Hirohiko Shinohara

Chromosome Binding Site of Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus Is Essential for Persistent Episome Maintenance and Is Functionally Replaced by Histone H1

ABSTRACT Latency-associated nuclear antigen 1 (LANA1) of Kaposis sarcoma-associated herpesvirus (KSHV; human herpesvirus 8) persistently maintains a plasmid containing the KSHV latent origin of replication (oriP) as a closed circular episome in dividing cells. In this study, we investigated the involvement of chromosome binding activity of LANA1 in persistent episome maintenance. Deletion of the N-terminal 22 amino acids of LANA1 (ΔN-LANA) inhibited the interaction with mitotic chromosomes in a human cell line, and the mutant concomitantly lost activity for the long-term episome maintenance of a plasmid containing viral oriP in a human B-cell line. However, a chimera of ΔN-LANA with histone H1, a cellular chromosome component protein, rescued the association with mitotic chromosomes as well as the long-term episome maintenance of the oriP-containing plasmid. Our results suggest that tethering of KSHV episomes to mitotic chromosomes by LANA1 is crucial in mediating the long-term maintenance of viral episomes in dividing cells.

Absence of gene mutations in KIT-positive thymic epithelial tumors

BACKGROUND Overexpression of KIT, a tyrosine kinase receptor protein encoded by the proto-oncogene c-kit, is observed in human neoplasms such as gastrointestinal stromal tumors (GISTs), myeloproliferative disorders, melanoma and seminoma. In patients with GIST, overexpression of mutated KIT within the tumor is predictive of response to molecular targeted therapy using imatinib. However, the role of KIT expression in thymic carcinoma is not fully understood. METHODS Thymic epithelial tumors from 37 patients (17 thymic carcinomas and 20 thymomas) were examined. Immunohistochemical staining with anti-KIT polyclonal antibody and anti-CD5 was performed. Mutation analyses in the juxtamembrane domains, exons 9 and 11, and in the tyrosine kinase domains, exons 13 and 17, were undertaken using polymerase chain reaction (PCR) and direct DNA sequencing in KIT-positive samples. RESULTS KIT- and CD5-positive staining was observed only in thymic carcinoma. Percentage of positive staining was 100% in squamous cell carcinoma, with no positive staining in other histologies, including atypical carcinoid. Mutation analysis of the KIT gene was performed in 11 squamous cell carcinomas, 1 adenocarcinoma and 1 adenosquamous cell carcinoma. None of the tested samples showed mutations in any of the four exons. CONCLUSIONS Squamous cell carcinoma of the thymus frequently expressed KIT and CD5 proteins, whereas other tumors did not. Unlike GIST, overexpression of KIT does not necessarily indicate gene mutation in thymic carcinoma. KIT and CD5 appear useful for evaluating and subtyping thymic epithelial tumors.

Complications associated with pulmonary resection in lung cancer patients on dialysis

BACKGROUND There are few studies available investigating the perioperative problems experienced by lung cancer patients on dialysis undergoing pulmonary resection. METHODS A retrospective review of 7 patients on dialysis undergoing pulmonary resection for lung cancer was performed. RESULTS The patient population consisted of 7 men, with a mean age of 59.9 years. The underlying kidney disease was glomerulonephritis in 5 patients and nephrosclerosis in 2. The mean levels of blood urea nitrogen and serum creatinine were 70.7 mg/dL and 9.4 mg/dL, respectively. Histologic diagnoses were adenocarcinoma in 2 patients and squamous cell carcinoma in 5. Standard lobectomy with lymph node dissection was performed in all cases. There was one operation related death due to pulmonary edema and subsequent development of pneumonia. There were two cases of sputum retention and four of hyperkalemia. One patient died of cerebral bleeding that occurred during dialysis 2 months postoperatively. CONCLUSIONS In patients on dialysis who undergo pulmonary resection, there is a high incidence of pulmonary complications, in addition to hyperkalemia, hemodynamic instability, and a tendency for postoperative dialysis-associated bleeding.

Results of surgical treatment for small (2 cm or Under) adenocarcinomas of the lung

PurposeThe objectives of this study were to identify the clinicopathologic characteristics and prognostic factors of small (2 cm or less in diameter) adenocarcinomas, and furthermore to assess the acceptability of performing a limited pulmonary resection in such patients.MethodsWe retrospectively reviewed 523 cases of cT1N0M0 peripheral adenocarcinoma measuring 2 cm or less on diagnostic images treated by a complete resection between 1991 and 2004.ResultsThe overall 5-year survival rate of the patients with small adenocarcinomas was 83.6%. Univariate and multivariate analyses identified an older age, male sex, wedge resection, advanced stage, and Noguchi classification of C, D, E, or F as independent prognostic factors that adversely affected overall survival. However, there were no significant differences in the survival according to surgical procedure in the patients whose tumors had a maximum diameter of 1.0 cm or less or in Noguchi type A and B cases.ConclusionsAge, sex, surgical procedure, p-stage, and Noguchi classification were independent prognostic factors for survival in patients with small adenocarcinomas. A segmentectomy is therefore considered to be an acceptable alternative to a lobectomy for adenocarcinomas of 2 cm or less in diameter. A wedge resection may be acceptable for tumors measuring 1 cm or less in diameter or Noguchi type A and B tumors.

Primary thymic adenocarcinoma coexisting with type AB thymoma: a rare case with long-term survival

Thymic carcinoma is a rare tumor. The most common histological subtype is squamous cell carcinoma, and only a few cases of thymic adenocarcinoma have been reported. A case of papillary adenocarcinoma of thymic origin that coexisted with type AB thymoma as a separate nodule is presented herein. The patient was found to have an abnormal mediastinal shadow on chest X-ray. A computed tomography scan revealed a round, 6.5-cm-diameter mass in the right anterior mediastinum. The preoperative diagnosis was thymoma, and thymothymectomy was performed. On pathological examination, two tumors, which were diagnosed as papillary adenocarcinoma and type AB thymoma, respectively, were present in the thymus without any connection with each other. The patient has been alive without any signs of recurrence for 11 years after surgery. We diagnosed the adenocarcinoma in this case was a primary thymic carcinoma.

Large bronchial granular cell tumor

We report a 20-year-old woman who underwent complete resection of a granular cell tumor (GCT). On chest computed tomography (CT) scan, a mass with a maximum diameter of 36 mm at the lower bronchus with atelectasis of the right lower lobe was noted. Bronchoscopic examination revealed a whitish mass in the truncus intermedius, and the middle and lower bronchus were unable to be seen. A cytopathological examination of the mass revealed GCT. A right middle and lower lobectomy was performed via a posterolateral thoracotomy. Microscopically, the tumor was composed of polygonal cells with oxyphilic granular cytoplasm and small ovoid nuclei. The cytoplasm of the neoplastic cells was positive for S-100 protein and neuron-specific enolase. The patient’s postoperative course was uneventful, and she was asymptomatic after 4 months. A large bronchial GCT is rare, which is why we report this case.

Segmentectomy for multiple adenocarcinoma presenting as ground-glass opacities after lung cancer surgery

During follow-up of patients after primary lung cancer resections, small nodules or ground-glass opacities (GGOs) are sometimes detected on chest computed tomography. We report a case with multiple GGOs that were noted after primary lung cancer resection. A 76-year-old woman, who had undergone right upper lobectomy, middle lobe partial resection, and mediastinal lymph node dissection 3 years earlier, was admitted owing to five GGOs in the right lower lobe that had been increasing in size or density. A right S6+10 segmentectomy was performed. On histology, one adenocarcinoma and four bronchioloalveolar carcinomas (BACs), as well as two additional BACs that had not been detected preoperatively, were identified. No complications occurred postoperatively. Three years 4 months later, no tumor recurrence or new lesions have been found. Given the high possibility of malignancy, the appearance of new GGOs in patients with a history of lung cancer requires appropriate investigation.

Superior vena cava reconstruction via a posterolateral thoracotomy without venous occlusion for locally advanced lung cancer: Report of a case

We performed a right upper lobectomy with prosthetic replacement of the superior vena cava (SVC) through a posterolateral thoracotomy in a 65-year-old man undergoing complete resection of a locally advanced non-small-cell lung cancer with invasion of the SVC. Instead of using a vascular shunt, the right atrium and a right brachiocephalic vein (BCV) were anastomosed using a ringed polytetrafluoroethylene (PTFE) graft. During the anastomosis, vascular flow was maintained through the left BCV. By using this technique, SVC resection and reconstruction during lung cancer surgery can be safely performed through a posterolateral thoracotomy without blood flow interruption.

Ross procedure for aortic insufficiency due to doubly committed subarterial ventricular septal defect in adults.

Abstract  A 52‐year‐old female, with aortic insufficiency due to doubly committed subarterial ventricular septal defect (VSD) underwent a successful surgical repair by the Ross procedure. Preoperatively, she developed congestive heart failure because of less compliance to oral medication, raising concerns regarding life‐threatening thromboembolism if she undergoes mechanical valve replacement. Despite the pulmonary autograft being defective, there were no difficulties in completing the surgery. The defect of pulmonary autograft and the VSD was closed by an expanded polytetrafluoroethylene patch. She tolerated the procedure well and now enjoys improved quality of life. We present a discussion of the indication of Ross procedure in the rare presentation of congenital heart disease, as well as several issues raised in this case.