Well-differentiated hepatocellular carcinoma detected as hypovascularity by only CT during hepatic arteriography.

We describe a well-differentiated hepatocellular carcinoma (HCC) with alcohol-related liver cirrhosis in a 69-year-old man. Ultrasonography (US) disclosed a 10 mm hypoechoic nodule in segment 4; Sonazoid contrast-enhanced US and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) revealed no defect in either the Kupffer phase or the hepatobiliary phase. Computed tomography during hepatic arteriography (CTHA), however, revealed a hypovascular nodule, but CT during arterial portography showed no perfusion defect. Histological analysis indicated a well-differentiated HCC. Thus, our detection of well-differentiated HCC disclosed by only CTHA attested to the efficiency of this modality, suggesting that it is more sensitive than Gd-EOB-GTPA-enhanced MRI.

Correlation between insulin resistance and outcome of pegylated interferon and ribavirin therapy, hepatic steatosis, hepatic fibrosis in chronic hepatitis C-1b and high viral load.

BACKGROUND/AIMS: Insulin resistance (IR) has been reported to be an independent predictor of treatment outcome in chronic hepatitis C patients. METHODS: We analyzed the relationship between IR and the outcome of pegylated interferon and ribavirin (PEG-IFN/RBV) therapy, taking into account host factors of body mass index and histological index, such as rate of fatty change and fibrosis. Japanese patients (n = 30; 19 men and 11 women; median age 60.0 ± 8.7 years) with chronic hepatitis C-1b with a high viral load were treated with PEG-IFN-α2b/RBV for 48 weeks. RESULTS: Sustained virological response (SVR) was seen in 60% (18/30) and non-SVR in 40% (12/30). HOMA-IR (homeostasis model of assessment-insulin resistance index) at the start and at 24 weeks of treatment showed no statistical difference between SVR and non-SVR. Correlation was observed between HOMA-IR and body mass index (r = 0.45, p = 0.013). Among 20 patients, steatosis and fibrosis were assessed by biopsy. Correlation was observed between HOMA-IR and steatosis (r = 0.57, p = 0.0093), whereas no correlation was observed between HOMA-IR and fibrosis. CONCLUSION: A larger prospective study is needed to clarify the role of IR in the outcome of PEG-IFN/RBV combination therapy and hepatic fibrosis in Japanese patients.

A case of takotsubo cardiomyopathy with ventricular fibrillation after gastroenterological endoscopy.

We describe a case of takotsubo cardiomyopathy with ventricular fibrillation after gastroenterological endoscopy in a 66-year-old woman. Ten minutes after the upper and lower gastrointestinal endoscopic examinations, the patient lost consciousness, went into respiratory arrest, and became cyanotic; an electrocardiogram (ECG) showed ventricular fibrillation. Electrical defibrillation was applied three times resulting in the patient's recovery. Subsequently, the ECG showed ST elevation in V2-V3; ultrasound cardiography showed a severely hyperkinetic base of the left ventricle, with the rest of the ventricle akinetic; and cardiac catheterization disclosed a normal coronary artery and normal contraction of the left ventricle.

Diagnostic sensitivity of imaging modalities for hepatocellular carcinoma smaller than 2 cm.

AIM: To compare the imaging results with histology and to evaluate the diagnostic sensitivity of imaging modalities for hepatocellular carcinoma (HCC) smaller than 2 cm. METHODS: Nodules smaller than 2 cm (n = 34) revealed by ultrasonography (US) in 29 patients with liver cirrhosis were analyzed. Histological diagnosis of HCC was performed by ultrasonographic guidance: moderately-differentiated HCC (n = 24); well-differentiated HCC (n = 10). The patterns disclosed by the four imaging modalities defined the conclusive diagnosis of HCC: (1) contrast-enhanced computed tomography (CECT), hypervascularity in the arterial phase and washout in the equilibrium phase; (2) Sonazoid contrast-enhanced US (CEUS), hypervascularity in the early vascular phase and defect in the Kupffer phase; (3) gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI), hypervascularity in the arterial phase and/or defect in the hepatobiliary phase; and (4) CT arterioportal angiography: hypervascularity by CT during arteriography and/or perfusion defect by CT during arterial portography. RESULTS: Overall, the sensitivity of diagnosing HCC smaller than 2 cm was 52.9% (18/34) (95% CI: 35.1-70.2) by CECT; 67.6% (23/34) (95% CI: 49.5-82.6) by Sonazoid CEUS; 76.5% (26/34) (95% CI: 58.8-89.3) by Gd-EOB-DTPA MRI; and 88.2% (30/34) (95% CI: 72.5-96.7) by CT arterioportal angiography. The diagnostic sensitivity of detecting moderately-differentiated HCC by CECT, Sonazoid CEUS, Gd-EOB-DTPA MRI and CT arterioportal angiography was 62.5% (15/24) (95% CI: 40.6-81.2), 79.2% (19/24) (95% CI: 57.8-92.9), 75.0% (18/24) (95% CI: 53.3-90.2) and 95.8% (23/24) (95% CI: 78.9-99.9), respectively. A significant difference (P < 0.05) was observed between CECT and CT arterioportal angiography in all nodules. There was no difference between Sonazoid CEUS, Gd-EOB-DTPA MRI, and CT arterioportal angiography. The combined sensitivity of Sonazoid CEUS and Gd-EOB-DTPA MRI was 94.1% (32/34). CONCLUSION: Changing the main diagnostic modality for HCC smaller than 2 cm from CT arterioportal angiography to Sonazoid CEUS and Gd-EOB-DTPA MRI is recommended.

Autoimmune thrombocytopenic purpura during pegylated interferon α treatment for chronic hepatitis C.

We describe a 72-year-old woman with chronic hepatitis C and autoimmune thrombocytopenic purpura (AITP) during pegylated interferon (PEG-IFN) alpha. Immunoglobulin G and antinuclear antibody were 2,113 mg/dL and 1,280 at the start, respectively. A liver biopsy negated autoimmune hepatitis. After a 48-week combination therapy with ribavirin, PEG-IFN alpha-2a was administered. At the 30th month, the platelet count was decreased to 1.1 x 10(4)/microL. Bone marrow biopsy disclosed normocellular marrow compatible with AITP. The platelet-associated IgG (PAIgG) titer rose to 500 ng/10(7) cells. Corticosteroid therapy was successful, and the platelet count and PAIgG titer reverted to 6.4 x 10(4)/microL and 57.3 ng/10(7) cells, respectively.

Well-differentiated hepatocellular carcinoma smaller than 15 mm in diameter totally eradicated with percutaneous ethanol injection instead of radiofrequency ablation.

We describe three cases of well-differentiated hepatocellular carcinoma (HCC) smaller than 15 mm in diameter completely eradicated with percutaneous ethanol injection (PEI) instead of using radiofrequency ablation (RFA). Ultrasound (US) examination revealed one nodule each in segment 2 (hypoechoic, near bile ducts, 10 mm), in segment 5 (hyperechoic, near the gall bladder, 15 mm), and in segment 7 (hypoechoic, near the diaphragm, 15 mm). Although imaging studies revealed isovascular (case 1) and hypervascular (cases 2 and 3) nodules, histological analysis of US-guided biopsy tissue revealed well-differentiated HCC. In consideration of the location of the nodules, PEI, instead of RFA, was administered and the nodules were rendered necrotic. Although RFA is superior to PEI in the treatment of small HCCs from the viewpoint of treatment response and long survival, PEI is strongly recommended for HCCs located near bile ducts, the gall bladder, and the diaphragm, especially when the nodules are smaller than 15 mm in diameter.

Scirrhous hepatocellular carcinoma displaying atypical findings on imaging studies.

We describe a 15-mm scirrhous hepatocellular carcinoma (HCC) in a 60-year-old man with B-type cirrhosis. Ultrasound disclosed a 15-mm hypoechoic nodule in segment 7. Contrast-enhanced US revealed heterogeneous, not diffuse, hypervascularity in the early phase and a defect in the Kupffer phase. Contrast-enhanced computed tomography (CT) revealed a heterogeneous hypervascular nodule in the early phase and a low-density area in the late phase. Magnetic resonance imaging (MRI) revealed iso- to hypointensity at T1 and high intensity at T2-weighted sequences. Contrast-enhanced MRI also revealed a heterogeneous hypervascular nodule in the early phase and washout in the late phase. Super-paramagnetic iron oxide-MRI revealed a hyperintense nodule. CT during hepatic arteriography and CT during arterial portography revealed heterogeneous hyperattenuation and a perfusion defect, respectively. Based on these imaging findings the nodule was diagnosed as a mixed well-differentiated and moderately-differentiated HCC. Histologically, the nodule was moderately-differentiated HCC characterized by typical cytological and structural atypia with dense fibrosis. Immunohistochemically, the nodule was positive for heterochromatin protein 1 and alpha-smooth muscle actin, and negative for cytokeratin 19. From the above findings, the nodule was diagnosed as scirrhous HCC. Clinicians engaged in hepatology should exercise caution with suspected scirrhous HCC when imaging studies reveal atypical findings, as shown in our case on the basis of chronic liver disease.

Two cases of non-alcoholic steato-hepatitis developing from simple fatty liver.

We describe two cases of non-alcoholic steatohepatitis (NASH) developing from simple fatty liver and detected by histological examination in two women. In both cases hypertension and diabetes mellitus showed no exacerbation during follow-up; hepatitis C antibody and hepatitis B surface antigen were negative; ultrasound (US) and computed tomography (CT) revealed fatty liver (moderate in one patient and severe in the other). Body mass index (BMI) was 48 and 44 in 2004 and 2007, respectively, in one and 24 in both 2006 and 2007, respectively, in the other. Liver function tests showed some fluctuation in aspartate aminotransferase and alanine aminotransferase. The first US-guided liver biopsy showed simple fatty liver; the second biopsy after two and a half years on one patient and one and a half years on the other, revealed histological features of NASH characterized by predominantly macrovesicular fatty change (40% in one and 80% in the other) with occasional ballooning, fibrosis (moderate in one and slight in the other) extending from zone 3 to zone 1, intraacinar inflammation with neutrophil infiltration, and mild portal chronic inflammation with piecemeal necrosis. Fibrosis progressed from stage 0 to stage 2 in two and a half years in one patient, and from stage 0 to stage 1 in one and a half years in the other. Clinicians should be vigilant during the clinical course of NASH developing from simple fatty liver.

Acute Pancreatitis Associated with Pegylated Interferon and Ribavirin Treatment of Chronic Hepatitis C, Genotype 1b with High Viral Load.

Acute pancreatitis, an uncommon side effect of pegylated interferon α (PEG-IFN α) and ribavirin (RBV) combination therapy, has rarely been reported in the English language literature. Here, acute pancreatitis associated with PEG-IFN plus RBV treatment is described in three patients with chronic hepatitis C, genotype 1b with high serum hepatitis C virus RNA levels. The patients had been started on weekly subcutaneous injections of PEG-IFN α (60, 80, and 90 µg) plus a daily oral dose of RBV (600 mg). The therapy was discontinued, however, because of the onset of acute pancreatitis (after 15 weeks, 48 weeks, and 3 weeks respectively). The drug-induced pancreatitis was diagnosed on the basis of elevated levels of amylase and lipase and the absence of other identifiable causes. High tumor necrosis factor-α was found in one patient and high interleukin-6 in the other two. The immune system stimulated by PEG-IFN and RBV combination therapy might have caused the acute pancreatitis. Further study is needed to clarify the mechanism of the onset of drug-induced pancreatitis by PEG-IFN and RBV combination therapy.

Utility of Gd-EOB-DTPA-Enhanced MRI in Diagnosing Small Hepatocellular Carcinoma.

We describe an 8-mm hepatocellular carcinoma (HCC) with hepatitis C virus-related cirrhosis in a 74-year-old woman. Ultrasound (US) revealed an 8-mm hyperechoic nodule in segment 6 of the liver. Contrast-enhanced computed tomography (CT) and US revealed no hypervascularity in the early phase and no washout in the late phase and the Kupffer phase, respectively. CT during arteriography revealed no hypervascularity and CT during arterial portography disclosed no perfusion defect. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) revealed no hypervascularity in the early phase, but disclosed a defect in the hepatobiliary phase. Histologically, the nodule was diagnosed as well-differentiated HCC characterized by more than two-fold the cellularity of the non-tumorous area, with a high nuclear:cytoplasmic ratio, increased cytoplasmic eosinophilia, fatty change, and slight cell atypia with an irregular thin trabecular pattern. Our case demonstrates the utility of Gd-EOB-DTPA-enhanced MRI in the diagnosis of small HCC.

[Expression of mesothelin as a potential diagnostic marker in mesothelioma].

Histological discrimination of mesothelioma from adenocarcinoma is often difficult, therefore, many investigators have tried immunohistochemical, ultrastructual, and molecular methods. Economically, immunohistological studies are more excellent, compared with ultrastractual and molecular biological methods. Immunohistologically, many well known markers are divided into two category; adenocarcinoma-related markers, which expressed by adenocarcinoma, and mesothelioma-related makers, which are positive for mesothelioma. CEA, TTF-1, and Ber-Ep4 are well known adenocarcinoma-related markers, mesothelin, TM, HBME-1 and calretinin, have been used as mesothelioma-related markers. Most previous reports associated with discrimination of adenocarcinoma and mesothelioma mentioned that a diagnosis of epithelioid mesothelioma would be excluded by the presence of adenocarcinoma-related antibody. The positive ratio of mesothelioma-related antibodies is lower than that of adenocarcinoma-related antibodies. Only a single mesothelioma-related marker cannot lead to a diagnosis of epithelioid mesothelioma and a correct diagnosis can be made by combination of several makers, which contain both mesothelioma-related markers and adenocarcinoma-related markers. We immunohistologically examined 41 cases of mesothelioma and 16 cases of adenocarcinoma of the lung, and re-evaluated the use of immunohistochemical markers, compared with previous reports. Reactivity for mesothelin was obtained in 19 (73%) of the epithelioid mesotheliomas, but none (0%) of the lung adenocarcinomas. None of the sarcomatoid mesotheliomas exhibited positivity for this marker, nor was any reactivity seen in the spindle cell component of the biphasic mesotheliomas. These findings indicate that, in some instances, mesothelin immunostaining can assist in the diagnosis of mesothelioma.

[A case of primary lung cancer with cervical tuberculous lymphadenitis].

A 66-year-old woman was admitted due to right cervical lymphadenopathy and an abnormal chest radiograph. Acid-fast bacilli smear of fine needle aspiration from a right cervical lymph node was positive. Histopathological examination of the specimen obtained by percutaneous right cervical lymph node biopsy showed necrotizing epithelioid granulomas and no malignant cells. Therefore, right cervical tuberculous lymphadenitis was diagnosed. Partial lung resection of the right S4 was carried out by video-assisted thoracoscopic surgery and primary lung cancer was diagnosed. To our knowledge, there has been no previous report of both primary lung cancer and cervical tuberculous lymphadenitis being present at the time of the first examination. We report this very rare case.

Case of adult genotype C HBV carrier after acute hepatitis B, losing HBsAg and acquiring HBsAb after IFN and lamivudine treatment.

Here we report the case of a 48-year-old man, carrier of genotype C HBV for longer than 6 months after contracting sexually transmitted acute hepatitis B, who eventually lost HBsAg and acquired HBsAb by IFN/lamivudine therapy. The patient had been negative for HBsAg in 2001, but, during his stay in China from January to July in 2003, he developed acute hepatitis B after having an extra-marital sexual contact there. HBsAg was still positive and a liver biopsy indicated chronic hepatitis when he was admitted to our hospital in December 2003 for detailed examination of liver dysfunction. HBV DNA in his serum, revealed to segregate to genotype C by sequencing on admission, decreased to undetectable levels at the end of a 3-month IFN therapy, and remained undetectable during and after the successive 6-month lamivudine therapy. HBeAg seroconverted to HBeAb during the therapy, and HBsAb appeared after the therapy. To our knowledge, this is the first case of genotype C chronic hepatitis B occurring after acute hepatitis.

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.

Eosionophilic pseudotumor of the liver due to Ascaris suum infection.

A case of eosinophilic pseudotumor of the liver due to Ascaris (A) suum is described in a 34-year-old-man with a high serum level of immunoglobulin E and hypereosinophilia ascribed to a history of atopic dermatitis since childhood. Multiple hepatic hypoechoic nodules detected by ultrasound were confirmed as low-density nodules on computed tomography (CT), and as low and high signal intensity lesions on T1-and T2-weighted magnetic resonance imaging (MRI), respectively. CT during arteriography (CTA) and arterial portography revealed multiple nodules with ring-shaped enhancement and perfusion defect, respectively. Biopsied liver tissue specimens did not contain tumor cells or atypical cells; instead, they showed marked infiltration of eosinophils with necrosis and Charcot-Leyden crystals in the portal tracts and hepatic sinusoides, suggesting parasitic infection, although neither larvae nor eggs were detected. The diagnosis of visceral larva migrans (VLM) due to A. suum was based on immunoserological tests. The patient was a habitual consumer of raw bovine liver, which may explain the A. suum infection. After drug therapy with albendazole, the hypoechoic nodules disappeared. Differential diagnoses and the possible transfection route of A. suum are discussed.