Kiyoshi Inokuchi

The clinical usefulness of preoperative CEA determination in gastric cancer

Between 1980 and 1984, preoperative serum carcinoembryonic antigen (CEA) was determined in 468 patients with gastric cancer to evaluate its clinical usefulness. The positive rate of preoperative CEA was 20.9 per cent in these 468 patients. A significantly higher CEA positive rate was obtained in those patients with liver metastasis (69.2 per cent), n3–4 (40.0 per cent), stage IV gastric cancer (37.0 per cent) and Pap, Tub1 histological type (26.3 per cent) (p<0.01). It is interesting that the positive rate of the 49 unresectable patients was 51.0 per cent, which was significantly higher than 17.4 per cent of the 419 resectable cases (p<0.01). CEA levels in 16 of the 39 patients with liver metastasis were more than 100 ng/ml. In contrast, serosal invasion and peritoneal metastasis were less correlated to the CEA positive rate. In the 419 resected cases, the 5 year survival rate in the higher CEA group of more than 50 ng/ml (35 cases) was 4.4 per cent, which was significantly lower than 64.0 per cent in the negative group (346 cases) (p<0.01). These results show that CEA determination in patients with gastric cancer is useful for the prediction of prognosis, as well as for a diagnostic tool to discover the presence of liver or lymph node metastasis.

Postoperative adjuvant immunochemotherapy with mitomycin C, futraful and PSK for gastric cancer. An analysis of data on 579 patients followed for five years.

In order to evaluate the combination of immunochemotherapy with mitomycin C (MMC), futraful (FT) and PSK, as an adjuvant to surgery for curatively resected gastric cancer, a randomized controlled study by the sealed envelope method was performed with the participation of 97 hospitals in the Kyushu and Chugoku districts of Japan. The MMC+FT+ PSK group showed a significant increase in 5 year survival from the other groups (p<0.05). Moreover the survival rate was significantly higher in the MMC+FT+PSK group than in the MMC+FT group (p<0.01). According to the analysis on stratification, the MMC+FT+PSK group showed the best survival rate in cases with positive lymph node metastases, positive serosal invasion and positive lymph node metastases plus serosal invasion, and in cases of undifferentiated carcinoma by histological type and in those with a preoperative positive PPD reaction (p<0.01 or p<0.05). Thus, the combination of MMC, FT and PSK was indicated to be useful as an adjuvant immunochemotherapy for those patients with gastric cancer submitted to curative resection.

Postoperative adjuvant chemotherapy for gastric cancer, the second report. Analysis of data on 2873 patients followed for five years

The effectiveness of combination chemotherapy with mitomycin-C (MMC) plus futraful (N1-(2′-tetrahydrofuryl)-5-fluorouracil), as an adjunct to surgery for gastric cancer was investigated in a prospective randomized controlled study. Three thousand and thirty-three Japanese patients in 344 hospitals were entered and 2873 could be followed for 5 years. All patients had undergone gastrectomy from April 1977 to May 1979 and were assigned, at random, to either Groups A, B or C. In Group A, bolus MMC was administered with no further treatment. In Group C, oral futraful was given for one year, without MMC induction. In Group B, both a bolus MMC injection and oral futraful were prescribed. This randomized study showed no statistical difference in the 5 year survival rate among the three groups. However, in patients given MMC and put on oral futraful for one year, the 5 year survival rate for those with stage III gastric cancer or for those with positive lymphnode metastasis plus obvious serosal invasion seemed to be improved.

Prognostic study of intramucosal carcinoma of the stomach with DNA aneuploidy

Cell nuclear DNA content was microspectophotometrically measured in 70 patients with a gastric carcinoma lesion of less than 4.0 cm in diameter and with mucosal or minimal submucosal invasion. Two groups were prepared; low ploidy and high ploidy, according to the degree of dispersion on the DNA histogram. Twenty-four cases of high ploidy were reviewed from the aspects of clinicopathology and prognosis and the findings compared with data on 46 of low ploidy. The high ploidy group was characterized by an elevated lesion and a differentiated carcinoma while the low ploidy group had a depressed lesion and an undifferentiated carcinoma Postoperative recurrence was confirmed in none of the low ploidy cases and 2/24 of the high ploidy cases. The five and ten-year survival rates of the patients with high ploidy were 100 per cent and 91.1 per cent, respectively. Compared to the finding that patients with submucosal carcinoma of high ploidy survived at a rate of only 64.8 per cent in the 5-year follow-up, efforts should be directed toward a higher detection of gastric carcinoma with aneuploidy at the stage limited to within the intramucosal layer. Endoscopic treatment for early gastric carcinoma is not recommended, especially for a differentiated carcinoma, even if the invasion is confined to the mucosa, since it may include aneuploid carcinoma.

Postoperative adjuvant immunochemotherapy with mitomycin C, tegafur, PSK and/or OK-432 for gastric cancer, with special reference to the change in stimulation index after gastrectomy

In order to evaluate the efficacy of combined immunochemotherapy with mitomycin-C, tegafur, PSK and/or OK-432 as an adjunct for curatively resected gastric cancer, a prospective randomized controlled study using the envelope method was performed, in which 266 institutions from around Japan participated. The 3 year survival rates for all cases, and for ps(+)·n(+) cases, were insignificantly higher in the immunochemotherapy groups receiving PSK and/or OK-432 than in the control group. However, because 28.2 per cent of the cases were excluded from the final statistical analyses, the results of this study may have questionable statistical credibility. Changes in the stimulation index (SI) suggest that the administration of PSK may result in an inhibition of the immunosuppressive activity of cancer patients. The high SI group showed a significantly higher 4 year survival rate than the low SI group.

Preoperative detection of a highly malignant type of early gastric carcinoma by cytophotometric DNA analysis.

A cytophotometric DNA analysis was made of gastroendoscopically biopsied materials of 43 patients with early gastric carcinoma and the data were compared with the DNA patterns of the resected specimens of these patients. The DNA patterns could be classified into two types, Low Ploidy and High ploidy, according to the degree of dispersion of the DNA value. The Ploidy to Ploidy coincidence of the DNA patterns between biopsied material and the resected specimen in the same lesion was noted in 93 per cent (39/42). The DNA patterns of the resected specimens were consistent in the majority of cases, regardless of the areas examined, center or periphery, and mucosa or submucosa of the same lesion. This study provides evidence that a highly malignant type of early gastric carcinoma, Pen A type, could be differentiated in gastroendoscopically biopsied materials by a cytophotometric DNA analysis.

Mitomycin C plus carmofur (HCFU) adjuvant chemotherapy for noncuratively resected cases of colorectal carcinoma (interim report).

In order to examine the efficacy of adjuvant chemotherapy employing Mitomycin C (MMC) and carmofur (HCFU) for patients with noncuratively resected colorectal carcinoma, a cooperative study was performed by 54 institutions in the Kyushu and Chugoku areas in Japan. The prospective randomized controlled study consisted of two groups, one receiving only MMC and the other receiving MMC as well as HCFU. Out of an original total of 200, 170 cases were evaluable. Concerning the 30-month survival rate, a better result was observed in the MMC+HCFU group than in the MMC only group (Z-test: p<0.05). Significantly better survival rates were obtained in those cases with disseminating peritoneal metastasis, hepatic metastasis and Stage V cancer in the MMC+HCFU group as when compared with the MMC only group (generalized Wilcoxon test: p<0.05). No significant side effects due to the combined administration of HCFU were recognized. The combined administration of MMC and HCFU were recognized. The combined administration of MMC and HCFU was suggested to be a safe and effective adjuvant chemotherapy in noncuratively resected cases of colorectal carcinoma.

The usefulness of CEA as an indicator for early detection and a guide to the treatment of recurrent gastric cancer

The usefulness of carcinoembryonic antigen (CEA) as an indicator for recurrence and a guide to the treatment was evaluated from a retrospective analysis of 88 patients with recurrent gastric cancer. Sixty-two of these patients (70.5 per cent), 25 of whom had a preoperative positive assay, and 37 a negative assay, had elevated levels of CEA after disease progression. Averaged CEA level in patients with liver metastasis was significantly higher (872 ng/ml) than in those with peritoneal metastasis (68 ng/ml), with lymph node metastasis (103 ng/ml) or with local metastasis (93 ng/ml) (p<0.01). An elevation of CEA was found prior to the clinical manifestation of recurrence, and the average lead time was 4 months. In 25 patients with a lead time of more than 4 months, survival time after CEA elevation was 13.3 months, which was longer than the 6.5 months of 28 patients with less than 4 months. Thirty-seven of the 88 patients were treated after recurrence. The average survival period after the detection of recurrence was 9.4 months in patients with surgical treatments followed by chemotherapy, 5.9 months in those with chemotherapy alone and 3.8 months in those with surgery alone. The average survival period of 26 patients with positive CEA assays in recurrence was 5.1 months longer than of patients with negative assays. This fact suggested that early detection of recurrence followed by various treatments, in the elevated CEA group, contributes to favorable results.

Development of erosive gastritis in a canine model of esophageal varices

We designed a reproducible canine model of esophageal varices, based on the concept of a regional hyperdynamic state in the upper stomach. Arterialization of the left gastric vein concomitant with the distal splenorenal shunt led to a stable hyperdynamic state and reproducible esophageal varices occurred. In the long-term follow-up of these dogs with varices, the erosive gastritis seen in the upper stomach learly resembled clinically observed lesions. Hemodynamic and morphological studies revealed that gastric mucosa of these animals was in an ischemic state, even though there was a remarkable increase in blood flow in the submucosal area. It is suggested that the decrease in mucosal blood flow, as induced by the hyperdynamic state caused erosive gastritis.

A cohort study on second malignancies in gastrectomized patients with gastric cancer I. Second malignancies other than cancer of the gastric remnant

In a retrospective cohort study, a total of 235 (2.32 per cent) second malignancies were clinically observed in 10,138 patients during the average 8.8-year follow-up period. The patients had undergone gastrectomy for gastric cancer during 1960–1975, in seven different institutions. This observed number was smaller than the expected one of 340.9 (p<0.01). Among the 235, cancers of the gastrointestinal tract (111) were the most frequent and followed by respiratory (54) and urogenital (25) cancers. Twelve cases of malignant lymphoma and five of leukemia were also noted. With regard to adjuvant chemotherapeutic agents such as mitomycin-C (MMC), 5-fluorouracil (5FU) or its derivative Tegafur, and cyclophosphamide (EDX), no significant differences in the rate of second malignancies were obtained between the chemotherapy and non-chemotherapy groups. The occurrence rate of second malignancies tended to be higher in the Billroth II group than in the Billroth I, the significance of which is yet to be determined.