Correlation between epidermal growth factor receptor concentration and the growth of human gastric cancer xenografts in nude mice.

Seven human gastric cancer xenografts with different concentrations of EGF receptor were established in nude mice. The expression of EGF receptor in the tumors was demonstrated by Western blotting with anti-EGF receptor antibody, binding assay with 125I-EGF and immunohistochemistry with anti-EGF receptor antibody. Western blotting revealed EGF receptor doublet bands at molecular masses of 150 KDa and 170 KDa in all of the samples. The concentration of 125I-EGF binding activity in the tumors ranged from 36.0 to 11,000 fmol/mg protein, with a mean of 345 fmol/mg protein. EGF receptor was also demonstrated immunohistochemically on the apical border of the glands and the cell membrane of the tumor cells. There seemed to be a close correlation between the concentration of 125I-EGF binding activity and the doubling time of these tumors in nude mice (gamma = -0.68). However, no definite correlation was observed between EGF ligand binding and histological features of intestinal type or diffuse type. The expression of EGF receptor appears to facilitate the growth of human gastric cancer xenografts in nude mice.     

Clinical characteristics of thrombotic microangiopathy following ABO incompatible living donor liver transplantation.

Thrombotic microangiopathy (TMA) may develop after living donor liver transplantation (LDLT), but the mechanism is not fully understood. We retrospectively analyzed all patients undergoing LDLT at our center, including TMA patients, to elucidate the clinical characteristics and presentation and to determine which patients have a higher risk of occurrence of TMA. In all, 57 adult patients were reviewed after LDLT at our institution. TMA was diagnosed by sudden and severe thrombocytopenia, followed by hemolytic anemia with fractionated erythrocytes in the blood smear. Clinical features were compared between the TMA group and the non-TMA group. Of the 57 patients, 4 were diagnosed with posttransplantation TMA. ABO blood group (ABO)-incompatibility, cyclophosphamide (CPA), and recipient blood group (type O) were closely correlated with the occurrence of TMA. Thrombocytopenia appeared 1 to 5 days before hemolytic anemia. Coagulative function markers stayed at the same level after TMA, while marked elevation was shown in fibrinolytic function markers such as plasminogen activator inhibitor type 1 (PAI-1). TMA occurred at a higher prevalence in ABO-incompatible graft recipients. Additional factors associated with ABO-incompatible transplantation, such as an overdose of immunosuppressants, may affect the likelihood of TMA. Sudden and severe thrombocytopenia presented before hemolytic anemia and the serum levels of PAI-1 correlated well with the clinical course of TMA. In conclusion, early recognition of thrombocytopenia and elevation of PAI-1 is crucial to diagnose TMA especially in ABO-incompatible LDLT.     

Chemo-endocrine therapy in patients with stage D2 prostate cancer

There have only been a few studies of chemo-endocrine therapy compared with endocrine therapy alone in newly diagnosed prostate cancer patients. We assessed the effects of these two therapies by comparing long-term survival rates. One hundred and twenty-nine patients were entered in this study between November 1977 and March 1992. Seventy-seven patients were treated with endocrine therapy alone. Other 52 patients received chemo-endocrine therapy, which included orchiectomy and/or diethylstilbestrol diphosphate (DES-DP) plus Cisplatin, with or without other cytotoxic agents. All patients had bone metastasis at the beginning of the study. There was a significant difference in survival between patients who received endocrine therapy and chemo-endocrine therapy (P = 0.0078). That is, survival rate was superior for the chemoendocrine therapy patients throughout the entire follow-up period. These data suggest that early chemo-endocrine therapy containing Cisplatin, with or without maintenance chemotherapy, is a potentially effective treatment for newly diagnosed metastatic prostate cancer and is worth further investigation via a randomized trial.     

A case of thymoma with thymic cyst]

A 43-year-old man was pointed out an abnormal shadow on chest X-ray film. Chest CT showed a solid mass and a cyst at anterior superior mediastinum. Operation revealed a capsulated thymoma and a multilocular thymic cyst. PTH and CA19-9 level in the cystic fluid was elevated. Histological examination demonstrated the clear separation of the mixed type thymoma and the thymic cyst. There were few reports for cases of thymoma with a thymic cyst.     

The diagnosis and treatment of esophageal perforations resulting from nonmalignant causes

Esophageal perforations are extremely difficult to diagnose and treat. We report herein our results of a review of 26 patients with esophageal perforation which were spontaneous in 11, iatrogenic in 11, and caused by a foreign body in 4. Surgical treatment was performed in 7 of the patients with spontaneous rupture, but the remaining 19 patients were treated conservatively. The abnormality was found by plain radiography (X-ray) in 22 (85%) of the 26 patients, and by computed tomography (CT) in all 13 patients who underwent this procedure. The detection rates by esophagography and esophagoscopy were 100%, or all of 25 patients examined, and 60%, or 9 of 15 patients examined, respectively. Of 12 patients with underlying diseases, 4 (33%) died after the perforation, whereas only 1 (7%) of 14 patients without any underlying disease died. Postoperative empyema developed in all of 3 patients treated by intraoperative unfixed intrathoracic drainage (UID), but in none of the 4 treated by fixed intrathoracic drainage (FID). Conservative treatment achieved satisfactory results for spontaneous esophageal ruptures confined to the mediastinum, and for iatrogenic perforations and esophageal perforations caused by foreign bodies, provided there was no serious underlying disease such as advanced cirrhosis. Moreover, intraoperative FID proved useful in helping to prevent postoperative empyema.     

Staged Fontan procedure for mitral atresia associated with severe tricuspid regurgitation, pulmonary hypertension, and pulmonary artery distortion

Optimal initial palliation and a subsequent staged approach is mandatory for high-risk Fontan candidates. We describe the case of mitral atresia with severe tricuspid regurgitation and pulmonary hypertension successfully managed by repeated palliation from the neonatal period and 2-stage Fontan surgery. A 1-month-old boy diagnosed with mitral atresia and double-outlet right ventricle underwent pulmonary artery banding at 1 month of age, followed by repeated pulmonary artery banding accompanied by tricuspid annuloplasty and atrial septal defect enlargement at 6 months. Because of the presence of pulmonary artery distortion, right ventricular dysfunction, and borderline pulmonary vascular resistance, a hemi-Fontan procedure was conducted with extended pulmonary artery plasty when the boy was 3 years and 8 months old. Cardiac catheterization done 3 months after showed improvement in risk factors, and the final Fontan operation (total cavopulmonary connection) was successfully done in conjunction with repeated tricuspid annuloplasty when the boy was 4 years and 5 months old. The patient remains in excellent clinical condition at the last follow-up 5 years after the final Fontan procedure with sinus rhythm and good ventricular function.     

Conditions of Alzheimer-type dementia in the old-old and oldest-old patients with special reference to extreme conditions of brain aging

A neuropathological study on 1540 consecutive autopsy brains ranging from 60 to 107 years of age revealed the following points. (1) Of the of the demented cases of the plaque-predominant type, 93% were complicated with multiple tiny cortical infarcts. They showed a tendency for dementia to develop before or after the appearance or worsening of a systemic disorder such as cardiovascular disease, respiratory infection and cancer. However, there was no case showing Alzheimer-type dementia (ATD). (2) The plaque-predominant type might be an extreme condition of brain aging in terms of senile plaques (SP). It is likely that although the pathological appearance of SP alone is not responsible for dementia, its coexistence with multiple cortical infarcts could be the cause of dementia. Therefore, this type should be distinguished from ATD. (3) Primary hippocampal degeneration could also be an extreme condition of brain aging in terms of neurofibrillary tangles. This condition was different pathologically from the hippocampal lesion in ATD. (4) Several characteristics of old-old and oldest-old patients were clarified.     

Percutaneous hepatic venous isolation and extracorporeal charcoal hemoperfusion for high-dose intraarterial chemotherapy in patients with colorectal hepatic metastases

The results of treating 12 consecutive patients with unresectable colorectal hepatic metastases with a hepatic arterial infusion of high-dose Adriamycin, 100–120 mg/m², using hepatic venous isolation (HVI) and charcoal hemoperfusion (CHP) are reported herein. Adriamycin was administered over 5–15 min under extracorporeal drug elimination by HVI-CHP. HVI was percutaneously accomplished by either the double-balloon technique using a Fogarty occlusion catheter (8/22F) or a balloon-tipped catheter (16F). During the infusion, isolated hepatic venous blood was filtered by CHP and pumped into the left axillary vein. There were no lethal complications, and good hemodynamic tolerance to HVI-CHP was confirmed. Tumor liquefaction accompanied by a sharp decrease in serum carcinoembryonic antigen levels by more than 50% of pretreatment levels was observed in 6 of the 12 patients 1 month after treatment. Apart from chemical hepatitis, which developed in 11 (92%) of the patients, the Adriamycin toxicities were well controlled following the development of nausea and vomiting in 2 patients (17%), leukopenia <2,000/mm³ in 3 (25%), and gastric ulcer in 1 (8%). These results indicate that this method is a safe and useful procedure for otherwise hazardous high-dose intraarterial chemotherapy in patients with unresectable hepatic tumors.     

Gerstmann-Sträussler syndrome — A variant type: amyloid plaques and Alzheimer's neurofibrillary tangles in cerebral cortex

Summary This report presents a variant of Gerstmann-Sträussler syndrome (GSS). A 53-year-old female had developed slowly progressive dementia and atactic gait since the age of 45. No myoclonic jerks and periodic synchronous discharges were observed throughout the illness. The neuropathological study revealed that many amyloid plaques and widespread Alzheimer's neurofibrillary tangles (NFTs) appeared in the cerebral cortex. Characteristically, the plaques reacted with anti-prion protein and none of them reacted with anti- protein, and they were made of many components, including amyloid cores, macrophages laden with lipid granules and/or degenerated neurites. Neuropil threads were seen mainly in amyloid plaques. Moreover, plaques appeared which were confluent and laminar in arrangement in the fifth and sixth cortical layers and had a close relationship to the neuronal loss. There was no spongiform change in the cerebral cortex or cerebellum. The cerebellum was almost intact except for a few amyloid plaques. Ultrastructurally, some of the plaques simulated kuru plaques and others had many degenerated neurites possessing paired helical filaments and other accumulated organelles. GSS has been proposed to include cases with progressive ataxia, dementia and massive multifocal plaques in the brain with or without cerebral spongiform changes. The case presented here is a very peculiar case of GSS. Recently, similar cases have been reported in some large families, diagnosed as familial Alzheimer's disease. These cases may be a telencephalic form with numerous NFTs of GSS.