Takaomi Hanaoka

Sublobar resection is equivalent to lobectomy for clinical stage 1A lung cancer in solid nodules

OBJECTIVES A single randomized trial established lobectomy as the standard of care for the surgical treatment of early-stage non-small cell lung cancer. Recent advances in imaging/staging modalities and detection of smaller tumors have once again rekindled interest in sublobar resection for early-stage disease. The objective of this study was to compare lung cancer survival in patients with non-small cell lung cancer with a diameter of 30 mm or less with clinical stage 1 disease who underwent lobectomy or sublobar resection. METHODS We identified 347 patients diagnosed with lung cancer who underwent lobectomy (n = 294) or sublobar resection (n = 53) for non-small cell lung cancer manifesting as a solid nodule in the International Early Lung Cancer Action Program from 1993 to 2011. Differences in the distribution of the presurgical covariates between sublobar resection and lobectomy were assessed using unadjusted P values determined by logistic regression analysis. Propensity scoring was performed using the same covariates. Differences in the distribution of the same covariates between sublobar resection and lobectomy were assessed using adjusted P values determined by logistic regression analysis with adjustment for the propensity scores. Lung cancer-specific survival was determined by the Kaplan-Meier method. Cox survival regression analysis was used to compare sublobar resection with lobectomy, adjusted for the propensity scores, surgical, and pathology findings, when adjusted and stratified by propensity quintiles. RESULTS Among 347 patients, 10-year Kaplan-Meier for 53 patients treated by sublobar resection compared with 294 patients treated by lobectomy was 85% (95% confidence interval, 80-91) versus 86% (confidence interval, 75-96) (P = .86). Cox survival analysis showed no significant difference between sublobar resection and lobectomy when adjusted for propensity scores or when using propensity quintiles (P = .62 and P = .79, respectively). For those with cancers 20 mm or less in diameter, the 10-year rates were 88% (95% confidence interval, 82-93) versus 84% (95% confidence interval, 73-96) (P = .45), and Cox survival analysis showed no significant difference between sublobar resection and lobectomy using either approach (P = .42 and P = .52, respectively). CONCLUSIONS Sublobar resection and lobectomy have equivalent survival for patients with clinical stage IA non-small cell lung cancer in the context of computed tomography screening for lung cancer.

Surgery for Mycobacterium avium complex lung disease in the clarithromycin era

OBJECTIVE Since the introduction of clarithromycin, it has been assumed that pulmonary Mycobacterium avium complex (MAC) disease can be treated with medication alone. This study examines whether surgery can still play an important role in the management of MAC lung disease in the current era. METHODS Between April 1993 and January 2001, 21 patients (11 men and 10 women) underwent a pulmonary resection for MAC infection. The median age of the patients was 56 years (range: 27-67 years). None of the patients were immunocompromised. Regimens employing clarithromycin were initiated preoperatively in all patients. The indications for surgery were failure of drug therapy in 19 patients and discontinuation of chemotherapy because of drug toxicity in two patients. The pulmonary resections (19 right lung, 2 left lung) performed included lobectomy in 16 patients, pneumonectomy in three, bilobectomy in one, and lobectomy plus segmentectomy in one. RESULTS All of the patients survived the surgery. Six major postoperative complications occurred in six patients (28.6%) and these included two bronchopleural fistulas after right pneumonectomy, two space problems, one prolonged air leak, and one case of interstitial pneumonia. All postoperative complications were manageable, and four of these were treated surgically. All patients had sputum-negative status after their operation. Relapse occurred in two patients (9.5%) at six months and two years postoperative, respectively. The first patient, who originally had a right upper lobectomy, underwent a left upper lobectomy during the follow-up period, attaining sputum conversion. The second patient underwent a right pneumonectomy and then died of respiratory failure four years postoperatively. This one late death was the only fatality. CONCLUSIONS Although it is associated with relatively high morbidity, surgery provides a high sputum conversion rate for patients whose MAC disease responds poorly to drug therapy. Even in the present clarithromycin era, pulmonary resection remains the treatment of choice when MAC lung disease has not been successfully eradicated by drug treatment alone.

CT screening for lung cancer: Importance of emphysema for never smokers and smokers

PURPOSE To address the prevalence of lung cancer in high and low-risk people according to their smoking history, age, and CT findings of emphysema. METHODS We reviewed the baseline low-dose CT scans of 62,124 current, former and never smokers, aged 40-90 to determine the prevalence of lung cancer. We performed logistic regression analysis of the prevalence of lung cancer to determine the odds ratio (OR) for emphysema, conditionally on age, female gender, and ethnicity. RESULTS The prevalence of lung cancer was 1.4% (95% CI: 1.3-1.6) for current smokers, 1.1% (95% CI: 1.0-1.2) for former smokers, and 0.4% (95% CI: 0.3-0.6) for never smokers. Emphysema was identified in 28.5% (6,684), 20.6% (5,422), and 1.6% (194) of current, former, and never smokers, respectively. The prevalence of lung cancer among current smokers was 1.1% for those without emphysema vs. 2.3% for those with emphysema (odds ratio [OR] 1.8; 95% confidence interval [CI]: 1.4-2.2) and the corresponding difference for former smokers was 0.9% vs. 1.8% (OR: 1.7; 95% CI: 1.3-2.2), and for never smokers, it was 0.4% vs. 2.6% (OR: 6.3; 95% CI: 2.4-16.9). CONCLUSIONS Identification of emphysema in low-dose CT scans increases the risk of lung cancer and is important in determining follow-up of current, former, and never smokers.

Immunohistochemical demonstration of apoptosis-regulated proteins, Bcl-2 and Bax, in resected non-small-cell lung cancers

AbstractObjective. Bcl-2 and Bax proteins regulate apoptosis independently, cooperatively, or both in vitro. The purpose of this study was to clarify the association between their expression with spontaneous apoptosis and various clinicopathologic features in patients with non-small-cell lung cancer (NSCLC). Methods. Bcl-2 protein, Bax protein, and spontaneous apoptosis were evaluated retrospectively in 70 resected specimens from NSCLC patients. Immunohistochemical (IHC) tests were used to assess the expression of Bcl-2 and Bax in the samples. The apoptotic index (AI) was also measured in these samples by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method. We then evaluated the clinicopathologic features of all 70 samples and their relationships with malignancy. Results. Bcl-2 overexpression was significantly associated with male sex and squamous cell carcinoma (SCC). Bax overexpression was not associated with any clinicopathologic features. AI was significantly associated with SCC and negative nodal metastasis. No clear associations were found among Bcl-2 expression, Bax expression, and AI. Bcl-2/Bax ratios were not associated significantly with AI. Bcl-2, Bax, Bcl-2/Bax ratio, and the grading of AI did not have prognostic values. Conclusion. Bcl-2 overexpression was significantly associated with SCC. Spontaneous apoptosis was significantly associated with SCC and with negative nodal metastasis. Apoptosis-regulated proteins, Bcl-2 and Bax, and AI lack significant associations with each other and prognostic values in patients with resected NSCLC.

HRCT Features of Small Peripheral Lung Carcinomas Detected in a Low-dose CT Screening Program

RATIONALE AND OBJECTIVES To define high-resolution computed tomography (HRCT) features of lung cancers detected by computed tomography (CT) screening according to histopathology and prognosis. METHODS AND MATERIALS Tumor size, CT value, morphology, and tumor volume doubling time (TVDT) were determined for 10 atypical adenomatous hyperplasias (AAH) and 50 lung cancers followed between 1996 and 1998 to 2007. RESULTS For the 10 AAHs, the density less than -500 HU in all lesions (mean, -654 HU) and the size was up to 14 mm (mean, 9 mm); all patients remain alive. Focal bronchioloalveolar cell carcinomas (BAC) were denser (mean, -537 HU) than AAH and mostly less dense than -350 HU; all patients remain alive. All 22 adenocarcinomas (ADC) were denser than -450 HU (mean, -186 HU); 6 were problematic and measured >-150HU and >10 mm or had >10 mm of central denser zone (CDZ) (partly solid tumors) or tumor size (solid tumor). Two of four squamous cell carcinomas (SCC) measuring 15 and 10 mm, respectively, were problematic. Two patients with small-cell lung carcinomas (SCLC) measuring 15 and 23 mm, respectively, remain alive. AAH, BAC, ADC, and SCC lesions were in general polygonal in shape. SCLC lesions appeared as round nodules with excrescence. The mean TVDT for AAH, BAC, ADC, SCC, and SCLC was 1278, 557, 466, 212, and 103 days, respectively. CONCLUSION The CT features reflected tumor aggressiveness. Non-SCLC lesions of >-150HU and >10 mm (or >-100HU and >10 mm for the solid portion of the tumor) are associated with unfavorable prognosis. Timely interventions should be undertaken before problematic increase in number of cases.

Pulmonary Nodules: Preliminary Experience with Semiautomated Volumetric Evaluation by CT Stratum

RATIONALE AND OBJECTIVES To evaluate the performance of custom-made software designed to quantify volume and weight of focal portions of lung tumors in regions of interest (ROI) and volume of interest on thin-section computed tomography (CT) images by stratum of CT values. METHODS AND MATERIALS Volume and weight of lung portions were measured three-dimensionally and semiautomatically by CT stratum and compared with standard manual measurements. One each of a partly solid tumor (including initial and follow-up high-resolution CT scans), partly solid tumor with most parts showing solid density, and nonsolid tumors in the mid-zone of the lung were analyzed. The doubling time (DT) of tumor volume and mass were calculated by stratum of CT values. RESULTS The software-measured tumor weight in lung periphery was reproducible, with and without trimming of intervening lung structures between borders of ROIs and tumor. For the lesion in the midlung zone, the fairly thick nearby pulmonary vessels degraded the measurements, with a higher measurement error, indicating the need to trim these structures off the ROI. Software measurements allowed quantification of tumor progress based on increase in tumor mass, without significant increase in tumor volume. The DTs for both tumor volume and mass were different among the four strata of CT values in the partly solid nodule. CONCLUSION Our semiautomated volumetric method involving measurement by CT stratum is promising for evaluation of lung tumor progress and aggressiveness.

Association of smoking with apoptosis-regulated proteins (Bcl-2, Bax and p53) in resected non-small-cell lung cancers

Apoptosis (genetically programmed cell death) is associated with the mechanism of oncogenesis. 1 However, the relationship between intensity of smoking and apoptotic status is still largely unknown in non-small-cell lung cancer (NSCLC) patients. We examined the correlation among the immunohistochemical assessments of apoptosis-regulated proteins (Bcl-2, Bax and p53), apoptotic index (AI) and intensity of smoking. Samples were from 114 patients who underwent resection of primary NSCLC from 1994 through 1998 at Shinshu University Hospital, Matsumoto, Japan. We analyzed immunohistochemically for Bcl-2, Bax and p53 on serial paraffin sections prepared from formalin-fixed, paraffin-embedded tissue blocks selected from the pathology files of Central Clinical Laboratories, Shinshu University Hospital, after which sufficient material remained from 79 samples for evaluation of apoptosis by the TUNEL (terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate-biotin nick end labeling) method. We used the following primary antibodies: mouse monoclonal antibody (MAb) anti-Bcl-2 (clone 124; Dako, Copenhagen, Denmark), rabbit polyclonal anti-Bax (clone P-19; Santa Cruz Biotechnology, Santa Cruz, CA) and mouse MAb anti-p53 (clone DO-7, Dako, Copenhagen, Denmark). Immunohistochemical results were assessed according to a scoring system based on the criteria of Basolo et al.2 The staining intensity ranged from 0 to 3 (0, absent; 1, weak; 2, moderate; 3, strong). In addition, the proportion of antigen-positive cells was graded from 0 to 3 (0,#5%; 1, 6% to 10%; 2, 11% to 50%; 3,

Radiological diagnosis of small pulmonary nodules detected on low-dose screening computed tomography

51%). The overall score for each sample was determined by adding the 2 individual scores. Based on the overall scores, expression of Bcl-2, Bax and p53 was evaluated as positive at

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