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The relationship between lymph node metastases and postoperative prognosis in 209 patients with early gastric cancer was studied. As to the postoperative prognosis in relation to the extent of lymph nodes dissection, no significant difference was observed among the age-corrected 5-year survival rates following three surgical procedures in patients with early gastric cancer. Age-corrected 5-year survival rates were 0.92 +/- 0.44 R1-resection, 0.95 +/- 0.44 in R2-resection, and 1.00 +/- 0.06 in R3-resection, respectively. In addition, in 71 patients including 33 with early gastric cancer and 38 patients with advanced but relative early gastric carcinoma, the relationship between the immunostatus and postoperative prognosis was investigated. Postoperative age-corrected 5-year survival rate (0.904 +/- 1.153) of the optimal responders with good immunostatus was significantly higher than that (0.582 +/- 1.153) of the suboptimal responders with impaired immunostatus (P less than 0.01). Thus, conservative surgery for regional lymphadenectomy may be an effective procedure for cure of early gastric carcinoma, particularly in cases of a carcinoma limited to the mucosal area of the stomach.

Intrarectal administration of 5-fluorouracil (5-FU) emulsion was compared experimentally with that of 5-FU solution as to the degree of absorption and tissue distribution. For the 5-FU levels in the rectal wall, the levels in the emulsion group remained at high levels during the 6 hour period after administration while the levels in the solution group decreased rapidly. For the 5-FU levels in the lymph nodes, those in the emulsion group were significantly higher (more than four times) and remained at relatively high levels for a longer period than those in the solution group. In the thoracic lymph, 5-FU levels in the emulsion group remained more than two times higher throughout the experimental period. The results suggest tha preoperative intrarectal administration of 5-FU emulsion may be effective as an adjunct to surgery for rectal cancer with lymph node metastasis, because of the long duration of high concentration resulting in the rectal lymphatics and rectal wall.

Anorectal manometric studies were performed on nine patients with Hirschsprung's disease and ten patients with idiopathic megacolon for the purpose of differentiation, comparing with those of the normal subjects. The anorectal reflex was absent in all nine of the patients with Hirschsprung's disease while in all of ten patients with idiopathic megacolon rectal distension produced a relaxation in the anal canal like that of the normal subjects. Manometric studies proved to be a reliable and non-invasive technique for the diagnosis of Hirschsprung's disease and were of particular value as simple screening tests in patients with a clinical suggestion of this disease. The manometric studies of the patients with Hirschsprung's disease or idiopathic megacolon in the present series also demonstrated that the pronounced internal sphincter contraction combined with a total absence of reflex relaxation or an inadequate response of the sphincter to rectal distension might be responsible for the obstructive symptoms in these diseases.

The monocyte count in the peripheral blood, chemotactic responsiveness (MCR) and chemotactic factor inactivator (CFI) were measured in 66 patients with gastric cancer. Monocyte counts in advanced gastric cancer patients were significantly increased. MCR was significantly depressed in gastric cancer patients in the advanced stage of the disease, as compared with findings in the control groups. Sixty-seven percent of the patients with stage IV carcinoma had abnormally depressed responses. The CFIs were significantly higher in gastric cancer patients than in the control groups, and there was a positive correlation between the degree of inhibition and extent of cancer progress. These data support the hypothesis that qualitative and quantitative abnormalities of circulating monocytes, as macrophage precursors, may hinder immunological host defense mechanisms.

Since somatostatin is a local hormone controlling gastric acid secretion and gastrin release, quantitative histopological distribution of the G-cells and D-cells in the canine whole stomach was investigated by the specific immunoperoxidase staining technique. The G-cells were identified only in the pyloric antrum and the estimated total number of G-cells was 15.5 X 10(6) cells. Most of the D-cells were also found in the pyloric antrum but a few were found scattered diffusely throughout body and fundus of the stomach. The estimated total number of D-cells was 11 X 10(6) cells in the pyloric antrum and 4 X 10(6) cells in the corpus and fundus. The G-/D-cell ratio in the antrum was 1.4:1. The number of G-cells as well as D-cells per unit mucosal surface area was significantly higher on the greater curvature and the proximal part of the antrum than on other areas of the antrum. Thus, the pattern of distribution in G-cells was similar to that of D-cells and there was a highly significant correlation between G- and D-cells per unit mucosal surface area. It would appear that under normal conditions, the number of G- and D-cells in the antrum are in good balance and may play an important role in the control mechanisms related to gastric secretion.

To prevent the reflux of gastric contents into the bronchial tree through the tracheoesophageal fistula in patients with esophageal atresia with tracheoesophageal fistula, Nissen fundoplication was performed in the first-stage repair of staged operations. After elimination of the pulmonary complication, a correction of esophageal atresia and tracheoesophageal fistula was successfully performed through the extrapleural route at the age of 16 days. Thus, because Nissen fundoplication is simple to perform and effective in preventing gastroesophageal reflux, this procedure is considered to be useful in the staged repair of esophageal atresia with tracheoesophageal fistula.

In order to evaluate the effect of anticancer drugs on the metastatic lesions of the regional lymph nodes from stomach cancers removed after oral administration of 5-FU emulsion, histological examinations of the specimens obtained from 107 surgical cases were carried out. In additional 13 cases with gastric cancer, the active 5-FU concentrations in the regional lymph nodes were determined. The effect of 5-FU emulsion in metastatic lesions as determined was histologically classified into Grades 0 to III according to the severity and extent of damaged cells and cell nests Grades II and III were judged to demonstrate the beneficial effect of the 5-FU emulsion. Such changes were identified in 62.0 per cent of the 242 metastatic lymph nodes, and the effectiveness increased as the total dose of the 5-FU emulsion administered increased (50.9 per cent for 5,000 mg or less, 70.9 per cent for 5,000 to 6,000 mg, and 72.7 per cent for 6,000 mg or more). The rate of effectiveness also varied with the histological type of the primary carcinoma, i.e. the differentiated type being more sensitive. The mean active 5-FU level in the regional lymph nodes was higher after the administration of 5-FU emulsion than of 5-FU solution supporting the earlier animal experiments.

To obtain information regarding the immunologic capacity of uninvolved regional lymph nodes (RLNs) draining tumor, the in vitro response of regional lymph node cells (RLNCs) to PHA was investigated in lymph nodes from 55 patients with gastric or colorectal cancer, and gastric ulcer. Evaluation of data relative to cancer progress demonstrated that, in gastric cancer patients, the response of stimulated RLNCs from patients with middle stage carcinoma was significantly higher compared with those of cells from patients with early or late stage carcinoma, such being similar to the response of RLNCs from control patients with gastric ulcer. The results from colorectal cancer patients were also similar to those from patients with gastric cancer. Our results suggest that RLNs without metastasis contain cells capable of responding to PHA despite the presence of growing tumors in these cancer patients. In the results of PHA stimulation in relation to the lymph node morphology, we observed in both groups of patients with gastric or colorectal cancer that, regardless of the extent of the cancer lymph nodes with lymphocyte predominance there was a high PHA response while lymph nodes with lymphocyte depletion and unstimulated nodes exhibited a low PHA response. These results show a close relationship between this lymph node morphology and immunologic status of nodes.

Oral administration of 5-fluorouracil (5-FU) emulsion was compared experimentally with that of 5-FU aqueous solution as to the degree of absorption and tissue distribution. After oral administration of both the 5-FU emulsion and the 5-FU solution, 5-FU was detected at the highest level in both the stomach and the duodenum. This seems to suggest that 5-FU is strongly affinitive to the tissues of the gastrointestinal tract. As to the relative concentration of these two forms of the drug, the oral administration of the 5-FU emulsion resulted in a maximum value 1.5 times higher than that of the 5-FU solution. An appreciable concentration of 5-FU was maintained for a considerably long time with the administration of 5-FU emulsion. In the lymph, the maximum level of the 5-FU emulsion was three times higher than that of the 5-FU solution. The drug concentration of the 5-FU emulsion remained higher than that of the 5-FU solution through the entire duration of the experiment. Regarding the drug concentration in the regional lymph nodes, the pattern demonstrated was almost the same as in the lymph itself. It is expected that the oral administration of 5-FU emulsion may be useful as an adjuvant to the surgical treatment of gastric cancer, because of the high drug concentration resulting both in the gastrointestinal tract and in the regional lymph nodes.

Histochemical and biochemical examinations of rectal biopsy specimens were performed in 13 patients with Hirschsprung's disease and in seven with idiopathic constipation and no megacolon. Serum and erythrocyte acetylcholinesterase (AchE) activity in these two groups was compared with that in 30 normal controls. AchE staining of rectal biopsy specimens proved to be a reliable and convenient diagnostic approach in patients with Hirschsprung's disease. Biochemical assay of AchE activity in rectal biopsy specimens was also of value in the diagnosis, however, there was an overlap between Hirschsprung's disease and idiopathic constipation. Erythrocyte AchE activity correlated well with AchE activity in rectal biopsy specimens. Therefore, assays of erythrocyte AchE activity provided useful additional information, especially in screening tests for Hirschsprung's disease.

Leucocytes from patients with gastric cancer and other malignant and non-malignant diseases of the gastrointestinal tract as well as from healthy controls were tested for leucocyte migration inhibition test (LMI) using five different, allogeneic 3M KCl soluble extracts from gastric cancer tissues. The normal range of migration index (MI) was considered to be between 0.77 and 1.18 by calculating the mean MI +/- 2SD of ten healthy controls with cancer extracts. MIs out of this range were considered to be pathologic. In LMI test with a single tumor extract, pathologic MI was found in 48% of 79 gastric cancer patients, such being significantly higher than in those (4-21%) of three other groups of patients. In the panel mode of LMI, i.e., testing each blood sample with five different tumor extracts, 79% (62/79) of patients with gastric cancer were reactive, while 25% (5/20) of colorectal cancer patients showed "positive" reaction and no "positive" reactivity was observed in two other groups of patients. Thus, the "positive" reactivity in patients with gastric cancer was observed significantly higher than those in the other 3 groups of patients. Gastric cancer extracts had a wide range of cross-reactivity when compared with colorectal tumor extracts which showed a relatively restricted cross-reactivity. Thus, the LMI tests, particularly when tested by a panel mode, seems to express cell-mediated immunity against tumor associated antigens of gastric cancer.

Sera from 60 gastric cancer patients and 20 patients with benign gastric diseases and 8 healthy controls were tested for inhibitory effects on the humoral response to sheep erythrocytes (SRBC) by the plaque forming cell assay (PFC R.I.) using mouse spleen cells and on the phytohemagglutinin (PHA)-induced blastogenesis of normal mouse spleen cells (PHA S.R.). Gastric cancer patient sera showed a significantly lower PFC R.I. than did sera from benign gastric disease patients and from the healthy controls. However, there was no appreciable interstage difference in the degree of depression. The PHA-induced blastogenesis of normal spleen cells was also decreased in the presence of sera from cancer patients, as compared to that in the presence of sera from benign disease patients and from the healthy controls. The depression progressed with advancing stage of cancer. The PHA S.R. showed significant negative correlations with serum levels of IAP, IS, alpha 1-acid glycoprotein and alpha 1-antitrypsin, but there were no such correlations between PFC R.I. and these glycoproteins in serum. There was also no correlation between the values of the PHA S.R. and the PFC R.I. These results suggest that these two assays may depict immunosuppressive activities operating through entirely different mechanisms.

Preoperative intrarectal administration of 5-FU emulsion was attempted as an adjuvant chemotherapy to surgery for rectal cancer. The drug concentrations of resected specimens were determined and histological examinations of them were carried out in order to evaluate the effect of anticancer drugs on the metastatic lymph nodes as well as on the primary tumors. 5-FU levels both in the regional lymph nodes and primary tumors of 18 patients with rectal cancer, who were given with the 5-FU emulsion (emulsion group) or 5-FU suppository (suppository group) intrarectally two hours before surgery, was found to be much higher in emulsion group than in suppository group. 46 patients with rectal cancer were treated preoperatively with intrarectal administration of 5-FU emulsion (25 cases) or 5-FU suppositories (21 cases) for a period of 10 days before surgery, and the histological effect of this regimen on the metastatic lesion in the lymph nodes, as well as in the primary tumor was examined. No detectable difference was found in the primary lesions between the emulsion group and the suppository group. In the metastatic lesions, however, the rate of effectiveness was higher in the emulsion group than in the suppository (68 percent versus 33 percent).

The antireflux mechanism of the Nissen fundoplication was investigated in 15 mongrel dogs by esophageal manometry. Nissen fundoplication increased the lower esophageal resting pressure for 2 weeks after operation; however, by 4 weeks it had decreased to a level which did not differ significantly from the preoperative value. Thus, lower esophageal sphincter (LES) length, unlike LES pressure, was maintained for a long period. These results suggest that restoration of competence at the gastroesophageal junction after Nissen fundoplication depends on an adequate length of LES as well as increased LES pressure. The gastrin-stimulated LES pressure 1, 2 and 4 weeks after operation was significantly higher than the preoperative stimulation pressure. Therefore, it seems that the antireflux mechanism is associated not only with the mechanical aspect of the wrapping but also with creation of a new muscular sphincter substitute that reacts sufficiently to gastrin stimulation.

To assess the resectability of retroperitoneal neuroblastoma and determine the timing of a "second-look" resection of primary tumor on the basis of aortographic findings, 32 abdominal aortographies performed on 26 patients with retroperitoneal neuroblastoma (22 adrenal, 4 paraspinal) were examined retrospectively. Angiographic findings of both displacement of aorta and narrowing of aorta indicate the difficulty of complete removal of the neuroblastoma. These findings were particularly useful in determining the resectability of retroperitoneal neuroblastoma. On the other hand, the absence of angiographic findings of both displacement of main vessels (celiac axis, origin of superior mesenteric artery, or renal arteries) and stretching of main vessels indicate the feasibility of complete removal of retroperitoneal neuroblastoma. On the basis of angiographic findings, the decision to resect the retroperitoneal neuroblastoma could be made in 6 patients, who underwent the "second-look" operation.

The studies reported here were designed to examine the effects of intratumoral preoperative administration of Bacillus Calmette-Guerin (BCG) on the cure rates of C3H mice transplanted with MH134 tumor cells and on the metastatic rates in the regional lymph nodes. Furthermore, the morphological findings occurring in the regional lymph nodes were monitored during tumor growth using H-E stain and non-specific esterase staining. The cure rate of the Group treated with BCG intratumoral injection and surgery was significantly higher than that of the Group treated with surgery alone, and in the BCG + surgery group metastatic rates of regional lymph nodes decreased consistently after operation. Moreover, in this group, extensive sinus histiocytosis and marked swelling of the regional nodes were frequently observed. Quantitative studies of the cell kinds using the esterase staining indicated that intratumoral injection of BCG has an effect on the influx of lymphoid cells into the regional nodes, but does not aid specific cell lineage to flow into the regional nodes. In cytostatic assays, it was shown that the regional lymph node cells and spleen cells in the BCG + surgery group always have a greater per cent of inhibition than those in the surgery alone group.

Anal sphincter function and rectal reservoir were studied in 27 patients after low anterior resection, in 6 after Welch or Turnbull type pull-through surgery and in 3 after Bacon type pull-through surgery. Sixteen patients who had undergone right hemicolectomy served as a control group. Anal sphincter function immediately after low anterior resection was diminished, but improved during the following 6 months. Rectal capacity was much reduced immediately after surgery, but increased with time, and the neorectum could to some extent adapt to its new role as a reservoir. After pull-through operations, anal canal pressure and rectal compliance were significantly lower than after low anterior resection or right hemicolectomy. These findings may explain the increased frequency of bowel action after pull-through operations.

The present study was undertaken to determine the adenosine deaminase (ADA) activity of peripheral lymphocytes in patients with gastric cancer, with respect to the cancer progression, the effect of surgery and/or immunotherapy. The gastric cancer patients showed lower lymphocyte ADA activity than did the normal control. The lymphocyte ADA activity did not decrease with the cancer progression. There was a significant correlation between lymphocyte ADA activity and blastogenesis of lymphocyte by phytohemaglutinin or concanavalin A. Six months following gastrectomy, the lymphocyte ADA activity was increased, as compared with the preoperative value. The ADA activity of patients on post-operative OK-432 showed a greater increase, as compared to that of patients not given this treatment. In conclusion, decreased lymphocyte ADA activity in gastric cancer patients might be due to either the cancer bearing status or to the immunological suppression.