Gastrectomy, peritonectomy, and perioperative intraperitoneal chemotherapy: The evolution of treatment strategies for advanced gastric cancer

Abstract

Gastric cancer disseminates by hematogenous, lymphatic, and transcoelomic routes. For maximal containment of the malignant process, perioperative intraperitoneal chemotherapy is necessary in two groups of patients in whom the primary cancer can be resected. Those patients who have been resected for cure and have a high likelihood of microscopic residual disease require intraperitoneal chemotherapy. This includes all T3 and T4 patients, and patients with N2 nodes present. A series of randomized and nonrandomized clinical studies have established the benefits of perioperative intraperitoneal chemotherapy in this group of patients. Patients with stage IV disease who are able to undergo a palliative resection require these treatments if peritoneal seeding is observed. Systemic chemotherapy is largely ineffective for peritoneal seeding, while intraperitoneal chemotherapy is most likely to produce a response with small volume, surgically debulked carcinomatosis. In addition, intraperitoneal chemotherapy can eliminate the future development of debilitating ascites. Sufficient data are available from the gastric cancer literature to support the use of these combined treatments on a routine basis if the primary cancer is resectable and gastrointestinal function can be reestablished.

The Role of Hyperthermic Intraperitoneal Chemotherapy in Gastric Cancer

“…Peritoneal recurrence after a curative resection for gastric cancer is thought to originate from intraperitoneal free cancer cells (IFCC), which in turn arise from two potential sources: spontaneous exfoliation of cancer cells from the primary tumor from the serosal surface, and iatrogenic dissemination of cancer cells as a result of the surgical trauma [26,29]. Sugarbaker et al proposed the Btumor cell entrapment hypothesis^ [26], according to which the IFCC adhere to the surgical raw area within minutes-a process facilitated by fibrin entrapment and assisted by cytokines released as part of the wound healing mechanism.…”

“…Sugarbaker et al proposed the Btumor cell entrapment hypothesis^ [26], according to which the IFCC adhere to the surgical raw area within minutes-a process facilitated by fibrin entrapment and assisted by cytokines released as part of the wound healing mechanism. This hypoxic environment renders the trapped cancer cells relatively immune to the effects of systemic chemotherapy.…”

“…This is due to the presence of the Bplasma-peritonal barrier^ [25]. The inability of systemic chemotherapy to provide long-term survival coupled with the belief that peritoneal recurrence remains confined to the abdomen [26] has prompted investigators to explore regional therapies. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is currently being used as a curative treatment in pseudomyxoma peritonei, peritoneal mesothelioma and selected patients with colorectal PM [27,28].…”

Update on Chemotherapeutic Agents Utilized for Perioperative Intraperitoneal Chemotherapy

“…However, in Japan, the early research with peritoneal carcinomatosis from gastric primary, utilizing combination treatment with etoposide, mitomycin C, and cisplatin, has been reported [37,38]. Limited but definite benefits were demonstrated when palliative gastrectomy was combined with intraperitoneal heated multidrug treatment in gastric cancer patients with limited peritoneal seeding [8].…”

“…Eight different phase III studies reported a survival advantage when perioperative intraperitoneal chemotherapy is added to surgery in patients with primary gastric cancer. Stage III patients projected the greatest survival advantage [8]. Although benefits have been reported in the literature, a standardization of the optimal management plans for prevention or treatment of peritoneal surface malignancy has not been developed.…”