[Experimental study on intraperitoneal and intravenous administration of anti-tumor agents for liver metastasis].

Intraperitoneal chemotherapy has been the treatment for peritoneal seedings. Most of the anti-tumor agent administered intraperitoneally is absorbed from visceral peritoneum, gets into the portal vein system and reaches the liver. Theoretically, intraperitoneal administration of anti-tumor agents must show equivalent effects on the liver metastasis to portal vein infusion. We compared the efficacy of intraperitoneal and intravenous administration of 5-FU, CDDP and CPT-11, using colon 26 mouse liver metastasis model. Intraperitoneal administration of 5-FU or CPT-11 was statistically superior to intravenous administration to diminish the liver metastatic deposits. CDDP experiment did not show a statistical difference, but the superiority intraperitoneal administration was recognized. Intraperitoneal administration of anti-tumor agents is more effective for not only peritoneal seedings but also liver metastases than intravenous administration. Intraperitoneal chemotherapy might be an effective adjuvant chemotherapy for gastrointestinal malignancies.

Clinical outcome of intraoperative pelvic hyperthermochemotherapy for patients with Dukes' C rectal cancer.

In attempts to prevent local recurrence after curative resection for rectal cancer, intraoperative pelvic hyperthermochemotherapy (IOPHC) was prescribed for 27 patients with Dukes' C cancer. The procedures used were as follows: immediately after amputation or resection of the rectum with extended lymphadenectomy, the pelvic cavity was filled with physiological saline containing 40 micrograms/ml mitomycin C, which was warmed at 45 degrees C for 90 min with an apparatus devised for IOPHC. Thirty-five patients who underwent surgery alone for Dukes' C rectal cancer within the same period served as controls. There was a local recurrence in three patients in the IOPHC group (11.1%), and in 13 in the control group (37.1%). With regard to hepatic or pulmonary metastasis, there was no difference between the two groups. There was no morbidity in the IOPHC treatment except for a large volume of exudate from the pelvic cavity. Thus, IOPHC can be considered as one option for limiting local recurrence after surgical resection of an advanced rectal cancer.

Relation between clinical and histologic outcome of intraperitoneal hyperthermic perfusion for patients with gastric cancer and peritoneal metastasis.

In 15 patients with refractory gastric cancer and peritoneal metastasis, the relationship among histologic outcome of intraperitoneal hyperthermic perfusion (IPHP), extent of peritoneal metastasis, and cause of death was studied. The IPHP treatment did not kill all the gastric cancer cells which had penetrated deeply into subperitoneal layers. In contrast, gastric cancer cells in the abdominal effusion and/or lavage vanished. Three patients with peritoneal metastasis, deeply invaded and spread all over the peritoneum, died of peritoneal recurrence and 1 died of pericardial metastasis. In the remaining 11 patients with a lesser extent of peritoneal metastasis, 5 are living without recurrence and among the other 6, 4 died of recurrence of the disease and 1 died of other causes.

Combined treatment of pelvic exenterative surgery and intra-operative pelvic hyperthermochemotherapy for locally advanced rectosigmoid cancer: report of a case.

A huge rectosigmoidal cancer which extended into the urinary bladder in a 64-year-old man is herein described. The tumor occupied the pelvic and lower abdominal cavities, while the rectosigmoid was totally obstructed. No hepatic or pulmonary metastasis was evident. The ventral and flank sides of the peritoneum in the right lower abdomen, right common iliac vessels, bilateral ureters, terminal ileum, cecum, ascending colon, and urinary bladder were all directly invaded by the tumor, but the aorta, sacrum, and lower rectum were free of cancer. Consequently, an anterior pelvic exenteration was carried out along with an ileal conduit and a right hemicolectomy. Immediately after the exenteration, intra-pelvic hyperthermochemotherapy was performed using a 46-47 degrees C perfusate containing 40 micrograms/ml of mitomycin C (MMC) and 200 micrograms/ml of cisplatin (CDDP), for 90 min, in an attempt to prevent any further local recurrence. A right hemicolectomy and a permanent colostomy were done simultaneously with the hyperthermia treatment. After an uneventful postoperative course, the patient was prescribed adjuvant chemotherapy, i.e., two administrations of 17 mg/m2 and 21 mg/m2 of MMC, and ten doses of 710 mg/m2 of 5-fluorouracil (5-FU) followed by five doses of 535 mg/m2 of 5-FU. At the time of this writing, the patient is still alive without recurrence at 21 months after surgery.

Cytohistologic assessment of antitumor effects of intraperitoneal hyperthermic perfusion with mitomycin C for patients with gastric cancer with peritoneal metastasis.

For 15 patients with refractory gastric cancer and peritoneal metastasis, intraperitoneal hyperthermic perfusion (IPHP) using mitomycin C combined with extensive surgery was prescribed. The antitumor effects were assessed cytohistologically in pre-IPHP and post-IPHP specimens of the abdominal effusion and peritoneal tissue. Gastric cancer cells in the abdominal effusion and/or lavage vanished from post-IPHP peritoneal exudate obtained from the pouch of Douglas. Peritoneal tissues from nine patients were harvested just after the IPHP treatment. All the nuclei of cancer cells were pyknotic in three of nine patients, and two of these three patients are alive with no local recurrence; one patient died of hepatic metastasis. In the remaining six patients, four with preoperative ascitic effusion and positive post-IPHP histologic findings died of peritoneal, intraabdominal, and pericardial metastases. The other two had some residual microscopic foci in the subperitoneal deep layer; one patient died of pleural recurrence, and the other is alive with no evidence of recurrence 42 months after the IPHP. Among the other six patients, whose post-IPHP peritoneal tissues were not available because of disappearance of disseminating foci as a result of the IPHP, two are living with no recurrence and, of the remaining four patients, three died of hepatic and intraabdominal metastases and the other one died of other causes. The histologic findings are suggestive of the following: (1) uniform heat and drug distribution in the abdominal cavity with IPHP treatment, except for an area adjacent to the inflow point of the perfusate; and (2) limited penetration of heat and drug through the subperitoneal layer. Thus, IPHP treatment results in complete destruction of cancer cells in the abdominal effusion and on and just beneath the peritoneum.

[Immunological study of the actions of auxiliary antitumor agents--effects on lymphocyte transformation reaction and natural cytotoxicity activity in nude mice].

P-aminobenzoic acid-N-xyloside (K-247) and dimethyl-2- (tetrahydro-2-furanyl) ethylsulfonium-p-toluene sulfonate (GT-101) were tested their in vivo effects on both mitogen-induced lymphoproliferative reactions and natural cell-mediated cytotoxicities in BALB/c nude mice (homozygous and heterozygous) spleen lymphocytes. The animals were injected i.p. either 400 mg/kg of K-247 or 5 mg/kg of GT-101 (for 7 days consecutively). GT-101 caused a positive increase in lymphoproliferations by PHA and SPA, while the administration of K-247 had no effect on PHA-and SPA-induced lymphoproliferations. Furthermore, in a 12-hour 51Cr release assay, both drugs had no effect on the natural cell-mediated cytotoxicity against YAC-1 cells.