Tetsuro Matsuda

The molecular mechanism of apoptosis induced by xenogeneic cytotoxicity

Abstract: In order to clarify the role of natural killer (NK) cells in delayed xenograft rejection (DXR) of discordant xenotransplantation, we used in vitro xenogeneic combination of human NK cells and pig kidney target cells (PK13, and investigated the mechanism of xenogeneic cytotoxicity caused by human NK cells. In the presence of decomplemented human serum or human IgG, freshly isolated human peripheral blood lymphocytes (PBLs) caused both membrane (51Cr release) and DNA (3H release) damage on PK15. In contrast, only membrane damage was detected in the presence of normal human serum. To clarify the participation of perforin/granzymes‐cell mediated cytotoxicity (P/G‐CMC), when EGTA or concanamycin B (CMB) was added to the cytotoxicity assays, both cytotoxicities were completely inhibited by these drugs in a dose‐dependent manner. In terms of the involvement of Fas/FasL‐based cytotoxicity (F‐CMC), while the cytotoxicity assays were performed in the presence of antagonistic anti‐human FasL mAb, this antibody was not able to block the cytotoxicity. From these results, it is concluded that xenogeneic cytotoxicity is due to NK cell dependent ADCC (antibody‐dependent cell‐mediated cytotoxicity), and their effector mechanism can cause apoptosis on target cells via P/G‐CMC.

Laparotomy versus interventional radiological procedures for the implantation of arterial infusion devices

Although there have been numerous reports on implantable infusion devices for chemotherapy of patients with malignancy, we occasionally face problems with this therapy due to trouble with implanfation. We performed a retrospective review of 81 implantations in 77 patients, who were treated with intraarterial chemotherapy via implanted devices from 1985 to 1993. They were divided into two groups according to the procedures: the operative procedure group (group A,n=41) and the interventional radiological procedure group (group B,n=36). Both groups were then analyzed regarding the respective complications. We experienced 25 complications: (a) 9 obstructions of the catheter, (b) 4 infections, (c) 4 dislocations of the catheter, (d) 3 hematomas, (e) 3 breakdowns of the device, (f) 1 pneumothorax, and (g) 1 hepatic artery occlusion. The results of a comparison of the complication rate between groups A and B were (a) 14.0%:8%, (b) 4%:0%, (c) 0%:10%, (d) 4%:2%, (e) 7%:0%, (f) 0%:2%, and (g) 2%:0%, respectively. A statistically significant difference was observed for (b) and (c) (P<0.05). Infection occurred mainly in the cirrhotic cases of group A, but not in group B. In addition, one case fell into fatal sepsis. Based on the above findings, the interventional radiological procedure is thus considered to be the appropriate method for the prevention of infection in the case of a compromised host.

Successful resection of advanced pancreatic tail cancer after neoadjuvant gemcitabine chemotherapy: report of a case.

Pancreatic cancer with distant metastasis is not an indication for surgery, and the median survival of these patients is less than 3 months. We report the case of a patient who has survived for 21 months without any signs of recurrence after resection of advanced pancreatic cancer following a course of chemotherapy with gemcitabine (GEM). A 75-year-old man was hospitalized for anorexia and emaciation. Examinations showed pancreatic cancer with distant peritoneal metastasis. After the main tumor and metastasis had been shrunk by GEM chemotherapy, we performed distal pancreatectomy combined with splenectomy. Microscopically, the main tumor was confirmed as moderately differentiated tubular adenocarcinoma with interstitium and fibrosis. The radicality of the surgery was R0, according to the TNM classification of the UICC. The patient recovered well and has had no clinical symptoms for 40 months since the initial chemotherapy. This case suggests that multidisciplinary treatment with GEM may prolong the survival of some patients with unresectable pancreatic cancer.

Obstructive ileitis secondary to colon cancer: Report of a case

Abstract.We report a case of obstructive ileitis (OI) secondary to colon cancer. A 62-year-old man was hospitalized for abdominal pain and a feeling of fullness. Examinations revealed a mechanical ileus caused by an obstructing carcinomatous lesion of the cecum. He underwent laparotomy on the tenth hospital day, and a right hemicolectomy was carried out with resection of the distended and edematous ileum. The histopathologic diagnosis was adenocarcinoma in the cecum involving the ileocecal valve and nonspecific inflammatory change of the ileum, with mucosal necrosis and neutrophilic infiltration involving the subserosal layer. His postoperative course was uneventful. OI does not always show similar histological features to obstructive colitis; however, they are both important types of obstructing lesions, and their possibility must be kept in mind during colorectal cancer surgery.

A Case of Alpha-fetoprotein Producing Gastric Cancer Suggestive of Multiple Differentiation and Proliferation.

最近われわれは, 術後経過中肝転移を呈し, 血清carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) 高値, alpha-fetoprotein (AFP) 陰性となったAFP産生胃癌の1例を経験したので若干の文献的考察を加えて報告する.症例は84歳の男性.C領域のBorrmam 3型進行胃癌にて胃全摘術を施行した.術前血清AFP 39.4ng/mlと高値を呈し, 病理組織学的にも腫瘍内にAFPの局在を証明しえた.術後10か月目に肝転移をきたしたが, その時の血清AFPは陰性化しており, CEA, CA 19-9が高値を呈した.腹水, および肝転移腫瘍嚢胞液にても同様のパターンを認めた.AFP産生胃癌は, 肝転移を含め, 腫瘍の増大とともに血清AFPが上昇するといわれているが, 本症例のごとく他の腫瘍マーカーが高値になる場合は, 腫瘍が分化増殖形式の異なるさまざまな細胞から構成されていることも推測され, 予後予測のためには, 種々の腫瘍マーカーの変動について十分注意する必要があると思われる.