treatment initiation. Median OS and progression-free survival for all patients were 38 (95% confidence interval: 28 to not reached) and 13 months (95% confidence interval: 7-16). Bev administration did not impact outcome. Conversion was the only factor associated with prolonged OS and progression-free survival in multivariate analysis. On landmark analysis, patients who had undergone resection had longer OS than those who did not undergo resection (3-year OS: 80% vs 26%). Currently, 10 of 49 (20%) patients have no evidence of disease (NED) at a median follow-up of 39 months (32-65 months). CONCLUSIONS: In patients with extensive unresectable CRLM, the majority of whom were previously treated, 47% were able to undergo complete resection after combined HAI and systemic therapy. Conversion to resection is associated with prolonged survival.

Failure patterns in resected pancreas adenocarcinoma: lack of predicted benefit to SMAD4 expression.

OBJECTIVE: To determine whether SMAD4 expression is associated with recurrence pattern after resection for pancreatic ductal adenocarcinoma (PDA). BACKGROUND: SMAD4 expression status has been reported to be associated with patterns of failure in PDA, but studies have not examined recurrence patterns after resection. METHODS: A tissue microarray was constructed including 127 patients with resected PDA and either short-term (<12 months) or long-term (>30 months) survival. SMAD4 expression was evaluated by immunohistochemistry and categorized as present or lost in tumor cells. Conventional pathologic features (lymph node metastases, positive resection margin, poor grade, and tumor size) were recorded, and disease-specific outcomes (eg, recurrence pattern and early cancer-specific mortality) were determined. RESULTS: Loss of SMAD4 expression in pancreatic adenocarcinoma was identified in 40 of 127 patients (32%). SMAD4 loss occurred in 27% of patients who experienced isolated local recurrence, 33% of patients with a distant recurrence, 33% of patients who experienced local and distant site recurrences, and 25% of patients who were without evidence of recurrence (Fisher exact, P = 0.9). In a multivariate analysis, the presence of regional lymph node metastases was the only factor associated with the development of distant metastases (odds ratio = 4.7, P = 0.02). SMAD4 was neither associated with recurrence pattern (odds ratio = 0.9, P = 0.9) nor associated with early death (odds ratio = 0.5, P = 0.15). CONCLUSIONS: Primary tumor SMAD4 expression status was not a predictor of recurrence pattern in a large cohort of patients with resected PDA.