Masanori Tsuchida

Early results of a prospective study of limited resection for bronchioloalveolar adenocarcinoma of the lung.

BACKGROUND We reported that bronchioloalveolar adenocarcinoma (BAC) without active fibroblastic proliferation of the lung had no lymph node and pulmonary metastasis and had a favorable prognosis. However, there has been no prospective trial regarding limited pulmonary resection for this type of BAC. The purpose of this study is to confirm the effectiveness of limited resection for histologically confirmed BAC without active fibroblastic proliferation. METHODS From 1996 through 1999, 42 patients who had small peripheral lung tumors (< or = 20 mm), suspected of being BAC, were enrolled in this trial. The patient population consisted of 24 men and 18 women with a mean age of 58.4 years. Limited resection was completed when BAC, without both active fibroblastic proliferation and lymph node metastasis, was confirmed histologically by intraoperative pathologic examination. RESULTS Limited resection was completed in 36 patients, wedge resection in 34, and segmentectomy in 2 patients. In 6 patients, the procedure was converted into lobectomy because of pathologic invasive sign in 3, active fibroblastic proliferation in 1, and for other reasons in 2 patients. All patients have been followed for a median follow-up period of 30 months and are alive without sign of recurrence. CONCLUSIONS Our early results indicate that limited resection may be an acceptable alternative to lobectomy for histologically confirmed BAC without active fibroblastic proliferation.

Pulmonary complications after surgical treatment of lung cancer in octogenarians

OBJECTIVE The purpose of this study was to analyze the risks associated with pulmonary resection for primary non-small cell lung cancer in octogenarians to help better management in these patients. METHODS We reviewed the outcome in our 35 patients aged 80 years and older who underwent pulmonary resection between 1981 and 1998. RESULTS The 5-year survival rate was 39.8%. The operative mortality rate was 0% and the morbidity 60%. There were ten major pulmonary complications, including respiratory insufficiency following bacterial pneumonia and sputum retention. Preoperative arterial pO(2) was significantly lower, A-aDO(2) was significantly higher, and operation time were significantly longer in patients with pulmonary complications after surgical treatment than in patients without complications (P<0.05). CONCLUSIONS Surgical treatment was not contraindicated for octogenarians with lung cancer. However, a relatively preoperative low arterial pO(2), high A-aDO(2), and long operation time may be risk factors for postoperative pulmonary complications in such patients. Surgeons must assess the preoperative data prudently to determine appropriate surgical strategy.

Risk factor analysis of locoregional recurrence after sublobar resection in patients with clinical stage IA non-small cell lung cancer.

OBJECTIVE Although lobectomy is the standard surgical procedure for operable non-small cell lung cancer (NSCLC), sublobar resection also has been undertaken for various reasons. The aim of this study was to identify risk factors of locoregional recurrence and poor disease-specific survival in patients with clinical stage IA NSCLC undergoing sublobar resection. METHODS We retrospectively reviewed 328 patients with clinical stage IA NSCLC who underwent segmentectomy or wedge resection. Demographic, clinical, and pathologic factors were analyzed using the log-rank test as univariate analyses, and all factors were entered into a Cox proportional hazards regression model for multivariate analyses to identify independent predictors of locoregional recurrence and poor disease-specific survival. RESULTS The 5- and 10-year locoregional recurrence-free probabilities were 84.8% and 83.6%, respectively, and the 5- and 10-year disease-specific survivals were 83.6% and 73.6%, respectively. Four independent predictors of locoregional recurrence were identified: wedge resection (hazard ratio [HR], 5.787), microscopic positive surgical margin (HR, 3.888), visceral pleural invasion (HR, 2.272), and lymphatic permeation (HR, 3.824). Independent predictors of poor disease-specific survival were identified as follows: smoking status (Brinkman Index; HR, 1.001), wedge resection (HR, 3.183), microscopic positive surgical margin (HR, 3.211), visceral pleural invasion (HR, 2.553), and lymphatic permeation (HR, 3.223). All 4 predictors of locoregional recurrence also were identified as independent predictors of poor disease-specific survival. CONCLUSIONS Segmentectomy should be the surgical procedure of first choice in patients with clinical stage IA NSCLC who are being considered for sublobar resection. Patients having tumors presenting with no suspicious of pleural involvement would be suitable candidates for sublobar resection.

Efficacy and safety of extended thymectomy for elderly patients with myasthenia gravis

BACKGROUND The number of elderly patients who are diagnosed as myasthenia gravis (MG) is increasing in Japan. Although several factors affecting thymectomy have been well documented, few studies have focused on the efficacy and safety of thymectomy for elderly patients older than 60 years. METHODS We evaluated 94 patients with MG who underwent extended thymectomy, and divided them into two groups: patients younger than 59 years and patients older than 60 years. Preoperative patient data, pathology of the thymus, complications, and clinical outcome were evaluated. RESULTS In 69 young patients and 25 elderly patients, we observed no significant differences between the two groups with regard to preoperative data. Thymic hyperplasia was present in 45% of the young group and 16% of the elderly group. Remission and improvement rate were 40% and 57% in the young group and 8% and 75% in the elderly group, respectively. There were no serious complications, except one early death due to gastrointestinal bleeding in the elderly group. CONCLUSIONS We conclude that thymectomy is a safe and effective alternative for elderly patients with MG.

Surgical strategy for clinical stage I non-small cell lung cancer in octogenarians

OBJECTIVE The purpose of this study was to determine whether lobectomy without radical systematic mediastinal lymphadenectomy (LA) is a satisfactory alternative surgical treatment for octogenarians with clinical stage I non-small cell lung cancer (NSCLC). METHODS From April 1985 through December 2001, 49 patients aged 80 years and older who underwent surgical treatment for clinical stage I NSCLC were reviewed. Lobectomy without radical systematic mediastinal LA was performed for 27 patients (LA0 group) and lobectomy with radical systematic mediastinal LA was performed for 22 patients (LA group). RESULTS The mortality rate was 0% in the LA0 group and 4.5% in the LA group. Five-year survival rate according to the type of surgery was 44.8% in the LA0 group and 55.5% in the LA group, a difference that was not significant (P=0.88). Although there was no significant statistical difference, postoperative pulmonary complication was more frequent in the LA group than in the LA0 group (32% in the LA group versus 11% in the LA0 group P=0.07). Five-year survival rates according to serum carcinoembryonic antigen (CEA) levels were 0% for patients with elevated CEA levels (n=9) and 56.5% for patients with normal CEA levels (n=40) (P<0.01). CONCLUSION Lobectomy without radical systematic mediastinal LA appears to be a satisfactory surgical procedure for octogenarians with clinical stage I NSCLC. However, mediastinoscopy is necessary in such octogenarians if their serum CEA level is elevated so that the precise clinical stage can be determined and an accurate prognosis can be given.

Delaying transplantation after total body irradiation is a simple and effective way to reduce acute graft-versus-host disease mortality after major H2 incompatible transplantation.

BACKGROUND We have previously reported that delaying histoincompatible transplantation after total body irradiation (TBI) conditioning markedly decreased the mortality of acute graft-versus-host disease (GVHD) in severe combined immunodeficiency mice. However, it was not clear whether the delayed transplantation would affect the final engraftment and acute GVHD mortality in normal hosts. METHODS BALB/c mice (H2d) were lethally irradiated with 8.5 Gy TBI and transplanted with C57BL/6 (H2d) bone marrow plus spleen cells on the same day (TBI+day 0) or 4 days after TBI conditioning (TBI+day 4). RESULTS We again demonstrated that delaying transplantation by 4 days after TBI conditioning markedly reduced acute GVHD mortality in normal hosts after major histoincompatible transplantation. The survival rates were 66% in TBI+day 4 vs. 0% in TBI+day 0 allogeneic transplanted animals by day +60 (P<0.001). Further analysis demonstrated that the 4-day rest between the TBI and allogeneic transplantation broke the interaction of cell/inflammatory tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-6 cytokine reactions stimulated by TBI and incompatible transplantation. Flow cytometry revealed 97% donor cells in host marrow by 2 weeks in TBI+day 0 transplantation versus 57% in TBI+day 4 transplantation. There was no difference in percentage of donor CD3+ T-cell engraftment between the TBI+day 0 and TBI+day 4 allogeneic transplanted animals. In TBI+day 4 transplantation, the percentage of donor cells in host marrow steadily increased to 74% by day +60 and 93% by day +100. CONCLUSIONS This 2- to 3-month early mixed chimerism in TBI+day 4 transplanted animals might be related to lower levels of tumor necrosis factor-alpha and IL-6 both of which have been shown to stimulate lymphohematopoiesis and was associated with lower acute GVHD mortality. The data again demonstrated in immunologically normal BALB/c mice that delaying allogeneic transplantation after TBI is a simple and effective way to reduce acute GVHD mortality, achieve satisfactory engraftment and significantly increase overall survival.

Masaoka Stage and Histologic Grade Predict Prognosis in Patients With Thymic Carcinoma

BACKGROUND Thymic carcinoma is a rare tumor. Limited data are available regarding the effectiveness of treatment and the prognosis of thymic carcinoma. The present study aimed to clarify the prognostic factors in patients who underwent resection. METHODS The study retrospectively reviewed 21 patients (15 men, 6 women) with thymic carcinoma who had undergone resection at Niigata University Hospital. RESULTS Masaoka stage was II in 4 patients, III in 9, IVa in 2, and IVb in 6. Histologic subtypes were squamous cell carcinoma in 14 patients, adenocarcinoma in 2, atypical carcinoid in 3, and undifferentiated carcinoma in 2. Histologic grade by degree of differentiation was low in 4 tumors, intermediate in 12, and high in 5. Treatment comprised resection alone in 6 patients and resection along with multimodal therapies in 15. Complete resection was achieved in 14 (67%). Eight patients died of tumor. Recurrence was documented in 7 of 14 patients with complete resection, and 5 received additional treatment. The overall 5-year survival rate was 61.1%, and the disease-free 5-year survival rate was 66.8% for the 14 with complete resection. By multivariate analysis, Masaoka stage and histologic grade were significant independent prognostic factors for overall survival. CONCLUSIONS The surgical outcome of patients with thymic carcinoma depends on the Masaoka stage and histologic grade. Patients with early Masaoka stage and low or intermediate histologic grade had favorable prognoses.

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.

Thoracoscopic stapled bullectomy supported by suturing

In 1985, a thoracoscopic technique for closing bullae with hemostatic clips was developed. However, the method was limited, and therefore clinical application was small. A linear endoscopic stapler (Endo-GIA) was developed in 1990. The advent of the Endo-GIA nearly made thoracoscopic treatment of spontaneous pneumothorax practicable, and ended the use of clipping. In addition, a new operative technique was developed, the 3-cm minithoracotomy bullectomy for the treatment of spontaneous pneumothorax. This technique has now become obsolete. The current method is that of a thoracoscopic stapled bullectomy using the Endo-GIA, supported by suturing. The recurrence rate was 2.7% (1/37) using this method. The one recurrence occurred in a case where no bullae were observed during the operation. Our findings suggest that thoracoscopic stapled bullectomy supported by suturing is a practicable treatment of spontaneous pneumothorax. An economical use of the endoscopic stapler and complementary suturing may be less expensive than using a laser. Pleurodesis should be performed in the patients in whom no distinct bullae are discovered thoracoscopically.