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K-ras Point Mutation in the Nerve Plexuses Around the Superior Mesenteric Artery in Resectable Adenocarcinoma of the Pancreatic Head
Distribution Pattern and Related Factors
Hiroaki Ohigashi, MDP;
Osamu Ishikawa, MD;
Yo Sasaki, MD;
Terumasa Yamada, MD;
Hiroshi Furukawa, MD;
Shingi Imaoka, MD;
Tsutomu Kasugai, MD;
Shingo Ishiguro, MD;
Kazuki Ueda, MD;
Yasuo Miyoshi, MD;
Yusuke Nakamura, MD
Arch Surg. 2000;135:1450-1455.
Background Adenocarcinoma of the pancreas is likely to spread into the nerve plexuses around the superior mesenteric artery (SMA) at a microscopic level. Since there has been no detailed report on how minute cancer invasion is distributed among the peri-SMA plexuses or which cases are more vulnerable to such an event, it has long been controversial how to treat this area when resecting the pancreatic head cancer.
Hypothesis The K-ras mutation assay is more sensitive than the conventional histologic diagnosis in detecting minute cancer invasion around the SMA.
Design Prospective consecutive series.
Setting Cancer center hospital.
Patients and Methods The entire circle of the peri-SMA tissues was obtained from 24 patients who had received an extended pancreatectomy for adenocarcinoma of the pancreatic head. They were divided into right and left hemicircular samples (48 samples), and each sample was used for both histologic and genetic diagnoses. Since all patients' primary tumors were positive for point mutation at codon 12 of the K-ras gene, the presence or absence of the mutation was determined for the peri-SMA plexuses using the mutant allele specific amplification method.
Results Compared with results of the histologic examination, the K-ras mutation assay was more sensitive in detecting positive findings in the peri-SMA plexuses (12 samples from 9 patients). According to the distribution of the K-ras mutation into the right- and left-half samples, 24 patients were classified into the following 4 patterns (right/left): negative/negative in 15 patients; positive/negative in 6 patients; positive/positive in 3 patients; and negative/positive in 0 patients. In 3 patients who showed a positive/positive pattern in the genetic diagnosis, their right-half samples included more cancer cells that were detectable by routine microscopy. There was no relation between K-ras mutation and lymphatic invasion, while K-ras mutation was particularly related with the invasion of portal vein (P = .04) and posterior peripancreatic tissues (P = .002). All 3 patients with K-ras mutation in bilateral plexuses were classified by the TNM staging system as T4 using Union Internationale Contre le Cancer classification.
Conclusions The K-ras mutation (at codon 12) assay indicated a simple and regular pattern of cancer extension into the nerve plexuses around the SMA from adenocarcinoma of the pancreatic head: (1) The left half of the plexus was unlikely to be involved by cancer in cases in which the right half was intact. (2) Cancer extension into the peri-SMA plexuses occurred after the posterior confine of the pancreas had been involved by direct invasion from the primary pancreatic tumor. (3) The left half was not involved in cancerous tumors classified as T1 to T3 but was occasionally involved in those classified as T4 tumors. These data seem to provide a useful indicator of some additional treatments (resection, irradiation, etc) for the peri-SMA region when a locally advanced pancreatic head cancer is treated with a curative intent.
From the Departments of Surgery (Drs Ohigashi, Ishikawa, Sasaki, Yamada, Furukawa, and Imaoka) and Pathology (Drs Kasugai and Ishiguro), Osaka Medical Center for Cancer and Cardiovascular Diseases, and the Department of Clinical Genetic Research (Drs Ueda, Miyoshi, and Nakamura), Biomedical Center, Medical School of Osaka University, Osaka, Japan.
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