Monitoring of hepatocellular carcinoma, following proton radiotherapy, with contrast-enhanced color Doppler ultrasonography

Background We have reported that proton radiotherapy for hepatocellular carcinoma (HCC) is a safe and effective therapeutic option. However, it is difficult to evaluate its effect in certain cases. Recently, it has been reported that the usage of contrast-enhanced color Doppler ultrasonography (CECDU) can improve diagnostic accuracy, both in terms of the presence of hepatic tumor and in the evaluation of treatment. The aim of this study was to determine the usefulness of CECDU in assessing the therapeutic response of HCC treated with proton radiotherapy.Methods Twenty-two patients treated with the proton radiotherapy were studied. We inspected HCC lesions by CECDU, before and after the irradiation, over time. The magnitude of blood flow in the HCC was quantified on still images by CECDU. The ratio of the number of color pixels against that of the total number of pixels in the tumor area was defined as the tumor blood flow ratio (TBFR).Results Immediately after the proton treatment, a transient increase of blood flow in the tumor was recognized in more than half of the patients, while the TBFR was unchanged or decreased in the remaining patients. At longer periods after irradiation, the TBFR in all HCCs gradually decreased, and this reduction of TBFR was statistically significant from 9 months after irradiation. These findings are consistent with those obtained previously by computed tomography (CT) as well as magnetic resonance imaging (MRI).Conclusions We propose CECDU as a useful diagnostic option for the evaluation of HCC treated with proton radiotherapy.Presented in part at the annual meeting of the American Gastroenterological Association in May 2001.     

Involvement of rho-kinase in agonists-induced contractions of arteriosclerotic human arteries

Coronary artery spasm plays an important role in the pathogenesis of a wide variety of ischemic heart diseases. We have recently demonstrated that Rho-kinase plays a key role in the spasm in our porcine model. However, it remains to be elucidated whether Rho-kinase-mediated pathway also contributes to vasoconstriction of human arteries. From 15 patients who underwent coronary artery bypass operation, segments of isolated left internal thoracic arteries were obtained, and the endothelium was gently removed. Serotonin and histamine caused contractions, which were markedly inhibited by a specific Rho-kinase inhibitor, hydroxyfasudil. Western blot analysis showed that, during the serotonin-induced contractions, the extent of phosphorylation of myosin-binding subunit of myosin phosphatase (MBS, one of the major substrates of Rho-kinase) was significantly increased in the specimens. Hydroxyfasudil again significantly suppressed the serotonin-induced increase in MBS phosphorylation. There was a significant positive correlation between the extent of MBS phosphorylation and that of the serotonin-induced contractions and between hydroxyfasudil-sensitive components of the contractions and the extent of arteriosclerosis. These results indicate that Rho-kinase plays an important role in vascular smooth muscle contractions of arteriosclerotic human arteries, suggesting that Rho-kinase could be regarded as an important target for the treatment of arteriosclerotic vascular diseases in humans.     

Efficacy and safety of benralizumab in Japanese patients with severe,uncontrolled eosinophilic asthma

Background

In the Phase III CALIMA trial, benralizumab significantly reduced asthma exacerbations, increased lung function, and alleviated symptoms for patients with severe, uncontrolled eosinophilic asthma. The aim of this subgroup analysis was to evaluate the efficacy and safety of benralizumab for Japanese patients in the CALIMA trial.

Prognosis of cough variant asthma: a retrospective analysis.

Patients with cough variant asthma, a common cause of chronic cough, may develop wheezing. We examined the determinants of this phenomenon and achievement of remission in 42 patients. During 4 years after diagnosis, wheezing developed in 13 of the patients. Early inhaled corticosteroid treatment was inhibitory against the development of wheezing by univariate analysis and by multivariate analysis with an odds ratio of 0.12 (95% confidence interval, 0.02 to 0.87, p = 0.037). Remission was achieved in 7 patients, who were younger than those without remission by univariate analysis (p = 0.048). Early treatment with inhaled corticosteroid may prevent the progression of cough variant asthma to classic asthma.     

Myoclonus and metabolic alkalosis from licorice in antacid

A 90-year-old woman with hypertension developed metabolic alkalosis and myoclonus. Her medications included diltiazem hydrochloride, benidipine hydrochloride, kallidinogenase, procaterol hydrochloride, sennoside, dihydrocodeine phosphate, and KM powder antacid that contained 354 mg of licorice and 900 mg of sodium bicarbonate per 3.9 g of powder. Endocrinological studies showed slightly reduced plasma renin activity and normal plasma aldosterone concentration. A provisional diagnosis of licorice-induced metabolic alkalosis was established and the patient was successfully treated after correction of serum pH and cessation of the medications. Licorice-induced metabolic alkalosis must be considered in the differential diagnosis of myoclonus.     

Esophageal small cell carcinoma effectively treated by cisplatin and irinotecan

Small cell carcinoma of the esophagus (SSCE) is regarded as a relatively uncommon neoplasm. Because of its aggressive characteristics with early systemic dissemination and widespread metastasis, SCCE is often associated with a poor prognosis. We report a case of carcinoembryonic antigen-positive SCCE coexistent with squamous cell carcinoma, which was successfully treated with cisplatin (CDDP) and irinotecan (CPT-11). The present case showed no evidence of distant metastasis at the time of preoperative examination. Therefore, the surgical resection was selected as a primary treatment followed by adjuvant therapy (CDDP and 5-flourouracil). However, multiple liver metastases appeared 8 months after the surgery. We changed the chemotherapy to CPT-11 and CDDP, because the regimen is effective for small cell carcinoma of the lung. After six courses of this regimen, the metastatic lesions had dramatically disappeared. These facts suggest that surgical intervention followed by a new regimen consisting of CDDP and CPT-11 is an effective treatment for SCCE.     

Accumulation of 7α-hydroxycholesterol in liver tissue of patients with cholesterol gallstones

Patients with cholesterol gallstones have a reduced pool of bile acids. This study was undertaken to clarify the mechanism by which bile acid biosynthesis does not increase to supranormal levels to cause a reexpansion of the pool. We investigated the first two steps of the bile acid biosynthesis pathway by assaying the activities of cholesterol 7α-hydroxylase, the rate-limiting enzyme in this pathway, and 3β-hydroxy-Δ⁵-C₂₇-steroid dehydrogenase/isomerase, and by measuring the concentrations of 7α-hydroxycholesterol and 7α-hydroxy-4-cholesten-3-one in liver specimens from ten patients with cholesterol gallstones and ten gallstone-free controls. In the patients with gallstones, cholesterol 7α-hydroxylase activity, 3β-hydroxy-Δ⁵-C₂₇ dehydrogenase/isomerase activity, and hepatic 7α-hydroxy-4-cholesten-3-one concentration did not significantly different from levels in controls, but hepatic 7α-hydroxycholesterol concentration was more than twofold that of controls (12.9 ± 2.6 vs 5.3 ±1.2 nmol/g liver,P<0.01). The concentration of 7α-hydroxycholesterol positively correlated with the ratio of cholesterol 7α-hydroxylase activity to 3β-hydroxy-Δ⁵-C₂₇ dehydrogenase/isomerase activity (r=0.93;P<0.005) in the gallstone-free controls. In contrast, this correlation disappeared in the patients with gallstones. These results suggest a derangement of the normal 7α-hydroxycholesterol metabolism in the patients with gallstones. The reason for the accumulation of 7α-hydroxycholesterol remains unclear; however, it is possible that, in patients with cholesterol gallstones, the accumulated 7α-hydroxycholesterol causes inappropriate suppression of cholesterol 7α-hydroxylase activity by product inhibition.     

Portal vein thrombosis following percutaneous ethanol injection therapy for hepatocellular carcinoma.

Percutaneous ethanol injection therapy was performed in a 66-year-old woman with hepatocellular carcinoma. She developed portal vein thrombosis that on color Doppler revealed no tumor vascular signal, and so was diagnosed as non-tumor thrombus. The thrombus resolved over 3 months.     

Systematic diagnostic method using magnetic resonance imaging to analyze viscero-bronchial-cardiovascular anomalies in pediatric patients with congenital heart disease

Segmental analysis of magnetic resonance imaging (MRI) was performed in 300 patients with congenital heart disease (CHD) (182 cyanotic CHD and 118 acyanotic CHD), between 20 days and 18 years of age. The usefulness of MRI in systematic diagnosis of CHD, which had previously been documented by angiography and echocardiography, was assessed. Electrocardiographyically gated MRI was performed by spin echo and gradient refocused imaging techniques operating at 0.5 tesla. In all 300 patients, not only cardiovascular anomalies of CHD but also viscerobronchial-cardiovascular anomalies were clearly visualized without serious complications due to MRI. In comparing 300 major cardiac anomalies and 1477 segments of the vein, the atrium, the ventricle, and the great arteries visualized by MRI and angiography, discrepancies were found in 7 anomalies (2.3%), and 22 segments (1.5%), respectively. Finally, in 86% (26/30) of patients manifesting atrioventricular valve regurgitation (AVVR), which had been evaluated by echocardiography, the AVVR was also detected on MRI. Based on these findings, segmental analysis of cardiac MRI was found to be safe and useful for systematic diagnosis of viscero-bronchial-cardiovascular anomalies in pediatric patients with CHD.Presented at the 36th Annual World Congress, International College of Angiology, New York, New York, July 1994     

A long-surviving patient with recurrences of hepatic alveolar echinococcosis after traumatic intra-abdominal rupture

Alveolar echinococcosis of the liver (AEL) takes a progressive and malignant course. Intra-abdominal dissemination of the parasite has a miserable outcome. Complete resection of the lesion is indispensable for the curative treatment of AEL. We experienced an extremely rare case of intra-abdominal rupture of AEL. The patient had repeated recurrences of AEL following the traumatic rupture of the lesion. After repeated resections of the lesions and appropriate medication, the patient is still alive more than 25 years since the initial onset of the disease. AEL differs from unilocular echinococcosis in terms of biological behavior. We compare the pathophysiology of the two conditions.