Kiyoshi Kotoh

Which subgroup of patients with dilated cardiomyopathy would benefit from long-term beta-blocker therapy ? A histologic viewpoint

OBJECTIVES The purpose of this study was to elucidate whether the effectiveness of long-term beta-blocker therapy could be predicted before this therapy is started. BACKGROUND Long-term beta-blocker therapy has recently been reported to provide a favorable effect in treatment of congestive heart failure due to dilated cardiomyopathy. METHODS Several measurements including histologic variables before administration of metoprolol were retrospectively compared among 18 good responders (showing improvement of at least one New York Heart Association functional class or an increase in ejection fraction > or = 0.10 12 months after drug administration) and 12 poor responders without such improvement. RESULTS Although there were no significant differences between the two groups in age, gender, functional class, heart rate, blood pressure, pulmonary capillary wedge pressure, cardiac index, left ventricular end-diastolic dimension and ejection fraction, percent fibrosis estimated by the point-counting method in endomyocardial biopsy specimens was significantly lower in good than in poor responders (7.6 +/- 5.7 vs. 14.2 +/- 9.7%, p < 0.05). Moreover, when the types of fibrosis were classified as interfascicular and intercellular by the dominance of counted points, there were 13 cases of interfascicular fibrosis and 5 cases of intercellular fibrosis in good responders and 1 case of interfascicular fibrosis and 11 cases of intercellular fibrosis in poor responders (p < 0.001, sensitivity 72%, specificity 91%, predictive accuracy 80%). These results suggest that improvement with long-term beta-blocker therapy may be more likely to occur in patients with less myocardial fibrosis, with interfascicular fibrosis the dominant type. CONCLUSIONS The extent and type of fibrosis may be important factors in the prediction of the effectiveness of long-term beta-blocker therapy for dilated cardiomyopathy.

New approach to the estimation of the extent of myocardial fibrosis in patients with dilated cardiomyopathy: Use of signal-averaged electrocardiography

To determine whether the extent of myocardial fibrosis in dilated cardiomyopathy could be estimated noninvasively, signal-averaged electrocardiograms were recorded in 32 patients with dilated cardiomyopathy, followed by left ventricular endomyocardial biopsy. The root mean square voltage for the last 40 msec (V40), the duration of the filtered QRS complex (fQRSd) and the duration of low amplitude signals < 40 microV (LAS) were obtained by signal-averaged electrocardiography. The extent of fibrosis in all biopsy samples was measured by the point-counting method. The extent of myocardial fibrosis closely correlated with fQRSd (r = 0.623, p < 0.001), LAS (r = 0.570, p < 0.001), and V40 (r = -0.355, p < 0.05). When fibrosis was classified into intercellular and interfascicular types, the extent of intercellular fibrosis more closely correlated with fQRSd (r = 0.695, p < 0.0001), LAS (r = 0.640, p < 0.0001), and V40 (r = -0.533, p < 0.005). These results suggest that signal-averaged electrocardiograms might be useful for estimation of the extent of myocardial fibrosis, especially intercellular fibrosis in patients with dilated cardiomyopathy.

Ectopic thymoma mimicking diffuse pleural mesothelioma: A case report

A case of ectopic thymoma of the pleura with a particular growth pattern mimicking diffuse pleural mesothelioma is reported. Diagnostic imaging showed that the pleural tumor encased the entire left lung. The specimen biopsied from the tumor was composed of lymphocytes and epithelial cells, consistent with the mixed type of thymoma. The autopsy found no evidence of a mediastinal tumor. An involuted thymus was found in the parietal pleural tissue adhered to the apex of the left lung. The thymoma was thought to originate from the ectopic thymic tissue in the parietal pleura, as a lesion independent from the primary mediastinal thymoma, and spread along the pleura like diffuse mesothelioma.

Histologic changes in small cell lung carcinoma after treatment

Small cell lung carcinoma (SCLC) has been divided into three subtypes: pure SCLC, mixed small cell/large cell carcinoma (mixed SC/LC), and combined SCLC. Patients with mixed SC/LC show a worse prognosis than those with pure SCLC.

Clinicopathological study of livers from brain-dead patients treated with a combination of vasopressin and epinephrine

Studies were made on the pathological lesions and biochemical indices of the livers of 22 patients in whom normal hemodynamics was maintained for 0-48 days after brain death by administration of vasopressin and epinephrine. Thirty-one specimens of liver tissues were obtained by percutaneous biopsy or at autopsy. The degrees of central venous congestion, central fibrosis, focal fibrosis, fatty metamorphosis, piecemeal necrosis, periportal fibrosis, and intrahepatic cholangitis in livers on various days after brain death were compared with those on the day of brain death (day 0). Central venous congestion was extensive on days 0-4, significantly less on days 5-14, and then again extensive on days 15-48. Central fibrosis and focal fibrosis showed no remarkable change during the 48-day period. Fatty metamorphosis, piecemeal necrosis, and periportal fibrosis showed no significant changes until day 16, but spread extensively on days 40-48. Intrahepatic cholangitis was scarcely observed on day 0 but began to increase after day 3, and spread extensively after day 5. The level of serum glutamic pyruvic transaminase did not increase in most patients until day 15. The mean value of prothrombin activity also did not decrease until day 15. However, the mean value of serum alkaline phosphatase increased gradually after day 3, and was correlated with cholangitis. The present study showed that during prolonged hemodynamic maintenance of brain-dead patients, pathological lesions did not spread or diminished and that biochemical indices did not become worse, or improved, in the first 2 weeks, except for increases in cholangitis and the serum alkaline phosphatase level.

Human leukocyte antigen DRB1 1302 protects against bile duct damage and portal lymphocyte infiltration in patients with chronic hepatitis C.

BACKGROUND/AIMS To confirm the immune reaction of hosts in chronic hepatitis C, we examined the association of human leukocyte antigen (HLA) DR with the histopathological outcome including bile duct damage and steatosis, which are characteristic of hepatitis C virus (HCV) infection. METHODS One hundred and fifty-five patients with chronic HCV infection were examined. The pathological appearance of liver biopsy specimens was evaluated by both Knodells histological activity index and examination of bile duct damage and steatosis. HLA DRB1 was determined by the polymerase chain reaction sequence-specific oligonucleotide probe method. RESULTS HLA DRB1 1302 was found with significantly higher frequency in patients without than with bile duct damage (34.8% vs. 4.7%, p=0.0001, p corrected by Bonferronis inequality method=0.002). It was also found more frequently in patients without marked portal lymphocyte infiltration (28.6% vs. 7.7%, p=0.0015, p corrected by Bonferronis method=0.03). HLA DRB1 1101 was found more frequently in patients without than with piecemeal necrosis (p=0.004). In contrast, the frequency of HLA DRB1 1502 tended to be higher in patients with than without piecemeal necrosis and marked portal lymphocyte infiltration (p=0.015 and p=0.03, respectively). HLA DRB1 1201 and 0802 were seen more frequently in bile duct damage-negative (p=0.02) and piecemeal necrosis-negative patients (p=0.03), respectively. Interestingly, serum HCV levels of HLA DRB1 1302-positive patients were significantly higher than those of 1302-negative patients (mean: 7.7 Meq/ml vs. 3.1 Meq/ml, p=0.0007). CONCLUSION These findings suggest that some histopathological changes in chronically HCV-infected livers could be caused by the hosts immune reaction regulated by HLA DR.

Effectiveness of long-term beta-blocker therapy for dilated cardiomyopathy—echocardiographical follow-up

SummaryTo evaluate the effectiveness of long-term beta-blocker therapy for dilated cardiomyopathy (DCM), two groups (Group I: 18 patients, Group II: 17 patients) with DCM divided by the order at the entry were followed echocardiographically for 16.9 ± 3.0 months in Group I and 21.4 ± 3.9 months in Group II. Metoprolol (final dose: 60 mg/day) was administered in Group I, but not in Group II (the control), although the conventional treatment for heart failure was continued. The left ventricular end-systolic dimension and ejection fraction assessed by echocardiography improved significantly after 6 months in Group I, but not in Group II, even after 48 months, although there were no significant differences in baseline data between the two groups. The end-diastolic dimension decreased significantly after 12 months in Group I only. It was estimated, using the point count method on a left ventricular endomyocardial biopsy specimen taken at entry, that the improvement (AEF) of the ejection fraction 12 months after metoprolol administration inversely correlated (r = - 0.677, p < 0.01) with percent fibrosis, indicating that the more myocardium remains, the more improvement is expected. These findings suggested a favorable effect of beta blockade in DCM, especially in cases with less fibrosis, showing that the endomyocardial biopsy could be of clinical use in selecting candidates for chronic beta-blocker therapy in DCM.

Malignant melanoma in the thymus

A case of malignant melanoma in the thymus is reported. Diagnostic imaging demonstrated a left anterior mediastinal mass in a patient with giant pigmented nevus without malignant change. Histologic and cytologic specimens obtained from the tumor revealed that the tumor was malignant melanoma. Surgery revealed malignant melanoma in the left lobe of the thymus. Many cell nests of pigmented nevi were observed throughout the thymus. The malignant melanoma was thought to have originated from the nevocellular nevus in the thymus. This is the first report of malignant melanoma in the thymus.