Improved hepatic microcirculation by human soluble urinary thrombomodulin in the xeno-perfused porcine liver.

PURPOSE: Both the protein C/thrombomodulin system and the heparin/anti-thrombin III system are major physiological anticoagulant systems, which may also play a major role in preserving the hepatic microcirculation in xenogeneic liver transplantation. To compensate for the functional incompatibilities of the porcine thrombomodulin (TM)-cofactor activity beyond species for human thrombin, soluble human TM protein was tested in xenogeneic perfusion of the porcine liver. MATERIALS AND METHODS: The livers were harvested from adult female pigs and perfused through the portal vein (PV) and hepatic artery (HA) for 2 hr, with fresh human blood in group 1 (n=5), fresh porcine blood (10 units/ml) in group 2 (n=5), and fresh human blood with TM (50,000 units/1.5 l) in group 3 (n=5). The tissue PO2 level, tissue blood flow, PV and HA pressures were all continuously monitored. Circulating perfusate and liver tissue samples were periodically obtained for blood chemistry and histologic analyses. RESULTS: The activated protein C (aPC) level was significantly elevated in the TM-treated group 3 (47.5%+/-3.5% at preperfusion and 51%+/-2.8% after 120 min of perfusion) in comparison to group 1 (32.3%+/-7.2% and 35.3+/-12.0%). The hepatocyte enzyme release of aspartate aminotransferase (AST) was suppressed significantly more in group 3 (238.2+/-107 IU/l), than in group 1 (672.3+/-160 IU/l) at 2 hr after reperfusion. In group 3, the tissue PO2 levels and tissue blood flow also remained significantly higher throughout the perfusion. The platelet counts in the perfusate remained significantly higher in group 3 (37.1% to 74.3% of the preperfusion level) than in group 1 (4.4% to 14.7%), after 0 to 80 min of perfusion. According to the histologic findings, the degree of interlobular hemorrhaging and congestion decreased remarkably more in group 3 than in group 1. CONCLUSION: These findings thus indicated that soluble thrombomodulin protein extracted from human urine remarkably improved hepatic microcirculation in the xenoperfused porcine liver. The thrombomodulin/protein C system might, thus, play an important role in restoring the physiological anticoagulant system in the xenoperfused porcine liver.

Resection of triple synchronous cancers: a case report.

We herein present a case of synchronous triple cancer, which was successfully resected in a curative manner. These cancers consisted of primary duodenal, pancreatic and lung cancers, which were diagnosed in an asymptomatic 74 year-old male, who was referred to our department on December 14, 1996. On admission, his laboratory data showed no abnormality, including tumor markers (CEA 1.0, CA 19-9 1.0, AFP 8.1 U/ml), but he did show an impaired pulmonary function (FEV1.0: 57%). Upper gastrointestinal endoscopy showed a smooth surfaced duodenal tumor measuring 4 cm in size. The second tumor was found at the head of the pancreas by computed tomography (CT), showing a hypervascular mass measuring 3.0 cm, along with neighboring multiple cysts. In endoscopic retrograde cholangiopancreatography (ERCP), marked mucous secretion was observed through the papilla, while a filling defect was found in the dilated pancreatic duct. In a routine chest X-ray, a third tumor, which measured 1.5 cm in diameter, was recognized in the right upper lobe of the lung, and a moderately differentiated squamous cell carcinoma was also detected by a percutaneous CT guided biopsy. The pancreatic and duodenal tumors were surgically resected by a pancreatoduodenectomy (Stage I) in January 1997 and, 5 months later, a lung tumor underwent partial resection (Stage I). This patient tolerated these surgical procedures well and presently leads a normal, healthy life after discharge. In summary, a successful resection of synchronous triple cancers, which has never been previously reported in this specific combination, is described.

Combined hepatocellular and cholangiocellular carcinoma in a non-cirrhotic liver.

Combined hepatocellular (HCC) and cholangiocellular carcinoma (CCC) (mixed carcinoma) is a rare subtype of primary hepatic carcinoma. We report a case of mixed carcinoma that developed in a non-cirrhotic liver, in a patient who was serologically negative for both hepatitis B and C viruses. A 65-year-old Japanese woman with a 25-year history of chronic rheumatoid arthritis had been treated with steroids and anti-inflammatory drugs, and was diagnosed by ultrasonography with an asymptomatic solitary tumor in the right lobe of the liver. On computed tomography scan and hepatic arteriography, the tumor was well enhanced by contrast medium in the early phase. Based on the findings of elevated serum alpha-feto protein (AFP, 245 ng/ml) and normal carcino-embryonic antigen (CEA, 2.6 ng/ml) levels, a preoperative diagnosis of hepatocellular carcinoma was made. Right lobectomy of the liver was performed on January 7, 1997. Histological examination showed that the resected tumor consisted of combined CCC cells and HCC cells in an intermingled form, with CCC being far more dominant than HCC. The tumor was therefore determined to be a combined carcinoma, subclassified as intermingled type. This case appears to indicate that mixed type carcinoma developed in a non-cirrhotic liver, with CCC being dominant; such a finding is extremely unusual, based on previously published reports.

[A case of acetaminophen-induced pneumonitis].

A case of acetaminophen-induced pneumonitis is described. A 63-year-old woman took 2350 mg of acetaminophen for fever. She subsequently developed a non-productive cough and dyspnea. Chest X-ray revealed diffuse reticulonodular shadows in bilateral lung field and she was admitted to our hospital. PaO2 was 45.0 Torr and PaCO2 35.7 Torr while breathing room air. Bronchoalveolar lavage examination showed an increase in the percentage of lymphocytes and a decrease of CD4/CD8 ratio. Microscopic examination of a transbronchial lung biopsy specimen showed alveolar septal thickening. The lymphocyte stimulation test was positive for acetaminophen, with a stimulation index of 237%, while other drugs used were negative. Because drug-induced pneumonitis was suspected, all drugs were stopped and she was administered methylprednisolone. Consequently her symptoms, laboratory data and chest X-ray findings improved. Based on these findings, we diagnosed this case as acetaminophen-induced pneumonitis. To our knowledge, there has been only one previously reported case of acetaminophen-induced pneumonitis.

[Adoptive immunotherapy for pulmonary tuberculosis caused by multi-resistant bacteria using autologous peripheral blood leucocytes sensitized with killed Mycobacterium tuberculosis bacteria].

A patient with pulmonary tuberculosis caused by bacteria resistant to various anti-microbial agents was treated with adoptively transferred autologous peripheral blood leucocytes (PBL) sensitized with killed Mycobacterium tuberculosis organisms in vitro. The 32-year-old man was admitted to our hospital from National Sanitarium Okinawa Hospital with weight loss, high fever, and rapid aggravation on chest X-ray. Patient's PBL obtained by leukapheresis and separated with Ficoll-Hypaque solution were cultured with killed Mycobacterium tuberculosis bacteria of 0.4 microgram per ml at 1 x 10(6) cells per ml for 7 days in media containing 0.5 U recombinant 1L-2 per ml. After incubation, PBL were layered and centrifuged on Ficoll-Hypaque solution and washed three times with saline. PBL (1-3 x 10(8)) were combined and concentrated for infusion in 20 to 30 ml saline. After injection, patient displayed fever and transitory drop of PaO2. Although the patient did not have an improved on chest X-ray, his fever was alleviated, weight was increased, accelerated ESR was slightly improved, and the number of organisms in sputum (Number of Gaffky) temporarily decreased. Adoptive immunotherapy using the autologous PBL which were sensitized with killed bacteria may be an effective anti-tuberculous immunotherapy.

[A case report of giant cell granuloma of the jaw].

A giant cell granuloma of the mandible seen in a 16 month-old boy was reported. Histopathology showed that the lesion consisted basically of granulation tissue with multinucleated giant cells, spindle-shaped and polygonal stromal cells. No atypia was seen in giant cells or stromal cells. Electron microscopic examination revealed that multinucleated giant cells possessed microvillous structure on their cytoplasm and were rich in organelles such as endoplasmic reticulum, mitochondria and dense bodies. Stromal cells consisted of macrophage-like and fibroblastic cells. Immunohistochemical examination demonstrated a large number of giant cells and stromal cells that were strongly positive for the antibodies of alpha-1-antitrypsin and alpha-1-antichymotrypsin. These morphological findings suggest that macrophage-like stromal cells are the precursors to giant cells.