This essay is on doctor-patient communication. It will specially focus on doctor-patient communication in oncological care. In this paper there are 4 models of doctor-patient communication presented, and a number of suggestions for using these different models are put forward. The paper compares a number of studies on Japanese and Dutch physicians' communication patterns with cancer patients. It concludes that between these groups of physicians similarities are more prominent than differences. The paper also discusses the implications of these findings. Finally, it presents some new developments in medical curricula, especially regarding doctor-patient communication.

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Chemotherapy has been shown to benefit patients with gastric cancer. The most effective regimen remains controversial. A recent large randomized clinical trial has demonstrated an advantage with the addition of docetaxel to 5-fluorouracil and cisplatin. New agents are being incorporated into the treatment of gastric cancer to maximize efficacy with minimal additional toxicity. Future clinical trials will explore the use of new agents as well as genetic polymorphisms that may influence drug metabolism and efficacy.

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This study examines the relation between the HRQOL-20, (a Japanese 20-item generic health-related quality of life (HRQOL) questionnaire, with acceptable reproducibility, internal consistency and discriminant validity), and the European Organization for Research and Treatment of Cancer QLQ-C30 (a valid, reliable measure of generic HRQOL in lung cancer patients in multicultural clinical research settings). Lung cancer patients (n=172) completed the HRQOL-20 and QLQ-C30. The response structures to the questionnaires were examined by corresponding analysis and Spearman's rank correlation coefficients. The item response structure of the HRQOL-20 was equivalent to that of the QLQ-C30 and similar to the one found in a previous study of stomach cancer patients. The correlation coefficients between the HRQOL-20 (positive and negative scale scores) and QLQ-C30 (global quality of life scale score) were 0.51 and 0.64. The results provided further support for the validity and reliability of the HRQOL-20 questionnaire for lung (as well as stomach) cancer patients, in Japanese clinical research setting.

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Reported differences in clinicopathological patterns of gastric carcinoma between the West and Japan suggest the presence of differences in cancer biology. The aim of the present study was to analyze clinopathological changing patterns of gastric cancer biology in a large series of patients from Japan, where mortality rates for GC are relatively high. Based on the registered data of 2569 patients diagnosed between January 1980 and December 2000, we analyzed the differences in clinicopathological patterns for two consecutive periods: 1980-1990 (A group) and 1991-2000 (B group). Patient age ranged from 21-92 years (median: 61 years), with 70.9% of the study participants being men. Analysis revealed that there were no significant differences in the conditions of lymph node metastasis, and also no significant differences in the frequencies of tumor depth, gender, and double cancer between A and B groups. With regard to differences in age (less than 49 years vs. 50 years and over), there was a significant increase in the incidence of cancer in the patients 50 years and over. The pattern of tumor location of the lower third of the stomach increased over the period of the study, while that of the upper third of the stomach decreased. With regard to histological type, there was a significant increase in the incidence of a moderately differentiated type of tubular adenocarcinoma and poorly differentiated adenocarcinoma (por), but a significant decrease in that of signet ring cell carcinoma. Taking every factor into consideration, the incidence of early-localized cancers appears to have increased and that of advanced invasive cancers appears to have decreased in Japan during the past 20 years.
In conclusion, adenocarcinomas of the stomach with intestinal types, which related with the HP infection, decreased and those of diffuse types, which did not relate with the HP infection increased during the past 20 years.

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Recent advances in genomics and molecular technologies have given a potential to revolutionize cancer therapy. Most of the existing chemotherapeutic treatments are palliative in the advanced solid tumors, and further responses to the therapies significantly vary among the patients. Genomic data and genome-wide analysis of gene expression derived from high throughput DNA sequencing and DNA chip have shown great promise for hunting novel drug targets in the broadest range and selecting optimal cancer therapy for individual patients through better diagnosis of an "at risk" subgroup. However, these challenges have not been always successful. To determine the critical genes from the large number of candidates, a tremendously large amount of data is statistically required. The methodology or the experimental design to exploit the full power of a global perspective is still controversial. Recent challenges for drug discovery and development of personalized medicine, including ours, are briefly reviewed.

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High expression of thymidylate synthase (TS), p53 protein and bcl-X_L protein has been suggested to be associated with chemoresistance of colorectal malignancies. The significance of TS, p53 protein and bcl-X_L protein as predictive parameters of effects of 5-fluorouracil (5-FU)-based chemotherapy on colorectal cancers was evaluated. Immunoperoxidase staining of TS, p53 protein and bcl-X_L protein was performed on formalin-fixed, paraffin-embedded, _??__??_opsied and resected specimens from 37 patients with advanced colorectal cancers, preoperatively treated with 5-FU derivatives per os. Suitable antigen retrieval was applied to the respective markers. Histologically, six tumors responded to the chemotherapy, while the remaining 31 tumors did not. Thirty-one control colorectal cancer cases without preoperative treatment were also analyzed. When more than one third of the cancer cells were stained, the lesions were considered high for antigen expression. High TS expression in the resected tumors was seen in 23 (74%) of 31 histologic non-responders but none in six responders. TS expression in preoperative biopsies and resected specimens was concordant in 80% of cases when two or more biopsy specimens were available. The rate of high TS expression was comparable in the control non-treated group. There was no difference between chemotherapeutic effects and the expression of p53 protein or bcl-X_L protein. Chemoresistance to 5-FU and 5-FU derivatives can be predicted by immunohistochemical detection of high TS expression in biopsy samples. This provides us with a useful guide for preoperative selection of patients unresponsive to 5-FU-based chemotherapy. Expression of p53 protein and bcl-X_L protein is unsatisfactory for predicting the 5-FU resistance.

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Several mutagens including benzo(a)pyrene (B[a]P) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in tobacco smoke are known to be metabolized by cytochrome P450 enzymes (CYPs). These mutagens may induce airway carcinogenesis. We measured the mRNA expression of CYPs 1A1, 1A2, 2A6/7, 2B6, 4B1, 2C, 2D6 and 2E1 the peripheral blood lymphocytes from 30 patients with lung cancer and 30 healthy controls by semi-quantitative competitive reverse transcription polymerase chain reaction (QC-RT-PCR) in order to determine the expression levels of these CYPs in patients with lung cancer. The mRNA levels of CYPs 1A1 (p<0.001), 4B1 (p<0.001) and 2C (p<0.001) were significantly higher and CYPs 2D6 (p<0.0001) and 2E1 (p<0.0001) were significantly lower in patients with lung cancer than in healthy controls. The same results were obtained when only smokers in both groups were compared. Our study revealed that the mRNA expression levels of CYPs in peripheral blood lymphocytes were different in patients with lung cancer and healthy controls. The elevated level of expression of some CYPs in the patients may reflect the risk of carcinogenesis of lung cancer.

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The immunohistological expression for Ki67, p53, p21 and CEA was studied in 10 normal colonic mucosa, 18 adenomas, 13 ca in adenomas, 12 sm cancers and 39 advanced cancers, respectively. In normal mucosa, Ki67 staining cells were topographically expressed in the crypts. Both p21 and CEA were inversely expressed in the upper crypts. On the other hand, p53 could not be detected. This topographic expression was abrogated in all examined tumors. The immunoreactivity was positively correlated with the progression of the tumor during normal→adenoma carcinoma sequence. The immunoreactivity for p21 expression tended to decrease in relation to the progress of malignancy. Cellular CEA expression showed apical cell membrane staining in the normal mucosa, but abnormal cellular CEA staining patterns such as depolarized cytoplasmic staining and extra stromal staining tended to increase during the progression of malignant transformation. These results indicate that loss of normal topographic expression and alteration of immunoreactivity may play an important role in colorectal oncogenesis.

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Background:
S-1 is a new anti-cancer drug. It was reported that the response rate of patients with gastric cancer treated with this drug is 49%. We reported that the serum and intraabdominal concentrations of 5-FU after the administration of S-1 are almost the same. This retrospective study was undertaken to examine the clinical efficacy of S-1 in patients with advanced gastric cancer and positive cytology.
Method:
Between 1995 and 1999, 26 patients with gastric cancer and positive cytology diagnosed during the operation were surgically treated. Fifteen underwent total, distal or proximal gastrectomy with D2 lymphadenectomy and 11 underwent simple laparotomy or bypass surgery because of peritoneal dissemination. These patients were divided into the S-1 group and the 5-FU group. Survival rate and median survival time (MST) were evaluated and compared between the two groups.
Results:
The MST of the S-1 group was 579 days and that of the 5-FU group was 211 days. Among the 15 resected cases, the MST of those administered S-1 was 768 days and that of patients administered 5-FU was 215 days. The survival rate of the S-1 group was significantly higher than that of the 5-FU group (p=0.0023).
Conclusion:
We conclude that S-1 is an effective adjuvant anti-cancer drug for patients with advanced gastric cancer and positive cytology.

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With the recent increasingly widespread use of triple therapy to eradicate Helicobacter pylori (H. pylori) consisting of a proton pump inhibitor (PPI), amoxicillin (AMPC), and clarithromycin (CAM) [PPI/AC], the issue of resistance to antimicrobial agents has risen. In this study, we investigated the rate of increase in antimicrobial resistance after eradication treatment and the mechanism of the increase in CAM resistance.
Subjects and Methods: The subjects were 277 patients with digestive diseases, all of whom were positive for H. pylori. Eradication therapy with PPI/AC was administered. Before and after the treatment, endoscopy was performed, and the gastric mucosal specimens were obtained from 2 sites, antrum and body. The presence or absence of H. pylori infection was evaluated by culture/histological examination. In all patients with positive reactions on culture, the susceptibility to AMPC, CAM, and metronidazole (MNZ) was measured by the agar plate dilution method.
Results: The rate of eradication was 83.7% (216/258, per protocol). Prior to the treatment, the rates of bacteria resistant strains to AMPC, CAM, or MNZ were 1.1%, 6.9%, and 2.6%, respectively. The susceptibility to AMPC/CAM in both the antrum and body regions could be measured in 212 and 208 patients, respectively. Prior to the treatment, 1.4% (3/212) and 8.6% (18/208) of the patients were resistant to AMPC and CAM, respectively. After the treatment, the percentages were increased to 5.4% (2/37) and 64.9% (24/37), respectively. In addition, concerning CAM, in 5 patients, CAM-sensitive bacteria were detected in one of the two regions, the antrum and body, while CAM-resistant bacteria were detected in the other region (mixture of resistant and sensitive bacteria). In these patients, eradication was all unsuccessful. After the treatment, CAM-resistant bacteria were detected in both the antrum and body.
Conclusions: The rate of eradication with PPI/AC therapy was 80% or more; however, the rate of CAM-resistant bacteria was increased after the treatment. These results suggest that the acquisition of CAM resistance by H. pylori and bacterial selection of H. pylori are involved in the increase after eradication treatment.

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A large number of trials have been done to improve the survival of the patients with advanced gastric cancer, but no chemotherapeutic regimen is superior to 5FU alone in the term of the survival. 5FU alone or FP has still been a referent regimen in gastric cancer. However, newly promising agents have been appearing, and several trials have been starting. These trials should be continued to break through the limitation of the survival in patients with advanced gastric cancer.

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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.

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A 64-year-old man underwent gastroscopy to investigate epigastric discomfort and marked weight loss. An 8-cm Borrmann type II lesion was detected in the body of the stomach on the greater curvature, so total gastrectomy was performed on December 15, 2000. Histopathological examination revealed mucinous adenocarcinoma of the stomach with metastases to the omentum and the paragastric lymph nodes (P1H0N1SE; stage IV). Postoperative chemotherapy was scheduled, but abdominal adhesiolysis had to be performed instead (January 12, 2001) because of repeated episodes of postoperative ileus. After the patient was discharged, two metastases in the right lobe of the liver were detected in April 2001 and systemic chemotherapy was started. The liver metastases disappeared after three courses of low-dose cisplatin plus 5-fluorouracil. After three more courses, his chemotherapy was changed to oral TS-1 plus leucovorin. At 2 years and 10 months after surgical resection, the patient is disease-free and receiving oral chemotherapy on an outpatient basis.

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Background: Recent advances in immunohistochemistry have revealed that the majority of the tumors originating from mesenchymal tissues of gastrointestinal tract (GI tract) are gastrointestinal stromal tumors (GISTs). The purpose of this study is to reevaluate the imaging findings of mesenchymal tumors of gastrointestinal tract pathologically proven as gastrointestinal stromal tumors.
Materials and Methods: Ten mesenchymal tumors of gastrointestinal tract were resected at our hospital from May 1993 till March 2001. These were examined immunohistochemically using antibodies against c-kit, CD34, alpha-smooth muscle actin, and S-100 protein. Their imaging findings in CT, MRI, and endoscopy and their clinical features were reviewed.
Results: A diagnosis of gastrointestinal stromal tumor was confirmed in all 10 cases by immunohistochemical studies. The imaging findings were similar in some respects to those of tumors that were conventionally diagnosed as leiomyosarcoma. However, gastrointestinal stromal tumors were less in vascularity than conventionally reported leiomyosarcomas. Moreover, the findings of necrosis or myxoid change in each small nodule of large multinodular tumor were characteristic of gastrointestinal stromal tumors.
Conclusions: The characteristic imaging findings of gastrointestinal stromal tumors in this study might be useful for their preoperative precise diagnosis.

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Among 370 patients who underwent radical resection of primary colorectal cancer over a 17-year period, 167 had stage II-Dukes' B cancer. After excluding 10 patients treated with intravenous drugs other than 5-FU or hepatic arterial injection and 11 patients with rare histological types other than typical differentiated adenocarcinoma, the remaining 146 patients were used to assess the utility of Japanese-style oral postoperative adjuvant immunochemotherapy. Ninety-one patients who received oral chemotherapy with/without immunotherapy as postoperative adjuvant therapy had a 5-year survival rate of 89.1%, while the rate was 66.5% for patients without such therapy (non-chemotherapy; n=55, p=0.0015). When the 91 patients were divided into those treated with chemotherapy plus immunotherapy (immunochemotherapy; n=61) and those treated with chemotherapy alone (chemotherapy-only; n=30), the 5-year survival rates of the immunochemotherapy, chemotherapy-only, and non-chemotherapy groups were 92.2%, 83.5%, and 66.5%, respectively (immunochemotherapy vs. non-chemotherapy, p=0.0022). When 30 patients were selected from each of the 3 groups and compared by the propensity score matching method, a significant difference was found between the immunochemotherapy and chemotherapy-only groups (p=0.0364), as well as between the immunochemotherapy and non-chemotherapy groups (p=0.0055). These results suggest that Japanese-style oral immunochemotherapy is useful as postoperative adjuvant therapy in patients with stage II-Dukes' B colorectal cancer.

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Among 370 patients who underwent the radical resection of primary colorectal cancer over a 17-year period, 114 had stage III-Dukes'C cancer. After excluding 10 patients treated intravenously with drugs other than 5-FU or with hepatic arterial injection and 9 patients who had uncommon tumors other than typical differentiated adenocarcinoma, the remaining 95 patients were investigated to assess the utility of Japanese-style oral postoperative adjuvant immunochemotherapy for stage III colorectal cancer. Sixty-one patients received postoperative oral chemotherapy with or without immunotherapy and had a 5-year survival rate of 60.7%, while the survival rate was only 48.8% for patients without such therapy (p=0.0136). When the 61 patients were further divided into those treated with chemotherapy plus immunotherapy (immuno-chemotherapy; n=38) and those treated with chemotherapy alone (chemotherapy-only; n=23), the 5-year survival rates of the immunochemotherapy, chemotherapy-only, and non-chemotherapy groups were 62.7%, 57.4%, and 48.8%, respectively (immunochemotherapy vs. non-chemotherapy, p=0.0172). The 5-year survival rate was also calculated for 69 patients whose background factors were matched by the propensity score matching method and a significant difference was found between the immunochemotherapy and non-chemotherapy groups (p=0.0265). These results suggest that Japanese-style oral immunochemotherapy is useful as postoperative adjuvant therapy for stage III-Dukes'C colorectal cancer.

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Pancreatic cancer has a dismal prognosis because most lesions are unresectable where as adjuvant and palliative chemotherapy exhibits poor results.
Six patients with locally unresectable pancreatic cancer were treated with mitomycin-C (MMC) 8mg/m² on day 1 and 5-FU 375mg/m² and LV 20mg/m² on days 1 to 5. Treatment cycles were repeated every four weeks if the patient's general condition permitted. All patients had measurable, histologically proven adenocarcinoma and had not undergone prior chemotherapy.
Three patients underwent hepaticojejunostomy whilst choledochal stents were endoscopically inserted in two patients. No significant side effects of grade 3 or 4 were observed. Five of six patients who received an average of 5 treatment cycles died of their disease with a medial survival of 8.9 months. The remaining patient received 12 treatment cycles and 8 additional treatments without mitomycin-C and exhibited a complete remission for 36 months.
Our data suggest that MMC plus 5-FU and leucovorin is a tolerable regimen and has promising effects. Further prospective studies are needed.

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The immune function in cancer patients is suppressed, however, the factors that promote this suppression are still obscured. We hypothesized that polyamine is one of the causative factors of the immune suppression, as polyamine levels in blood and tissues are increased in cancer patients. In this study, the effects of increased polyamine concentration on cellular immunity were investigated. For this, human peripheral blood mononuclear cells (PBMCs) from volunteers were cultured in RPMI-1640 medium supplemented with 10% human serum. Freshly prepared polyamine was added to cultured PBMCs at various concentrations, and their effects on the production of tumor necrosis factor (TNF), adhesion capacities, and cytotoxic activities upon stimulation with interleukin-2 were examined. Spermine and spermidine, but not putrescine, immediately suppressed lipopolysaccharide-stimulated TNF production in a dose-dependent manner. PBMCs cultured either with spermine or spermidine decreased their ability to adhere to plastic. The decreases in adhesion capacity were observed in a dose-dependent manner, but were not observed in PBMCs cultured for 24 hours with spermine and spermidine. PBMCs cultured overnight with spermine and spermidine decreased their cytotoxic activities. Spermine and spermidine did not affect the cell viability. These suggest that the increased polyamine levels in cancer tissues and in blood may be one of the factors that hinder the immune function of cancer patients.

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In this study, we examined the correlation of in vitro sensitivity to anti-cancer drugs, histological tumor response and alteration of apoptosis in breast cancer. In vitro sensitivity was examined by the method of succinate dehydrogenase inhibition test. Histological changes and alteration of apoptosis in tumor cells were investigated by staining with hematoxylin and eosin and immunohistochemical staining, respectively. Patients with locally advanced breast cancer were treated with adriamycin (ADM). Using resected specimens, in vitro sensitivity and apoptosis were examined before and after treatment. After three courses of treatments with ADM, in vitro sensitivity in tumor cells to anticancer drugs including ADM significantly decreased. On the other hand, apoptotic index altered independent of in vitro sensitivity.
It is concluded that in vitro sensitivity is useful in predicting tumor response to treatment with anticancer drugs in breast cancer. The alteration of apoptosis in tumor cells induced by treatment with an anticancer drug is independent of the in vitro sensitivity to the drug.

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The purpose of this study was to examine the antitumor effect of strangulation to cease blood flow on tumor tissue. AH130 cells were implanted in the mesentery near the ileocecal portion of rats 10 days previously. A recovery rate of blood flow was observed in the tumor tissue and normal tissue (cecal wall) after reperfusion with a charge-coupled device microscope (CCD). Five days after reperfusion, the tumor volume ratio was measured. On the death or sacrifice of the animals, the tumor necrotic area ratio was examined. The vascular morphology and the changes of a recovery rate of blood flow after reperfusion differed from the tumor tissue and the normal tissue by CCD observation. In the 15-min and 30-min groups, the tumor vessels underwent little or no destruction, with only a few showing a cessation of blood flow. However, the 60-min and 90-min groups showed a cessation of blood flow and hemorrhage due to vascular destruction in many vessels, and few vessels showed intact blood flow. In 60 and 90-minutes strangulated groups, a recovery rate of blood flow after 60 minutes was lower in tumor tissue than in the normal tissue. The tumor volume ratio decreased more in the 60 and 90-minutes strangulated groups than in the non-strangulated group and the tumor necrotic area increased more in all strangulated groups than in the non-strangulated group. These findings suggest that strangulation for ischemia for 60-90 minutes injures the tumor tissue and shows the antitumor effect.

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