[A patient with gastric small cell carcinoma who died from meningitis carcinomatosa after CDDP+CPT-11 chemotherapy with good response].

A-63-year-old man was admitted to our hospital because of epigastralgia. On gastrointestinal fiberscopy, a complete obstruction of the pylorus was found, and endoscopic biopsy specimens from this region revealed gastric small cell carcinoma. CT scans showed the primary tumor at the pylorus with many regional lymph node metastases invading the pancreas. We performed gastrojejunostomy, followed by chemotherapy with irinotecan plus cisplatin (CDDP 30mg/m² and CPT-11 60mg/ m² on day 1 and 15). Three courses of treatment resulted in a marked reduction of both the primary tumor and regional lymph nodes. Subsequently, the patient underwent distal gastrectomy. Micro examination, revealed that the tumor had mostly changed to necrosis and fibrosis, and the pathological TNM grading was pT3 (SS) pN0M0, stage II A. Postoperatively, three courses of the same chemotherapy were performed. However, the patient died 5 months after the second operation, due to meningitis carcinomatosa without metastases of other organs.

Long-term acceptance of rat cardiac allografts on the basis of adenovirus mediated CD40Ig plus CTLA4Ig gene therapies.

BACKGROUND: We have previously demonstrated that blockade of either CD80/86-CD28 or CD40-CD154 costimulatory pathways by using adenovirus vector coding CTLA4Ig (AdCTLA4Ig) or CD40Ig (AdCD40Ig) genes induced donor-specific tolerance in rat liver transplantation. In this study, we asked whether these gene-therapy-based costimulation blockade would induce tolerance in cardiac transplantation. METHODS: Heterotopic heart transplantation was performed in a full major histocompatibility complex (MHC) barrier combination of ACI (RT1avl) to Lewis (LEW, RT1l) rats. Vector (1 x 10(9) plaque forming unit [PFU]), AdLacZ, AdCTLA4Ig, or AdCD40Ig, was administered intravenously to recipient animals immediately after grafting, and graft survival, serum CTLA4Ig/CD40Ig levels, and graft histology were assessed. Tolerance was determined by secondary skin-graft challenging. RESULTS: Allografts of both untreated and AdLacZ controls were promptly rejected within 7 days, whereas a single treatment with AdCTLA4Ig or AdCD40Ig significantly prolonged median graft survival to 55.5 and 28.5 days, respectively. In contrast, the combined AdCTLA4Ig and AdCD40Ig gene therapy maintained high CTLA4Ig and CD40Ig levels through the posttransplant period and allowed long-term cardiac allograft survival for more than 270 days. However, both donor and third-party skin grafts were rejected in the animals who harbored cardiac grafts over 150 days. Also, typical features of chronic rejection were evident in the long-term surviving grafts. CONCLUSION: Simultaneous blockade of CD28 and CD154 pathways by AdCTLA4Ig plus AdCD40Ig induces a strong immunosuppression that allows long-term acceptance of full MHC mismatched cardiac graft in rats. This strategy, however, was not enough to induce tolerance to skin grafts and to avoid chronic rejection, as shown in the liver-transplantation model.