Subtotal peritonectomy with chemohyperthermic peritoneal perfusion for peritonitis carcinomatosa in gastrointestinal cancer.

Treatment for peritonitis carcinomatosa in gastrointestinal cancer remains to be established though it is one of the commonest causes of cancer death. Subtotal peritonectomy (SP) with chemohyperthermic peritoneal perfusion (CHPP) was developed for the new therapeutic strategy for peritoneal dissemination in gastrointestinal cancer in our department. SP includes resection of stomach, colon, small bowel, spleen, gall bladder, and parietal peritoneum. CHPP was carried out by heated saline containing 25 mg/l cisplatin, 10 mg/l mitomycin C, and 20 mg/l etoposide. Intraperitoneal temperature was maintained at 42 degrees C for 60 min. Fifteen gastric cancer and three colon cancer patients with severe peritoneal dissemination underwent these procedures. The averages of operating time, intraoperative bleeding volume, and total perioperative transfused blood volume were 9 h, 4400 ml, and 5600 ml, respectively. The patients estimated as complete resection and residual disease by histopathological study numbered 11 and 7. There was no treatment-related deaths though bleeding occurred in 5 patients; perforation in 2 patients; and abscesses in 2 patients. The 1-year survival rate (1ysr) and the 2-year survival rate (2-ysr) of all the patients were 57% and 21%, respectively. The 1-ysr and the 2-ysr of the patients who underwent complete resection were 67% and 40% significantly greater than the 43% and 0% of the patients who had residual tumors (p=0.02). The combination therapy of SP and CHPP is feasible in spite of its morbidity and has great possibilities in complete resection of peritoneal dissemination and prolongation of patient's survival.

Chemohyperthermic peritoneal perfusion for peritoneal dissemination in various intra-abdominal malignancies.

A total of 25 patients with severe peritoneal dissemination underwent chemohyperthermic peritoneal perfusion (CHPP). The primary tumors in these patients comprised colorectal cancer (n = 14), ovarian cancer (n = 6), cervical cancer, (n = 1), small bowel cancer (n = 1), pseudomyxoma retroperitonei (n = 1), cystoadenocarcinoma of liver (n = 1), and pancreas cancer (n = 1). The intraperitoneal perfusion was carried out with a magnet pump for 60 min. The heated perfusate contained anticancer drugs to act synergistically with the hyperthermia. The intraperitoneal temperature was maintained at 42.0-42.5 degrees C. Eight of 25 patients showed CR, four PR, ten NC, and three PD, and the percentage (CR+PR) representing the overall efficacy rate was 48.0%. The morbidity rate was 8% (2/25) and there was no treatment-associated mortality. The percentage (CR+PR) of the patients with colorectal cancer was 57%; ovarian cancer, 50%; and other malignancies, 20%. The 1 year-and 3 year-survival rates of all the patients were 55% and 26%, respectively. The median survival periods of the CR, PR, NC, and PD groups were 4.0, 1.0, 1.0, and 0.7 years, respectively. The survival curve of the CR group was the best of all the groups (P = 0.02). These results indicated that CHPP was a feasible therapy and exerted a direct anticancer effect on peritoneal dissemination especially in the case of ovarian cancer, and the prognosis of complete responders was improved.

A new surgical approach (peritonectomy) for the treatment of peritoneal dissemination.

BACKGROUND/AIMS: Despite the improvements of chemotherapy and surgical techniques, treatment results of peritoneal dissemination still remain pessimistic. METHODOLOGY: During a 10-year period, 106 patients with peritoneal dissemination from gastric cancer were treated with chemo-hyperthermic peritoneal perfusion (CHPP), peritonectomy + CHPP, systemic PMUE therapy, and surgery alone in 51, 15, 13, and 27 patients, respectively. In peritonectomy, disseminated nodules were resected as much as possible in combination with the combined resection of the abdominal organs and parietal peritoneum covering diaphragm, pelvis and abdominal wall. After resection, the abdominal cavity was treated with heated saline at 42-43 degrees, containing cisplatinum (CDDP), Mitomycin C (MMC), and etoposide for 1 hour. PMUE therapy was administered with one course of i.v. infusion of 75 mg/m2 of CDDP and 30 mg/body of MMC on the 1st day, followed by etoposide 50 mg/body on the 3rd, 4th, and 5th day, and with oral intake of 400 mg/body of UFT every day from the 1st day. RESULTS: No post-operative or chemotherapeutic deaths were observed. Systemic PMUE therapy showed no survival improvement, and survival of the peritonectomy + CHPP group was the best, following CHPP, systemic PMUE and surgery alone. CONCLUSIONS: Peritonectomy and CHPP may be the best choice for the treatment of peritoneal dissemination.

[Chemohyperthermic peritoneal perfusion and high-dose chemotherapy followed by peripheral blood stem cell transplantation in advanced colon cancer--a case report].

A 49-year-old woman who suffered from caecal cancer in 1988 underwent chemohyperthermic peritoneal perfusion for peritoneal and ovarian metastases in 1990, and high dose chemotherapy (HDC) with peripheral blood stem cell transplantation (PBSCT) for lung metastases in 1995. Heated saline containing anticancer drugs such as cisplatin, mitomycin C, etoposide (ETP), and pirarubicin, was intraperitoneally perfused at 43 degrees C for 60 minutes. The CD34 positive cells were mobilized by intravenous 500 micrograms G-CSF administration on five consecutive days. These cells were transplanted three days after the last day in the course of HDC, which included intravenous administration of 475 mg carboplatin, 2,020 mg cyclophosphamide, and 540 mg etoposide. The patient has survived with no sign of the disease.

Effects of intraoperative chemohyperthermia in patients with gastric cancer with peritoneal dissemination.

BACKGROUND: The most common cause of noncurative resection and recurrence is gastric cancer is peritoneal seeding. However, the results of treatment of peritoneal dissemination with chemotherapy have been poor with 5-year survival rates of 0%. METHODS: A new in vitro thermochemosensitivity test was performed on gastric cancer cells obtained from 19 surgically resected specimens by using tetrazolium-based colorimetric assay (MTT assay). A novel treatment of the intraoperative chemohyperthermia was undertaken in 83 patients with gastric cancer with peritoneal dissemination. After aggressive resection of primary tumor, lymph nodes, and peritoneal metastases, warmed saline solution containing mitomycin C 30 mg, etoposide 150 mg, and cisplatin 300 mg was introduced into the peritoneal cavity via a closed circuit continuous hyperthermic peritoneal perfusion (CHPP) for 60 minutes to keep the abdominal temperature at 42 degree to 43 degrees C by means of a heat exchange mechanism. RESULTS: The in vitro thermochemosensitivity test that 43 degrees C enhanced the cytotoxin effects on gastric cancer cells under clinically achievable drug concentrations. During CHPP, drug concentrations of cisplatin, mitomycin C, and etoposide in the perfusate remained statistically higher than in the peripheral venous circulation. Among 43 evaluable patients with residual peritoneal seeding, eight (19%) and nine (21%) exhibited complete response and partial response, respectively. The overall 1- and 5-year survival rates were 43% and 11%, respectively. Patients who underwent complete resection survived significantly longer than those with residual disease, and those with complete response had a significantly better prognosis than did those with partial response, and nonresponders. One-year survival rates with complete response, partial response or nonresponders were 88%, 27% and 22%, respectively. Five patients survived longer than 5 years. CONCLUSIONS: Our triple treatment combining surgery and CHPP is an effective therapy for selected patients with gastric cancer with peritoneal dissemination.

[Chemohyperthermic peritoneal perfusion and subtotal peritonectomy for peritonitis carcinomatosa in gastroenteric cancer].

A new operative procedure, called subtotal peritonectomy (SP), in combination with chemohyperthermic peritoneal perfusion, was developed for the treatment of peritonitis carcinomatosa in gastrointestinal cancer. SP includes resection of primary lesion, colon, small bowel, spleen, and gall bladder and parietal peritonectomy. Six patients with gastric cancer and two patients with colon cancer underwent these procedures. A great deal of discharge from the peritoneal cavity, an increase in systemic vascular resistance index, and a decrease in central venous pressure represented much decrease in circulatory volume on days 1 to 2 postoperatively. This state improved at 3 to 4 days after operation. Histopathological study revealed multiple peritoneal seedings with negative surgical margins in all patients. There were no related deaths though bleeding, perforation, and abscess occurred in two patients each. One patient died of peritoneal recurrence after one year, but the other have survived.

Intraperitoneal hyperthermic treatment for peritoneal dissemination of colorectal cancers.

Continuous hyperthermic peritoneal perfusion (CHPP) combined with administration of anticancer drugs was performed in eight colorectal cancer patients with peritoneal dissemination. An overall response rate of 50 percent was achieved in the eight patients. Two of three complete responders are long, recurrence-free survivors for 15 and 30 months. The two-year survival has been achieved in 18.8 percent of the patients receiving CHPP, and this rate is significantly higher than the rates in P2 and P3 patients who did not receive CHPP. The complications of CHPP with administration of anticancer drugs were mild bone marrow suppression in two (25 percent) of the eight patients and also a mild grade of renal dysfunction in one (12.5 percent), though not lethal. The results suggest that the combination of CHPP with the administration of anticancer drugs is a safe and effective therapy for peritoneal dissemination of colorectal cancers.

Hyperthermo-chemotherapy combined with cytoreductive surgery for the treatment of gastric cancer with peritoneal dissemination.

Continuous hyperthermic peritoneal perfusion (CHPP) with anticancer agents (mitomycin C and cisplatin) in warm saline was performed in patients with peritoneal dissemination of gastric cancer following resection of the primary lesion. The effect of CHPP was examined by a second-look operation. This study includes 41 cases of gastric cancer with peritoneal dissemination but without liver metastasis treated during the past 6 years. The overall median survival was 14.6 months to 64.2 months from CHPP to death and the 3-year survival rate was 28.5%. Second look surgery revealed a remarkable diminution in the degree of peritoneal dissemination in 7 (50%) of 14 patients with disappearance of ascites after only one course of CHPP in 7 (77.8%) of 9 patients. Long-term 3 year-survival was noted in 4 (9.8%) patients on CHPP. Side effects were renal insufficiency in 2 (5%) patients, leukopenia in 2 (5%) patients, and perforation of the small intestine in 1 (2%) patient. These results suggest the effectiveness of CHPP in the treatment of gastric cancer with peritoneal dissemination.

[Clinical experiences with hyperthermochemotherapy of hepatic metastasis from gastric cancer].

Thermochemotherapy was performed on gastric cancer cases of hepato-metastasis. The subjects were 12 gastric cancer cases having hepato-metastatic lesions (10 synchronous, 2 heterochronous). Using 8 or 13.58 MHz-dielectric heating apparatus, thermotherapy was carried out for 40-60 min (twice a week, 5-35 times, averaging 12.8 per case) at an intra-tumoral temperature greater than 42 degrees C. Chemotherapy consisted of hepato-arterial infusion of MMC 10 mg/BW, CDDP 75 mg/m2 once per 3-4 weeks and consecutive daily administration p.o. of UFT 800 mg/BW. Effect greater than PR was noted in 75% (9/12) on the whole and in 100% (5/5) and 57% (4/7) for H1-2 and H3, respectively. Mean and 50% survival periods were 9.3 and 7.2 months, respectively, with a one-year survival rate of 38%. Chemotherapy-induced side effects were nausea and vomiting in 83% and leukopenia and thrombopenia in 67%, while the only thermotherapy-induced side effect was subcutaneous fatty tissue necrosis in 3 cases. The above results suggested the effectiveness of the present thermochemotherapy in the treatment of hepato-metastasis of gastric cancer.

Continuous hyperthermic peritoneal perfusion for the treatment of peritoneal dissemination in gastric cancers and subsequent second-look operation.

A total of 31 patients with gastric cancer showing peritoneal dissemination received continuous hyperthermic peritoneal perfusion (CHPP) in combination with the administration of cisplatin (CDDP) and mitomycin C (MMC). The authors developed a new special device named the peritoneal cavity expander (PCE) for sufficient perfusion and direct temperature measurement in the peritoneal cavity. As complications of CHPP three patients presented with bone marrow suppressions (leukocytes less than or equal to 3000/mm3 and/or platelets less than or equal to 30,000/mm3): one, leakage of intestinal anastomosis; one, intestinal perforation; and one, acute renal failure. But none of them was lethal. Twelve of 31 patients who had received CHPP during the initial operation underwent second-look operation (SLO) for the assessing the effects of CHPP and for resecting residual or recurrent tumors. Among 12 patients who received SLO complete response (CR) was observed in four patients, partial response (PR) in one, no change (NC) in three, and progressive disease (PD) in four, with the overall response rates (%CR + %PR) standing at 41%. Two-year survival rate of the complete and partial responders was 50%, which was significantly higher than 0% of the other responders (NC + PD). The survival curves of the two groups were significantly different (P less than 0.05, generalized Wilcoxon test). These results supported that CHPP was well tolerated and effective for the treatment of patients with peritoneal dissemination in gastric cancer when combined with anti-cancer drugs having synergism with hyperthermia. Since the outcome of SLO was one of prognostic factors it was important to follow up these patients by SLO.

[Multimodal therapy using hyperthermia for gastric cancer--with special reference to histological studies].

We carried out a combination preoperative therapy involving radiofrequency hyperthermia (8 MHz or 13.56 MHz) with radiation (10-MV X-ray) or chemotherapy (Mitomycin C, CDDP or UFT) for 24 advanced gastric cancers with the aim of preventing local recurrence and improving resectability. The tumor and histological effects were evaluated in each case. Furthermore, an agar phantom possessing a cavity, for simulating the stomach, was employed in an experiment to evaluate temperature distribution upon RF-heating. In the experiment using the agar phantom, the rising temperature around the cavity at 3 o'clock was higher than at 5' and 6 o'clock. This suggested that gastric juice and air must be aspirated when treating a patient by RF-heating. Of the 24 tumors, 4 (17%) showed partial response. Histological effects were observed in 67% of 21 primary tumors. The rate of histological effects in metastases of lymph nodes, liver and peritoneum were 29% (4/14), 100% (2/2) and 0% (0/4), respectively. Tumor response was closely correlated with irradiation and the temperature in the stomach cavity (over 42.5 degrees C). Almost all patients showed good tolerance of this combined therapy. These results show that combined treatment involving radiation, chemotherapy and hyperthermia appears to be a potentially useful from of preoperative therapy for patients with advanced gastric cancer.