Advances in the Molecular Biology of Malignant Mesothelioma

Malignant mesothelioma (MM) is a highly aggressive tumor with a dismal prognosis. The incidence of MM is increasing as a result of widespread exposure to asbestos. As for the molecular alterations that occur in MM, chromosome alterations including homo-deletion of the P16 and P14 genes located in the 9p21 are well known. Mutations are rare in the P53 and Ras genes, which are frequently present in epithelial solid tumors. However, mutations are frequently present in the neurofi bromatosis type 2 gene. Epigenetic alterations including DNA methylation have been found in the MM, the profi le of which is diff erent from that of lung cancer, although differential diagnosis is sometimes clinically difficult. As in other malignant tumors, genes that are related to immortalization, proliferation, metastasis, angiogenesis, and anti-apoptosis are also overexpressed in MM, contributing to its malignant phenotype. It is of interest that simian virus 40 has been implicated to be one of the causative factors of MM in western countries. Although the causative role of asbestos is well-known in MM, much less information is available for MM than for other malignant tumors regarding the molecular alterations that occur in the disease. In terms of future tasks, it will be necessary to apply the knowledge that is learned about molecular alterations to clinical practice and to further elucidate the pathogenesis of MM with extensive research.</p

Dry Small Pleural Dissemination of Adenocarcinoma of the Lung Preoperatively Detected by PET/CT: A Report of Two Cases

Dry pleural dissemination in non-small cell lung cancer, defined as solid pleural metastasis of lung cancer without pleural eff usion, is a condition occurring in T4 lung cancer. Positron emission tomography (PET) has been reported to be useful for the diagnosis and staging of lung cancer. It has been reported that positive findings on PET scans of indeterminate pleural abnormalities at computed tomography (CT) are sensitive to malignancy. We encountered two cases of dry small pleural dissemination of adenocarcinoma of the lung preoperatively detected by PET/CT. A 75-year-old man and a 66-year-old man underwent CT scan, which demonstrated solitary tumor in the lung, an enlarged mediastinal lymph node, and a small pleural nodule less than 10 mm in size, all of which were positive findings on the fluorine 18 fluorodeoxyglucose (FDG) PET portion of an integrated PET/CT. Both patients underwent thoracoscopic biopsy of the dry pleural nodule revealing dissemination of adenocarcinoma of the lung (T4). Whereas histological thoracoscopic diagnosis remains mandatory before planning treatment, our cases may suggest that PET/CT will be useful as a screening modality for dry pleural dissemination of lung cancer.</p

Salvage endovascular embolization of the left pulmonary artery for recurrent pseudoaneurysm

Background: Pulmonary pseudoaneurysm (PPA) is a potentially lethal complication of lung resection with a high risk of recurrence after endovascular coiling. Case presentation: We report a case in which recurrent hemoptysis due to PPA after left lower lobe sleeve resection was treated by endovascular embolization of the left main pulmonary artery as a salvage treatment. The first hemoptysis was managed by endovascular coil embolization with extracorporeal membrane oxygenation, but refractory hemorrhage occurred 3 months later due to penetration of the endovascular coil into the bronchial anastomosis site. Because left completion pneumonectomy was considered too high risk, the left main pulmonary artery was palliatively embolized using an Amplatzer vascular plug (St. Jude Medical, MN, USA) to totally disrupt the left pulmonary arterial flow. Conclusions: Total embolization of the left main pulmonary artery for repeated PPA rupture may be useful as a palliative treatment in patients unable to tolerate pneumonectomy

Diagnosis of Rejection in the Allografted Rat Lung: Using Monoclonal Antibodies to T Cell Subsets for Immunologic Monitoring

Early diagnosis of rejection and timely immunosuppression are absolutely important in clinical lung transplantation. We studied surface markers of peripheral blood lymphocytes (PBL), graft infiltrating lymphocytes (GIF) and bronchoalveolar lavage fluid (BALF) in a rat using flow cytometric monitoring to diagnose rejection. Left lung transplantation was performed on Brown Norway (BN) rats and Lewis (LEW) rats in the following groups; Group 1: LEW-LEW (isograft), Group 2: BN-LEW (allograft; no immunosuppression), Group 3: BN-LEW (allograft; treated with Cyclosporine A at a dose of 15 mg/kg/day i.m.). In each group, rats were killed 3, 5, 7 days postoperatively (n = 6 on each day). Monoclonal antibodies investigated in this study were W3/25 (anti-helper T lymphocyte), OX8 (anti-suppressor/cytotoxic T lymphocyte), and OX39 (anti-interleukin 2 receptor). Histological classification of rejection in Group 2 showed vascular phase at 3 days, alveolar phase at 5 days, and destructive phase at 7 days, respectively. No evidence of rejection was found in Group 1 or 3. In Group 2, W3/25 positive cell proportion in GIL and BALF significantly decreased as the rejection progressed, but OX8 positive and OX39 positive cell proportion increases were significantly greater than in Groups 1 and 3 as the rejection progressed. These results lead us to speculate that the studies of T cell subsets in GIL and BALF lymphocytes are useful for diagnosis of rejection in lung transplantation.</p

Experimental study on veno-venous extracorporeal membrane oxygenation for respiratory failure after lung transplantation.

Extracorporeal Membrane Oxygenation (ECMO) has been adopted as a means of strong respiratory support. In lung transplantation, reimplantation response is still a serious problem. It causes severe respiratory failure which is refractory to mechanical ventilation in some cases. The purpose of this study was to evaluate the effects of veno-venous ECMO after lung transplantation using a canine autotransplantation model. The autotransplantation model was created by keeping the left lung in a warm ischemic state for 2 h. After reperfusion, the right pulmonary artery was ligated. The following two groups were studied: Group 1, Control group, (no ECMO group) (n = 6). After reperfusion, both lungs were ventilated without ECMO. Group 2, ECMO group (n = 7). After reperfusion, veno-venous ECMO support was introduced with reduction of mechanical ventilation. In the no ECMO group, four of the animals died within 210 min after reperfusion. In the ECMO group, two of the animals died of severe pulmonary edema. Data of blood gas analyses (PaO2, PaCO2, and SvO2) after reperfusion were significantly better in the ECMO group, whereas there were no significant differences in both shunt fraction and pulmonary vascular resistance index. In this model with severe pulmonary edema induced by warm ischemia, veno-venous ECMO contributed to the improvement of hypoxemia and hypercapnia, but did not improve pulmonary hemodynamics.</p

Intraoperative margin assessment by wireless signals in thoracoscopic anterior (S3) segmentectomy using a radiofrequency identification marker

Despite the use of near-infrared thoracoscopy with intravenous indocyanine green, intraoperative assessment of the surgical margin for the resection of non-palpable tumors located near the intersegmental plane requires highly advanced surgical skill for the prevention of local recurrence. Because the demarcation line is limited to the pleural surface, to overcome uncertainty in tumor palpation for deeply located small-sized lesions, other supplemental localization techniques have been proposed. Here, we present a novel surgical technique using radiofrequency identification markers for intraoperative assessment of the lateral surgical margin in segmentectomy

A Case of Ovarian Strumal Carcinoid. A Histochemical, Immunohistochemical and Ultrastructural Study

A histochemical, immunohistochemical and electron microscopic study was made on a case of ovarian strumal carcinoid arising from a mature cystic teratoma. This tumor formed a solid nodule and was histologically composed of both thyroid tissue and carcinoid tumor. In this nodule, the carcinoid component was predominant and a trabecular pattern was observed with ribbons of identical cells. Carcinoid cells had argyrophilic granules with Grimelius stain, but argyrophilic granules could not be detected in the thyroid tissue. Both components were negative to Masson-Fontana reaction. By immunoperoxidase technique, immunoreactive thyroglobulin was demonstrated within the thyroid follicles and their epithelial cells. Serotonin was positive in some of the carcinoid cells, but negative in the thyroid components. Carcinoembryonic antigen (CEA), calcitonin, cdetoprotein and adrenocorticotropic hormone (ACTH) were all negative in these components. Microfollicles or acinar structures in the intermediate zone from the thyroid tissue to the carcinoid component showed a mixed characteristic, being positive for thyroglobulin and Grimelius stain. Electron microscopically, round and densecored neurosecretory granules could be seen in the cytoplasm of the trabecular part. These findings suggest that strumal carcinoid developed in close association with the teratomatous thyroid tissue in the mature cystic teratoma of the ovary