Motoharu Hamatake

Prognostic influence of the co-expression of epidermal growth factor receptor and c-erbB-2 protein in human lung adenocarcinoma.

The epidermal growth factor receptor (EGFR) is structurally similar to the c-erbB-2 oncogene protein. One hundred and nineteen specimens of primary human lung adenocarcinoma were investigated immunohistochemically for the expression of EGFR and the c-erbB-2 protein. Positive staining for EGFR was evident in 55 (46%), and c-erbB-2 protein in 33 (28%) cases. Of the 119 cases, the number staining positively for both the EGFR and c-erbB-2 protein totalled 16 (13%). The incidence of both the expression of EGFR and the c-erbB-2 protein was greater in patients with metastasis1 (M1) than in those with M0 (P < 0.01). The 5-year survival rates of patients with EGFR positivity and those with EGFR negativity were 51% and 42% respectively, however, the results did not show statistical significance. On the other hand, the 5-year survival rates of patients with c-erbB-2 positivity and c-erbB-2 negativity were 30% and 52%, respectively, with statistical significance (P < 0.05). Of the cases with EGFR positivity the 5-year survival rates of patients with c-erbB-2 positivity (n = 16) and negativity (n = 39) were 33% and 59%, respectively, with statistical significance (P < 0.05). In contrast, for the EGFR negative cases, the 5-year survival rates of patients who were positive (n = 17) and negative (n = 47) for c-erbB-2 expression were 27% and 46%, respectively, which were not significantly different. Our data thus suggested that erbB oncogenes may play an important role in both the development of cancer and the prognosis of adenocarcinoma of the lung.

Kinetic analysis of recurrence and survival after potentially curative resection of nonsmall cell lung cancer

About two‐thirds of the patients with nonsmall cell lung cancer (NSCLC) who undergo a potentially curative resection eventually suffer from recurrent disease. However, it has yet to be elucidated as to how survival after recurrence is influenced by different variables, including timing, type of recurrence, or other clinicopathological features. There have been few studies concentrating on the kinetics of growth of occult micrometastatic tumor cells that eventually manifest as tumor recurrence.

Results of a pulmonary metastasectomy in patients with colorectal cancer

PurposeThe lung is one of the key sites of hematogenous metastasis in patients with colorectal cancer. A metastasectomy of the lung is reported to improve the prognosis of colorectal cancer. We reviewed our experience in evaluating the surgical outcomes in colorectal cancer patients who have undergone a pulmonary metastasectomy.MethodsA single-center retrospective evaluation of clinical prognostic factors (1996–2008) related to a pulmonary metastasectomy of patients with colorectal cancer was conducted. Fifty-seven consecutive patients in our hospital who had undergone a resection of pulmonary metastasis from colorectal cancer were retrospectively investigated.ResultsThe mean age of the patients who underwent an initial pulmonary metastasectomy was 63.8 years. The average number of pulmonary metastases was 3.8. Pulmonary metastasectomy was performed an average of 1.6 times per head. A total of 32 patients had undergone a liver metastasectomy, and the 5-year survival of these 32 patients was 43.1%. The 5-year survival of the time from first pulmonary metastasectomy was 53.9%. There were no statistical differences with regard to the disease-free interval, interval from primary resection, or the number of pulmonary metastasectomies.ConclusionsA pulmonary resection for colorectal pulmonary metastases is therefore considered to be a favorable treatment for long-term survival even in the presence of liver metastases. Thoracic surgeons should therefore aggressively perform a pulmonary metastasectomy of colorectal cancer.

Prognostic value and clinicopathological correlation of thrombomodulin in squamous cell carcinoma of the human lung.

Aggregation of host platelets by circulating tumor cells is believed to play an important role in the metastatic process. Because thrombomodulin (TM) is one of the major mediators of the activation of the anticoagulant protein C by thrombin, we examined 136 primary tumor tissues and 45 metastatic lymph node tissues of lung squamous cell carcinomas for TM expression using immunohistochemical methods. The number of tumors with positive TM staining was less in metastatic tumors (44%) than in primary tumors (74%) (P < 0.01). Of various clinicopathological factors, better differentiation and lower N stage were significantly associated with TM expression. A loss of TM expression was associated with a shortened survival in 113 patients who underwent complete resection of the lung tumor (P < 0.01). In this group, TM expression and tumor-node-metastasis staging were independent significant determinants for survival, determined using Coxs multivariate survival analysis. Since TM is apparently associated with tumor progression and differentiation, this correlation may serve as a prognostic indicator in squamous cell carcinoma of the lung.

Duodenal metastasis from large cell carcinoma of the lung: Report of a case

Duodenal metastasis from primary lung cancer is extremely rare. It rarely shows any symptoms, and the prognosis for this condition is poor. We herein describe the case of a 46-year-old woman with primary lung cancer who underwent a left upper lobectomy. Severe anemia was observed about 20 days after lobectomy. Gastroduodenoscopy showed duodenal metastasis. Simultaneously, brain metastasis was also detected using magnetic resonance imaging. The patient underwent a local resection of the duodenum and a tumor resection of the brain. Postoperative irradiation of the brain metastases and systemic chemotherapy of the lung metastases were performed, and complete remission occurred. However, abdominal lymph node metastasis recurred, and the patient died 1 year after the lobectomy.

Concurrent chemoradiotherapy using cisplatin plus s-1, an oral fluoropyrimidine, followed by surgery for selected patients with stage III non-small cell lung cancer: A single-center feasibility study

PurposeThis single-institutional study was designed to determine whether S-1, an oral fluoropyrimidine, plus cisplatin with concurrent radiotherapy is feasible as an induction treatment for locally advanced non-small cell lung cancer (NSCLC).MethodsEighteen patients were analyzed in this study from July 2005 to March 2008. The patients received 40 mg/m2 S-1 orally twice per day on days 1 through 14 and 22 through 35, and cisplatin (60 mg/m2) was injected intravenously on days 8 and 29. The patients also underwent radiotherapy, and received a total dose of 40 Gy in 20 fractions beginning on day 1. Surgical resection was performed from 3 to 6 weeks after completing the induction treatment.ResultsNine (50%) of the 18 patients who received the induction treatment achieved a partial response. One patient refused to undergo surgery. The remaining 17 patients underwent a complete surgical resection. There were no deaths nor any major morbidities during the perioperative period. The recurrence-free survival and overall survival rate at 2 years for the patients who underwent resection were 63.3% and 88.2%, respectively.ConclusionInduction treatment using S-1 plus cisplatin and concurrent radiotherapy and surgical resection for selected patients with stage III NSCLC is a feasible and promising new treatment modality.

Preoperative concurrent chemoradiotherapy of S-1/cisplatin for stage III non-small cell lung cancer.

BACKGROUND Concurrent chemoradiotherapy using S-1 containing tegafur, an oral 5-FU prodrug, plus cisplatin has been reported to show promising efficacy against locally advanced non-small cell lung cancer with acceptable toxicity. The purpose of this study is to assess the impact of this induction treatment followed by surgery on survival for those patients. METHODS Potentially resectable locally advanced non-small cell lung cancer patients were eligible. The concurrent phase consisted of S-1 (orally at 40 mg/m² twice a day on days 1 to 14 and 22 to 36) and cisplatin (60 mg/m² on days 1 and 22) with radiation of 40 Gy/20 fractions beginning on day 1 followed by surgical resection. RESULTS Forty-two consecutive patients, between June 2005 and February 2011, were retrospectively analyzed. The median age was 59 (42 to 77) years, there were 34 males and 8 females, 26 cStage IIIA and 16 IIIB, each 21 adenocarcinomas and others. There were 26 partial responses and 16 stable disease cases after current induction treatment without uncontrollable toxicity. Of the 42 patients, 39 underwent surgical resection; 27 underwent a lobectomy and 12 pneumonectomies. One patient died due to thoracic empyema 65 days after surgery. The median follow-up time was 32.0 months. Three- and 5-year disease-free survival rates in all 39 resected patients were 52.0% and 44.0%, respectively, and 3- and 5-year overall survival rates were 77.4% and 61.7%, respectively. CONCLUSIONS Concurrent chemoradiotherapy using S-1 plus cisplatin followed by surgery may provide a better prognosis for locally advanced non-small cell lung cancer patients. Further prospective clinical investigation should be required.

Relationship between the loss of heterozygosity and tobacco smoking in pulmonary adenocarcinoma.

A loss of heterozygosity (LOH) is a major cause of lung carcinogenesis, and it is considered to be related to tobacco smoking in central type lung cancer. We investigated the relationship between LOH in lung adenocarcinoma and tobacco smoking. In a consecutive series of 50 patients with lung adenocarcinoma who underwent a surgical resection, cancer tissue specimens and corresponding normal peripheral lung and central bronchial tissue specimens were analyzed for LOH at the regions of D3S1234 (FHIT), D3S1300 (FHIT), D9S171 (CDKN2), and D17S796 (p53) by polymerase chain reaction using four fluorescence-labeled dinucleotide markers. To examine how cells are influenced by smoking, the A549 cell line was exposed to benzo[a]pyrene (B[a]P) for 24 weeks and then was subjected to the above analysis. The LOH in cancer tissue was thus detected in four (17%) patients at D3S1234, six (14%) at D3S1300, and seven (18%) at D17S796, but no LOH was detected in any normal tissue specimens. The incidence of LOHs in cancer tissue specimens from active smokers was 21% at D3S1234, 11% at D3S1300, and 19% at D17S796, whereas that of LOHs from nonactive smokers was 0% at D3S1234, 19% at D3S1300, and 14% at D17S796. Analyzing the relationship between the pack-year index and the presence of LOH, a significant difference was found among the active smokers. Besides, in the A549 cell line exposed to B[a]P, LOH was de novo detected in one (D2S123) of the nine regions examined. The incidence of LOH could be influenced by tobacco smoking in lung adenocarcinoma, thus suggesting the presence of an important event in the carcinogenesis of this disease.

Evaluation of p53 alterations in occult lymph node metastases

This study was designed to evaluate p53 alterations in occult lymph node metastases.

Aggressive Pulmonary Metastasectomies for Synovial Sarcoma

A 51-year-old woman underwent a bilateral wedge resection of lung metastases through a median sternotomy 10 months after an initial operation for synovial sarcoma of the left lower extremity. Since then, five right and two left posterolateral thoracotomies have been performed over a 6-year period. The patient is presently doing well 7 years after the initial operation of the left lower extremity without any evidence of recurrence.