Strategies to improve local control of resected pancreas adenocarcinoma.

BACKGROUND: Only approximately one in ten pancreas cancer patients is a candidate for potentially curative resection of this disease. Even this small fraction of patients has a poor prognosis following pancreatico-duodenectomy. The disease has an anatomic location that makes it difficult for the surgeon to maintain adequate margins of resection and prevent tumor spillage at the time of resection. Also, the disease is biologically aggressive and even with a complete visible resection of the disease, micrometastases are likely to remain behind.
METHODS: A survey of the sites for surgical treatment failure of resected pancreas cancer was performed. Also, the multiple modalities used in an attempt to improve the results of cancer resection are scrutinized.
RESULTS: The surgical treatment failures are regional in nature and occur at the resection site and on peritoneal surfaces, within the liver, and within the regional lymph nodes. These anatomic sites account for nearly 100% of the initial sites of disease progression. Current hypothesis suggests that micrometastases released from the cancer specimen by the trauma of surgery account for the high incidence of resection site progression and peritoneal metastases. Although surgical trauma may contribute to micrometastases within the liver and lymph nodes, these are most likely present though not detected by preoperative radiologic studies. Adjuvant treatments such as neoadjuvant chemotherapy or combination systemic chemotherapy have not been associated with improved survival. Extended resections such as total pancreatectomy or extended lymphadenectomy have not been associated with benefit. However, resection with a negative margin of excision along with the removal of at least 12 lymph nodes in and around the pancreaticoduodenectomy specimen is associated with superior outcomes. A regional chemotherapy treatment that consists of hyperthermic intraperitoneal chemotherapy (HIPEC) with gemcitabine and long-term normothermic intraperitoneal chemotherapy (NIPEC-LT) gemcitabine for 6 months postoperatively is suggested as a new treatment that has demonstrated decreases in local-regional failure and promises to more adequately target micrometastases in the peritoneal space, in the liver and lymph nodes.
CONCLUSIONS: Pancreas cancer surgery should attempt to achieve negative margins of resection with the removal of at least 12 lymph nodes. Hyperthermic intraperitoneal gemcitabine can adequately eradicate malignant cells dislodged from the cancer specimen into the bed of the resection at high density and on distant peritoneal surfaces as peritoneal metastases. Long-term intraperitoneal gemcitabine may act on micrometastases in the liver through absorption into the portal vein blood and the lymph nodes as a result of gemcitabine absorption by subperitoneal lymphatic channels. The use of HIPEC and NIPEC-LT gemcitabine may improve local control of resected pancreas cancer.