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Biomedical subjects

Masatoshi Kudo

Publications and source records attributed to Masatoshi Kudo.

At least 37 records · Page 2Linked to original sources

Differential diagnosis of nodular lesions in cirrhotic liver by post-vascular phase contrast-enhanced US with Levovist: comparison with superparamagnetic iron oxide magnetic resonance images.

BACKGROUND: We investigated the diagnostic utility of post-vascular phase contrast-enhanced ultrasonography (US) and superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) as compared to the histological diagnosis of differential grades of hepatocellular carcinomas (HCCs). METHODS: Forty-nine patients with histologically characterized liver nodules (well-differentiated HCC, n = 20; moderately differentiated HCC, n = 19; poorly differentiated HCC, n = 1; dysplastic nodule, n = 9) received contrast-enhanced US and SPIO-MRI. Subsequently, we quantitatively evaluated the relationships between the images of the nodules and their histological diagnosis and differential grades. RESULTS: The ratio of the echogenicity of the tumorous area to that of the nontumorous area with post-vascular phase contrast-enhanced US (post-vascular phase ratio) decreased as nodules became less differentiated (P < 0.05; Kruskal-Wallis test). The ratio of the intensity of the nontumorous area to that of the tumorous area on SPIO-enhanced MR images (SPIO intensity index) also decreased as nodules became less differentiated (P < 0.01). The post-vascular phase ratio correlated with the SPIO intensity index for HCCs and dysplastic nodules (r = 0.76). The conformity of the result from the post-vascular phase contrast-enhanced US and SPIO-MRI was 96%. CONCLUSIONS: Contrast-enhanced US is a valuable method for predicting the histological grade of HCCs in cirrhotic patients, and may be a good alternative to SPIO-enhanced MRI.

Aged↗

Early detection and curative treatment of early-stage hepatocellular carcinoma.

The method for early detection of hepatocellular carcinoma (HCC) has been well-established in Japan by means of regularly screening patients at risk for developing HCC by using imaging and tumor markers. An important issue is the accurate characterization of nodular lesions found in cirrhotic livers. This problem has been addressed by development of imaging modalities such as ultrasonography angiography with intra-arterial injection of CO2, computed tomography during hepatic arteriography, and computed tomography during arterial portography. It is most important to differentiate the typical hemodynamic patterns of low-grade dysplastic nodule including arterial hypovascularity with preserved portal perfusion from those of HCC characterized by arterial hypervascularity with decreased portal perfusion. At present, these findings are easily obtained by contrast-enhanced phase-invasion harmonic imaging, which is a noninvasive ultrasound technology. Radiofrequency ablation is an efficient technique to curatively treat early-stage HCC. The 5-year survival rate of RFA at our institution is 76%. Although local recurrence rate after curative RFA is as low as 6.2%, the intrahepatic distant metastasis is as high as 85% at 5 years. The prevention of intrahepatic distant recurrence by maintenance interferon therapy is thus very important. The 5-year survival rate and first, second, and third recurrence rates after curative RFA in patients who had maintenance interferon therapy were much better than those in patients who did not receive interferon therapy after curative RFA. In conclusion, recent progress in screening, diagnostic, and therapeutic strategy for early-stage HCC has improved the prognosis of patients with HCC. Furthermore, advances of prognostic staging system, such as Japan Integrated Staging score, facilitate the management of HCC.

Antineoplastic Agents↗

Multiple hypervascular liver nodules in a heavy drinker of alcohol.

A case of hypervascular nodules in the liver, but without hepatitis B or C virus infection in a 38-year-old woman with a history of alcohol abuse is presented. An ultrasound disclosed 1-2-cm hypoechoic tumors in the right and left lobes. Magnetic resonance imaging showed high-intensity tumors at both the T1-weighted and T2-weighted sequences. Incremental dynamic computed tomography and hepatic angiography revealed hypervascular tumors. Ultrasound-guided needle biopsy revealed no evidence of hepatocellular carcinoma, metastatic liver cancer, hemangioendothelioma, inflammatory pseudotumors or pseudolymphoma, but demonstrated stellate-scar fibrosis septa, which contained small unpaired arteries without hyperplasia dividing the nodule. Moreover, marked pericellular fibrosis, neutrophilic infiltration and Mallory bodies were observed in the cytoplasm. There was no evidence of bile duct proliferation. From these findings, the diagnosis of alcohol-induced fibrosis, distinctly different from focal nodular hyperplasia, was tenable. Further studies may provide insights into the pathogenesis of nodule formation and hypervascularity in heavy drinkers of alcohol.

Adult↗

Low-dose, long-term, intermittent interferon-alpha-2b therapy after radical treatment by radiofrequency ablation delays clinical recurrence in patients with hepatitis C virus-related hepatocellular carcinoma.

OBJECTIVE: To assess whether or not interferon (IFN) therapy prevents recurrence, and eventually improves the prognosis of patients with hepatocellular carcinoma (HCC) after completion of radical radiofrequency ablation (RFA) therapy. METHODS: Included as the IFN group in this study were 24 patients in total, who received radical RFA therapy first, followed by medication with IFN-alpha2b at such a low dose of 3 MIU x 2/week for as long as possible. On the other hand, the control group comprised 33 patients in total, who received radical RFA therapy without subsequent treatment with IFN. The control group was matched to the IFN group in age, platelet counts and size of nodules. RESULTS: Of the 24 patients treated with IFN, only one patient showed sustained virologic response. The median tumor-free period until the first recurrence after radical RFA therapy was 3.4 years in the IFN group and 1.4 years in the control group (p = 0.02). During the first 3 years after commencement of IFN administration, the cumulative recurrence rate in the IFN group was found to be lower than in the control group (p = 0.01); however, with the lapse of time over 3 years, the recurrence rate in the IFN group increased. There was no difference in the cumulative survival rates between the IFN group and the control group (p = 0.25). CONCLUSION: Subsequently after radical RFA therapy, long-term, low-dose, intermittent IFN therapy successfully delayed clinical recurrence of HCC.

Aged↗

Primary sclerosing cholangitis and hepatitis C virus infection.

Two cases of primary sclerosing cholangitis with hepatic C virus infection in a 62-year-old man and a 60-year-old woman are presented. The infection in the man was eradicated with interferon therapy in 1992. Seven years thereafter, endoscopic retrograde cholangiography revealed a diffuse 2.5-cm-long stenotic lesion in the common bile duct which was consequently resected. Histological examination of the resected specimen revealed proliferation of epithelial cells, plasma cell infiltration, and fibrosis in the submucosal layer of the common bile duct. The human leukocyte antigen DR loci were 2 and 9. In the woman, a 6-month course of interferon therapy in 1992 failed to eradicate the infection. Cholangiography in 1999 revealed multiple narrowings and dilatations of intra- and extrahepatic bile ducts. Ultrasound guided biopsy of the liver in 1992 had revealed onionskin lesions around the bile duct epithelium in the portal tract. The human leukocyte antigen DR locus was 2. From these findings, the 2 cases were diagnosed as primary sclerosing cholangitis. Further studies may provide insights into the relation between the pathogenesis of the disease and the infection.

Bile Ducts↗

Studies on the variation in clinical laboratory data and safety evaluation of pharmaceuticals.

The safety of pharmaceuticals has become increasingly important not only in daily medical treatment but also in clinical trials. Although clinical laboratory data are more objective than clinical symptoms, the determination as to whether they indicate abnormal variations depends largely upon the clinical judgment of physicians. The process of determination has not been sufficiently objectified. The present study investigated the indices of criteria for variations in clinical laboratory data obtained in clinical trials. Then, detection rates of abnormal variations were compared between our determination method that employs the reference change value (RCV) expressing the width of biological variation for each test component and conventional determination methods. The study also demonstrated that by combining standard values and the RCV for determination, abnormal variations were found at a rate greater than 50%. The method we propose was applied to the safety evaluation of pharmaceuticals. In clinical trials on the antiviral drug ribavirin administered alone, components of laboratory tests were selected that should be noted in studies on its effects. Expect for decreases in red blood cell counts and hemoglobin values, which are closely associated with anemic symptoms and well known to hepatologists, the increasing trend in platelet counts and decreasing trend in albumin were found to be laboratory test components that should be paid attention to, even though they may not be obvious.

Antiviral Agents↗

Validation of a new prognostic staging system for hepatocellular carcinoma: the JIS score compared with the CLIP score.

The Japan Integrated Staging score (JIS score), which combines the Child-Turcotte-Pugh classification and tumor-node-metastasis staging, has been proposed as a better prognostic staging system for hepatocellular carcinoma (HCC) than the Cancer of the Liver Italian Program (CLIP) scoring system. In this study, validation was performed among a larger patient population. A total of 4,525 consecutive patients with HCC who had been diagnosed at five institutions were included. Stratification ability, prognostic predictive power, and reproducibility were analyzed and compared with results from the CLIP scoring system. Only 45% (1,951 of 4,525) of all patients were categorized as early stage HCC according to JIS score (0 or 1), whereas 63% (2,878 of 4,525) of the patients were categorized as having a CLIP score of 0 or 1. Significant differences in survival curves were not observed among CLIP scores 3 to 6. In contrast, survival curves showed significant differences among all the JIS scores. The same JIS scoring subgroups showed a similar prognosis, and good internal reproducibility was observed in each of the institutions. Multivariate analysis of the prognosis in all 4,525 patients proved the JIS score to be the best prognostic factor. Furthermore, the Akaike information criteria proved that the JIS scoring system was statistically a better model for predicting outcome than the CLIP scoring system. In conclusion, the stratification ability and prognostic predictive power of the JIS score were much better than that of the CLIP score and were simple to obtain and remember.

Adult↗

Mucin phenotypic expression and background mucosa of esophagogastric junctional adenocarcinoma.

BACKGROUND: In the West, the incidence of adenocarcinoma of the cardia or esophagogastric junction (EGJ) is increasing. This carcinoma is variously defined, however, and it contains heterogeneous tumors. In Japan, the frequency of this carcinoma is low, and little is known about it. We studied small esophagogastric junctional adenocarcinoma to determine its characteristics in Japanese patients. METHODS: Fifty-four patients with Siewert type II junctional adenocarcinoma (with tumors <<4 cm in maximum diameter) were studied. The carcinomas were classified into two types: tumors straddling the EGJ (EGJ-type) and tumors occurring entirely below the EGJ (bEGJ-type). Characteristics of the tumors and surrounding mucosae were evaluated. Phenotypic expression of mucin, p53 overexpression, and Helicobacter pylori infection were investigated histologically and immunohistochemically. RESULTS: Twenty-three (43%) patients had EGJ-type and 31 (57%) had bEGJ-type carcinomas. The ratio of advanced cancers was significantly higher in EGJ-type. Some between-group similarities and differences existed in histological type, mucin phenotype, and p53 protein overexpression, but they were not statistically significant. In the mucosa surrounding EGJ-type tumors vs bEGJ-type tumors, oxyntic glands were significantly better preserved, gastric intestinal metaplasia occurred significantly less frequently, and the H. pylori infection rate was lower. Barrett's metaplasia was seen in only 2 patients, with the EGJ-type. CONCLUSION: EGJ-type and bEGJ-type adenocarcinomas have different background mucosa of the stomach. EGJ-type has less atrophy of the oxyntic glands and less intestinal metaplasia in the stomach. This type appears to be the Western-type junctional adenocarcinoma that is still rare in Japan. Many cases of advanced junctional adenocarcinoma in Japan are of subjunctional origin.

Adenocarcinoma↗

Hypervascular liver nodules in heavy drinkers of alcohol.

BACKGROUND: Three cases of hypervascular nodules in the liver, without hepatitis B or C virus infection and with a history of alcohol abuse (120 ml/day for 15 to 30 years), are presented. RESULTS: Ultrasound examination revealed hypoechoic nodules in segment 6 (2 cm in diameter, case 1), in the right and left lobes (1-2 cm multiple type, case 2), and in segment 4 (4 cm, case 3). Hepatic angiography and computed tomography during arteriography revealed hypervascular nodules in the three cases. First, hepatocellular carcinoma, focal nodular hyperplasia, hemangioma, hemangioendothelioma, inflammatory pseudotumor, and pseudolymphoma were diagnostically differentiated. Histologically, there was no evidence of hepatocellular carcinoma or of any of the pathologies considered in the differential diagnosis by imaging studies. In case 1, the lesion was composed of an irregular, thin, trabecular-patterned hepatic acinus with slighter hypercellularity than in the nonnodular area. In cases 2 and 3, the lesions were composed mainly of fibrosis without hyperplasia, showing stellate scar-like fibrosis septa dividing the nodule. Marked pericellular fibrosis, neutrophilic infiltration, and Mallory bodies in the cytoplasm were also observed. In cases 1 and 2, small unpaired arteries explaining the hypervascularity of the nodules were observed. CONCLUSION: These hypervascular nodules were classified as regenerative, not neoplastic, nodules according to the classification of the International Working Party.

Adult↗

Afferent and efferent vessels of premalignant and overt hepatocellular carcinoma: observation by color Doppler imaging.

Afferent and efferent vessels of premalignant and overt hepatocellular carcinoma (HCC) were analyzed using color Doppler imaging. With afferent blood flow, constant waveform signals reflecting portal inflow are a characteristic finding in dysplastic nodules and early well-differentiated HCC. Among advanced HCCs lacking portal blood flow, inflow of arterial pulsatile blood flow signals is characteristic for advanced HCC with increased arterial vascularity. Efferent blood flow enters the hepatic vein of the lowest pressure system in dysplastic nodules and early well-differentiated HCC with afferent portal blood flow. Analysis of waveforms of efferent blood flow signals in advanced HCC detects in the opposite direction adjacent to an accompanying afferent arterial pulsatile blood flow signal. In conclusion, during multistep human hepatocarcinogenesis hemodynamics show characteristic changes; the state of afferent portal blood with low arterial vascularity loses the portal blood flow, and arterial vascularity gradually increases. The efferent blood flow pathway also changes with the pathological multistep development process.

Aged↗

Differentiation of hepatic tumors by color Doppler imaging: role of the maximum velocity and the pulsatility index of the intratumoral blood flow signal.

Doppler spectral analysis using color Doppler ultrasonography (US) was performed in a total of 133 patients with 135 hepatic tumors, including 88 hepatocellular carcinomas (HCCs), 30 metastatic hepatic cancers, 15 hemangiomas and 2 focal nodular hyperplasias (FNHs). Mean +/- SD of maximum velocity (Vmax) in hemangiomas (15.0 +/- 16.0 cm/s) was significantly lower than in HCCs (34.9 +/- 26.7 cm/s) and in metastases (37.9 +/- 17.4 cm/s). Mean +/- SD of the pulsatility index (PI) in hemangiomas (0.45 +/- 0.41) was significantly lower than in HCCs (1.52 +/- 0.71) and metastases (1.44 +/- 0.43). Mean +/- SD of Vmax and PI in FNH was 20.0 +/- 11.3 cm/s and 0.90 +/- 0.35, respectively. HCC showed a wide spectrum in terms of Vmax and PI; however, 18% of the HCC nodules had relatively high PI (>2.0). Specificity of Vmax more than >60 cm/s and PI more than 2.0 for the diagnosis of HCC were 92 and 94%, respectively. On the other hand, 87% of hemangiomas showed relatively lower Vmax (<30 cm/s) and 87% of hemangiomas showed relatively low PI (<1.0 cm/s). Specificity of Vmax less than 30 cm/s and PI less than 1.0 for the diagnosis of hemangioma were 47 and 78%, respectively. When taking account of both parameters, Vmax and PI, diagnostic efficacy for hemangioma and HCC was greatly improved (sensitivity, specificity, accuracy, positive predictive value and negative predictive value of 80, 86, 85, 41 and 97%, respectively, in hemangioma, and 38, 85, 54, 83 and 58%, respectively, in HCC) as compared with the results with Vmax or PI alone. In conclusion, in addition to the information obtained by Vmax, simultaneous measurement of PI adds valuable information useful in the noninvasive differentiation among hepatic tumors by Doppler spectral analysis at color Doppler US.

Adult↗

Detection of intratumoral vascularity in small hepatocellular carcinoma by coded phase inversion harmonics.

OBJECTIVE: To investigate the value of contrast-enhanced coded phase inversion harmonic imaging (PIHI) in the depiction of intratumoral vascularity in small hepatocellular carcinoma (HCC). METHODS: Eighty-five patients with 106 HCCs < or =3 cm in diameter were evaluated with coded harmonic angio (CHA), a coded PIHI, with use of an intravenous contrast medium, Levovist. Intratumoral vessels were detected in the early arterial phase, and tumor parenchymal stain was demonstrated in the late vascular phase. The detectability of intratumoral vascularity on contrast-enhanced CHA was compared with that on dynamic computed tomography (CT) and digital subtraction angiography (DSA). RESULTS: With a combination of both vessel images and parenchymal flow images demonstrated by contrast-enhanced CHA, 98 of 106 small HCCs were evaluated as being hypervascular or isovascular. Using the results on dynamic CT as a gold standard, the sensitivity, specificity and accuracy were 95.1, 100 and 95.3%, respectively. The detection rate of intratumoral vascularity by contrast-enhanced CHA was 92.5% (98/ 106), compared with 97.2% (103/106) on dynamic CT (p = 0.14) and 88.9% (40/45) on DSA (p = 0.53). CONCLUSIONS: Contrast-enhanced coded PIHI is a sensitive tool for depicting intratumoral vascularity of small HCC.

Adult↗