Tomofumi Yohena

Combined evaluation of Rad51 and ERCC1 expressions for sensitivity to platinum agents in non-small cell lung cancer

DNA repair enzyme expression in tumor cells possibly affects sensitivity to anti‐cancer agents. The aim of this study was to determine the relationship between expression status of DNA repair enzymes and chemosensitivity in patients with non‐small cell lung cancer (NSCLC). NSCLC tissues prepared from the surgical specimens of 41 patients were subjected to immunohistochemical analysis for Rad51 and ERCC1 proteins and to a chemosensitivity test using the MTT assay. The relationships between the expression status of the DNA repair enzymes and ex vivo chemosensitivity to various agents were evaluated. A positive expression for Rad51 and ERCC1 was observed in 17 cases (41%) and 20 cases (49%), respectively. The positivity of Rad51 was closely related to a certain histologic type of squamous cell carcinoma and poor differentiation, and the positivity of ERCC1 tended to be related to squamous cell carcinoma. In chemosensitivity tests, sensitivities to CDDP and CBDCA were significantly lower when both 2 enzymes were positive (p = 0.012 and 0.04 in CDDP, 0.014 and 0.03 in CBDCA). Both Rad51 and ERCC1 expressions showed no significant relationship with sensitivities to paclitaxel, etoposide, vinorelbine, gemcitabine, 5‐FU, or irinotecan. In conclusion, combined expression of Rad51 and ERCC1 expression is associated with resistance to platinum agents in the ex vivo study of clinical NSCLC, and evaluation of expression status of both DNA repair enzymes would be a predictor for clinical response to platinum‐based chemotherapies.

Induction of epithelial-mesenchymal transition-related genes by benzo[a]pyrene in lung cancer cells

It is believed that epithelial‐mesenchymal transition (EMT) occurs during the development and progression of cancer; however, the correlation between tobacco smoking and EMT remains to be elucidated.

Overexpression of jun activation domain-binding protein 1 in nonsmall cell lung cancer and its significance in p27 expression and clinical features

Decreased expression of p27, which is an inhibitor of cyclin‐dependent kinase, is associated with cancer aggressiveness. It is believed that Jun activation domain‐binding protein 1 (Jab1) plays a role in p27 degradation in a manner that is independent from the role played by S‐phase kinase‐associated protein 2 (Skp2). To examine the clinical significance of Jab1 in nonsmall cell lung cancer (NSCLC), the protein expression of Jab1 in tumor tissues was investigated with regard to the expression of p27 and Skp2.

Salvage Operation for Late Recurrence After Stereotactic Body Radiotherapy for Lung Cancer: Two Patients With No Viable Cancer Cells

We report two patients who underwent salvage lung resection for suspected local recurrence on computed tomography image findings after stereotactic body radiotherapy; however, the pathologic findings indicated no viable tumor cells. Distinguishing between posttreatment changes and tumor recurrence after stereotactic body radiotherapy on the image findings is difficult; therefore, the determination of surgical indications requires comprehensive evaluations.

Expression of mismatch repair proteins, hMLH1/hMSH2, in non-small cell lung cancer tissues and its clinical significance

hMLH1 and hMSH2 have been implicated to be involved in the DNA mismatch repair (MMR) system. The purpose of this study is to investigate the expression of hMLH1 and hMSH2 DNA MMR proteins in non‐small cell lung cancer (NSCLC) tissue and to elucidate their clinical significance.

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.

An analysis of and new risk factors for reexpansion pulmonary edema following spontaneous pneumothorax

BACKGROUND The major risk factor for reexpansion pulmonary edema (RPE) following the treatment of spontaneous pneumothorax is thought to be chronic lung collapse. However, a long-term collapsed lung does not always cause RPE. The purpose of this study was to define other risk factors for RPE among patients undergoing drainage for the treatment of spontaneous pneumothorax. METHODS We retrospectively reviewed all the patients with spontaneous pneumothorax who had been treated at our hospital during a 5-year period. The duration of symptoms, location and size of the pneumothorax, size of the chest tube, and pleural effusion, which can occur coincidentally with pneumothorax, were compared in patients who did and did not experience RPE. RESULTS Forty patients were underwent drainage for the treatment of a spontaneous pneumothorax between January 2007 and December 2012. RPE developed in 13 of the 40 (32.5%) patients. In the multivariate analysis, the presence of pleural effusion coincident with pneumothorax contributed to the risk for RPE [odds ratios (OR), 1.557; 95% confidence intervals (CI), 1.290-1.880]. The duration of symptoms, location and size of the pneumothorax and size of the chest tube were similar between the groups. Symptomatic RPE was associated with a larger pneumothorax size. CONCLUSIONS The rate of RPE following spontaneous pneumothorax is higher than was previously reported. Our findings suggest the presence of pleural effusion coincidentally with pneumothorax may therefore be a new risk factor for RPE.

Long-term Survival after Surgical Treatment of Metachronous Bilateral Adrenal Metastases of Non-small Cell Lung Carcinoma

Patient: Male, 70 Final Diagnosis: Bilateral adrenal metastasis Symptoms: — Medication: — Clinical Procedure: Surgery Specialty: Surgery Objective: Unusual or unexpected effect of treatment Background: Although resection of the metastases is the treatment of choice for unilateral solitary adrenal metastasis of non-small cell lung carcinoma (NSCLC), the surgical treatment for bilateral adrenal metastases is quite rare, likely due to the coexistence of multiple synchronous metastases at other sites and/or primary adrenal insufficiency following bilateral adrenalectomy. We herein report a rare case of asynchronous metastasis of NSCLC to the bilateral adrenal glands with long-term survival after bilateral adrenalectomy. Case Report: A 70-year-old male underwent right upper lobectomy for lung adenocarcinomaT2aN2M0, stageIIIA following induction chemotherapy. Forty-four months later, right adrenalectomy of a right adrenal tumor was performed, which revealed metastatic lung carcinoma. Following the administration of adjuvant chemotherapy, a metastatic tumor was detected in the left adrenal gland. Although there were no other signs of distant metastasis on radiological examinations, he underwent the chemotherapy due to the risk of adrenal insufficiency. However, on follow-up CT the adrenal lesion was found to have enlarged; therefore, left adrenalectomy was performed. Three years and six months later, he was doing well, with no evidence of recurrence. Conclusions: Selected patients with solitary adrenal metastases of NSCLC can benefit from an aggressive treatment approach, even if such metastases are bilateral.

The long-term prognosis of induction chemotherapy followed by surgery for N2 non-small cell lung cancer: A retrospective case series study

Introduction The long-term prognosis of induction chemotherapy followed by surgery for N2 non-small lung cell cancer (NSCLC) remains controversial. Patients and methods We retrospectively reviewed the data and assessed the prognosis of 31 N2-NSCLC patients who underwent induction chemotherapy followed by surgery at our institution between January 1999 and December 2013. Potential prognostic factors, such as age, gender, tumor histology, tumor marker levels, tumor size, the number of N2 lymph nodes, the time from the last induction chemotherapy to the date of surgery, induction chemotherapy, RECIST response, downstaging status, pathological stage, adjuvant chemotherapy, and EF, were analyzed. Results The chemotherapy regimens of 30 of the 31 patients included a platinum agent. Complete resection was performed in 96.7% of the cases. Pathological downstaging was induced in 9 (29%) of the 31 patients. The median follow-up period was 7.89 years. The median DFI was 13.9 months. The recurrence rate was 74.2%. The 5-year OS was 56.9%. Univariate analyses revealed that none of the factors significantly affected OS, while the tumor histology had a significant effect on the DFI. Conclusion Although the recurrence rate in our study was similar to previous studies, our survival data were much better than those of past reports. Although the tumor histology was the only factor that had a significant association with DFI in the current study, the possibility of bias exists.

Partial Anomalous Pulmonary Venous Connection Coexisting with Lung Cancer: A Case Report and Review of Relevant Cases from the Literature

A 45-year-old man had an abnormal shadow in the right lung field on an annual screening chest X-ray. He was diagnosed with Stage IA (cT1bN0M0) lung cancer. Initially, we did not notice an anomalous vein on non-contrast computed tomography. However, we found that the right upper lobe bronchus branched from the lateral wall of the right main bronchial orifice, above the level of the common right upper lobe bronchus. Therefore, the bronchus was thought to be a tracheal bronchus. We carefully reevaluated the patient using three-dimensional computed tomography angiography. This technique showed that the anomalous right superior pulmonary vein drained into the azygos vein along the superior vena cava. These findings confirmed a partial anomalous pulmonary venous connection of the right upper lobe. We performed video-assisted thoracoscopic right upper lobectomy and mediastinal lymph node dissection for definitive treatment for lung cancer and partial anomalous pulmonary venous connection. No hemodynamic problems occurred in the postoperative course.