Phylogenetic and phylodynamic analyses of hepatitis C virus subtype 1a in Okinawa, Japan.

Okinawa Island, located in Southern Japan, has a higher prevalence rate of hepatitis C virus subtype 1a (HCV-1a) infection than that in mainland Japan. Okinawa has a history of US military occupation after World War II. To elucidate the transmission history of HCV-1a in Okinawa, 26 whole-genome sequences were obtained from 29 patients during 2011-2016. Phylogenetic trees were reconstructed to identify the origin and characteristics of HCV-1a in Okinawa with epidemiological information. A phylogenetic tree based on whole-genome sequencing revealed that all of the samples were located below the US branches. Additionally, we identified one cluster comprised of 17 strains (Okinawa, n = 16; United States, n = 1). The majority of the patients in this cluster were people who inject drugs (PWID), indicating the presence of a people who inject drugs (PWID) cluster. Subsequently, Bayesian analyses were employed to reveal viral population dynamics. Intriguingly, a phylodynamic analysis uncovered a substantial increase in effective population size of HCV-1a from 1965 to 1980 and a slight increase in mid-2000, which were associated with an increase in illicit drug use in Okinawa. The estimated divergence time of the PWID cluster was 1967.6 (1964.2-1971.1). These findings suggest that HCV-1a was introduced into Okinawa from the United States in the late 1960s, coincident with the Vietnam War. Subsequently, HCV-1a might have spread among the Japanese population with the spread of injecting drug use. Our study provides an understanding of HCV transmission dynamics in Okinawa, as well as the key role of PWID in HCV transmission.

Inhibition of intracellular hepatitis C virus replication by nelfinavir and synergistic effect with interferon-alpha.

Liver diseases associated with hepatitis C virus (HCV) infection have become the major cause of mortality in patients with human immunodeficiency virus (HIV) infection since the introduction of highly active anti-retroviral therapy. HCV-related liver disease is more severe in HIV-infected patients than in non-HIV-infected patients, but the standard therapies used to treat chronic hepatitis C in HCV/HIV coinfected patients are the same as those for patients infected with HCV alone. HIV protease inhibitors might have potential to down-regulate HCV load of HCV/HIV coinfected patients. In this study, we evaluated the effects of nelfinavir on intracellular HCV replication using the HCV replicon system. We constructed an HCV replicon expressing a neomycin-selectable chimeric firefly luciferase reporter protein. Cytotoxicity and apoptosis induced by nelfinavir were assessed and synergism between nelfinavir and interferon (IFN) was calculated using CalcuSyn analysis. Nelfinavir dose-dependently repressed HCV replication at low concentrations (IC(50), 9.88 micromol/L). Nelfinavir failed to induce cytotoxicity or apoptosis at concentrations that inhibited HCV replication. Clinical concentrations of nelfinavir (5 micromol/L) combined with IFN showed synergistic inhibition of HCV replication in our replicon model. Our results suggest that the direct effects of nelfinavir on the HCV subgenome and its synergism with IFN could improve clinical responses to IFN therapy in HCV/HIV coinfected patients.

[Pneumothorax and abdominal free air occurred after percutaneous tracheostomy (PCT)].

We report a case of pneumothorax and abdominal free air after percutaneous tracheostomy (PCT). A 80-year-old female was intubation for upper respiratory stenosis. We thought tracheal stenosis recurrence after extubation. PCT was performed. Respiratory insufficiency and subcutaneous emphysema appeared rapidly at face, neck and precordia Subcutaneous emphysema was pushed away. PCT was performed once more. Chest X-ray showed pneumothorax in right thoracic cavity. Thoracostomy tube was intubation. Chest computed tomography (CT) scan showed pneumothorax another thoracic cavity and abdominal free air. Vital signs was not worse, so observation. Postoperative course was uneventful. The patient was recovered. We thought that PCT was effective under bronchofiber.

Bile duct schwannoma developed in the remnant choledochal cyst-a case associated with total agenesis of the dorsal pancreas.

A 59-year-old Japanese woman was referred to our hospital due to upper abdominal pain. At the age of 44, she was diagnosed with a congenital choledochal cyst, Todani's type Ic. She then underwent bypass operation with end-to-side choledochojejunostomy with Roux-en-Y technique as well as cholecystectomy. Magnetic resonance cholangiopancreatography revealed an 'oval' shaped cystic lesion with a maximal diameter of 25 mm, which had been 'spindle' shaped with a maximal diameter of 18 mm, 15 years ago. It also showed an anomalous pancreaticobiliary ductal union. In addition, a complete absence of the dorsal primordia of pancreas was revealed by magnetic resonance image and computed tomography scan. The patient underwent the surgical exploration for the resection of the 'oval' shaped cystic lesion. Haematoxylin and eosin staining of the thin section of the resected cyst showed a compact spindle cell pattern which was compatible with schwannoma, Antoni type A, which was confirmed by immunocytochemical technique. We present a very interesting case showing choledochal cyst, anomalous pancreaticobiliary ductal union, total agenesis of the dorsal pancreas and late-development of bile duct schwannoma in the remnant choledochal cyst.

Alcoholic liver cirrhosis complicated with torsade de pointes during plasma exchange and hemodiafiltration.

A 36-year-old man with severe alcoholic hepatitis was treated with plasma exchange combined with hemodiafiltration to remove endotoxins and inflammatory cytokines. During the treatment, he had critical arrhythmia (torsade de pointes [TdP]). His laboratory data showed hypomagnesemia, which was suspected to be responsible for the development of TdP. Patients with alcoholic liver disease tend to have hypomagnesemia and Q-T interval prolongation. Furthermore, hemodiafiltration may cause hypomagnesemia. Careful observation for electrolytic imbalance is necessary when clinicians treat patients with alcoholic liver failure with a liver support system.

Superficial temporal artery interposition graft after resection of bilateral anterior cerebral arteries. Case report.

A patient with an olfactory neuroblastoma in the frontal skull base was treated with primary tumor excision and partial resection of the A2 segment of both anterior cerebral arteries (ACA's). Revascularization was carried out using a superficial temporal artery (STA) interposition graft between the proximal and distal stumps with A3 segment-to-A3 segment end-to-side anastomosis. This technique established flow to the peripheral territories of the ACA's through the interposed STA graft. The technical aspects and possible role of this procedure are presented.

Meningiomas arising from the falcotentorial junction. Clinical features, neuroimaging studies, and surgical treatment.

Meningiomas arising from the falcotentorial junction are extremely rare. The authors describe the clinical features, neuroimaging studies, and results of surgical treatment of meningiomas of the falcotentorial junction and clarify the characteristics of this lesion based on a review of the literature and seven patients treated at their institution. The most common symptoms resulted from intracranial hypertension. Upward-gaze palsy appeared in only one patient. Computerized tomography (CT) showed no specific findings, but there was no evidence of edema around the tumor. Magnetic resonance (MR) imaging revealed a round, smooth-bordered mass with a peritumoral rim, without edema, and showing marked contrast enhancement. The multiplanar capability of MR imaging delineated the relationship between the tumor and adjacent structures better than did CT. Detailed knowledge of the vascular structures, especially evidence of occlusion of the galenic venous system and the development of collateral venous channels, is critical for successful surgery; stereoscopic cerebral angiography is necessary to achieve this aim. The seven patients described developed five types of collateral venous channels: through the basal vein of Rosenthal to the petrosal vein, through the veins on the medial surface of the parietal and occipital lobes to the superior sagittal sinus, through superficial anastomotic veins, through veins of the posterior fossa to the transverse or straight sinus, and through the falcian veins to the superior sagittal sinus. The first three types mainly developed after occlusion of the galenic system. The tumors were removed through the occipital transtentorial approach with a large window at the posterior part of the falx. A favorable prognosis for patients undergoing surgical treatment of falcotentorial junction meningiomas can be expected if detailed neuroimaging studies and microsurgical techniques are used.

Alanine aminotransferase elevation not associated with fatty liver is frequently seen in obese Japanese women.

OBJECTIVE: To determine the prevalence of fatty liver and alanine aminotransferase (ALT) elevation in obese Japanese women and to clarify the factors contributing to fatty change and ALT elevation in the cohort. DESIGN: Cross-sectional and population-based study. SUBJECTS: From 4366 women who received their annual health check-up, 4211 women were selected for analysis. All 4211 women were negative for hepatitis virus markers. MEASUREMENTS: Peripheral blood cell counts, liver biochemical tests, fasting glucose, cholesterol and triglyceride levels, uric acids, glycosylate hemoglobin A1c, and ultrasound examination. RESULTS: Ultrasonographic evidence of fatty liver and ALT elevation was seen in 391 (9.3%) and 238 (5.7%), respectively, of the 4211 women. Frequencies of both fatty liver and ALT elevation increased with increase in the degree of obesity. The frequency of ALT elevation was higher in women with fatty liver than in women without fatty liver among the nonobese or mildly obese group. However, the frequency of ALT elevation was not significantly different between women with fatty liver and women without fatty liver among the severely obese group. Multivariate analysis showed that obesity, hemoglobin (> or = 14 g/dl), triglyceride (> or = 150 mg/dl), diabetes mellitus, and fatty liver were significant predictors of ALT elevation. However, only two variables, hemoglobin (> or = 14 g/dl) and presence of diabetes, were significant in the severely obese group. CONCLUSIONS: ALT elevation not associated with fatty liver was frequently seen in obese women, suggesting that obesity is directly associated with the elevated ALT level in Japanese obese women. In addition, hemoglobin (> or = 14 g/dl) was a strong predictor of ALT elevation in the severely obese group.

Correlation between serum transaminase activity and virus load among patients with chronic liver disease type B.

Newly developed hepatitis B virus (HBV)-DNA quantitative assays, transcription-mediated amplification and hybridization protection assay (TMA-HPA) and branched-DNA assay were clinically evaluated. The subjects consisted of 160 chronic HBV carriers; 48 were hepatitis Be antigen (HBeAg)-positive, whereas 109 were anti-HBe-positive (three were both negative). All subjects with HBeAg, except one, showed high HBV-DNA replication levels (>/=10(5.8) copies/ml). In HBeAg negative subjects, there was a strong correlation between the serum HBV-DNA and alanine aminotransferase (ALT) levels; ALT level was usually normal if the samples tested showed an HBV-DNA level less than 10(5)/ml, whereas, the majority of the sera with an HBV-DNA concentration greater than 10(7)copies/ml showed elevation in serum ALT level. An intermediate range of HBV-DNA level (10(5)-10(7) copies/ml) was associated with variable ALT activity. In conclusion, a serum HBV-DNA level associated with ALT elevation was lower in patients with type B chronic liver disease negative for HBeAg compared with their HBeAg-positive counterparts. There was usually no or mild liver disease activity when patients with chronic HBV infection have serum HBV-DNA levels less than 10(5)copies/ml.

Successful surgical resection of solid cystic tumor of the pancreas with multiple liver metastases and a tumor thrombus in the portal vein.

We report a case of solid cystic tumor of the pancreas with widespread liver metastases and a tumor thrombus in the portal vein. The patient was a 43-year-old woman. She was referred because of an upper abdominal mass and weight loss. Computed tomography disclosed a 10-cm cystic and calcified mass in the body and tail of the pancreas and multiple masses in the liver. She underwent a distal pancreatectomy with splenectomy, extended right lobectomy, and partial resection of the liver. All the tumors were completely resected despite the presence of 20 liver metastases. Histopathological studies showed a tumor thrombus in the intrahepatic portal vein. The patient is well without any signs of recurrence 8 months after the operation. Aggressive surgical resection is considered to yield a good outcome for solid cystic tumor with liver metastases and tumor thrombus of the portal vein.

Benign biliary stricture associated with atherosclerosis.

We report a case of benign bile duct stricture that could not be differentiated from intrahepatic bile duct carcinoma preoperatively. The patient was a 79-year-old man. Computed tomography showed dilatation of the intrahepatic bile duct in the left lobe. Direct cholangiography showed segmental stricture of the left bile duct. Angiography showed narrowing of the left hepatic artery. Although bile cytology did not show malignant cells, we suspected intrahepatic bile duct carcinoma preoperatively. We performed extended left hepatic lobectomy. Histopathologic examination of the resected duct also showed no malignant cells; fibrosis with infiltration by lymphocytes was seen at the bile duct stricture. In addition, the resected liver specimen showed sclerotic change in the intrahepatic arteries. The postoperative course was uneventful for more than 26 months, without recurrence or cholangitis. We encountered a very rare case of benign segmental bile duct stricture, which was difficult to differentiate from bile duct carcinoma. We think the biliary stricture was secondary to atherosclerosis which may have caused bile duct ischemia.

Preliminary results of interstitial 192Ir brachytherapy for malignant gliomas.

Twenty-six patients with recurrent or unremovable malignant gliomas were treated by interstitial brachytherapy with iridium-192 seeds. Stereotactic implantation of the afterloading catheters using the Brown-Roberts-Wells computed tomography (CT)-guided stereotactic system was performed in 24 patients and surgical implantation in two patients with pontine glioma. The response to therapy was measured by serial CT, magnetic resonance imaging, and clinical examination. Tumor regression was seen in 17 patients 1-3 months after implantation. Tumor progression was seen in only three patients. After interstitial brachytherapy, the most commonly observed CT finding was central low density. Median survival time was 18 months after implantation. Autopsies in five patients revealed the delayed effects of radiation injury such as typical vascular changes, microcalcification, and coagulative necrosis in the implant area and tumor recurrence at the periphery. The results suggest that brachytherapy is not curative but prolonged the median survival time by 6 months.

[Basal ganglia germinoma treated with interstitial brachytherapy; case report].

A case of primary intracranial germinoma in the left basal ganglia treated with interstitial brachytherapy was reported. A 15-year-old boy was referred to our hospital for evaluation of right hemiparesis. A CT scan showed a slightly hyperdense mass with multiple cystic low density in the left basal ganglia. The mass was heterogeneously enhanced after intravenous administration of contrast material. T1 weighted image showed a slightly hyperintense mass with cystic components and the mass was heterogeneously enhanced with Gd-DTPA. T2 weighted MR image showed a mixed intensity mass and peritumoral edema. Stereotactic needle biopsy and implantation of 3 catheters for interstitial brachytherapy were performed simultaneously using BRW CT guided stereotactic apparatus. After the histological diagnosis was confirmed to be two cell pattern germinoma, 9 iridium-192 seeds were inserted into the catheters and maintained for 10 days to give 35Gy of irradiation at the tumor periphery. Subsequent CT scans showed marked tumor regression and the clinical symptoms were improved. Germinoma originating in the basal ganglia is rare and hard to diagnose previous to biopsy. Histological confirmation is essential before initiation of treatment because germinoma is commonly thought to be radiosensitive tumor. The interstitial brachytherapy enables selective irradiation of the tumor and actually causes no complications such as bone marrow suppression or cerebral atrophy. The neuroradiological findings, especially of CT scan and MRI, were presented and the strategy for treatment of germinoma in basal ganglia was discussed.

[A case of glial microtumor treated with brachytherapy using MRI guided stereotactic system].

A 34 year old male suffered from convulsion on his right side with loss of consciousness. Neither plain nor enhanced CT could clearly demonstrate a lesion. However, a Gd-DTPA enhanced T1 weighted image (T1WI) demonstrated an enhancing lesion (2 cm in diameter) in the left frontal lobe including the motor cortex. This lesion was not identified on plain T1WI. A T2 weighted image (T2WI) showed a high intensity lesion without mass effect slightly larger than the enhanced area on T1WI. This lesion was suspected to be a glial microtumor, but, because it was difficult to differentiate it from a cerebral infarction, it was confirmed to be a neoplasm by means of an MRI guided stereotactic biopsy. The histological diagnosis of the frozen section was a grade 2 astrocytoma. Subsequently brachytherapy with 192Ir seeds was performed, and about 80Gy of interstitial irradiation was given to the edge of the enhanced area on MRI. The minimum dose in the high intensity area on T2WI was about 50Gy. The patient was discharged with no neurological deficits. The Gd-DTPA enhanced lesion decreased in size six months after the treatment. MRI guided stereotactic system makes it possible to target a high intensity lesion on T2WI in brachytherapy. Brachytherapy using this system is considered to be useful in the treatment of glial microtumor in an area in which it is difficult to identify it on CT.

[Study on the extent of peritumoral edema in glioma: its correlation with the proliferative potential and tumor-infiltrating mononuclear cells].

The correlation between the extent of peritumoral edema and the proliferative potential or the infiltration of mononuclear cells was studied in 17 gliomas. The peritumoral edema was evaluated on contrast enhanced CT scan as the ratio of the low density area around the tumor to the enhanced high density area. The proliferative potential and the infiltration of mononuclear cells into the tumor were investigated immunohistochemically using monoclonal antibody (MAb) against DNA polymerase alpha and anti-Leu MAb's respectively. There was a significant correlation between the extent of the peritumoral edema and the percentage of DNA polymerase alpha positive cells. The degree of the infiltration of mononuclear cells into the tumor tissue also correlated with the extent of peritumoral edema. In gliomas with high proliferative potential and/or severe infiltration of mononuclear cells, the peritumoral edema may be aggravated by disruption of the blood-brain-barrier and increased vascular permeability.

[Interstitial brachytherapy for malignant gliomas using the Brown-Roberts-Wells (BRW) stereotactic system].

Eleven patients harboring recurrent or deep-seated malignant gliomas were treated by interstitial brachytherapy with 192Ir seed assembly, between June 1987 and September 1989. Implantations for the afterloaded catheter were performed using the Brown-Roberts-Wells (BRW) CT guided stereotactic system. The number of seeds and the distribution of the implants were chosen in such a way that the minimum tumor dose of 30-50Gy could be delivered to the surface or 1cm beyond the rim of the contrast enhancement. The radioactive sources were held in the afterloaded catheters that were removed after the desired dose had been delivered. Response to therapy was measured by serial CT scans and clinical examination. Tumor regressions were seen by CT scans made 2 or 3 months after implantation. One tumor showed complete regression (CR), four showed partial response (PR), one showed minor response (MR) and 5 showed no change (NC). Overall response rate was 54%. Six patients died 3 to 18 months following implantation, and five are still alive 7 to 27 months after implantation. No complications such as infection or hemorrhage were observed during the treatment. A patient harboring large (6.5cm in diameter) recurrent glioblastoma in the rt. parietal robe required a craniotomy due to the mass growing for one and half month after implantation, and radiation necrosis of the entire tumor mass was documented. The technique of stereotactic interstitial implantation was clinically well tolerated and easily reproducible and our preliminary results seemed encouraging. Technical improvement to achieve an adequate isodose distribution to cover the tumor volume might lead to improved survival rates.

[Analysis of tumor-infiltrating lymphocyte in primary malignant lymphoma of the central nervous system using double immunofluorescence staining method].

Three cases of malignant lymphoma were examined immunohistochemically using anti-Leu monoclonal antibodies (MAB) against B lymphocytes, T lymphocytes subsets, NK cells, IL-2 receptor. In all three cases tumor cells were stained with anti-B cell's MABs, that is they were diagnosed as B cell type of malignant lymphoma. Moderate tumor-infiltrating lymphocytes in the parenchyma or around blood vessels were observed, and majority of these cells were T lymphocytes, demonstrating Leu 2a or Leu 3a + 3b positive phenotypes. IL-2 receptor positive cells also found in the parenchyma of these tumors. T lymphocyte subsets, such as Leu 2a positive cells and Leu 3a + 3b positive cells, were analyzed by means of double immunofluorescence staining method using the combination of Leu 2a and Leu15, or Leu 3a + 3b and Leu 8 MABs. This method demonstrated that most of Leu 2a positive cells were negative for Leu 15 and that the majority of Leu 3a + 3b positive cells were negative for Leu 8. These results suggested that tumor-infiltrating lymphocytes in the malignant lymphoma were mainly activated cytotoxic or helper T cells.

[Sclerosing cholangitis-induced biliary cyst formation: complication of hepatic artery infusion chemotherapy].

A 60-year-old man underwent resection of a sigmoid colon adenocarcinoma, left hepatic lobe, part of segment 6 and 8, due to its metastasis. He received hepatic artery infusions of 5-FU total amount, 15.5 g. There was no recurrence in the liver, but he developed sclerosing cholangitis, and a large biliary cyst formed in segment 8. After drainage of the cyst by percutaneous-trans-hepatic approach, bile leakage persisted, and liver dysfunction was progressive. Sclerosing cholangitis-induced biliary cyst formation is rare. Occlusion, or necrosis of the peripheral bile duct may be the cause.

[Evaluation of hepatic resection and hepatic arterial infusion chemotherapy for multiple liver metastases from colon cancer].

We examined the significance of hepatic resection and hepatic infusion chemotherapy for multiple liver metastases from colon cancer. Twelve patients underwent curative hepatic resection for multiple liver metastases (more than five), and 10 of them received arterial infusion chemotherapy. The number of metastases ranged 5 to 30 (mean 9.4). Recurrence rates in the remnant liver were 50%, and five-year survival rates were 31%.