Tsuyoshi Shoji

Clinical Significance of p21 Expression in Non–Small-Cell Lung Cancer

PURPOSE The clinical significance of p21 expression remains unclear, whereas many experimental studies have demonstrated that p21, the product of the WAF1/CIP1/SDI1 gene, plays an important role in regulation of the cell cycle as an inhibitor of cyclin-dependent kinases. The purpose of this study was to clarify the clinical significance in resected non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS A total of 233 consecutive patients with completely resected pathologic stage I to IIIA NSCLC were retrospectively reviewed. Expression of p21 and the status of p53 were examined immunohistochemically. Proliferative activity was also evaluated immunohistochemically. The incidence of apoptotic cell death was evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling staining. RESULTS Expression of p21 was positive in 120 patients (51.5%). The 5-year survival rate of p21-positive patients was 73.8%, significantly higher than that of p21-negative patients (60.7%; P =.006). Aberrant expression of p53 was positive in 98 patients (42.1%). When combined with p53 status, the prognostic value of p21 status was enhanced: the 5-year survival rate of p21-positive and p53-negative patients was 80.7%, markedly higher than that of p21-negative and p53-positive patients (50.0% for both; P =.001). Multivariate analysis confirmed that positive expression of p21 was a significant factor for predicting a favorable prognosis. There was no significant correlation between p21 expression and p53 status, proliferative activity, or incidence of apoptosis. CONCLUSION p21 expression was shown to be an independent prognostic factor in NSCLC.

Comparison of pulmonary function test and computed tomography volumetry in living lung donors.

BACKGROUND We previously proposed calculating forced vital capacity (FVC) by the number of segments for size matching in living-donor lobar lung transplantation (LDLLT). The primary purpose of this study was to compare spirometry-obtained calculations of lower lobe volumes with three-dimensional (3D) computed tomography (CT) volumetric images. Our second goal was to compare the data of pulmonary function tests with CT volumetry in living lung donors. METHODS Pulmonary function test, including FVC and total lung capacity (TLC), and 3D CT volumetry were performed pre-operatively in 21 healthy donor candidates for LDLLT. The relationship of 3D CT volumetric data and calculated volume of lower lobes by the number of segments was investigated. Also studied were 3D CT volumetric data in relation to FVC and TLC. Various pre-operative variables were analyzed retrospectively. RESULTS According to 3D CT volumetry, the right and left lower lobe volume was 26.3% ± 2.9% and 22.6% ± 3.1% of the total lung volume, respectively. We found a significant, strong correlation between each lower lobe volume and the total lung volume. Because the calculated volumes of right and left lower lobes by the number of segments were 26.3% and 21.1%, respectively, our results implied that the volume of both lower lobes was accurately described by the number of segments. FVC was significantly associated with TLC and the total lung volume. CONCLUSIONS We confirmed that it would be justified to estimate graft FVC by the number of segments according to the CT volumetric data in LDLLT.

Prognostic factors in patients with resected pathologic (p-) T1-2N1M0 non-small cell lung cancer (NSCLC)

OBJECTIVES To clarify prognostic factors in resected pathologic (p-) T1-2N1M0 non-small cell lung cancer (NSCLC). METHODS A total of 95 consecutive patients who underwent complete tumor resection and mediastinal dissection for pT1-2N1M0 NSCLC between 1976 and 1997 were retrospectively reviewed. p53 status and proliferative activity were evaluated immunohistochemically. RESULTS The extent of N1 stations and p53 status proved to be significant prognostic factors. The 5-year survival rate for tumor without hilar node (#10) involvement was 66%, significantly higher than that for tumor with #10 involvement (39%, P<0.01). The 5-year survival rate for tumor with aberrant p53 expression was 37%, significantly lower than that for tumor without aberrant p53 expression (74%, P<0.01). There proved to be no significant difference in the prognosis between pT1 disease and pT2 disease; the 5-year survival rates for pT1 and pT2 diseases were 62 and 56%, respectively. Age, gender, performance status, grade of tumor differentiation, histological type, or proliferative activity were not significant factors. Multivariate analysis of prognostic factors using Coxs proportional hazard model confirmed these results. CONCLUSIONS Involvement of the hilar node and aberrant p53 expression were significant factors to predict a worse prognosis in resected T1-2N1M0 NSCLC.

Clinical features of surgical resection for pulmonary metastasis from breast cancer

BACKGROUND AND OBJECTIVES Metastatic breast cancer has been defined as a systemic disease. The discussion concerning the resection of lung metastases in patients with breast cancer is controversial. To confirm the role of resection of pulmonary metastases from breast cancer and to identify possible prognostic factors, we reviewed our institutional experience. METHODS Between 1991 and 2007, 41 patients with pulmonary metastases from breast cancers underwent complete pulmonary resection. All patients had obtained or had obtainable locoregional control of their primary tumors. Various perioperative variables were investigated retrospectively to confirm the role of metastasectomy and to analyze prognostic factors for overall survival after metastasectomy. RESULTS All patients were female with a median age of 55 years (range, 35-81 years). The overall survival rate after metastasectomy was 51% at 5 and 10 years. On multivariate analysis, fewer than four pulmonary metastases and a disease-free interval of more than 3 years were significantly favorable prognostic factors for overall survival (p=0.023 and 0.024, respectively). CONCLUSIONS The current practice of pulmonary metastasectomy for breast cancers in our institution was well justified. Pulmonary metastasectomy in patients with previous breast cancer might be justified when fewer than four pulmonary metastases or a disease-free interval of more than 3 years.

Less Maintenance Immunosuppression in Lung Transplantation Following Hematopoietic Stem Cell Transplantation From the Same Living Donor

Living‐donor lobar lung transplantation (LDLLT) is one of the final options for saving patients with pulmonary complications after hematopoietic stem cell transplantation (HSCT). We retrospectively investigated 19 patients who had undergone LDLLT after HSCT in Japan. Eight patients underwent LDLLT after HSCT in which one of the donors was the same living donor as in HSCT (SD group), while 11 received LDLLT from relatives who were not the HSCT donors (non‐SD group). In the SD group, three patients underwent single LDLLT. The 5‐year survival rate was 100% and 58% in the SD and non‐SD groups, respectively. In the SD group, postoperative immunosuppression was significantly lower than in the non‐SD group. Two patients died of infection and one died of post‐transplant lymphoproliferative disease (PTLD) in the non‐SD group, while only one patient died of PTLD 7 years after LDLLT in the SD group. Hematologic malignancy relapsed in two patients in the non‐SD group. For the three single LDLLTs in the SD group, immunosuppression was carefully tapered. In our study, LDLLT involving the same donor as for HSCT appeared to have advantages related to lower immunosuppression compared to LDLLT from relatives who were not the HSCT donors.

Significance of tumor recurrence before pulmonary metastasis in pulmonary metastasectomy for soft tissue sarcoma.

BACKGROUND Resection for pulmonary metastasis from soft tissue sarcomas is an accepted method for treatment, but it is still debatable which patients will benefit from surgical intervention. To find an entity of patients benefiting from pulmonary metastasectomy, we reviewed our institutional experience. METHODS Between 1990 and 2007, 23 patients with pulmonary metastases from soft tissue sarcomas underwent complete pulmonary resection. All patients had obtained locoregional control of their primary tumors. Various perioperative variables were investigated retrospectively to confirm the role of pulmonary metastasectomy and to identify possible prognostic factors for survival after metastasectomy. RESULTS Overall survival rate after metastasectomy was 43% and 29% at 5 and 10 years, respectively. Disease-free survival rate was 9% at 1 year after pulmonary resection. On multivariate analysis, no tumor recurrence (neither locoregional recurrence nor extrapulmonary metastasis) before pulmonary metastasis provided a significantly favorable overall survival (P=0.038). In addition, repeat metastasectomy for recurrent pulmonary metastasis also provided a favorable overall survival (P=0.041). CONCLUSIONS Our data suggested that patients most likely to benefit from pulmonary metastasectomy for soft tissue sarcoma have no tumor recurrence before pulmonary metastasis. Furthermore, patients with repeat metastasectomy for recurrent pulmonary metastasis also presented a significantly longer survival.

Pulmonary resection for metastasis from renal cell carcinoma

The treatment of metastatic renal cell carcinoma still represents a widely debated issue due to the introduction of several immunotherapies. To confirm again a role for resection of pulmonary metastases for such tumors, we reviewed our institutional experience. Between 1992 and 2007, eight patients with pulmonary metastases from renal cell carcinoma underwent complete pulmonary resection. All patients had undergone curative resection of their primary renal cell carcinomas and also had obtained or had obtainable locoregional control of their primaries. Various perioperative variables were investigated retrospectively. Disease-free interval varied from 25 to 156 months, with a median of 73 months. In three patients, lung metastases were found to be unilateral and solitary. Four patients presented two metastases in the unilateral lungs. One patient showed five metastases in the bilateral lungs. Six patients underwent wedge resection or segmentectomy, while two patients underwent more than lobectomy. Five patients showed recurrence after pulmonary metastasectomy. Five-year and 10-year overall survival rate was 83.3% and 41.7%, respectively, while 3-year and 5-year disease-free survival rate was 35.0% and 17.5%, respectively. Our study suggested that pulmonary metastasectomy for renal cell carcinoma might be well justified.

Outcomes and pulmonary function in living lobar lung transplant donors.

Successful living‐donor lobar lung transplantation (LDLLT) largely depends on donor outcome; however, there are few studies that have assessed outcomes of LDLLT donors, particularly pulmonary function. We investigated the outcomes and pulmonary function after donor lobectomy in LDLLT donors. Retrospective evaluation of consecutive 33 LDLLT donors was performed. Preoperative characteristics and perioperative and postoperative variables were investigated. Evaluation of pulmonary function 3, 6 and 12 months after donor lobectomy was performed prospectively. All donors were well alive after donor lobectomies. Morbidity was found in five donors (15%). Postoperative complications consisted of re‐accumulation of pleural effusion requiring readmission in three donors and prolonged air leakage in two donors. Sacrifice of pulmonary arteries was performed in 20 donors (61%) with 1.4 ± 0.6 branches. Forced vital capacity was 77.8 ± 6.1%, 84.8 ± 6.0% and 89.4 ± 6.6% of the preoperative value 3, 6 and 12 months after donor lobectomy, respectively. Forced expiratory volume in 1 s was 80.5 ± 7.8%, 85.6 ± 8.9% and 89.3 ± 8.7% of the preoperative value 3, 6, and 12 months postoperatively. Living‐donor lobectomy was performed with low morbidity. Pulmonary function even after lobectomy was better preserved than expected.

Perioperative assessment of oversized lobar graft downsizing in living-donor lobar lung transplantation using three-dimensional computed tomographic volumetry

A 15‐year‐old boy with bronchiolitis obliterans after bone marrow transplantation successfully underwent bilateral living‐donor lobar lung transplantation (LDLLT) with segmentectomy of the superior segment of an oversized right lower lobe graft. As the recipient was small for his age, the predicted value of his functional vital capacity of the recipient was difficult to determine preoperatively. Three‐dimensional computed tomography (CT) volumetry revealed that the ratio of donor graft volume to recipient hemithorax volume was 159% on the right side and 82% on the left side. The patient is alive and well 7 months after transplantation, and three‐dimensional CT volumetry revealed that the right and left donor lungs were still compressed to 73% and 84% of the original size, respectively. In LDLLT, segmentectomy of the superior segment of the lower lobe is a useful option for downsizing an oversized graft and three‐dimensional CT volumetry can provide meaningful data for size matching.

Outcome of living-donor lobar lung transplantation using a single donor

OBJECTIVE Living-donor lobar lung transplantation usually requires 2 healthy donors who donate either a right or a left lower lobe; however, finding 2 healthy donors is difficult. Several case reports have been published on successful living-donor lobar lung transplantation using a single donor; however, little is known about its outcome. METHODS We retrospectively investigated 14 critically ill patients who had undergone single living-donor lobar lung transplantation at 3 lung transplant centers in Japan. There were 10 female and 4 male patients, including 10 children and 4 adults. Size matching was assessed by estimated graft forced vital capacity and 3-dimensional computed tomography volumetry. The diagnoses included complications of allogeneic hematopoietic stem cell transplantation (n = 6), pulmonary hypertension (n = 4), and others (n = 4). RESULTS At a mean follow-up of 45 months (range, 2-128), the 3- and 5-year survival rate was 70% and 56%, respectively. There were 4 early deaths, for a hospital mortality of 29%, with 1 additional death at 40 months. The main cause of early death was primary graft dysfunction, most likely related to size mismatching. The survival among these 14 patients was significantly worse than the survival in a group of 78 patients undergoing bilateral living-donor lobar lung transplantation during the same period (P = .044). CONCLUSIONS Single living-donor lobar lung transplantation provides acceptable results for sick patients who would die soon otherwise. However, bilateral living-donor lobar lung transplantation appears to be a better option if 2 living donors are found.