Detection of hepatocellular carcinoma after interferon therapy for chronic hepatitis C: Clinical study of 26 cases

The clinical findings in 26 patients in whom hepatocellular carcinoma (HCC) was detected after the start of interferon (IFN) therapy for chronic hepatitis C were analysed. Histological study before IFN therapy showed that 34.6% of patients were categorized as stage 3 (septal fibrosis with architectural distortion; the 0–4 scale) and 80.8% demonstrated at least some evidence of septal fibrosis or more advanced features. The AFP levels examined before IFN therapy were more than 20 ng/mL in 13 patients (84.6% of those studied). One of 26 patients had a complete response to IFN therapy, while six of 26 patients had only a partial response. HCC was detected within 1 year after the start of IFN therapy in 76.9% of patients. Thus, the possibility of the early occurrence of HCC or its existence at the time of therapy should be seriously considered when IFN therapy is contemplated. Patients with stage 3 or 3–4 histology may already have a small undetectable HCC before IFN therapy. Thus, for this reason, every patient treated with IFN should be examined at short regular intervals for the development of HCC during and after IFN therapy.     

Epstein-Barr Virus-induced Lymphoblastoid Cell Lines from Patients with Primary Immunodeficiency Diseases

Peripheral lymphocytes from eight patients with congenital immunodeficiency diseases were infected with Epstein-Barr virus (EBV) in an attempt to establish B lymphoblastoid cell lines (LCL). These patients included three boys with congenital agammaglobulinaemia, two girls with hypogammaglobulinaemia, one boy with common variable immunodeficiency, one boy with severe combined immunodeficiency with adenosine deaminase deficiency, and one boy with DiGeorge syndrome. Five of the patients bore no surface immunoglobulins (slg) on their peripheral lymphocytes. LCL were established from seven of the eight patients. All the LCL established formed rosettes with EAC3 and had the ability to produce cytoplasmic immunoglobulins (clg) of various classes. Culture supernatants concentrated up to 100-fold developed precipitin bands by Ouchterlony's method with antisera to human Ig in all the established LCL. These results suggested that both slg^-, clg^- and C3⁺ cells and slg⁺, clg^- and C3⁺ cells might be the target cells for EBV and that slg^-, clg^- and C3⁺ cells might be the precursor cells of B lymphocytes.     

Diagnosis of Small Pancreatic Carcinoma

A retrospective analysis was performed to evaluate the clinicalsymptoms and abnormal test findings in small pancreatic carcinoma.Five hundred and thirty-six cases of pancreatic carcinoma withthe histology of duct cell carcinoma were collected from 14medical centers in Japan. In 440 of the cases, tumor size wasmeasured at the time of laparotomy or from the resected specimen.Three hundred and seventy-seven patients (86%) had a carcinomalarger than 3.0 cm; only 30% of these were resectable. Sixty-threepatients (14%) had a carcinoma of 3.0 cm or less, with resectabilityof 97%. Detecting a tumor of "3 cm or less" with a high probabilityof resectability is the objective of early diagnosis with theresulting possibility of a cure. In most cases these small carcinomaswere found easily when obstructive jaundice was present (73%).However, the estimated occurrence of obstructive jaundice associatedwith carcinomas of 3 cm or less was only 10% among the totalcases of pancreatic carcinoma studied. Therefore, it is necessaryfor early diagnosis to detect carcinomas of 3 cm or less presentingwithout jaundice. The symptoms of small carcinoma without jaundiceare weight loss, anorexia, upper abdominal pain, back pain anda palpable abdominal mass. Among the various available examinations,endoscopic retrograde cholangiopancreatography, computerizedtomography and ultrasonography were valuable in diagnosing thesesmall carcinomas.     

A Case of Pneumocytoma (So-Called Sclerosing Hemangioma) With Lymph Node Metastasis

A case of "sclerosing hemangionia" (pneumocytoma) of the lungwith lymph node metastasis is reported. A 22-year-old Japaneseman was found to have a well-defined round lesion in the rightlung (S⁷), which increased in size slightly during a 2-yearfollow-up period. He underwent right lower lobectomy with a preoperative diagnosisof a benign lung tumor. The pulmonary tumor revealed histologicalfeatures characteristic of "sclerosing hemangioma" of the lung,in addition to which there were many large polygonal foamy cells,forming tubular or papillary structures. These cells were foundby electron microscopy to contain numerous cytoplasmic lamellarbodies and showed a positive reaction with anti-surfactant apoproteinantibody immunohistochemically. Therefore, they were consideredto be cells differentiating toward type II pneumocytes. Reviewof 21 typical "sclerosing hemangionia" disclosed a few or somesuch foamy cells in 10 cases. A single hilar lymph node wasthe site of microscopic metastases, which consisted of "largeclear foamy cells" and smaller polygonal or round cells withslightly eosinophilic cytoplasm, both of which were componentsof the pulmonary "sclerosing hemangioma" This case supportsthe theory that "sclerosing hemangioma" is a neoplasm of typeII pneumocyte lineage. Although it is said to be benign, rarecases apparently show metastatic potential.     

THE IMPACT OF DIABETES MELLITUS ON THE PROGNOSIS OF ALCOHOLICS

In this study, the mortality of clinically treated Japanesealcoholics with diabetes mellitus was analysed. Fifty-one diabeticalcoholics without liver cirrhosis (DM), 23 diabetic and cirrhoticalcoholics (DM LC), 44 cirrhotic alcoholics without diabetes(LC), and 354 alcoholics without either complication (AL) admittedto the National Institute on Alcoholism in 1985 were studied.Thirty-seven diabetics required insulin treatment, and 12 oralhypoglycemic agents. The 4.4-year survival and drinking statusafter discharge were studied in 1990. Stepwise logistic regressionanalysis showed that the estimated odds for death increased8.10, 4.38, 3.70, and 3.27 times for the subjects with the alcoholmisuse after discharge, DM, DM LC, and LC, respectively. The4.4-year survival rate of alcoholics who continued misusingalcohol was much lower in DM (26%, P < 0.0005) and LC (35%,P < 0.0001) than in AL (73%). The survival rate of thosewho stopped misusing alcohol was significantly higher in DM(90%, P < 0.0001), LC (88%, P < 0.0001) and AL (94%, P< 0.0005) than those who continued misusing alcohol. Therewas no significant difference in the survival rate between thealcoholics with DM LC who continued misusing alcohol (50%) andthose who stopped misusing alcohol (73%). In the dead patients,56% of DM died unexpectedly or suddenly, whereas 71% of LC diedof liver failure after hospitalization. These results suggestthat diabetic alcoholics should be intensively educated forabstinence.     

Benign Tumors and Tumor-Like Lesions (Excluding Adenomas) of the Lung: Radiological and Clinicopathological Analysis of 48 Cases

Forty-eight cases of surgically resected benign tumors and tumor-likelesions of the lung were analyzed, with the following results:1) Hamartoma and sclerosing hemangioma have well defined borders,compressing bronchi and blood vessels, and are loosely boundto the surrounding lung parenchyma. 2) Hamartomas, in 90% ofthe cases, showed "nodularity" on film tomograms. Histologically,nodularity at the edge was produced by lobules of cartilage.3) Fifty-three percent of the patients with sclerosing hemangiomawere middle-aged females and asymptomatic. Only two patientscomplained of hemosputum. Routine roentgenograms showed a roundshadow with homogeneous density. Cut surfaces were solid withvarious degrees of hasemorrhage. 4) Roentgenograms of benignmesothelioma showed large tumors more than 4 cm in diameter,in which extrapleural signs could be observed. 5) "Calcification"was seen on the roentgenograms of seven out of 27 hamartomasand one out of 15 sclerosing hemangiomas. Pleural retractioncould not be seen in our series. Xerotomography was superiorto film tomography in showing calcification. 6) One of the sclerosinghemangiomas was double, and the other 47 benign tumors and tumor-likelesions were solitary; the lesions were peripheral in 45 casesand central in three. All of the patients were free of localrecurrence and distant metastasis.     

Fatal cytomegalovirus myocarditis in a seronegative ALL patient

Fatal cytomegalovirus (CMV) myocarditis occurred in a 2 year old boy with acute lymphoblastic leukemia (ALL) in remission. The patient showed mild hepatic dysfunction and a rapid progress of pancytopenia after complete remission had been achieved. At the fifth week of complete remission, he presented signs of heart failure such as tachycardia, S4 gallop on auscultation and decreased ejection fraction on echocardiography. However, no significant electrocardiographic changes were recognized. In addition to the cardiac dysfunction, the patient presented a marked tachypnea and dyspnea associated with hypoxemia. These were dramatically improved by methylprednisolone pulse therapy (30 mg/kg per day, for 3 days) and CMV high titer immunoglobulin (400 mg/kg per day, for 3 days). On the sixth day after signs of respiratory failure were improved, the patient suddenly presented a paroxysmal atrial tachycardia followed by a fatal ventricular fibrillation. Although we could detect neither a specific IgM antibody, a significant increase of IgG antibody, nor CMV genome by DNA hybridization techniques during the course of the illness, microscopic examination of necropsy specimens of the heart showed a marked disruption and disintegration of muscle bands associated with cytomegalic inclusion bodies. Polymerase chain reaction (PCR) yielded a 305 bp amplification product in the heart and lung tissues, supporting the view that myocarditis was caused by CMV.     

Epidemiology of school urinary screening over a 30 year period in Tokyo

BACKGROUND: A school urinary screening (SUS) system has been conducted for 30 years in Japan, but the cross-sectional data have never been reported or analyzed. The purpose of the present study was to analyze the data epidemiologically. METHODS: All elementary and junior high school children in public school in Tokyo who had SUS performed by the Tokyo Health Service Association from 1974 to 2002 (approx. 400,000-600,000 children per year) were involved. The cross-sectional data were analyzed with Pearson's correlation coefficient. RESULTS: During the first 10 years of SUS, the prevalence of abnormal urinalysis in both the first and second screenings varied widely, and the result of the second screening was affected by that of the first screening. The results of both first and second screening were highly correlated with the prevalence of hematuria, especially microhematuria, in both elementary and junior high school children. They were also correlated with the prevalence of proteinuria in junior high school children. Important factors that affected the prevalence of hematuria and/or proteinuria were reagent strips and sampling method of urinalysis. CONCLUSIONS: In order to validate SUS, attention should be paid to quality controls of the screening method, such as the selection of reagent strips, and the participants should be instructed to strictly adhere to the sampling method.     

Possible Involvement of Tissue-Type Plasminogen Activator in Gastric Ulcer Formation —Biochemical Evaluation Using Biopsy Specimens From Gastric Mucosa—

Abstract: Microvascular endothelial changes are thought to be a crucial step in the development of hemorrhagic changes in various pathological states. Tissue-type plasminogen activator (t-PA) is an endothelium-derived fibrinolytic mediator which regulates microvascular permeability. In this study, we determined the activity and amount of t-PA in the biopsy specimens taken from gastric mucosa of patients with gastric ulcers to evaluate endothelial alterations and vascular permeable changes in situ. In addition, to elucidate the relationship between local fibrinolytic disturbance and systemic blood coagulation, several factors such as plasminogen activator inhibitor were also assayed. The results of this investigation revealed that the mucosal t-PA amount in the active ulcer proved to be 2–3 folds higher than that in healthy controls, however, t-PA levels in plasma samples showed no remarkable differences among the groups. Increased t-PA activity appeared to well correlate to the degree of inflammation of gastric mucosa in contrast to t-PA amount which was still increased in healed ulcer lesion. PAI-1 in plasma samples from gastric ulcer patients showed a significantly high level as compared with healthy subjects. The present study indicates that t-PA activation may play an important role in the pathogenesis of gastric ulcer formation and that t-PA determination in gastric biopsy specimens may be useful for the evaluation of clinical activity of gastric ulcers in terms of the mucosal microvascular endothelial changes.     

Comparison of statistical power between 2×2 allele frequency and allele positivity tables in case-control studies of complex disease genes

In case-control studies of complex disease genes, allele frequencies or allele positivities at candidate loci or markers are compared between cases and controls. Although 2 × 2 contingency tables based on allele frequency and allele positivity are generally used to perform simple statistical tests (e.g. a comparison of two proportions and a χ² test), little is known about the difference in power between the two tables. In this study, we investigated the number of subjects required to obtain a power of 1 −β with a significance level of α for the allele frequency and allele positivity tables. A large difference in the required number of subjects was found between the two tables. Allele positivity tables were suitable for the detection of susceptibility alleles showing a dominant mode of inheritance (MOI). On the other hand, allele frequency tables were suitable for the identification of susceptibility alleles showing a recessive MOI or a multiplicative MOI. In the case of an additive MOI, a suitable table was determined by combining the frequency of the susceptibility allele and the penetrance. These results imply that there are cases in which true association is detected based on one contingency table and is not detected based on another. A simulation analysis revealed that the type I error rate was not much inflated under the null hypothesis of no association, even when a statistical test was performed twice using both allele frequency and allele positivity tables. In contrast, under the alternative hypothesis, the loss of power was marked when a test was performed once using an unsuitable table. In conclusion, statistical tests should be performed using both tables, without adjustment of multiplicity, in case-control studies of complex disease genes when the study objective is exploratory.