Tara M. Breslin, Nora A. Janjan, Jeffrey E. Lee, Peter W. T. Pisters, Robert A. Wolff, James L. Abbruzzese, Douglas B. Evans

Pancreatic Tumor Study Group: Departments of Surgical Oncology (TMB, JEL, PWTP, DBE), Radiation Oncology (NAJ), and Gastrointestinal Oncology and Digestive Diseases (RAW, JLA), The University of Texas M. D. Anderson Cancer Center, Houston, TX

Received 6/4/98 Accepted 5/5/98

5. PATHOLOGIC ASSESSMENT OF SURGICAL SPECIMENS

Accurate pathologic assessment of surgical specimens is critical for both the evaluation of innovative preoperative treatment strategies and the development of reproducible prognostic predictors of patient survival and treatment failure. Retrospective pathologic analysis of archival material does not allow accurate assessment of margins of resection or number of lymph nodes retrieved. The standard pathologic evaluation of the pancreaticoduodenectomy specimen developed at MDACC¹⁸ begins by first performing frozen-section evaluations of the common bile duct transection margin and the pancreatic transection margin. A positive bile duct or pancreatic transection margin is treated with re-resection. The retroperitoneal transection margin is defined as the soft-tissue margin directly adjacent to the proximal 3- to 4- cm of the SMA. This margin is evaluated by permanent-section microscopic examination of a 2- to 3-mm full-face (en-face) section of the margin. Re-resection (for a microscopically positive margin) is not possible in the retroperitoneum where the aorta and SMA origin limit the extent of surgical resection. Samples of multiple areas of each tumor, including the interface between tumor and adjacent uninvolved tissue, are submitted for paraffin-embedded histologic examination (5 to 10 blocks). Four-microns-thick sections are cut and stained with hematoxylin and eosin. Final pathologic evaluation of permanent sections include a description of tumor histology and differentiation, gross and microscopic evaluation of the tissue of origin (pancreas, bile duct, ampulla of Vater, or duodenum), and assessments of maximal transverse tumor diameter, the presence or absence of perineural, lymphatic, and vascular invasion, and lymph node status and location (as outlined on the anatomical pathology dissection board). When segmental resection of the superior mesenteric vein is required, the area of presumed tumor invasion of the vein wall is serially sectioned and examined in an attempt to discriminate benign fibrous attachment from direct tumor invasion. In patients who receive preoperative chemoradiation, the grade of treatment effect is assessed on permanent sections (table 2)(19).

The high incidence of local recurrence following pancreaticoduodenectomy mandates that greater attention be paid to the retroperitoneal margin. This margin can be studied accurately only at the time of specimen removal, and attempts at retrospective analysis of this important excision margin are prone to inaccuracy. Recent reports of patients who underwent pancreaticoduodenectomy and were found to have a positive margin of resection demonstrate the impact of margin positivity on survival duration. The survival duration of 8 to 12 months in margin-positive patients was no different than the median survival reported for patients with locally advanced disease treated with palliative chemoradiation without surgical resection of the pancreas (table 3)(7, 10, 20-24). These studies did not precisely define the retroperitoneal margin, however, it is reasonable to assume that the margin most frequently reported as positive in patients who undergo pancreaticoduodenectomy is along the superior mesenteric vein or proximal SMA (24).

Several other tumor characteristics have been evaluated as potential prognostic indicators. In a recent study by Allison and colleagues, aneuploid DNA content (and the % of S-phase cells), tumor size (> 2.5 cm), and the percentage of tumor-positive lymph nodes were the tumor characteristics predictive of decreased survival duration by multivariate analysis (25). The presence of mutant K-ras DNA (85% of specimens) and positive surgical resection margins were not prognostic indicators for patient survival. However, median survival for the 96 patients included in this analysis was only 10 months. In contrast, recent data from MDACC reported by Bold and colleagues demonstrated that the presence of mutant K-ras DNA was the most powerful predictor of tumor recurrence (26). In agreement with the study by Allison, poorly differentiated histology and lymph node metastases predicted tumor recurrence and decreased survival. The median survival for the 104 patients reported by Bold was 23 months.

To determine which patient subsets may benefit from the most aggressive treatment strategies, accurate pathologic staging and histologic assessment of response to preoperative therapy are mandatory.