[A case in which dihydropyrimidine dehydrogenase deficiency was strongly suspected during adjuvant chemotherapy with capecitabine for colon cancer].

Severe toxicity in patients with a deficiency of dihydropyrimidine dehydrogenase(DPD), an enzyme that reduces fluoropyrimidine, is very rare, and reports on this condition are few. Accordingly, diagnosis is very difficult. The patient was 70-year-old man who was admitted for adjuvant chemotherapy with capecitabine(3,600mg/day)for rectal cancer. He was admitted to our hospital because of severe oral mucositis(grade 3)and hand-foot syndrome(grade 3). After hospitalization, he experienced complications with neutropenia(grade 4)and thrombocytopenia(grade 4). The patient died 25 days after the onset of chemotherapy. Despite the measurement of the DPD value in mononuclear cells of peripheral blood and urophanic uracil and dihydrouracil, we were unable to diagnose DPD deficiency. However, we suspected a partial deficiency of DPD on the basis of the clinical course.

[A case of primary adenocarcinoma of small intestine responding to XELOX chemotherapy and leading to a partial metabolic response].

We report a case of adenocarcinoma of the small intestine responding to XELOX chemotherapy, leading to a partial metabolic response(PMR). The patient was a 58-year-old male with multiple peritoneal dissemination of adenocarcinoma of the small intestine. Chemotherapy with XELOX(L-OHP 130 mg/m² on day 1 , and capecitabine 1,000 mg/m2 on days 1-14)was performed. After 4 courses, a significant tumor reduction was obtained. This case suggests that chemotherapy with XELOX is a potential regimen for small intestinal adenocarcinoma.

[A case of resected rectal cancer with hepatic node and multiple liver metastases effectively treated by preoperative modified FOLFOX6 and sLV5FU2 chemotherapy].

A 55-year-old male had complained of melena.Colonoscopy revealed a type 2 tumor at the rectum.CT demonstrated hepatic lymph nodes and multiple liver metastases(stage IV).Low anterior resection was performed(tub2, RsRa, circ, type 2, pSS, pN1, sH3, cHN1, sP0, cM0: fstage IV).The patient was treated with mFOLFOX6 and sLV5FU2 after operation.CT revealed a partial response after 14 courses of systemic chemotherapy.sLV5 FU2 therapy was converted to capecitabine because he experienced bone marrow suppression.CT showed that the liver metastases had enlarged but the hepatic lymph nodes disappeared.Right portal vein embolization was performed.After 4 weeks, right hepatectomy and hepatic lymph node dissection were performed.Preoperative chemotherapy with mFOLFOX6 seems beneficial as a neoadjuvant chemotherapy for hepatic lymph node-positive advanced colorectal cancer.

[A case of early poorly-differentiated neuroendocrine carcinoma of stomach].

A 45-year-old male was admitted to our hospital complaining of anemia. Gastric endoscopy showed a type IIa+IIc tumor at the anterior wall of the gastric angle. Based on the pathology of the biopsy specimen, poorly-differentiated adenocarcinoma was diagnosed. Computed tomography scans showed regional lymph node swelling. Distal gastrectomy with a D2 lymph node dissection was performed. On pathology, the tumor was immunohistochemically positive for chromogranin A and synaptophysin. The Ki67 index was 70%. The tumor was diagnosed as poorly-differentiated neuroendocrine carcinoma of the stomach. He was treated with S-1 and CPT-11. Neuroendocrine cell carcinoma of the stomach is rare and usually has a very poor prognosis. Thus, we are reporting this case of early poorly-differentiated neuroendocrine carcinoma of the stomach that was curatively resected and had 12-month survival without recurrence.

[A case of gastric cancer with peritoneal dissemination who achieved long survival by successive treatments with S-1 in combination with CDDP, paclitaxel and irinotecan].

The patient was a 63-year-old male with multiple peritoneal disseminations of advanced gastric cancer. He underwent chemotherapy with a combination of S-1 120 mg/day (3 weeks administration and 2 weeks rest) and cisplatin (CDDP) 60 mg/m(2) (day 8). After 3 courses of this regimen, CT revealed no evidence of ascites. He then underwent laparatomy. Peritoneal dissemination appeared, and the findings were sT3, N0, H0, P1, CY1, M1(PLE), sStage IV. A bypass operation was performed. As second-line chemotherapy, he received combination chemotherapy with S-1 and paclitaxel (PTX) 60 mg/m(2) (div), 20 mg/m(2) ( ip) (day 1, 8). However, he complained of ascites after 16 courses. We tried weekly administration of PTX and tri-weekly administration of irinotecan (50 mg/m(2)) with S-1. This treatment was successfully continued for 20 courses. The adverse effect was anemia (grade 2). He died two years eight months after surgery. The chemotherapy with S-1/CDDP, S-1/PTX, and S-1/PTX/irinotecan was thought to be effective for advanced gastric cancer with peritoneal dissemination.

[A case of stage IV AFP producing cecal cancer responding to mFOLFOX6 leading to a partial response].

We report a case of stage IV AFP producing cecal cancer responding to mFOLFOX6 leading to a partial response. The patient was a 72-year-old female with multiple liver metastases of cecal cancer. She underwent a right hemicolectomy and right salpingo-oophorectomy in a non-curative resection. Final findings revealed cecal cancer, type 3, 60 x 55 mm, pSI (right ovary), pN3, sH3, sP0, cM0, fStage IV, respectively. After surgery, chemotherapy with mFOLFOX6 was performed. After 4 courses, a significant tumor reduction (PR) was obtained. She died 1 year 2 months after surgery. This case suggests that chemotherapy with mFOLFOX6 is a potential regimen for AFP producing colon cancer.

Annexin V assay-proven anti-apoptotic effect of ascorbic acid 2-glucoside after cold ischemia/reperfusion injury in rat liver transplantation.

Controversy exists over whether the predominant cell death of hepatocytes is due to apoptosis or necrosis after ischemia/reperfusion injury. In this study we investigated the predominant cell death of hepatocytes after cold ischemia/reperfusion injury using the Annexin V-based assay, and evaluated the anti-apoptotic effect of ascorbic acid 2-glucoside (AA-2G) added to the University of Wisconsin solution (UW solution) in rat liver transplantation. The retrieved liver was preserved in 4 UW solution for 24 h, and then transplanted orthotopically to the syngeneic Wistar recipient. The animals were divided into 2 groups, a control group (n=10), in which liver grafts were preserved in UW solution (4), and an AA-2G group (n=10), in which liver grafts were preserved in UW solution (4) with AA-2G (100 ug/ml). The serum AST level 4 h after reperfusion in the control group was significantly suppressed in the AA-2G group, and the bile production of the liver graft in the AA-2G group was well recovered. The mean survival time in the AA-2G group was significantly improved compared with that in the control group. Annexin-V and Propidium iodide staining 4 h after reperfusion showed a significantly higher percentage of viable hepatocytes in the AA-2G group compared with the control group (93.4 +/- 2.0 vs. 80.3 +- 2.1%, P<0.05). In the control group, the main cell death of hepatocytes was apoptosis (early apoptosis: 10.0 +- 4.7%, late apoptosis: 6.4 +/- 1.7%). The addition of AA-2G to the UW solution significantly inhibited both early and late apoptotic cell death 4 h after reperfusion (early apoptosis: 0.98 +/- 0.88%, late apoptosis: 2.2 +/- 1.1%). The expression of caspase 9 in the immunostaining of the liver graft was suppressed in the AA-2G group compared with in the control group. Our study using the Annexin V-based assay provided evidence that the predominant cell death of hepatocytes was apoptosis after 24 h cold ischemia/reperfusion injury in rat liver transplantation. The addition of AA-2G to the UW solution attenuated 24 h cold ischemia/reperfusion injury by inhibiting the apoptosis of hepatocytes.

Induction of indirect donor-specific hyporesponsiveness by transportal RT1-peptide pulse in rat skin transplantation.

In the present study, we examined whether transportal pulse of class I major histocompatibility complex (MHC) allopeptides can induce indirect (non-chimeric) donor-specific hyporesponsiveness, using a high-responder rat skin transplantation model. Two donor-specific 8-amino acid peptides corresponding to residues 58-65 and 70-77 in the alpha(1) helical region of RT1.A(a) were synthesized. In order to test immunogenicity of these peptides, mixed lymphocyte reaction (MLR) was performed. Then, 100-microg portions of peptides were injected into recipient Lewis (LEW, RT1.A(l)) rats via the portal vein 14 days before skin transplantation. Skin allografts from August Copenhagen Irish (ACI, RT1(a)) or Wistar King A (WKA, RT1(k), third-party) donors were transplanted to LEW (RT1(l)) recipients. Transportal pulse of residues 58-65 and 70-77 prolonged graft survival significantly in ACI-to-LEW skin transplantation (17.6+/-0.40 and 18.0+/-0.45 days) compared with control (14.2+/-0.37 days). However, pulse of residues 106-113, a non-donor-specific control, did not prolong graft survival time (14.6+/-0.40 days) in the same combination. Regarding the third-party donor, residues 58-65 injected into LEW recipients had no effect on survival time of skin grafts (19.0+/-0.84 days) derived from WKA donors compared with the untreated WKA-to-LEW control (19.4+/-0.93 days). Transportal pulse of RT1.A(a) peptides induced donor-specific hyporesponsiveness even in a high-responder rat skin transplantation model. Our results suggest that graft enhancement by transportal exposure to donor cells may not be induced by a chimeric process but, instead, by an indirect mechanism not involving intervention of viable donor cells.