Tadashi Kano

Late results of postoperative long term cancer chemotherapy for advanced carcinoma of the stomach

Postoperative long term cancer chemotherapy (PLCC) with the combination of Mitomycin-C, FT-207*, a furanyl analog of 5-fluorouracil, and PSK**, an immunopotentiator, was prescribed for patients with advanced gastric cancer. Five year survival rates for all stage III and stage IV patients were 52.8 and 19.3 per cent in the PLCC group. The rates were 26.7 and 2.2 per cent in the control groups (p<0.05). In curative cases of stage IV, the 5-year survival rate was 50.0% in the PLCC group while the rate was 11.1% in the controls. Mean survival time of patients with peritoneal dissemination or hepatic metastases was 12.8 and 10.9 months, respectively, for the PLCC group, in contrast to the lower 6.4 and 4.3 months for the controls. Thus, the 5-year survival rate of advanced gastric cancer patients in stage III and stage IV was markedly improved when these patients were treated with the protocol. Our findings clearly show that adjuvant chemotherapy should be administered for a long period postoperatively in order to achieve a significant improvement in patients with gastric cancer.

Combined effect of prophylactic lymphadenectomy and long term combination chemotherapy for curatively resected carcinoma of the stomach

Effectiveness of prophylactic extensive lymph node dissection (PELD) plus postoperative long term combination chemotherapy (PLCC) for patients with curatively resected gastric carcinoma was assessed in terms of the degree of serosal invasion and lymph node metastasis. Either the Group 1 and Group 2 lymphnodes were eradicated by PELD. PLCC included intermittent intravenous administration of mitomycin C (0.4 mg/kg intraoperatively followed by 0.2 mg/kg every 3 months) and oral administration of Tegafur (600–800 mg/day) and PSK (3.0 g/day), an immunostimulator, for as long a period as possible. PELD alone resulted in a cure when the malignancy was confined to the mucosal and muscular layers of the stomach as well as to the Group 1 lymph nodes. In cases when the carcinoma involved the serosa and/or the Group 2 lymph nodes, the 5 year survival rate was about 55 per cent the PELD and PLCC groups, such being significantly higher than about 27 per cent in the PELD alone group. Therefore, PELD plus PLCC is highly effective for advanced gastric carcinoma, under a condition of curative resection.

Late results of postoperative long-term cancer chemotherapy for the gastric cancer patients subjected to curative resection

Postoperative long-term cancer chemotherapy (PLCC) with a combination of Mitomycin-C (MMC), FT-207 and PSK (an immunostimulant) was prescribed for gastric cancer patients subjected to curative resection. The 5 year survival rates for patients with stage III and stage IV cancer were 58.3 per cent and 50.0 per cent in the PLCC groups, 48.0 per cent and 15.4 per cent in MMC groups, and 46.3 per cent and 13.3 per cent in no chemotherapy groups, respectively. In stage IV, the survival rate in PLCC group was significantly higher than that in MMC or no chemotherapy group (p<0.05). In the PLCC group, there was a tendency toward a dose-dependent effect in each group, and 5 year survival rate of stage III group administered over 60 mg of MMC, 60 g of FT-207 and 270 g of PSK was 70 per cent, such being remarkably higher than 46.3 per cent in those given no chemotherapy (p<0.07). There was no drug related death and only a slight leukopenia and hepatotoxicity occurred in some patients.

Postoperative long-term cancer chemotherapy (PLCC) extends life-span of non-curatively resected patients with stage IV gastric cancer

Postoperative long-term cancer chemotherapy (PLCC) with a combination of Mitomycin-C, Tegafur and PSK (an immunostimulant) was applied to non-curatively resected cases with stage IV gastric cancer (invading the adjacent organs and/or with metastasis to the liver, peritoneum, and/or distant lymph nodes). This approach has a significant life-prolongation effect. The two-year survival rate was 16.8 per cent in the PLCC group, such being higher than 6.7 per cent and 1.7 per cent in MMC and no chemotherapy groups (p<0.05). 50 per cent survival periods in those with liver metastasis were 8.3 months in the PLCC group, such being longer than 5.2 and 2.8 months in MMC and no chemotherapy groups (p<0.002) respectively. Combination therapy of PLCC and intra-arterial infusion of 5-FU through the proper hepatic artery prescribed for 8 patients with liver metastasis resulted in a 3-month prolongation of 50 per cent survival periods, compared with PLCC alone (p<0.05). In those with peritoneal dissemination the rate was 10.5 months in the PLCC group, that is longer than 6.5 months in the MMC group (p<0.02). In cases of invasion to other organs plus distant lymph node metastasis, the time was 11.0 in PLCC and 7.0 months in MMC groups (p<0.05). Thus, PLCC is a palliative approach for non-curatively resected carcinoma of the stomach.

Serial determinations of carcinoembryonic antigen for early detection of recurrent gastric cancer

In attempts to predict the recurrence of gastric cancer, postoperative changes in serum carcinoembryonic antigen (CEA) levels are monitored in our clinic by radioimmunoassay (Dainabot, Japan). Recurrences are suspected when serum CEA levels are 4 ng/ml, in the postoperative period. Out of 34 patients in whom there were increases in serum CEA, 18 were confirmed to have a recurrence and 15 of these 18 patients were assessed accurately by serial postoperative levels of CEA, two patients died of a recurrence after elevation of serum CEA levels. Thus, recurrence was predicted in 17 out of 34 patients (50 per cent) and in 12 out of 17 patients there was a metastasis to the liver. In 14 out of 34 patients there are no signs of recurrence 9 to 25 months after serum CEA elevations.

Combination of hepatic arterial infusion and systemic chemotherapy for gastric cancer with synchronous hepatic metastases

Between 1964 and 1981, seventy-two Japanese patients with gastric cancer associated with hepatic metastases, in whom the primary tumor had been resected, were treated in a nonrandomized manner at the Second Department of Surgery, Kyushu University Hospital. Fourteen received hepatic arterial infusion (HAI) of 5-FU and Mitomycin C (MMC) combined with systemic chemotherapy, 26 combination systemic chemotherapy of MMC, Futraful and PSK, 18 single drug (MMC) therapy, and 14 no chemotherapy. The average survival was 264 days in HAI combined with systemic chemotherapy, 208 in the combination systemic chemotherapy, 156 in the single drug therapy and 135 in those given no chemotherapy. One year survival and nine month survival rates were 21.4 per cent and 42.9 per cent in HAI combined with systemic chemotherapy, 11.5 per cent and 19.2 per cent in the combination systemic chemotherapy, 5.6 per cent and 11.1 per cent in the single drug therapy and 7.1 per cent and 14.3 per cent in the no chemotherapy group, respectively (HAI vs single drug therapy and no chemotherapy, p<0.01). Five of 14 patients treated with HAI combined with systemic chemotherapy showed a partial response (>50 per cent reduction in tumor size), and the average survival time was 335 days, while that of nonresponders was 224 days. Six of 14 patients treated with combination infusion therapy with MMC and 5-FU survived 314 days, as compared to 201 days for patients with infusion of 5-FU alone.

Oral Administration of Vancomycin in Preventing Postoperative Methicillin-Resistant Staphylococcus aureus Enterocolitis

Summary152 patients who had undergone elective surgery of the digestive organs during the period April 1993 to June 1994 were retrospectively investigated. The patients were divided into 2 groups: a control group (n = 111) and a vancomycin (VCM) group (n = 41), in which vancomycin 1.5 g/day was administered orally from preoperative day 1 to postoperative day 2. In the control group, 11 patients (9.9%) exhibited methicillin-resistant Staphylococcus aureus (MRSA) enterocolitis within 7 days of having surgery. However, there was no incidence of postoperative MRSA enterocolitis in the VCM group (p<0.05 by Fisher’s exact probability test), nor any Clostridium difficile-induced enterocolitis. No adverse effects related to VCM administration were seen. The short term perioperative oral administration of VCM is thus considered to be useful in preventing MRSA enterocolitis after surgery involving the digestive organs. However, it should be borne in mind that this regimen has the potential risk for development of VCM-resistant enterococci.

Combination chemotherapy enhances survival of patients with unresectable gastric cancer.

Of 177 Japanese patients with a gastric cancer which could not be resected and seen at our institution during the period from 1964 to 1979, 153 were investigated with regard to the efficacy of anticancer agents, in terms of prolongation of life. The average survival time was 23 weeks in the combination chemotherapy group (57 cases), 17 weeks in the single drug chemotherapy group (42 cases) and 13 weeks in no chemotherapy group (54 cases). Three and 6 month survival rates in the overall patients were 57.1 per cent and 16.7 per cent for single drug chemotherapy group, and 37.0 per cent and 11.1 per cent for no chemotherapy group, while in the combination chemotherapy group, the rates were higher at 64.9 per cent and 29.8 per cent, respectively (combination chemotherapyvs. no chemotherapy group, p<0.05). In patients with peritoneal dissemination, hepatic metastasis and carcinomatous ascites, there was a significant difference in survival rates between those prescribed combination chemotherapy and those given no chemotherapy (p<0.05). Of 57 in the combination chemotherapy group, 6 and 9 month survival rates were 45.5 per cent and 22.7 per cent in the postoperative long-term cancer chemotherapy (PLCC) group (22 cases), such being higher than other combination chemotherapy group (35 cases), 22.9 per cent and 11.4 per cent, respectively. There was a significant difference in the survival rates between the two groups (p<0.05).