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Objectives There is limited evidence on methods to allocate budgets to healthcare providers under capitation schemes. The objective of this study was to construct and test models that predict outpatient visits and expenditure for each healthcare facility using subscriber data from the preceding year. Study design We used the database of the Universal Coverage Scheme in Bangkok, Thailand that stores subscriber information and healthcare service utilization data. One-percent and ten-percent random samples of subscribers were selected as training and testing groups, respectively. Methods Using data of the training group, we constructed a model using a random forest algorithm to predict outpatient visits and expenditure in 2017 from the 2016 data. The model was applied to the testing group and facility-level predicted number of visits and expenditure were compared with actual data. Results The identically-structured training and testing groups consisted of 37,259 and 371,650 subscribers, respectively. Approximately 25% of subscribers utilized outpatient services. The R2 for models predicting facility-level utilization rate (visits/subscribers) and expenditure per subscriber in 2017 were 0.85 and 0.75, respectively. Conclusions The model to predict outpatient visits and expenditure performed well. Such a prediction model may be useful for allocating budgets to healthcare facilities under capitation systems.

Relationships between leaf expansion and MeOH-soluble (cytosol) and cell-wall fractions, and their sugar composition prior to silking in flint corn lines were studied. A greater husk leaf area of one genotype, X-15 is mainly due to prolonged and higher rate of expansion. Prior to rapid expansion of husk leaf area, neutral sugars in the cytosol fraction accounted for most of the non-starch carbohydrates (56–62%), while hemicellulose and cellulose fractions accounted for less than 20%. In mature leaf parts, however, sugars in the cytosol fraction decreased but those in hemicellulose and cellulose fractions increased by 30% and 42%, respectively. The predominant sugar in the cytosol fraction was glucose (Glc), while in the hemicellulose fraction xylose (Xyl) and arabinose (Ara) dominated. During rapid expansion of husk leaves, 13C was incorporated at a higher rate into hemicellulose than cellulose, and this process was more active in X-15 than in other genotypes. During an identical period, 13C atom % excess in Xyl increased markedly in the hemicellulose fraction, however it remained low in the cytosol one. The current results suggest that synthesis of Xyl and xylan plays an important role in renewal of hemicellulose, which may be required for expansion.

This chapter describes the Fukushima Daiichi nuclear power plant (NPP) accident starting with the reactors’ location and sequence of events which caused the accident. The amount of radioactive materials released and its composition, dispersion of radioactive materials over land and sea, contamination effects on food and the environment and radiation effects on human health are all addressed along with the current clean-up programme and future plans. However, it is expected that it will take 30–40 years to decommission the damaged facilities.

Esophageal cancer patients with distant organ metastasis have usually been treated only to palliate symptoms without multimodality therapy. The current study evaluates the role of multimodality therapy in esophageal squamous cell cancer patients with distant organ metastasis. Between February 1988 and January 2007, 80 esophageal squamous cell cancer patients with distant organ metastases were treated at our institution. Multimodality therapy was performed in 58 patients: 43 patients received chemoradiotherapy, 13 underwent surgery followed by chemotherapy and/or radiation therapy, and two received chemotherapy or chemoradiotherapy followed by surgery. Thirteen patients received single-modality therapy; chemotherapy, radiotherapy, or surgery alone. The remaining nine patients received best supportive care alone. The metastatic organ was the liver (n= 40), the lungs (n= 33), bone (n= 10), and other (n= 6). Nine patients had metastasis in two organs. There was no difference in the median survival among the sites of organ metastasis, lung, liver, or bone (P= 0.8786). The survival of patients treated with multimodality therapy was significantly better than that of the patients who received single-modality therapy or best supportive care alone (P0.0001). In patients treated with multimodallity therapy, there was no difference in survival for patients treated with surgery compared with patients treated without surgery (P= 0.1291). This retrospective study involves an inevitable issue of patient selection bias. However, these results suggested that multimodality therapy could improve survival of the esophageal squamous cell cancer patients with distant organ metastasis.

Esophageal small cell carcinoma (SmCC) has been regarded as a rare and aggressive tumor with early metastasis. The optimal treatment has not yet been established, and the role of surgery has remained controversial. In this retrospective study, we report seven cases studies of SmCC of the esophagus and analyze the clinical outcomes after surgery. Between 1986 and 2007, there were seven patients with esophageal SmCC treated surgically in our institution. All the patients with clinically limited disease underwent transthoracic esophagectomy with lymphadenectomy. Lymph node involvement was found in all cases irrespective of the depth of tumor invasion. Three of the seven patients were diagnosed as having an extensive disease on pathological examination after esophagectomy. Five patients received postoperative chemotherapy. Two patients are alive with no recurrence at 16 months and at 45 months after surgery. Another one without chemotherapy survived 93 months and died of another disease. The remaining four patients died of recurrent disease or another disease. The median overall survival to date of these patients was 16 months (range 12-93 months). Esophagectomy with lymphadenectomy resulted in a relatively better survival in some patients with esophageal SmCC. We concluded that surgery may be helpful as part of multimodality treatment in selected patients with esophageal SmCC.

The tumor-rejection antigen SART3 possesses two antigenic epitopes (SART3(109-118) and SART3(315-323)) capable of inducing HLA-A24-restricted and tumor-specific CTLs. To determine its safety and ability to generate antitumor immune responses, 12 patients with advanced colorectal cancer were administered s.c. vaccinations of these peptides. No severe adverse events were associated with the vaccinations. Significant levels of increased cellular immune responses to both HLA-A24+ colon cancer cells and the vaccinated peptide were observed in the postvaccination peripheral blood mononuclear cells in 7 of 11 and 7 of 10 patients tested, respectively, and the higher responses were observed in those patients vaccinated with the highest dose (3 mg/injection) of the peptides. These results encourage further development of SART3 peptide vaccine for colorectal cancer patients.

p21/WAF1 (p21) inhibits the activity of the cyclin/cdk complex and controls the G1 to S cell phase transition. In the present study, we used a recombinant adenoviral approach and gene gun technology to introduce p21 into esophageal cancer cells in order to assess the effect of p21 on cell growth. Infection with the p21 adenovirus (AdV) using gene gun technology resulted in inhibition of TE9 and KE3 cell growth. The levels of involucrin, which is a marker of squamous epithelium differentiation, markedly increased at 48 h and 72 h after p21 AdV infection in TE9 cells. These results indicate that p21 plays an important role in esophageal cancer cell proliferation. Overexpression of the p21 gene can inhibit cell growth and induce differentiation in esophageal cancer cells. p21 gene therapy may prove beneficial in the treatment of esophageal cancer.

Intrapelvic recurrence of the rectal cancer after surgery is a challenging status. We report here a case of intrapelvic tumor due to the recurrence of rectal cancer postoperatively treated by adoptive cellular immunotherapy.A 57-year-old Japanese man with an intrapelvic tumor showing bone destruction due to the recurrence of rectal cancer after abdomino-peritoneal resection was diagnosed by CT scan. He consented to simultaneous adaptive cellular immunotherapy for local recurrent lesions by administration of the activated lymphocytes. The tumor sample used for the activation of PBMC was obtained by operation. Tumor cells were prepared by mincing and enzymatic digestion of the tumor sample, and they were irradiated with a dosage of 50 Gy. Peripheral blood samples were collected from the same patient. PBMC for about 2 weeks to prepare cells for treatment were obtained from the blood sample. One million PBMC were incubated in 2 ml of the culture medium containing 10(5) irradiated autologous tumor cells and 100 IU/ml recombinant IL-2. The activated PBMCs, as autologous cancer specific killer T cells, were administered by direct regional injection (from 2 million to 8 x 10(7) cells). These injections were given repeatedly about once a week at 2-week intervals for three months. The surface phenotypes of activated PBMC or PBMC were tested by two color immunostaining technique with anti-CD3, -CD4, -CD8 and also anti-CD16, -CD25 or -CD56. Natural killer cell activity was also investigated. The clinical outcome was evaluated by CT scan and serum CEA levels. In the cultured activated PBMCs, NK cell activity was 40%, both CD3 and CD4 positive cells was 30%, and both CD3 and CD8 positive cells was 48%. There were far more CD8 cells than CD4 cells. In the PBMC, NK cell activity had increased, both CD3 and CD4 positive cells had decreased and both CD3 and CD8 positive cells had increased. There were then predominantly more CD8 cells than CD4 cells by repeated administration of the cultured activated PBMCs. The only adverse effect was grade 2 fever. Serum CEA levels fell from 293.7 ng/ml to 160 ng/ml, but the tumor size on the CT scan was slightly increased except for the directly administered region. We have been observing him as an outpatient.

The objectives of the present study were to determine the safety of locoregional administration of autologous lymphocytes stimulated with autologous tumor cells and interleukin (IL) 2 in vitro and to find laboratory markers to predict either clinical toxicity or clinical response. Eleven patients with advanced (n = 4) or recurrent (n = 7) esophageal cancers received the locoregional administration of these activated lymphocytes every 2 weeks for two to nine times (mean, 5.6 times), and mean numbers of the administered cells were 0.8 x 10(9) cells per treatment. The activated lymphocytes that were pretested for their surface markers and CTL activity were endoscopically injected into primary tumor sites (n = 4) or directly injected into metastatic lymph nodes (n = 2), pleural (n = 4) or ascitic (n = 1) regions. Grade 3 hypotension, grade 2 diarrhea, and grade 1 fever were observed in 1, 1, and 6 patients, respectively, and there was no adverse effect in the remaining three patients. The clinical outcome was as follows: one, complete response (CR); three, partial response (PR); two, stable response (SR); and five, progressive disease (PD). CTL activity in the administered cells was observed in 5 of the 11 patients (1 CR, 3 PR, and 1 PD) and was not observed in the remaining 6 patients (2 SR and 4 PD). Percentages of CD16+ cells in the peripheral blood of the responder group (CR+PR) significantly increased when compared with those before treatment or with those of the nonresponder group before as well as after treatment. Because the clinical toxicity was moderate and tolerable, this new method of locoregional immunotherapy will be applicable for use in treatment of patients with advanced and recurrent esophageal cancers. Both CTL activity in the administered cells and the percentages of CD16+ cells in the peripheral blood may be useful laboratory markers for predicting of clinical response.

In responders to neoadjuvant chemoradiotherapy for locally-advanced esophageal cancer, there was no significant difference in the long-term outcome between patients who underwent esophagectomy and those who did not. Esophagectomy might be unnecessary for patients who achieve a complete response with chemoradiotherapy for an esophageal cancer, in cases when salvage surgery is considered in order to treat any future recurrence.

One of the most significant advances in the field of modern tumor immunology is the identification of genes encoding tumor-rejection antigens that are recognized by human leukocyte antigen (HLA) class I-restricted and tumor-specific cytotoxic T lymphocytes (CTLs). Several peptides encoded by these genes are now under clinical trial as cancer vaccines, and major tumor regression has been observed in some melanoma patients. These results indicate that identification of the peptides capable of inducing CTLs may provide a new modality of cancer therapy. We investigated tumor-rejection antigens from epithelial cancers, and reported 7 genes encoding tumor-rejection antigens and peptides available for specific immunotherapy of HLA-A26 or -A24 patients with epithelial cancers. Furthermore, we identified more than 10 genes encoding tumor-rejection antigens and peptides available for specific immunotherapy of HLA-A2 patients with epithelial cancers. Therefore these new antigens and peptides could be applicable to the treatment of numerous epithelial cancer patients worldwide. Phase I clinical trials of cancer vaccine with these peptides for epithelial cancer patients are in progress at our university. Basic and clinical research will provide new insights for a better understanding of the molecular basis of T cell-mediated recognition of cancer cells and be important for the development of cancer vaccines.

Radioimmunoguided surgery has been attempted using intraoperative tumor detection with radiolabeled monoclonal antibody (mAb). Directly radiolabeled mAb showed poor tumor imaging due to high blood-pool radioactivity. In 1991, three-step immunoscintigraphy of the avidin-biotin system was reported. This three-step method improved tumor imaging because it reduced background radioactivity. Although there were some problems such as a human anti-mouse response and anti-avidin response, the three-step clinical protocol was performed in various cancer patients, and many good results (the tumor detection rate was about 85%) were reported. On the other hand, recent major trials on tumor localization and sentinel lymph node detection have been performed using FDG-PET. However, radioimmunoscintigraphy has the major advantage of simultaneous tumor diagnosis and treatment. In the near future, radioimmunoscintigraphy may become a useful diagnostic method with anticancer effects when its adverse effects are ameliorated by the application of gene technology.

With the recent progress in molecular biology and gene technology, many new cancer-specific antigens have been identified. Many studies have demonstrated the role of HLA class I-restricted cytotoxic T lymphocytes (CTLs) in cancer specific-immunotherapies. We have also established HLA-A24- and A26-restricted and cancer-specific CTLs from a patient with squamous cell carcinoma of the esophagus. Using CTLs, we identified a new gene SART-1 by cDNA-expression cloning and some SART-1-derived cancer rejection peptides were also identified. Further more, using the same approach, we identified a cyclophilin B gene that encodes antigenic epitopes recognized by HLA-A24-restricted and tumor-specific CTLs. Now we are performing phase I trials using these peptide vaccines and have found an increase in CTL precursor frequency in some cases in an in vitro study. However, other recent studies have reported that many tumors escape from CTL recognition by downregulation of HLA class I expression. Moreover, most cancer cells produce a suppressor agents against the immune system. Therefore, we must resolve these major problems to produce successful cancer vaccine therapy soon.

We recently reported a gene encoding the human CDw108, a glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein that is preferentially expressed on activated T lymphocytes and erythrocytes. The present study investigated the expression of CDw108 on various tissues and cells, particularly on T cells during development. The murine CDw108 cDNA was cloned initially, and it was highly homologous to the human CDw108 (88.0% or 89.3% similarity at the nucleotide or amino acid level, respectively) or identical to the murine semaphorin K1/Sema7A. The CDw108 mRNA was demonstrated in a few tissues including thymus and brain with the highest expression coming on day 7 in whole embryo followed by relatively consistent expression during development. Cell-surface expression of the CDw108 during T-cell development was further examined by flow cytometry in the human umbilical cord blood and thymus. It was preferentially expressed on a CD34+ stem cell population of umbilical cord blood, and CD3dull CD34+/- CD117 (c-kit)+ CD4bright CDbright cells in the thymus that are involved in the stage of positive selection. These results suggest the contribution of CDw108 in T-cell development, especially in the stage of positive selection in the thymus.

Thymidine phosphorylase (dThdPase) is the rate-limiting enzyme that metabolizes 5'-deoxy-5-fluorouridine (5'-dFUrd, doxifluridine), an intermediate metabolite of capecitabine, to the active drug 5-fluorouracil (5-FUra), while dihydropyrimidine dehydrogenase (DPD) catabolizes 5-FUra to an inactive molecule. The susceptibility of tumors to fluoropyrimidines is reported to correlate with tumor levels of these enzymes. To obtain some insight into the tumor types susceptible to fluoropyrimidine therapy, we measured expression levels of these two enzymes in various types of human cancer tissues (241 tissue samples) by the ELISA methods. DPD exists in all the cancer types studied, such as bladder, breast, cervical, colorectal, esophageal, gastric, hepatic, pancreatic, prostate, and renal cancers. Among them, the cervical, hepatic, pancreatic, esophageal, and breast cancer tissues expressed high levels of DPD (median >70 U/mg protein), while high concentrations of the dThdPase were expressed in esophageal, cervical, breast, and pancreatic cancers and hepatoma (median >150 U/mg protein). The dThdPase/DPD ratio, which was reported to correlate with the susceptibility of human cancer xenografts to capecitabine, was high in esophageal, renal, breast, colorectal, and gastric cancers (median ratio of >1.5). In any of these three parameters, the inter-patient DPD variability for each cancer type was much larger than the DPD variability among cancer types; highest/lowest ratios for dThdPase, DPD, and dThdPase/DPD were 10-321, 7-513, and 2-293, respectively. These results indicate that measurements of the three parameters, DPD, dThdPase and dThdPase/DPD, would be useful criteria for selecting cancer patients suitable for fluoropyrimidine therapy rather than for selecting cancer types.

Genes encoding tumor epitopes that are capable of inducing CTLs against adenocarcinomas and squamous cell carcinomas, two major human cancers histologically observed in various organs, have rarely been identified. Here, we report a new gene from cDNA of esophageal cancer cells that encodes a shared tumor antigen recognized by HLA-A2402-restricted and tumor-specific CTLs. The sequence of this gene is almost identical to that of the KIAA0156 gene, which has been registered in GenBank with an unknown function. This gene encodes a Mr 140,000 protein that is expressed in the nucleus of all of the malignant tumor cell lines tested and the majority of cancer tissues with various histologies, including squamous cell carcinomas, adenocarcinomas, melanomas, and leukemia cells. However, this protein was undetectable in the nucleus of any cell lines of nonmalignant cells or normal tissues, except for the testis. Furthermore, this protein was expressed in the cytosol of all of the proliferating cells, including normal cells and malignant cells, but not in normal tissues, except for the testis and fetal liver. Two peptides of this protein were recognized by HLA-A2402-restricted CTLs and were able to induce HLA-A24-restricted and tumor-specific CTLs from peripheral blood mononuclear cells of most of HLA-A24+ cancer patients tested, but not from peripheral blood mononuclear cells of any healthy donors. These peptides may be useful in specific immunotherapy for HLA-A24+ cancer patients with various histological types.

We investigated effects of a combination therapy of a methionine-mitomycin C conjugate (M-M conj) and methionine-free nutrition both in vitro and in vivo, compared to mitomycin C (MMC) administration alone.The human esophageal cancer cell line, KE-3, incubated in either standard or methionine-free media, was treated with phosphate buffered saline (PBS), M-M conj in PBS, or MMC in PBS. The rate of cell survival was determined. The tumor bearing mice were maintained on either a standard or methionine-free diet (MFD) and treated with PBS, MMC, or M-M conj.The lowest tumor cell survival rate was found with the M-M conj plus methionine-free media at every dose tested (p0.05). Tumor weight was significantly lower with the M-M conj plus MFD than in any other group (p0.003).Methionine targets MMC to tumor during administration of MFD.

In spite of postoperative chemo- and/or radiation therapy, the prognosis of advanced cancer patients undergoing palliative operation is still poor. Therefore, in order to improve the effect of chemotherapy, we made a mixture of MMC and fibrin glue (MMC-FIB) as a local chemotherapy. Using FIB with MMC, we expected to enhance the efficiency of MMC by sustained release of MMC. We examined cytotoxic effects and anti-tumor effects of the MMC-FIB using a gastric cancer cell line (MKN-28) and an esophageal cancer cell line (KE-3). Effects of the MMC-FIB were twice as strong as those of MMC on in vitro and in vivo studies. MMC-FIB is easy to make and apply to residual tumor. These results suggest that MMC-FIB is an effective treatment as a local chemotherapy for postoperative residual cancer.

The CD4-CD8+ CTL (KE-4 CTL) cell line against autologous tumor cells was established in a patient with esophageal cancer. This KE-4 CTL recognized a peptide antigen on esophageal and lung squamous cell carcinomas in an HLA A2601-restricted manner, as evaluated by cytotoxicity against a panel of tumor cells, transfection experiments with HLA A2601 cDNA, and reconstitution with eluted peptides. None of the normal cells tested was lysed by this CTL. These results suggest the existence of HLA A2601-restricted CTL precursors recognizing a peptide antigen on SCC in a patient with esophageal cancer.

In the past 20 years, 403 patients with thoracic esophageal carcinoma underwent radical surgery. The aim of this study was to determine whether extended lymph node dissection improved the prognosis of these patients. All of the patients were divided into 4 groups every 5 years from group A to group D. Group A (n = 39) underwent radical esophagectomy with lower mediastinal and abdominal lymphadenectomy by the left thoracoabdominal approach. Majority cases in Group B (n = 94) also underwent radical esophagectomy with right upper, lower mediastinal and abdominal lymphadenectomy (incomplete 2-field dissection) by the right thoraco-abdominal approach. About 40% cases in Group C underwent radical esophagectomy with extended cervicothoraco-abdominal lymph node dissection (3-field dissection) and almost all of the others had radical esophagectomy with 2-field dissection. About 60% of the cases in group D underwent radical esophagectomy with 3-field dissection and the majority of the others had complete 2-field dissection (i.e.) radical lymphadenectomy around bilateral upper, lower mediastinal and abdominal lymph nodes. The five-year survival rate was 21% in group A, 23% in group B, 37% in group C and 55% in group D. The survival curve was improved according to the extent of lymph node dissection. Especially significant improvements of survival rate were found in group C and D compared with those in group A and B. Furthermore, group D showed significantly better survival than that of group C. Complete 2-field and 3-field dissection resulted in a better prognosis than incomplete 2-field dissection, while no significant difference in prognosis was found between complete 2-field and 3-field dissection. However, neither 2-field nor 3-field dissection resulted in improved prognosis in cases involving 7 or more positive lymph node metastases. These results suggest that radical esophagectomy and lymph node dissection involving bilateral upper mediastinal area are important factors to improve postoperative prognosis in patients with thoracic esophageal carcinoma. However, more effective adjuvant therapy is needed for the patients with many positive node metastases.

Expression of human epidermal growth factor (EGF) and matrix metalloproteinase-9 (MMP-9/gelatinase B) was examined immunohistochemically in 62 cases of surgically resected esophageal carcinomas, and the correlation between EGF expression and the proliferative activity of the tumors was studied by analysing the number of proliferating cell nuclear antigen (PCNA)-positive cells. Expression of EGF and MMP-9 was observed in 16 (38.1%) and 18 (42.9%) of the 42 superficial carcinomas and 8 (40%) and 14 (70%) of the 20 advanced carcinomas, respectively. The differences in the MMP-9 expression between the superficial carcinomas and the advanced carcinomas was significant (p

To evaluate significant postoperative prognostic factors for esophageal carcinoma, clinicopathological findings and several markers for biological malignant potential were studied, including cell nuclear DNA contents, EGF receptor, p53 protein, MMP-2, Ki-67 positive cell rate, and tumors infiltrating Leu 7 cells. The subjects of this study were 96 patients with thoracic esophageal carcinoma, who underwent radical surgery with extended lymphadenectomy. In the pathological findings, the postoperative survival rate significantly correlated with depth of invasion (pT1(-2) vs. pT3, p = 0.003), lymph node involvement (pNo vs. pN1, p = 0.0002), vascular invasion (-vs. +, p = 0.0003), stage (pSt. 1-2A vs. 3, p = 0.0018), and the number of node involvements (1-3 vs. more than 4, p = 0.025). Analyzing the markers for the malignancy, a significant difference in postoperative mortality due to the relapse was recognized with p value of 0.0009 between Ki-67 positive (under 1%) and Ki-67 negative (over 1%) tumor. Ki-67 positive tumor significantly correlated with the mortality in both cases with pNo (p = 0.024) and pN1 (p = 0.020). Low-grade tumor infiltrating Leu 7 cells significantly correlated with the mortality (Grade 1+ vs. 2+, p = 0.013; Grade 1+ vs. 3+, p = 0.008). These results suggest that Ki-67 study is a useful prognostic factor after radical surgery for thoracic esophageal carcinoma.

Background The prognosis of gastric cancer with peritoneal metastasis is extremely poor. Neither systemic chemotherapy nor surgery alone prolongs survival of patients significantly. Methods Patients diagnosed with advanced gastric cancer underwent staging laparoscopy and received chemotherapy when peritoneal dissemination and/or cancer cells on peritoneal cytology were confirmed. The chemotherapy regimen consisted of S-1, weekly intravenous and intraperitoneal paclitaxel, which was verified in our phase II trial (Ann Oncol 2009). S-1 was administered at 80 mg/m2/day for 14 consecutive days, followed by 7 days rest. Paclitaxel was administered intravenously at 50 mg/m2 and intraperitoneally at 20 mg/m2 on days 1 and 8. Clinical response of chemotherapy was assessed by computed tomography, gastroendoscopy, peritoneal cytology and second-look laparoscopy. Radical gastrectomy was carried out when macroscopic curative resection was made achievable by chemotherapy. Chemotherapy was restarted after operation as soon as possible. Overall survival, relapse free survival, morbidity and mortality of gastrectomy were evaluated. Results Out of 100 patients with peritoneal metastasis who received chemotherapy, 60 patients underwent gastrectomy after response to chemotherapy, including 54 with macroscopic metastasis and 6 with positive peritoneal cytology only. A median of three courses were administered preoperatively (range 1–16). Total or distal gastrectomy with lymphnode dissection was carried out in 54 or 6 patients, respectively. The median survival time was 34.5 months. The median relapse-free survival was 16.7 months. The first site of relapse was the peritoneum in 24 patients and the other organ site in 17 patients. Postoperative complications included anastomotic leakage and pancreatic fistula in two patients each, which were healed conservatively. There were no treatment-related deaths. Conclusions Gastrectomy combined with S-1, intravenous and intraperitoneal paclitaxel is safe and active for gastric cancer patients with peritoneal metastasis.

By analyzing expired gas with exercise testing, we examined the relationship between test results and postoperative cardiopulmonary complications. The analysis was evaluated for its accuracy and reliability in comparison with general pulmonary function tests including spirometry, flow volume curves, diffusing capacity and arterial blood gas analysis. Enrolled were 52 of patients admitted between a period from 1991 to 1993 for thoracic esophageal cancer, who underwent a radical operation of right thoracolaparotomy. Patients were divided into two groups according to postoperative cardiopulmonary complications; one with complications (group C, n = 11) and the other without complication (group NC = 41). The two groups were compared in maximum oxygen consumption (VO2 max)/m2, anaerobic threshold (AT)/m2, VC/m2, %VC, FEV1.0/m2, V25/m, V50/V25, %DLCO and PaO2. In the results, there were significant differences between the two groups only in VO2 max/m2 (p0.001), AT/m2 (p0.001), and V50/V25 (p0.05), while there were no significant differences between the two groups in VC/m2, %VC, FEV1.0/m2, FEV1.0%, V25/m, %DLCO or PaO2. The above results suggest that analysis of expired gas with exercise testing is able to measure easily both cardiac and pulmonary reserve forces, which conventional pulmonary function tests are unable to do, and is evaluating surgical indications for esophageal cancer patients and predicting postoperative cardiopulmonary complications.

This report describes a rare case of superficial spreading esophageal carcinoma with a long sclerosis of the esophageal wall and dysphagia. The patient was a 64-year-old male with dysphagia. An esophagogram showed a long sclerosis from the upper-third to the lower-third of the esophagus. An esophagoscopy revealed a small ulcerative tumor (approximately 3 cm in size) at the level of 33 cm from the incisor teeth, and intraepithelial spread, 16 cm in length. However, esophageal stricture was not found in preoperative examinations. Histopathologically, most of the cancerous lesions were mucosal cancers with severe lymphocyte infiltration and the marked thickening of muscularis mucosa. These findings suggest the possibility that the sclerosis of the esophageal wall and esophageal dysfunction may be caused by these pathological changes.

The analysis of expired gas with exercise testing was conducted preoperatively with lung cancer patients in order to examine the relationship between maximum oxygen consumption (VO2 max) and postoperative complications, determining the cut-off of VO2 max/m2. The usefulness of the test as a preoperative screening test for both pulmonary ventilation and circulation was evaluated in comparison to pulmonary ventilation tests with spirometry and pulmonary circulation tests with Swan-Ganz catheter. Preoperative VO2 max/m2 was calculated from VO2 max in 111 patients with lung cancer who underwent lobectomy of more than one lobe. Also preoperatively conducted were pulmonary ventilation tests by spirometry and pulmonary circulation tests using the Swan-Ganz catheter to measure VC, %VC, FEV1.0, FEV1.0%, mean pulmonary arterial pressure (PPA) and cardiac output coefficient (C.I.). Form theses measurements, VC/m2, FEV1.0/m2 and total pulmonary vascular resistance (TPVR) were calculated. After the cut-off values of VO2 max/m2 were set tentatively at three stages, 600, 650 and 700 ml/min/m2 based on the incidence of postoperative complications, the 111 patients were divided into two groups in each cut-off value; one with VO2 max/m2 greater than the cut-off value and the other less than the cut-off value. Comparison of measurements obtained by spirometry between the two groups disclosed significant differences (p0.001) in VC/m2, %VC and FEV1.0/m2 in all cut-off values. Similarly, comparison of measurements obtained using the Swan-Ganz catheter between the two groups yielded significant differences (p0.05 to p0.01) in PPA and TPVR in all cut-off values.(ABSTRACT TRUNCATED AT 250 WORDS)

This study was conducted to evaluate the numerical changes and the recovery process in exercise capacity over time, and to establish new criteria that will objectively evaluate the recovery in exercise capacity after lung surgery using an expired gas analysis incorporating an exercise test. The subjects consisted of 47 patients that underwent curative resection (only lobectomy) for lung cancer in the four years from 1989 to 1992 that were able to undergo expired gas analysis incorporating an exercise test before and after surgery. The expired gas analysis were performed within one week prior to surgery and over a period from 14 to 449 days after surgery, maximum oxygen consumption (VO2max) and anaerobic threshold (AT) measured, and the VO2max/m2 and AT/m2 were calculated as an index by dividing by the body surface area (m2). In addition, in order to examine the changes in exercise capacity after surgery, the presurgical values were used as 100, and the rate of change after surgery found. These rate were divided into the following measuring times, and the postsurgical changes over time analyzed. The postsurgical measuring times were divided into five groups from 14-30 days (n = 11), from 31-90 days (n = 25), from 91-180 days (n = 8), from 181-270 days (n = 19), and greater than 271 days (n = 8) after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Eight unusual esophageal carcinomas chiefly composed of basaloid cells were defined as "esophageal carcinomas with basaloid features", and analyzed by clinicopathologic findings and immunohistochemical staining with antibodies against S-100, actin, vimentin, and cytokeratin. These tumors were classified into five basaloid-squamous cell carcinomas (BSC), 2 adenoid cystic carcinomas (ACC), and 1 non-small cell type-undifferentiated carcinoma based on the Guidelines for the Clinical and Pathologic Studies on Carcinoma of the Esophagus edited by the Japanese Society for Esophageal Disease. Some histologic patterns of BSC, ACC, or undifferentiated carcinoma were resembled to each others. However, BSC was characterized by solid growth of basaloid cells with microcystic pattern or peripheral palisading arrangement, and it showed simultaneous presence of squamous cell carcinoma or squamous differentiation. In immunohistochemical staining, immunoreactivity for cytokeratin alone was positive in one of five BSCs. On the other hand, ACC showed cribiriform pattern and high mitotic activities, excluding typical cribriform pattern in ACC of the salivary gland. In addition to these features, the presence of foci of squamous cell carcinoma was occasionally found and positive immunoreactivities for S-100 and actin were recognized. Therefore, the immunohistochemical staining was useful for distinction among ACC and other tumors. As to the prognosis, BSC and ACC have been reported that both tumors are aggressive neoplasm with poor prognosis. In our studies, all of 5 patients with BSC were survived more than three years after surgery. In contrast, the patients with ACC or undifferentiated carcinoma died within one year.(ABSTRACT TRUNCATED AT 250 WORDS)

Between 1981 and 1991, we conducted 3 trials of surgical adjuvant therapy for esophageal carcinoma. The first randomized trial was pre- and post-operative radiotherapy, 30 Gray for preoperative therapy and 50 Gray for postoperative therapy. The 2nd trial was performed with postoperative radiotherapy and postoperative chemotherapy, 30 Gray for radiotherapy and cisplatin (CDDP, 50 mg/m2) plus vindesine (VDS, 3 mg/m2) for chemotherapy. The 3rd trial was postoperative chemotherapy (CDDP+VDS) and surgery alone. In the survival rate of the first trial, no significant difference was noted between the 2 groups (n = 20 and n = 16), while in the 2nd trial, the 5-year survival rate in the chemotherapy group (n = 12) was significantly longer (p = 0.017) than that of the radiotherapy group (n = 12). At the present time, the 3rd trial shows no significant difference in survival between patients with (n = 15) and without (n = 15) postoperative chemotherapy. Therefore, we are now performing a new randomized trial with surgery alone and postoperative chemotherapy using a more effective regimen (CDDP 80 mg/m2 + 5-FU 800 mg/m2). In the near future, the most effective therapy will be selected for individual patients with esophageal carcinoma, thanks to developments in clinical oncology, new anticancer drugs, drug delivery systems and molecular biology.

The reductive extraction of f-elements between molten chloride and liquid metal deserves an examination as a possible alternative technique for reprocessing nuclear fuels. Particularly, its application for the group separation of actinides and lanthanides (Ln, hereafter) is promising owing to the high separation factors between lanthanides and actinides achievable in this system [1, 2]. The separation efficiency of lanthanides and actinides is greatly influenced by the standard free energy of formation of their chlorides and metallic alloys in two phases. In order to evaluate the effectiveness of the extraction and separation by this technique, the thermodynamic activities of lanthanides dissolved in liquid metal have to be determined. The standard free energies of the formation of lanthanide-metal alloys can be experimentally measured by the electromotive force measurement method. The standard free energies of few liquid Ln-Zn alloys at 873 K have been obtained [1, 3], but information on the quantitative systematic variation along the 4f-series is still insufficient. Identifying such systematic changes is very useful as it enables to predict those Ln that are difficult or impossible to measure experimentally. It is of great interest to predict the unknown formation free energies of Ln-Zn alloys from the known thermodynamic properties. Sverjensky et al. [4] have developed an empirically based linear free energy equation applicable to cations of any charge, radius or chemical types, which allows estimates of the free energy of solids with uncertainties of less than ±4.18 kJ/mol. This equation is directly analogous to the linear free energy relations of Hammett and others [5, 6] for aqueous organic reactions, but applies instead to crystalline solids of the following structure, MO, M(OH)2, MCO3, MF2, MCI2, and MSO4. Within an isostructural family of solids, the free energy change in going from one compositional endmember to another containing cations with the same (or similar) ionic radii is paralleled by the free energy change between the corresponding aqueous cations [4, 7–9]. The lanthanides have the similar ionic radii and charge; this equation has been successfully applied to predict the standard free energies of formation of liquid Ln-Bi alloys [10]. Therefore, it is desirable to apply this linear free energy relationship for Ln-Zn alloys in order to accurately predict of the standard free energies not previously amenable to pyrochemical analysis. Small amount of Ln dissolved in liquid Zn (mole fraction less than 0.01 in the reductive extraction systems)

To study the biological characteristics of undifferentiated carcinoma of the esophagus, the nuclear DNA content, the growth fraction using monoclonal antibody Ki-67 (Ki-67), immunohistochemical expression of epidermal growth factor receptor (EGFR) and the grade of Leu-7 positive cells infiltrating at the marginal area of the cancerous tissue were measured in 5 cases of undifferentiated carcinoma and 131 cases of squamous cell carcinoma. The following results were obtained. 1) DNA aneuploid was found in 60% of undifferentiated carcinoma, 47% of squamous cell carcinoma. 2) The Ki-67 labeling rates of undifferentiated carcinoma were higher than those of squamous cell carcinoma, and a variable proportion of Ki-67 labeling rates of undifferentiated carcinoma was ranging from 12% to 34%. It was demonstrated that undifferentiated carcinoma had high proliferative potential. 3) The expression of the EGFR was stained in the basal cell and parabasal layers of normal epithelia. In squamous cell carcinoma, EGFR was located on the cancer cell membrane and was observed 79%, while in all cases of undifferentiated carcinoma, it was not detected. 4) The grade of Leu-7 positive cells was related to pathological stage and prognosis in squamous cell carcinoma. The patients with low grade of Leu-7 positive cells frequently had early recurrences of the carcinoma after esophagectomy, and their prognosis was poorer than those with higher grade of Leu-7 positive cells. The patients of undifferentiated carcinoma, independently of pathological stage, were observed low grade of Leu-7 positive cells and had poor prognosis except only one case. Therefore undifferentiated carcinoma seems to be escaped from defensive mechanism of host immune response.(ABSTRACT TRUNCATED AT 250 WORDS)

Nowadays, surgery for a thoracic esophageal carcinoma is accomplished safely, however, there still remain many problems concerning curative resection. Cancerous recurrences of the lymph node is still high against to lymph node dissection around thoracoabdominal region. Therefore, surgery should endeavour to prevent such lymphatic recurrences. In the patients with a carcinoma in the upper or middle third of the esophagus, who underwent extended radical esophagectomy, a significantly high incidence of metastasis in the recurrent nerve lymphatic chain was noted in comparison with that in patients with that in those who underwent standard radical resection. Complete resection of the recurrent nerve lymphatic chain is generally difficult through the thoracic approach alone, and such approach might be the factor causing the poor prognosis after standard radical surgery for an upper or middle thoracic esophageal carcinoma. Accordingly, extended radical surgery by the cervicothoracoabdominal approach can produced improved surgical curability for an upper or middle thoracic esophageal carcinoma. On the other hand, pulmonary complications are still a major postoperative complication following radical esophagectomy due to extended radical lymphadenectomy around the paratracheobronchial region. So, it is now clear that we should preserve the right bronchial artery and pulmonary nerves branched from the vagus nerve during the thoracic procedure, if these unaffected by cancerous invasion. Adopting this procedure resulted in a marked decrease in the incidence rate of postoperative severe pulmonary complications. Finally, in the near future we expect to develop criteria to select the best treatment for each specific individual based on preoperative studies of the biological characteristics of the carcinoma.