Kokuriki Kobayashi

Successful intraperitoneal hyperthermic chemoperfusion for the prevention of postoperative peritoneal recurrence in patients with advanced gastric carcinoma

The majority of advanced gastric carcinoma patients with serosal invasion die of peritoneal recurrence, even when a curative gastrectomy is performed, because peritoneal recurrence occurs due to intraperitoneal free tumor cells that detach from the serosal‐invaded focus. In an attempt to prevent peritoneal recurrence, intraperitoneal hyperthermic chemoperfusion (IHCP) treatment was combined with aggressive surgery.

Intraperitoneal hyperthermic perfusion combined with surgery effective for gastric cancer patients with peritoneal seeding

Fifteen patients with far-advanced gastric cancer were given surgical treatment followed by intraperitoneal hyperthermic perfusion (IPHP) with mitomycin C (MMC) and misonidazole (MIS), a thermosensitizing drug. Immediately after extensive resection of the abdominal tumors, a 2-hour IPHP was performed at the inflow temperature of 44.7 to 48.7 C, using equipment designed for treatment of cancerous peritoneal seeding as a closed circuit, and under hypothermie general anesthesia at 30 to 31 C. In nine of the 15 patients with peritoneal seeding and/or ascites, cancerous ascites was absent after this treatment. In all cases, repeated cytologie examinations of the lavage from Douglass pouch were negative. The postoperative courses were uneventful except for Patients 1 and 10, in whom slight leakage occurred. All patients were discharged and are in good health at the time of this writing, 7.2 ± 4.6 months after the treatment. The Case 4 Patient recently died in a traffic accident. In all patients, transient hepatic dysfunction and hypoproteinemia occurred after the operation. This extensive surgery combined with IPHP using MMC and MIS was well tolerated and is a safe antitumor treatment for gastric cancer with peritoneal dissemination. Neurotoxicity due to MIS was nil.

Improved mortality rate of gastric carcinoma patients with peritoneal carcinomatosis treated with intraperitoneal hyperthermic chemoperfusion combined with surgery

Peritoneal carcinomatosis from gastric carcinoma has a very poor prognosis. The purpose of this study was to evaluate the efficacy of intraperitoneal hyperthermic chemoperfusion (IHCP) in advanced gastric carcinoma patients with peritoneal carcinomatosis.

Positive results of combined therapy of surgery and intraperitoneal hyperthermic perfusion for far-advanced gastric cancer.

To evaluate the clinical efficacy of intraperitoneal hyperthermic perfusion (IPHP) for far-advanced gastric cancer, particularly with peritoneal seeding, we investigated the survival times of 59 patients who underwent distal subtotal gastrectomy, total gastrectomy, or total gastrectomy combined with concomitant resection of some of the remaining intra-abdominal organs. In all the 30 patients given IPHP, no cancer cells were present posthyperthermically in the lavage from the Douglas pouch. The 30 patients given IPHP lived longer than the 29 patients not given IPHP (p = 0.001), with a 1-year survival rate of 80.4% in the former group compared to 34.2% in the latter. With respect to a comparison of survival time of patients with peritoneal seeding, 7 patients not given IPHP had a 6-month survival rate of 57.1% and did not survive more than 9 months, whereas 20 patients given IPHP had 1- and 2-year survival rates of 78.7% and 45.0%, respectively; here the difference was significant (p = 0.001). The IPHP and control groups without peritoneal metastasis included 10 and 22 patients, respectively, and the 1-year survival rates are 85.4% and 45.3%, respectively. The survival rates of the former exceeded those of the latter, with p = 0.015 by the generalized Wilcoxon test. Thus this combined therapy offers the promise of extended survival for patients with far-advanced gastric 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.

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.

Stapled or manual suturing in esophagojejunostomy after total gastrectomy: A comparison of outcome in 379 patients

From January 1983 to December 1989, we performed esophagojejunostomy on 379 patients who underwent total gastrectomy for gastric cancer. A mechanical EEA stapler or conventional manual suturing was used. The clinical outcomes of 199 patients in whom stapling was used (stapler group) and 180 patients in whom manual suturing was done (manual group) were compared. Two of the 199 patients in the stapler group and 3 of the 180 patients in the manual group died of causes directly related to the anastomosis. In the stapler group, 16 stapled anastomoses were formed supradiaphragmatically, and manual suturing was done for 6 patients. The highly placed anastomosis was formed without left thoracotomy or with median sternotomy in 8 of the 16 patients in whom the stapling device was used and in 1 of the 6 patients in whom manual suturing was used. The incidence of anastomotic leakage and stenosis did not differ between the groups. Thus, the mechanical stapler facilitated the construction of a rapid, reliable esophagojejunostomic anastomosis.

Clinical pilot studies on pre-operative hyperthermic tumour ablation for advanced breast carcinoma using an 8 MHz radiofrequency heating device.

The multimodality treatment approach for advanced breast cancer provides survival advantages with decreased locoregional and distant recurrences, but these intensive anti-tumour treatments cause severe myelosuppression. Thus, in this study, the usefulness of pre-operative anti-tumour treatment without myelosuppression was investigated. Nine patients with advanced breast carcinoma underwent pre-operative hyperthermic tumour ablation (HTA) using an 8 MHz radiofrequency (RF) heating device (Thermotron RF-8) combined with a grounded needle electrode. The patients had a mean age of 58.3±13.9 years and included four patients with stage IIIA, two with stage IIIB and three with stage IV cancer. The target temperature was over 50°C. They tolerated pre-operative HTA therapy well with no early or late complications. The initial mean tumour size was 122.1±71.5 cm 3 and the post-HTA tumour size was 82.2±63.4 cm 3 ; the reduction rate was significant ( p = 0.000 293). After the pre-operative HTA, all patients underwent surgery with Level III nodal extirpation. Post-operatively, no locoregional recurrence was observed. Microscopic examination of the primary focus showed complete coagulation necrosis expanding for a diameter of 3.5-5.0 cm. Taken together, the pre-operative HTA was a safe, well-tolerated and effective treatment, achieving tumour reduction as well as complete coagulation necrosis that resulted in a large volume of destruction in breast cancer tissue.

Prevention of scald injury on the peritoneo-serosal surface in advanced gastric cancer patients treated with intraperitoneal hyperthermic perfusion

In attempts to avoid the side-effects derived from a scald on the peritoneo-serosal surface during intraperitoneal hyperthermic perfusion (IPHP) for advanced gastric cancer, a randomized study using cimetidine, a histamine H2-receptor antagonist, was carried out on 18 patients with advanced gastric cancer. Cimetidine, 50 mg/kg, was administered intravenously and immediately before IPHP. The background characteristics of the patients and the types of surgical treatment used were almost the same between each group of patients, whether or not cimetidine was given. The perfusion time in the cimetidine and control groups was 123 +/- 9 and 117 +/- 9 min, respectively. The inflow and outflow temperatures of the perfusate were 46.3 +/- 0.4 and 44.2 +/- 0.1 degrees C in the cimetidine group, respectively, whereas in the control group the temperatures were 46.0 +/- 0.3 and 44.1 +/- 0.2 degrees C, respectively. In the nine patients who were given cimetidine, the histamine concentrations in the peripheral blood increased significantly, compared to those in the nine controls; this resulted from the release of histamine into the circulating blood. Higher concentrations of protein were observed in the post-hyperthermic intraperitoneal exudate of the control group for 3-24 h after IPHP and, consequently, post-hyperthermic hypoproteinaemia was remarkable in the control group. These data suggest that when pre-IPHP cimetidine was prescribed for patients with gastric cancer treated with IPHP, the peritoneo-serosal surface was protected from scald injury and the side-effects of IPHP were reduced.

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°C perfusate containing 40 μg/ml of mitomycin C (MMC) and 200 μg/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.