Yushi Saito

Thymectomy and malignancy

Three hundred ninety patients who underwent thymectomy for myasthenia gravis (MG) were followed up to investigate the development of associated malignancies. There were 102 patients with thymoma and 288 without thymoma. Malignant neoplasms were detected in ten patients, four of whom already had the tumor at the time MG was diagnosed. Thus, malignancy developed after thymectomy in six patients. Malignant fibrous histiocytoma (MFH) developed in three patients, as well as gastric cancer, gastric leiomyosarcoma, rectal cancer, liver cancer, lung cancer, breast cancer, and thymic carcinoid in one patient each. Nine of the ten malignancies developed in the thymoma group, and only one in the non-thymoma group. The predicted number of patients with malignancy was 2.63 in the thymoma group and 2.65 in the non-thymoma group. Our findings suggest that the presence of thymoma facilitates the occurrence of extrathymic malignancy, and that thymectomy never enhances the occurrence of malignancy but possibly inhibits it.

Increased matrix metalloproteinase 9 activity and mRNA expression in lung ischemia-reperfusion injury

OBJECTIVES In lung ischemia-reperfusion injury, neutrophil migration from the vasculature to the interstitial spaces plays a major role in tissue injury. Degradation of the basement membrane, which is composed of extracellular matrix (ECM) molecules, is necessary for neutrophil migration. Matrix metalloproteinases (MMPs) might play a role in ECM degradation in lung ischemia-reperfusion injury. We evaluated the changes in the activity of MMP-2 and MMP-9, and tissue inhibitor of metalloproteinase 1 (TIMP-1) gene expressions using rat lung transplantation models. METHODS We divided animals into 4 groups. Groups I and II served as control groups with intact lungs (Group I) and 24-hour cold-preserved lungs (Group II). Groups III and IV received lung grafts after 24-hour cold preservation. The recipient animals were sacrificed 1 hour (Group III) or 24 hours (Group IV) after transplantation. We evaluated lung injury histologically. We assessed MMP activity using zymography. We assessed MMP-2, MMP-9, and TIMP-1 gene expression using biplex reverse transcriptase-polymerase chain reaction method. RESULTS In Groups III and IV, we noted severe ischemia-reperfusion injury. We noted no significant difference in enzyme activity and gene expression of MMP-2 between Groups I and IV. The MMP-9 activity and gene expression were low during ischemia and increased on reperfusion. TIMP-1 gene expression was low during ischemia and at the early phase of reperfusion, and showed a dramatic increase at the late phase of reperfusion. CONCLUSIONS Matrix metalloproteinase 9, but not MMP-2, may play an important role in ischemia-reperfusion injury. TIMP-1 increases at the late phase of reperfusion and may compensate for the activity of MMP-9.

The spectrum of micronodular thymic epithelial tumours with lymphoid B-cell hyperplasia

The spectrum of micronodular thymic epithelial tumours with lymphoid B‐cell hyperplasia

Histopathologic changes of thymoma preoperatively treated with corticosteroids

Abstract. Preoperative treatment of thymoma in advanced stages with corticosteroids may reduce the size of the tumor, but no precise histologic evaluation has been performed. We examined the histopathologic features of pretreatment biopsy and posttreatment surgical specimens of eleven cases of thymoma with such treatment to see the changes of the histologic subtypes based on Muller–Hermelink classification. All specimens were also assessed immunohistochemically for MIB-1 labeling and apoptotic cells to verify the effectiveness of this pretreatment. Seven tumors clinically diminished in size after the treatment with corticosteroids. Fungal infection occurred in three cases postoperatively. The histology of mixed thymomas (two cases) was converted to that of medullary thymoma. Predominantly cortical thymomas (four cases) and cortical thymomas (three cases) changed to show similar histologic features; both became epithelial-rich thymoma with large polygonal tumor cells having indistinct cell borders. In contrast, two well-differentiated thymic carcinomas showed at surgery more prominent squamoid appearance with distinct cell borders. The apoptotic indices of epithelial cells were increased (P=0.001), and the MIB-1 indices tended to be decreased with corticosteroid treatment. These results suggest that there may be a histogenetic relationship between medullary and mixed thymomas and also between predominantly cortical and cortical thymomas. Corticosteroids may cause degenerative changes in the epithelial cells and lymphocytes and, in thymomas in advanced stages, corticosteroid pretreatment may be warranted, although attention should be paid to infection after surgery.

Adverse events of pulmonary vascular stapling in thoracic surgery

OBJECTIVES The use of staplers for thoracic surgery has been widely accepted and regarded as a safe procedure. However, adverse events (AEs) of stapling are occasionally experienced. The aim of this retrospective study was to analyse the AEs of stapling in pulmonary vascular surgery. METHODS A retrospective multi-institutional review was conducted by the 29 institutions of the Central Japan Lung Cancer Surgery Study Group. All staplings of the pulmonary artery (PA) and vein in thoracic surgery were reviewed during the research period. RESULTS Stapling of the PA and vein was performed 3393 times. The total number of AEs related to stapling was nine (0.27%). Eight events occurred intraoperatively and one occurred immediately after the operation. Intraoperative AE occurred more frequently than postoperative AE. AE in the PA occurred more frequently than in the pulmonary vein. The intraoperative AEs were oozing (n=3), stapling failure (n=2), laceration of the peripheral vasculature at compression (n=2) and technical injury of the vasculature at insertion (n=1). The causes of AEs were reported to be tissue fragility (n=3), stapler rocking during stapling (n=2), stapler-tissue thickness mismatch (n=2) and technical failure (n=1). The only postoperative AE was staple line rupture of the PV stump. No relationship was seen between the incidence of AE and cartridge colours, compression types of staplers or numbers of staple lines. CONCLUSIONS Generally, stapling of the pulmonary vasculatures in recent thoracic surgery has been safe. Furthermore, the knowledge of the possible risks of pulmonary vascular stapling may help to decrease the AEs of stapling.

Elevated plasma thymosin-α1 levels in lung cancer patients

Objective: Prothymosin-a, the precursor of thymosin-a1, may play a role in cell proliferation, and the plasma level of thymosin-a1 may reflect the degree of proliferation of the tumor cells. Methods: Recently, a new sandwich immunoradiometric assay for thymosin-a1 was developed using monoclonal and polyclonal antibodies. In this investigation, we used this assay to measure plasma and tissue level of thymosin-a1 in 131 lung cancer patients. Results: We found that the mean plasma thymosin-a1 levels in lung cancer patients were higher than in normal individuals (PB 0.001). However, half of the patients showed normal levels. Thymosin-a1 levels correlated neither with the stage nor pathological subtype of the lung cancer, and did not decrease significantly in the 4 weeks after the resection of the tumor. Thymosin-a1 levels of lung cancer patients with another cancer were higher than those without evidence of other cancers (P0.03). Survival of patients with normal levels of plasma thymosin-a1 was significantly better than that with higher levels (P0.04). Conclusions: The plasma level of thymosin-a1 may be used as a marker for the prognosis of lung cancer patients. Further investigations are warranted to determine its role in the lung cancer.

Left diaphragmatic hernia complicated by perforation of an intrathoracic gastric ulcer into the aorta: report of a case.

Abstract: We describe herein a rare but fatal complication of diaphragmatic hernia that occurred in a 51-year-old man 3 years after his diaphragm had been repaired by a polytetrafluoroethylene sheet following resection during pleuropneumonectomy for a left pleural mesothelioma. He was admitted to our hospital in shock status, and was found to have massive bleeding from the nasogastric tube. An emergency operation revealed that an ulcer of the stomach, which had been displaced into the left thorax, had perforated directly into the descending aorta.

PE-35-related antigen expression and CD1a-positive lymphocytes in thymoma subtypes based on Müller-Hermelink classification. An immunohistochemical study using catalyzed signal amplification.

Abstract PE-35 monoclonal antibody, detecting a cell-surface antigen of various types of carcinoma and normal epithelium, reacts exclusively with the medullary epithelium in the thymus; therefore, the antigen has been considered as a marker of medullary differentiation in thymomas. Using the catalyzed signal amplification method, which made it possible to apply PE-35 to routinely processed, archival tissues, we examined expression of this antigen, together with CD1a reactivity of lymphocytes, in 40 thymic epithelial tumors subclassified using the Mü1ler-Hermelink system. Medullary thymomas infiltrated with a small number of CD1a-negative lymphocytes were PE-35 positive, although many of the long spindle tumor cells were PE-35 negative. Mixed thymomas and predominantly cortical thymomas, both with prominent CD1a-positive lymphocytes, were also PE-35 positive, although some areas of the latter type were PE-35 negative. Cortical thymomas with decreased numbers of CD1a-positive lymphocytes were largely PE-35 negative. In well-differentiated thymic carcinomas with a few CD1a-positive lymphocytes, two cases were negative, but four cases were at least focally positive with PE-35. All high-grade thymic carcinomas infiltrated with some CD1a-negative lymphocytes were PE-35 positive. These results suggested that medullary thymoma generally possesses the medullary nature, although the latter tends to be lost in the long spindle tumor cells. Mixed and predominantly cortical thymomas may have mixed medullary phenotype and cortical function. Cortical thymoma and many well-differentiated thymic carcinomas may possess the cortical nature, while the large polygonal tumor cells tend to lose immature T-lymphocyte-retaining function.

Evaluation of new TNM lung cancer classification

OBJECTIVE A new staging system for lung cancer was proposed by the Union Internationale Contre le Cancer in 1997, with Stages I and II subdivided and T3N0M0 assigned as stage IIB. We studied the usefulness of this new classification. METHODS Subjects were 753 patients with non-small-cell lung cancer undergoing pulmonary resection and follow-up data were retrospectively reviewed. RESULTS A significant difference was seen between stage IA and IB survival--70.4% vs 52%. No significant difference was seen between survival for T3N0M0, T1N1M0 and T2N1M0--35.3%, 42.3%, and 43.8%--at 5 years. We found, however, that the prognosis for T3N2M0 tumors--6.5% 5-year survival--is too poor to be grouped with other N2 diseases having a better prognosis--23.9% 5-year survival. Significant differences were also seen in the survival of T3N0 or T3N1 patients by organ and diseases involving the rib, diaphragm, or mediastinum may be classified as T4. CONCLUSION The new staging system predicts patient outcome fairly well and the modification is well grounded. It appears, however, to be appropriate to subdivide T3 tumors by invaded organs and T3N2M0 disease may be better classified as stage IIIB. The classification of pulmonary metastasis appears to require further improvement.

A comparative study of PD-L1 immunohistochemical assays with four reliable antibodies in thymic carcinoma

Currently, four immunohistochemical assays are registered with the US Food and Drug Administration to detect the expression of PD-L1. We investigated the PD-L1 expression in thymic carcinomas using these four diagnostic assays. The cases of 53 patients were reviewed and their specimens were subjected to four PD-L1 assays with different antibodies (SP142, SP263, 22C3, and 28-8). The PD-L1 expression in tumor cells (TCs) and immune cells (ICs) was evaluated. In TCs, the four assays showed similar scores in each case. Histopathologically, high TC scores were observed in squamous cell carcinomas (SqCCs). Meanwhile, there were no significant relationships among the IC scores in the four assays. In SqCCs, the high expression of PD-L1 (defined as ≥50% TC score) in TCs tended to be associated with early stage cancer. The patients with high expression levels of PD-L1 tended to show longer overall survival in the 22C3 assays (p=0.0200). In thymic carcinomas, the staining pattern showed high concordance among the four assays when TCs – rather than ICs – were stained. High PD-L1 positivity in TCs, especially in SqCCs, indicated that PD-1/PD-L1 targeted therapy may be a promising therapeutic approach.