Objective: To improve the understanding of the etiology of perforated peptic ulcers (PPUs) and their association with cancer development.

Introduction: Some patients are more susceptible to multiple primary malignancies (MPMs). However, understanding of the effects of this susceptibility on the benefits and detriments to patient survival are poorly understood.

Background and Purpose: Based on the homogenous human leukocyte antigen (HLA) properties of the Japanese population, patients who have undergone examination of their HLA antigens have exhibited more beneficial outcomes than those without HLA examination. This study aimed to evaluate whether HLA type and location of the institutes and hospitals where patients were enrolled affected patient outcomes. Materials and Methods: A total of 1753 patients from member hospitals of the Japanese Society of Strategies for Cancer Research and Therapy throughout Japan were enrolled in this study from August 1977 to August 2005. HLA antigens were serologically tested using the NIH standard microlymphocytotoxicity method for HLA-A, -B, -C, - DR and -DQ. We used a method of quantification for the response pattern and classified similar HLA antigens into four groups: type 1, 2, 3 or 4, and classified patients into four groups: patients who received effective therapy, ineffective therapy, or neither effective nor ineffective therapy, and unclassified. Effective therapy was defined as therapy that resulted in a patient's survival for a period of at least 5 to 10 years, and ineffective therapy as a therapy that resulted in a patient's survival for a period of less than 5 years. The location of the institutes and hospitals where patients were enrolled was classified into three groups: eastern Japan, western Japan and Tokai University. Conclusions: There were no significant differences among HLA types, the locations and patient outcomes. Our idea is promising as a path toward individual treatment. HLA information could provide personalized therapy based on the homogenous HLA properties of the Japanese population.

Benzo[1,2-b:4,3-b']dithiophene/triphenylamine copolymers P-2eh (with no methyl substituents) and P-Me and P-2Me (with methyl substituents at triphenylamine sites) were synthesized by Stille coupling reactions. In the ground state, the methyl substituents at the ortho positions to the BDT unit oil the triphenylamine (TPA) moiety in P-Me and P-2Me caused twisting of the polymer structure and clearly limited conjugation of the polymer backbones. However, in their excited states, all of these copolymers were shown to have planar structures, and almost the same emission maxima were observed. This result indicates that, in the excited states, pi-conjugation of the polymer backbone results in the adoption of a more stable planar structure rather than the twisted structure observed in the ground state. The maximum EL efficiencies of devices based on P-Me and P-2Me were about three times higher than that of P-2ch due to restricted pi-stacking/aggregation of the Conjugated copolymers in the solid state and improvements in thermal and electrochemical stability.

To assess the roles of the extent of gastric resection and duodenal food passage reconstruction in gastric cancer, we examined a consecutive series of 1,061 patients who underwent total or partial (proximal and distal) gastrectomies with or without duodenal food passage reconstruction between August of 1974 and January of 2002, and received gastrectomies with D2-3 lymph node dissection. Patients who underwent distal or proximal gastrectomy were found to have significantly better survival rates than those who underwent total gastrectomy in stages 1A (10-year survival: 86.6 and 78.9 vs. 61.6%), 2 (56.5 and 65.6 vs. 34.4%), 3A (45.9 and 33.3 vs. 15.2%), and 4 (5-year survival rates: 23.7 and 50.0 vs. 7.1%). Additionally, patients with duodenal food passage reconstruction or double tract reconstruction also showed significantly better survival rates than those without duodenal food reconstruction in stages 1A (10-year survival: 86.4 and 82.5 vs. 61.7%), 1B (69.9 and 90.6 vs. 54.1%), 2 (60.5 and 63.3 vs. 16.5%), and 3A (39.9 and 47.4 vs. 23.1%). In multivariate analysis, the independent prognostic factors were age at operation, depth of tumor, duodenal food passage reconstruction, and lymph node metastasis. Our results indicate that both the extent of gastric resection and duodenal food passage reconstruction were important factors in the outcome of gastric cancer patients, and that surgeons should perform minimal gastric resection with preservation of the duodenal food passage when the gastric stump is tumor-free.

In Japan, mass screening has probably contributed to improvements in long-term survival because of early detection and early treatment. We evaluated whether gastric cancer patients without symptomatic signs show better outcomes than those with symptoms. The symptoms at hospital admission of a consecutive series of 1633 gastric cancer patients who underwent standard gastrectomy between July 1975 and Dec. 2000 were analyzed. Patients were classified into three groups at hospital admission according to their reasons for coming to our hospital; the no-symptom group included asymptomatic patients, the pain group patients who had abdominal pain, and the other group patients who had symptoms such as weight loss, vomiting, anorexia and so on. If the patients had symptoms and had participated in a mass screening, they were placed in the symptomatic group. Asymptomatic stage 1A and 2 gastric cancer patients showed better survival than those with symptoms, except pain. Further, those who have undergone postoperative adjuvant therapy might have better outcomes than those who did not. Mass screening for gastric cancer was beneficial for early-staged patients who have no symptoms. Mass screening is a useful tool for detecting stage 1A-2 cancer that can respond to therapy.

The optimal extent of resection for proximal gastric adenocarcinoma is controversial. We evaluated a consecutive series of 214 patients to identify the best principal method of surgical therapy for resectable proximal gastric cancer and its longterm outcome. We focused on the relationships among the extent of gastric resection, the consequent duodenal passage (DFP) reconstruction and the type of postoperative adjuvant therapy. The patients underwent total or proximal gastrectomy between August 1974 and May 1997. They ranged in age from 28 to 80 years (median: 60 years), and 75.2% were men.Among the patients at stage 1A or stage 4 gastric cancer, those who received subtotal rather than total gastrectomy had significantly better survival rates. Patients at stage 1A who received duodenal passage reconstruction also had significantly higher survival rates than those who did not receive it. Multivariate analysis revealed that DFP reconstruction and the extent of the gastric resection were significant independent prognostic factors for patients at all stages. In patients who underwent gastrectomy alone without postoperative therapy the extent of the gastric resection was an independent prognostic. On the other hand, in patients who underwent either proximal or total gastrectomy followed by postoperative adjuvant therapy, DFP reconstruction was an independent prognostic factor. Though the actual mechanism underlying this is unclear, our findings indicate that surgeons dealing with proximal gastric cancer must take into consideration the relationships among the extent of gastric resection, DFPR and the type of postoperative adjuvant therapy.

A consecutive series of 570 patients with middle gastric cancer were evaluated in order to assess their prognosis, focusing on the relationship among the extent of gastric resection, consequent duodenal passage reconstruction, and postoperative adjuvant therapy.These patients underwent total, subtotal (distal or proximal) gastrectomy between Aug. 1974 and May 1997. Patients receiving subtotal gastrectomy had significantly better survival than those receiving total gastrectomy in stage 1A and 3A gastric cancer. On the other hand, patients with duodenal food passage (DFP) reconstruction had better survival than those without DFP reconstruction, though the difference between these groups was not significant.Multivariate analysis revealed that the duodenal food passage and the extent of the gastric resection were independent prognostic variables; in patients who underwent only gastrectomy, the extent of resection and DFP were independent prognostic variables, whereas in patients who underwent gastrectomy with postoperative adjuvant therapy, these two factors were not independent prognostic variables. Though the actual mechanism behind this difference is unclear, our findings indicate that gastric surgeons must carefully consider among the surgical resection procedures when treating adenocarcinoma of the middle gastric cancer.

To determine the optimal surgical management of resectable distal gastric cancer, we evaluated the long-term prognoses of 516 consecutive patients who underwent total or distal gastrectomy with D2 lymph node dissection between August 1974 and May 1997. We focused on the relationships among the extent of gastric resection, the consequent duodenal passage reconstruction and the type of postoperative adjuvant therapy. For patients with stage 2 or 3A gastric cancer, survival rates were significantly higher among those who received subtotal rather than total gastrectomy, and among those who received duodenal food passage reconstruction versus those who did not. Multivariate analysis revealed that the extent of the gastric resection and the reconstruction of the duodenal food passage were the significant independent prognostic variables, which also included residual tumor, age at operation, depth of tumor and lymph node metastasis. In patients who received gastrectomy alone, the extent of the gastric resection and the reconstruction of the duodenal food passage were not independent prognostic variables. On the other hand, in patients who underwent gastrectomy with postoperative adjuvant therapy, the extent of the gastric resection and the condition of the duodenal food passage were significant independent prognostic factors. In conclusion, gastric surgeons must ensure that their surgical resection procedures follow more physiological DFPR and postoperative adjuvant therapy when they treat distal gastric adenocarcinoma.

Reported differences in clinicopathological patterns of early gastric carcinoma (GC) between the West and Japan suggest the presence of changes in cancer biology. The aim of this study was to analyze clinopathological-changing patterns of early gastric cancer (GC) biology in a large series of patients from Japan, where mortality rates for GC are high. Using the collected data of 1005 early GC patients treated surgically between 1975 and 2000, we analyzed differences in clinicopathological patterns for five consecutive periods: 1975-80 (group I), 1981-1985 (group II), 1986-1990 (group III), 1991-1995 (group IV), and 1996-2000 (group V). The mean age of the patients was 58 years (range, 21-88), which increased from 57 years (range 32-78), 55 years (21-78), 57 years (range 28-86), 58 years (range 24-87), and 60 years (range 32-84) in groups I, II, III, IV, and V, respectively (group II vs. IV, p<0.05). Analysis revealed differences in histological type (differentiated vs. undifferentiated adenocarcinoma in male and female) between groups; no tendency to decrease or increase was observed in either histological type in men, whereas a significant trend toward increasing of undifferentiated type and decreasing incidence of differentiated type was observed in women (p<0.05). The number of female patients with poorly differentiated adenocarcinoma increased from 50% to 69.7% over the period of the study. The patterns of GC location, macroscopic type, condition of lymph node metastasis and gender have no changed during the analyzed period of time, while those of GC histology, aging changed.

The purpose of this study was to investigate the association between patients' prognosis and the discrepancy between macroscopic and pathological findings in gastric cancer. Consecutive 900 patients with gastric cancer who underwent resection for gastric cancer, were studied for the discrepancy between naked-eye and pathological findings of gastric cancers and for immunological makers, such as CD3 T, CD4 T cell, CD8 Tcell and immunosuppressive acidic protein (IAP). We demonstrated that patients whose tumors were both macroscopically and histologyically diagnosed early cancers showed significantly lower IAP levels than those whose tumors were macroscopically diagnosed adcanced, but histologyically diagnosed early cancers, and they also had better outcome than the other. In conclusion, surgeons' naked-eye determinations are very important to fight against gastric cancer, especially in patients with well differentiated adenocarcinoma, and moreover, patients who have more immunosuppressive conditions are tend to take misdiagnose.

Four hundred forty-two patients underwent gastrectomy for carcinoma of the stomach to determine the impact of various gastrectomy procedures on patients' prognosis, and to assess the phenotypes of lymphocytes before and after gastrectomy. During the 3-6 postoperative months, there were significant differences between patients who received total gastrectomy and subtotal gastrectomy as regards the CD4+/CD8+ ratio. The 10-year survival rates of patients who received a subtotal gastrectomy were significantly better than those of patients who underwent total gastrectomy. A Cox multivariate analysis revealed that the extent of resection was a significantly related to independent covariate with patient prognosis.

There are no strategies to predict a patient's response to therapy. In a previous report, we classified Japanese patients into four groups according to the incidence of HLA antigens, by using quantification method III. In that study, we examined the patients' incidence of HLA antigens before surgery and evaluated their outcome according to the HLA classification by quantification method III. The aim of the present study is to evaluate whether HLA classification should be used in the treatment of individual cancer patients.A consecutive series of 76 Japanese patients who had undergone gastrectomy between July 1998 and January 2000 was evaluated to compare the patients HLA classifications, derived from quantification method III, with their prognoses following gastrectomy.Retrospective analysis of 193 gastric cancer patients revealed that HLA type I, type II, and type IV patients who had received postoperative adjuvant chemotherapy concomitant with PSK survived longer than those who had received postoperative adjuvant chemotherapy, whereas HLA type III patients who had received postoperative adjuvant chemotherapy showed significantly longer survival than those with chemotherapy+PSK. Following these results, we started a prospective study; we treated patients with HLA type I, type II, and type IV for postoperative chemotherapy+PSK, and those with HLA type III for postoperative chemotherapy following gastrectomy. The prospective study showed that patients who had been examined for HLA antigens showed significantly longer survival than those who had not been examined for HLA antigens.From the results of our retrospective and prospective studies, it can be inferred that it is necessary to examine gastric cancer patients for HLA antigens, and that HLA-oriented therapy is a very promising strategy for cancer treatment. We are planning to conduct an important study with control subjects.

術前にHLA抗原を測定した単発胃癌切除例564例を対象として, リンパ節高転移群の抽出を試みた結果, すでに報告しているように, HLA-DR4陽性例ではリンパ節転移が高頻度に認められたが, 組織型別に検討すると, 低分化腺癌 (por) でのみDR4陽性例は, correctedp値で有意にリンパ節転移が高頻度に認められた.そこで, HLA-DR4抗原に注目して, リンパ節転移を予測した外科的治療が将来可能かどうか検討を行った.DR4陽性例, 陰性例の5年生存率は, それぞれ, 85.4%, 94.0%と有意の差が認められた.特に, 低分化腺癌 (por) 例では, 59.5%, 83.1%と有意の差が認められた.HOPO症例でD1-3以上の郭清を行ったDR4陰性例では, 癌の占居部位A, AMおよびC, CMでは#8以上の転移が見られず, D1+# (7) リンパ節重点郭清の適応症例と考えられた.

We retrospectively evaluated the efficacy of postoperative adjuvant therapy in 541 gastric cancer patients who underwent gastrectomy. Postoperative adjuvant chemotherapy consisted of the intravenous injection of MMC and/or the oral administration of fluoropyrimidines, while immunochemotherapy was done by adding the oral administration of PSK.The overall survival rate (Kaplan-Meier method) was improved by postoperative adjuvant therapy. However, there was no significant difference in survival between the patients receiving chemotherapy and those receiving PSK.Cox multivariate regression analysis of the factors related to survival (including sex, age, tumor size, pTNM stage, histological grade and therapy) indicated that postoperative therapy was a significant prognostic factor. The age and sex of patients receiving chemotherapy were also significant prognostic factors, but this was not so far patients receiving chemotherapy plus PSK. Patients given chemotherapy plus PSK showed a better relative survival rate than those receiving only chemotherapy.We conclude that postoperative adjuvant chemotherapy and immunochemotherapy may give better results than gastrectomy alone, and that the age of the patients needs to be considered before postoperative adjuvant chemotherapy started.

1978年から1990年に選択的近位迷走神経切離術(SPV)を施行した十二指腸潰瘍穿孔例86例,非穿孔例33例の計119例を対象とし,術後5年までの基礎酸分泌量,テトラガストリン刺激時の最大酸分泌量(gastrin-MAO),インスリン刺激時の最高酸分泌量(insulin-PAO),血中ガストリン分泌反応,胃排出能,Kaplan-Meier法を用いた術後累積再発率を検討した.非穿孔例は術後高ガストリン血症を,穿孔例は術後高酸を示すが,1年以後は一定状態となる傾向がみられた.術後潰瘍再発例は穿孔例86例中8例(9.3%),非穿孔例33例中9例(27.2%)で術後10年累積再発率はそれぞれ26.6%,31.6%であった.穿孔例の術後1年のgastrin-MAOが20mEq/h以上の症例または術後1年のinsulin-PAOが12mEq/h以上の症例の累積再発率がそれ未満であった症例に比べ有意に高値を示したことより,SPV術後1年時にgastrin-MAOやinsulin-PAOが高値を示す症例は消化性潰瘍の再発をきたしやすいものと考えられた.