Junki Koike

Narrow Band Imaging Applied to Pleuroscopy for the Assessment of Vascular Patterns of the Pleura

Background: Narrow band imaging (NBI), which enhances blood vessels, is a new endoscopic technology for diagnosing malignancies, but it has not been investigated for pleuroscopy. Objectives: To evaluate the efficacy of NBI applied to pleuroscopy for detecting malignant lesions by assessing vascular patterns of the pleura. Methods: From May 2006 to September 2008, 45 patients with undiagnosed pleural ef-fusion underwent pleuroscopy using a pleura-videoscope with white light (WL) and NBI under local anesthesia. For this prospective study, 73 biopsy specimens were obtained from sites where images under both WL and NBI were recorded and classified regarding vascular patterns. Results: Of the 73 lesions, WL showed blood vessels in 32 lesions, and NBI in 52 lesions (WL vs. NBI; p = 0.0014). The accuracy, sensitivity and specificity in the detection of irregular vascular patterns, e.g. blood vessels with irregular caliber or punctate vessels indicating malignant lesions, were 60.3, 76.5 and 55.4% in WL, and 80.8, 85.3 and 76.9% in NBI, respectively, resulting in a significant increase in NBI (p = 0.0106 for accuracy and p = 0.0494 for specificity). For flat lesions, NBI revealed a higher accuracy rate (90.6%) in the detection of irregular vascular patterns indicating malignant lesions. Conclusion: Our study demonstrated that NBI applied to pleuroscopy displayed blood vessels significantly better than WL. NBI was useful to detect irregular vascular patterns suggesting malignant lesions, especially for flat lesions. Therefore, NBI was considered useful in the selection of optimal biopsy sites by assessing vascular patterns.

Involvement of cell‐mediated killing in apoptosis in histiocytic necrotizing lymphadenitis (Kikuchi‐Fujimoto disease)

Histiocytic necrotizing lymphadenitis, also called Kikuchi‐Fujimoto (KF) disease, is a benign disorder characterized histologically by paracortical necrotic foci surrounded by histiocytic aggregates. We analysed affected lymph node tissues from 34 patients with the disease in an attempt to elucidate its histogenesis. The ‘necrotizing’ cells showed typical apoptotic changes, including cell shrinkage and condensed and fragmented nuclei. Apoptotic bodies with a peculiar ultrastructure were demonstrated, and DNA fragmentation was detected in these cells by in situ end labelling. Immunostaining for the apoptosis‐regulating proteins bcl‐2, bax, c‐myc and p53 failed to show their involvement in KF disease. However, perforin, a killer cell‐specific cytolytic protein essential for provoking apoptosis in target cells, was found to be expressed abundantly by the infiltrating cells, which were thought to be cytotoxic T‐lymphocytes. Perforin‐expressing cells were present in the apoptotic foci of 28 of the 34 patients (82.4%). Virtually no cells containing perforin granules were present in non‐pathological regions, lymph node tissues from control subjects with reactive or tuberculous lymphadenitis or those from patients with KF disease with negligible apoptosis. Therefore, the ‘necrosis’ associated with KF disease appears to be attributable to trans apoptotic death of the killer cell target in the affected nodes. We propose that KF disease should be called apoptotic lymphadenitis.

E3 ubiquitin ligase synoviolin is involved in liver fibrogenesis.

Background and Aim Chronic hepatic damage leads to liver fibrosis, which is characterized by the accumulation of collagen-rich extracellular matrix. However, the mechanism by which E3 ubiquitin ligase is involved in collagen synthesis in liver fibrosis is incompletely understood. This study aimed to explore the involvement of the E3 ubiquitin ligase synoviolin (Syno) in liver fibrosis. Methods The expression and localization of synoviolin in the liver were analyzed in CCl4-induced hepatic injury models and human cirrhosis tissues. The degree of liver fibrosis and the number of activated hepatic stellate cells (HSCs) was compared between wild type (wt) and Syno+/− mice in the chronic hepatic injury model. We compared the ratio of apoptosis in activated HSCs between wt and Syno+/− mice. We also analyzed the effect of synoviolin on collagen synthesis in the cell line from HSCs (LX-2) using siRNA-synoviolin and a mutant synoviolin in which E3 ligase activity was abolished. Furthermore, we compared collagen synthesis between wt and Syno−/− mice embryonic fibroblasts (MEF) using quantitative RT-PCR, western blotting, and collagen assay; then, we immunohistochemically analyzed the localization of collagen in Syno−/− MEF cells. Results In the hepatic injury model as well as in cirrhosis, synoviolin was upregulated in the activated HSCs, while Syno+/− mice developed significantly less liver fibrosis than in wt mice. The number of activated HSCs was decreased in Syno+/− mice, and some of these cells showed apoptosis. Furthermore, collagen expression in LX-2 cells was upregulated by synoviolin overexpression, while synoviolin knockdown led to reduced collagen expression. Moreover, in Syno−/− MEF cells, the amounts of intracellular and secreted mature collagen were significantly decreased, and procollagen was abnormally accumulated in the endoplasmic reticulum. Conclusion Our findings demonstrate the importance of the E3 ubiquitin ligase synoviolin in liver fibrosis.

Hepatocellular carcinoma with silent and cirrhotic non-alcoholic steatohepatitis, accompanying ectopic liver tissue attached to gallbladder.

A 70‐year‐old man had been obese since youth. He had been treated for hypertension and diabetes mellitus. An abdominal ultrasound showed a mass in the liver. He was admitted to St Marianna University School of Medicine Hospital for further evaluation. There was no history of alcohol use, and hepatitis viral markers and autoantibodies were all negative. Several imaging studies showed overt hepatocellular carcinoma (HCC). Transcatheter arterial embolization was performed, followed by surgical resection. Histopathological examination revealed moderately differentiated HCC. The non‐tumor areas had pseudolobules in a diffuse pattern similar to alcoholic cirrhosis. The histological findings in the ectopic liver tissue attached to the gallbladder, which was also resected during surgery, were that there was no cirrhosis, but fine fibrosis with inflammatory cell infiltration of sinusoids. These findings were consistent with non‐alcoholic steatohepatitis (NASH). There was probably a progression of similar findings that had developed into cirrhosis. These findings confirmed a diagnosis of HCC, cirrhosis, and underlying NASH in this patient. The present case is important for investigation of the development into cirrhosis and carcinogenesis of NASH. The present case demonstrates the importance of evaluating obese patients with fatty liver for underlying NASH and ongoing follow up for development of cirrhosis and HCC.

Activated extracellular signal-regulated kinase correlates with cyst formation and transforming growth factor-β expression in fetal obstructive uropathy

Human renal dysplasia is frequently associated with urinary tract obstruction and the abnormal expression of mitogen-activated protein kinase (MAPK). Here, we determined the renal responses and MAPK expression in developing kidneys that were obstructed in fetal lambs. Kidneys were harvested at various times after obstruction (gestation day 60) through normal term (day 145). Dilation of Bowmans capsule and proximal tubules was seen 2 days after obstruction and involved the whole cortex 18 days later, with numerous cysts present throughout the kidney at term. The proliferation marker Ki-67 and transforming growth factor-beta (TGF-beta) were detected 2 days after obstruction and progressively increased in tubules, cysts, and the interstitium. In control kidneys, p38 was expressed in tubules only during the fetal stage, whereas phosphorylated extracellular signal-regulated kinase (P-ERK) was limited to ureteric buds and collecting ducts at all stages examined. However, Jun-N-terminal kinase (JNK) was absent in the fetal kidney but present in tubules at term. In obstructed kidneys, cyst epithelia were positive for p38 and P-ERK but negative for JNK throughout all stages. These studies show that P-ERK correlated spatially and temporally with Ki-67 and TGF-beta expression, which suggests that ERK may contribute to cyst formation and fibrosis in the obstructed fetal kidney.

Can a pressure-limited vesico-amniotic shunt tube preserve normal bladder function?

INTRODUCTION We have previously shown that a vesico-amniotic shunt (V-A shunt) produces fibrotic bladders with poor compliance in normal fetal lambs. We hypothesized that using a ventriculo-peritoneal shunt (V-P shunt) as a V-A shunt in normal bladders may preserve the filling/emptying cycle and normal bladder development. MATERIALS AND METHODS The V-A shunting in normal fetal lambs was performed at 74 days of gestation using a V-P shunt (group A) and a free-draining shunt tube (group B). Sham-operated lambs were used as controls (group C). They were all delivered at term (145 days), and the pressure-volume curve, bladder volume, and histologic features of the bladder wall were compared. RESULT The mean bladder volume in group B (n = 5), 5 +/- 2.4 mL, was significantly smaller (P < .01) than that in group A (n = 6), 53 +/- 14 mL, and group C (n = 10), 57.3 +/- 12 mL. The bladder wall thickness in group A was 338 + 94.2 microm; group B, 741 +/- 128 microm; and group C, 374 +/- 120 microm. Group B bladders had very poor compliance with thick bladder wall (P < .01). Histologically, group B bladders showed prominent submucosal fibrotic change, but group A bladders were similar to controls. CONCLUSION This study shows that a pressure-limited shunt tube for V-A shunting preserves the normal fetal bladder development.

BK polyomavirus nephropathy complicated with acute T-cell-mediated rejection in a kidney transplant recipient: a case report

Tanabe T, Shimizu T, Sai K, Miyauchi Y, Shirakawa H, Ishida H, Honda K, Koike J, Yamaguchi Y, Tanabe K. BK polyomavirus nephropathy complicated with acute T‐cell‐mediated rejection in a kidney transplant recipient: a case report.
Clin Transplant 2011: 25 (Suppl. 23): 39–43.
© 2011 John Wiley & Sons A/S.

Clinical and pathological assessment of acute vascular rejection in the transplant kidney.

Koike J, Yamaguchi Y, Horita S, Tanabe K, Fuchinoue S, Toma H, Nihei H. Clinical and pathological assessment of acute vascular rejection in the transplant kidney. Clin Transplantation 2001: 15 (Supplement 5): 41–44. ©Munksgaard, 2001

Renal dysplasia produced by obstructive uropathy in the fetal lamb

Aim: This study was undertaken to investigate the renal changes associated with obstruction of the urinary tract in the fetal lamb early in gestation (50 days). It was also undertaken to determine if urinary tract obstruction proximal or distal to the urinary bladder would result in varying renal morphology. Methods: Timed‐gestation ewes at 50‐days gestation were anaesthetised, and the lambs exposed. Males had their urethra and urachus ligated with a fine silastic tubing. Females had one ureter ligated with the same tubing. They were delivered at term and sacrificed. The kidneys were weighed, measured and processed for histological examination. Results: Three lambs (2 males and 1 female) survived. All 5 kidneys were small (2.2+/−0.4g, normal 17.3+/−1.3g), and had lost their normal architecture. Microscopically, these kidneys had few glomeruli, a relative abundance of stroma with apparent nodular collections of tubules surrounded in some instances by a cuff of fibrous stromal tissue. Conclusion: The morphologic features produced by urinary tract obstruction at 50‐days gestation in the lamb resembled those normally associated with human cystic renal dysplasia. The site of the obstruction had no effect on the development of subsequent renal pathology.

Hepatic veno-occlusive lesions in severe alcoholic hepatitis and alcoholic liver cirrhosis: a comparative histopathological study in autopsy cases.

Clinicopathological features of veno-occlusive lesions in hepatic veins were studied in autopsy cases of severe alcoholic hepatitis (15 cases) and alcoholic liver cirrhosis (15 cases). All the cases were heavy drinkers and died of liver failure or variceal rupture. The frequency and degree of veno-occlusive lesions, and the diameter and number of hepatic veins were studied from stained sections of liver blocks from each case. The hepatic veins observed ranged from 60 to 3000 μm in diameter. The veno-occlusive lesions were found in hepatic veins mainly 60 to 1200 μm in diameter. These findings were recognized in the majority of severe alcoholic hepatitis cases and alcoholic liver cirrhosis cases. Furthermore, more severe veno-occlusive lesions were noted in severe alcoholic hepatitis, compared with alcoholic liver cirrhosis. In the cases with obstruction in hepatic veins of <400 μm, a decrease in the number of hepatic veins and zonal necrosis were noted. In addition, some of the veno-occlusive lesions were recognized focally in the same cases. Clinical findings also indicated that ascites increased with the progression of the veno-occlusive lesions. We conclude that investigation of veno-occlusive lesions in severe alcoholic liver disease has clinicopathological significance.