Hisami Yamakawa

Diagnostic Usefulness of p16/CDKN2A FISH in Distinguishing Between Sarcomatoid Mesothelioma and Fibrous Pleuritis

The distinction between sarcomatoid mesothelioma and fibrous pleuritis is difficult based on histology, especially when the amount of tumor tissue examined via biopsy is small and immunohistochemical examination is inconclusive. We studied the usefulness of deletion of p16 with fluorescence in situ hybridization (FISH) and p16 hypermethylation with polymerase chain reaction for the diagnosis and prognosis of malignant pleural mesothelioma (MPM). We analyzed 50 MPMs, including 22 sarcomatoid mesothelioma cases and 10 fibrous pleuritis cases. We set the cutoff value of homozygous deletion pattern as 14.4% based on FISH signaling patterns using samples of fibrous pleuritis. The percentage of homozygous deletion pattern was higher than 14.4% in 55.6% of the epithelioid mesotheliomas (10/18) and in all of the sarcomatoid mesotheliomas (22/22). Methylation of p16 was observed in 7 (20.6%) of 34 informative cases. p16 FISH analysis can be a reliable test for distinguishing between sarcomatoid mesothelioma and fibrous pleuritis and a prognostic factor for MPM.

Prognostic implication of Ki-67 immunostaining in treating subclinical pleural cancer found at thoracotomy in lung cancer patients

BACKGROUND Therapeutic principles for managing subclinical pleural cancer found unexpectedly during intraoperative examination are unclear. We analyzed prognostic factors including the tumor proliferative marker Ki-67 in these circumstances. METHODS The cases of 65 surgically treated patients with lung cancer and subclinical T4 pleural cancer, microscopic in 25 and macroscopic in 40, were reviewed. RESULTS The overall 5-year survival rate of patients undergoing lobectomy was 14.3%. For patients with T4 NO disease, the 5-year survival rate was 46.7%. In patients with a low Ki-67 labeling index, the 5-year survival rate was 28.6%. The Ki-67 labeling index was a significant (p < 0.05) indicator of survival. Multivariate analysis demonstrated Ki-67 labeling index, lymph node involvement, and tumor differentiation to be the most influential prognostic factors for postoperative survival (p < 0.01). CONCLUSIONS In the treatment of lung cancer patients with subclinical pleural cancer found at thoracotomy, tumor resection is not necessarily contraindicated. Resection appears to be beneficial in patients with no nodal involvement or a low tumor Ki-67 labeling index. This index is a good therapeutic indicator for lung cancer patients.

Rupture of the descending thoracic aorta caused by blunt chest trauma: report of a case.

A 66-year-old man fell from a tree and was diagnosed to have multiple fractured ribs and hemopneumothorax based upon the chest roentogenogram findings. He underwent chest tube drainage and evacuation using video-assisted thoracic surgery. One week after the operation, he exhibited recurrent hemothorax. He underwent a thoracotomy, and the hemothorax was found to be due to a penetration of the lower descending thoracic aorta by a fractured rib. We performed a direct closure of the penetrated portion of the descending thoracic aorta. The patient has remained well for 1 year following the second operation.

Diffuse malignant pleural mesothelioma: A multi-institutional clinicopathological study

PurposeThe relative rarity of malignant pleural mesothelioma (MPM) in Japan makes it difficult to perform a large-scale clinicopathological study of this tumor at a single institute. Thus, we performed a multiinstitutional study to evaluate the current status of diagnosis and treatment in Japan.MethodsWe analyzed the records of 65 patients with MPM, obtained from the 13 institutions comprising the Japanese Chiba Multicenter Study Group.ResultsIn 56 patients, the tumor was detected after a visit to a medical facility for subjective symptoms such as chest pain, shortness of breath, and cough. It took a median period of 2 months from the initial visit to establish the diagnosis. The overall survival rates of 33 patients with unresectable MPM 1, 2, and 3 years after the diagnosis were 40.5%, 10.8%, and 0%, respectively, whereas those of 32 patients who underwent surgery were 67.9%, 35.0% and 10.9%, respectively (P = 0.0035). According to multivariate analysis, histological type, International Mesothelioma Interest Group clinical stage, sex, and the presenting symptom of shortness of breath were significant prognostic factors.ConclusionsThe definitive diagnosis of early MPM is difficult, but establishing the best diagnostic modality would improve survival rates, since radical surgery is likely to be effective for resectable disease.

Usefulness of p16/CDKN2A fluorescence in situ hybridization and BAP1 immunohistochemistry for the diagnosis of biphasic mesothelioma ☆

Malignant mesothelioma is a highly aggressive neoplasm, and the histologic subtype is one of the most reliable prognostic factors. Some biphasic mesotheliomas are difficult to distinguish from epithelioid mesotheliomas with atypical fibrous stroma. The aim of this study was to analyze p16/CDKN2A deletions in mesotheliomas by fluorescence in situ hybridization (FISH) and BAP1 immunohistochemistry to evaluate their potential role in the diagnosis of biphasic mesothelioma. We collected 38 cases of pleural mesotheliomas. The results of this study clearly distinguished 29 cases of biphasic mesothelioma from 9 cases of epithelioid mesothelioma. The proportion of biphasic mesotheliomas with homozygous deletions of p16/CDKN2A in total was 96.6% (28/29). Homozygous deletion of p16/CDKN2A was observed in 18 (94.7%) of 19 biphasic mesotheliomas with 100% concordance of the p16/CDKN2A deletion status between the epithelioid and sarcomatoid components in each case. Homozygous deletion of the p16/CDKN2A was observed in 7 (77.8%) of 9 epithelioid mesotheliomas but not in fibrous stroma. BAP1 loss was observed in 5 (38.5%) of 13 biphasic mesotheliomas and in both epithelioid and sarcomatoid components. BAP1 loss was observed in 5 (62.5%) of 8 epithelioid mesotheliomas but not in fibrous stroma. Homozygous deletion of p16/CDKN2A is common in biphasic mesotheliomas, and the analysis of only one component of mesothelioma is sufficient to show that the tumor is malignant. However, compared with histology alone, FISH analysis of the p16/CDKN2A status and BAP1 immunohistochemistry in the spindled mesothelium provide a more objective means to differentiate between biphasic mesothelioma and epithelioid mesothelioma with atypical stromal cells.

Successfully treated postbronchoplasty bronchial stenosis using short-interval repeated endobronchial balloon dilation

A 63-year-old man with a history of lung cancer underwent lobectomy of the right upper lobe and bronchoplasty. At the 2-month follow-up, bronchial stenosis due to a granuloma was observed. Endoscopic débridement and balloon dilation were performed. At 1 month after the dilation, atelectasis occurred owing to cicatricial stenosis. We repeated balloon dilation, but the patient suffered from cicatricial restenosis. After a failed stent placement, balloon dilation was then performed every 2 weeks under local anesthesia; the stenosis was resolved after performing dilation 7 times. Short-term repeated balloon dilation was effective in this case.

Factors influencing survival after endoscopic Nd:YAG laser surgery for unresectable advanced malignancies of the trachea

The effects of endoscopic Nd:YAG laser surgery were studied in 36 patients with unresectable advanced primary and metastatic malignancies in the trachea with special reference to the factors influencing long-term survival. Overall effectiveness of YAG laser treatment was demonstrated in 34 of the 36 patients (94 per cent), while the overall 1, 3 and 5 year survival rates after the first laser treatment were 25 per cent, 13 per cent and 13 per cent, respectively. Neither histologic type nor the severity of clinical symptoms before laser treatment showed any significant influence on the survival curves, however, endoscopic findings of stenosis, the effect of laser treatment and irradiated longitudinal length were all significantly correlated with the survival curves. In other words, endoscopically protruding type tumors with a longitudinal length of irradiation of 3.0 cm or less, and good responses not only to laser treatment but also to other combined modalities are favorable factors for achieving long-term survival in patients with tracheobronchial malignancies undergoing endoscopic Nd:YAG laser treatment. Endoscopic Nd:YAG laser surgery is considered to be a promising part of the multi-modality treatment for unresectable advanced primary and metastatic malignancies of the trachea.

Completion pneumonectomy after fenestration for empyema due to nontuberculous mycobacteriosis associated with destroyed lung as a result of cancer surgery

Long-term follow-up of post-operative lung cancer patients indicates that some patients develop lung complications. Destroyed lung cannot be ignored because it predisposes the patient to recurrent infection. We report a case of thoracic empyema with bronchopleural fistula that developed in lung tissue damaged due to cancer surgery and associated with an infection of Mycobacterium gordonae (M. gordonae); a class of bacterium responsible for nontuberculous mycobacterial infection. The patients cancer did not recur after surgery and followed a typical course that began with sub-pleural cystitis followed by repeated infection. We performed fenestration because the patient developed fistulous empyema and the infection became difficult to control using antibiotics. The patient then underwent a radical pleuropneumonectomy and his postoperative course was excellent. Thus, in cases of impaired lung function due to cancer surgery and where pharmacologic control of infection is challenging, we suggest that radical surgical intervention should be considered.

Cavernostomy for Pulmonary Aspergillosis Associated with Destroyed Lung after Surgery for Lung Cancer: Report of 3 Cases

Slow, progressive, and destructive changes in the residual lung after surgery for lung cancer, known as “destroyed lung,” are delayed nonrecurrent complications. Destroyed lung can be a difficult condition to treat due to repeated infections and is therefore a complication that should not be ignored. We had three cases of intractable pulmonary aspergillosis difficult to treat associated with destroyed lung, after lung cancer surgery. Two of these patients followed a characteristic clinical course, which started with a cystic change just below the pleura and subsequently led to respiratory failure and death due to repeated infections. The third patient followed a similar clinical course and is currently under regular follow-up. Our cases suggest that concomitant occurrence of severe complications following surgery for lung cancer, such as destroyed lung and pulmonary aspergillosis, should be monitored because these complications can lead to respiratory failure and fatal clinical course. Radical surgery is not possible, especially when medical treatment is ineffective in controlling repeated infections and the patients general condition is worsened due to prolonged chronic inflammation. Therefore, aggressive surgical intervention should be considered before patients worsen.

Pyothorax-Associated Lymphoma Diagnosed by Preoperative Pleural Effusion Aspiration Cytology: A Case Report

BACKGROUND Pyothorax-associated lymphoma (PAL) is a comparatively rare tumor, and it is difficult to definitively diagnose it preoperatively, especially in patients with only pleural thickening without mass formation. Pleural effusion aspiration cytology is a useful and easy diagnostic method for a large number of chest diseases. However, the cytologic findings of PAL have been rarely described. Here we report on the cytologic findings in a patient with PAL, manifested by pleural thickening without mass formation, and which was diagnosed preoperatively by pleural effusion aspiration cytology. CASE A 64-year-old man was admitted to our hospital because of pleural thickening involving an empyema sac located in the left thorax and rapidly increasing pleural effusion. He had a 30-year history of chronic empyema and a 10-year history of diabetes mellitus. Left pleural effusion aspiration cytology showed malignant lymphoma. The patient was admitted to our hospital for PAL treatment. Because of poor respiratory function, he only underwent decortication with complete resection of the thickening pleural peel. However, he was well, without recurrence, 5 years after the operation. The histologic examination revealed that lymphoma cells were located only in the thickening pleural peel. CONCLUSION This is a very rare case of PAL diagnosed by preoperative aspiration cytology for an increasing pleural effusion. This report demonstrates that pleural effusion aspiration cytology can be valuable for the diagnosis of PAL.