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Tumor infiltrating lymphocytes (TILs) are candidates for adoptive cellular immunotherapy. Here we report on a patient whose TILs presented unusual lymphocyte antigens. Pleural effusions were collected from a 47-year-old man with recurrent cholangio cell carcinoma and malignant effusion. Effusion- associated lymphocytes (EALs) were separated by Ficoll-Hypaque gradient, and the EAL phenotype was determined by flow cytometry. The percentage of positive cells was determined for each lymphocyte-related differentiation antigen. The percentages of CD3[sup +], CD19[sup +], and CD16[sup +] lymphocyte subpopulations among EALs were 20%, 7%, and 3%, respectively. Nearly 70% of EALs were CD3[sup -]/CD19[sup -]/CD56[sup -]/CD16[sup -] cells. The phenotypes of peripheral blood lymphocytes (PBLs) collected simultaneously from the patient's peripheral blood were CD3[sup +] (52%), CD19[sup +] (20%), and CD16[sup +] (20%). When EALs were cultured in medium without pleural effusion, T cell-related antigens, but not B cell- or natural killer (NK) cell-related antigens, were newly expressed on EALs, and this expression reached a plateau after 48 h in culture. The proportions of CD3[sup +], CD19[sup +], and CD16[sup +] cells were 69%, 7%, and 3%, respectively. However, when EALs were cultured in medium with pleural effusion, increased expression of T cell-related antigens was not observed; the proportions of CD3[sup +], CD19[sup +], and CD16[sup +] cells were 16%, 6%, and 1%, respectively. Neither total cell numbers nor cellular viability of EALs changed significantly after in-vitro culture, suggesting that significant proliferation or death of EALs did not occur during the culture period. Co-culture of the patient's PBLs with autologous pleural effusion for 96 h did not alter the expression of lymphocyte-related antigens on the PBLs. These results indicate that expression of T cell-related antigens, but not B cell- or NK cell-related antigens, on EALs was blocked temporarily by the... [ABSTRACT FROM AUTHOR]

Anorectal malignant melanoma(AMM)is a relatively rare disease with an extremely poor prognosis. We experienced a case of this disease detected by colorectal cancer screening and report it here with a literature review. Our 67-year-old female patient was referred to the Department of Gastroenterology at our hospital for a thorough examination of the gastrointestinal tract after an abnormal fecal occult blood count(+/+ on 2 occasions)was noted during a colorectal cancer screening. Lower gastrointestinal endoscopy revealed a small easily bleeding lesion near the anal verge for which endoscopic mucosal resection was performed. A histopathological examination revealed a primary malignant melanoma of the rectum, and the patient underwent abdominoperineal rectal amputation. According to the rules for the treatment of T1b (1,200 μm), N0, P0, H0, M(-), StageⅠ, Cur A colorectal cancer. A histopathological examination of the resected specimen showed no remnant tumor cells. About 2 years have passed since the surgery, and the patient is still alive without recurrence. Considering its characteristics, patients with AMM will require further careful follow-up. Here we summarize our experience diagnosing and treating a case of early-stage AMM.

Bisphenol A (BPA) is an endocrine-disrupting chemical used in polycarbonate and epoxy resins. Previously, we found that BPA stabilized the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) by inducing Ca 2+ efflux into the cytosol, followed by nitric oxide synthase activation, resulting in the enhanced nitrosylation of Keap1, which is a negative regulator of Nrf2. However, the mechanisms behind the stimulation of Ca 2+ efflux by BPA remain unknown. In the present study, we found that BPA stimulated Ca 2+ efflux into the cytosol from the ER, but not from outside of cells through the plasma membrane in Hep3B cells. Ca 2+ efflux and Nrf2 stabilization by BPA were inhibited by an inhibitor of the inositol 1,4,5-trisphosphate (IP 3 ) receptor, 2-aminoethoxydiphenylborane, in the endoplasmic reticulum. IP 3 is produced by activation of phospholipase C (PLC) from a membrane lipid, phosphatidylinositol 4,5-bisphosphate (PIP 2 ). The induction of Nrf2 by BPA was not inhibited by a PLC inhibitor, U-73122, suggesting that BPA does not induce the production of IP 3 via PLC activation. We found that BPA bound directly to the IP 3 binding core domain of the IP 3 receptor, and BPA competed with IP 3 on this site. In addition, overexpression of this domain of the IP 3 receptor in Hep3B cells inhibited the stabilization of Nrf2 by BPA. These results clarified that the IP 3 receptor is a new target of BPA, and that BPA induces Ca 2+ efflux from the endoplasmic reticulum via activation of the IP 3 receptor.

Pancreas transplantation has been recognized as the best treatment for advanced type 1 diabetic patients. In Japan, we have performed 64 SPK, PAK or PTA from 62 brain-dead donors and two non-heart beating donors since the enforcement of Organ Transplant Act in 1997. In addition, 18 cases have been performed from living related donors. The patient survival, pancreas graft survival and kidney graft survival rate of the cadaveric transplantation at five years are 97.5%, 73.9% and 71.0%, respectively. The QOL of the recipients in both mental and physical aspects has been wonderfully improved leading to the happy second life. In front of the revised low in this year, the number of the donor and the transplantation are expected to increase.

The pancreas transplantation is widely performed for the patients with type 1 diabetes. To date in Japan we had 20 SPK or PAK transplants under the new brain death law launched in 1997. Despite severe shortage of organ donors and marginal donors such as old age, unstable homodynamic situation at agonal phase and atherosclerosis, all patients enjoy a post-operative life except two patients who had grafts removed due because of thrombosis and perforation. There are some reports recently presented at the meeting with respect to simultaneous pancreas kidney transplantations from living donors. It will be expected to have more donors and transplantation with satisfactory results in Japan as well.

Hypothesis: Frozen section diagnosis and permanent diagnosis of bile duct margin predict local recurrence after surgical resection of gallbladder or bile duct carcinoma., Design: Retrospective review., Setting: University, tertiary care., Patients: A total of 20 patients underwent frozen section diagnosis of bile duct margin for resection of gallbladder and bile duct carcinoma., Main Outcome: Diagnosis of frozen and permanent section of bile duct margin, and local recurrence., Results: The permanent diagnosis was identical in 15 patients but changed in 5 (from positive to negative in 3 and from negative to positive in 2). The reasons for these changes were overdiagnosis (mucosal lesions in two and mesenchymal components in another) and new recognition of malignant cells on permanent section in the other two. In seven patients with a positive bile duct margin by permanent histology, mucosal spread was evident in two and involvement of the subepithelial layer was present in the other five. No local recurrence occurred in the two patients with epithelial spread and four of the five with subepithelial infiltration., Conclusions: Frozen section and permanent diagnoses of the bile duct margin in gallbladder and bile duct carcinoma may be inconsistent in 25% of patients due to overdiagnosis of frozen section or new recognition of cancer cells by permanent histology. In situ carcinoma does not always produce local recurrence, while cancer cells in the subepithelial layer strongly predict occurrence of local recurrence.

Since October 1, 1999, a total of 17 pancreas transplantations have been performed in Japan, involving 15 brain-dead donors and 2 non-heart beating donors. The donor ages were relatively high with 67% (10/15) over age 40 and brain death was typically attributable to cerebrovascular accidents (70.6%; 12/17). The majority of donors could be defined as marginal (13/17; 76.5%). Because of these adverse donor characteristics, the gastroduodenal artery of the graft was usually reconstructed to increase blood supply to the pancreas head when liver procurement was undertaken. Also, intensive insulin therapy was used to rest graft islets in some centers during the acute phase of transplantation. Patient survival was 100% with a mean follow-up period of 21 months (range: 4-54 months). All recipients have remained insulin-free without any need for dialysis. One patient lost a pancreatic graft to venous thrombosis, but was successfully retransplanted 2 years later. All recipients have displayed good QOL after transplantation. Nine recipients made a complete return to their jobs, while 5 patients made a partial return to light jobs, such as housework or office work.

Background/aims: The outcome of advanced gallbladder carcinoma is dismal despite aggressive surgery. The aim of this study was to evaluate the surgical outcome and prognostic factors for patients with gallbladder carcinoma and to identify patients who may benefit from radical surgery., Methodology: Fifty-six patients who underwent surgical resection of gallbladder carcinoma were retrospectively reviewed. Their tumor markers, operative management, pathological factors and survival were analyzed., Results: The serum carcinoembryonic antigen level was elevated in 9 of 51 patients (18%) with data available as was the serum carbohydrate antigen 19-9 level in 14 of 47 patients (30%). Univariate analysis showed that jaundice, serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels, the number, size, macroscopic type, and histological grade of the tumor, the depth of tumor invasion (pT), pathological stage, lymph node metastasis (pN), lymphatic invasion, vascular invasion, perineural infiltration, curability of lymph node dissection and surgical margins have prognostic significance for survival. Multivariate analysis revealed jaundice, high histological grade, pT3 or pT4, and surgical margins were independent prognostic factors for survival., Conclusions: Preoperative serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels are potential predictors and informative for survival. There are still difficulties to treat gallbladder carcinoma infiltrating beyond subserosa or revealing jaundice.