Segmentectomy versus lobectomy: does FEV1.0 change accurately reflect the postoperative cardiopulmonary function?

OBJECTIVE: The postoperative respiratory function has been compared between lobectomy and segmentectomy based on the resting spirometric change in many previous studies. However, spirometric change has only been assessed in static conditions, and it is unclear whether it accurately reflects the cardiopulmonary function. METHODS: We used spirometry and a 6-min walk test to evaluate patients who underwent lobectomy and segmentectomy and examined the changes in heart rate (HR), respiratory rate (RR), and saturation of percutaneous oxygen (SpO2) before and after walking between the two groups. RESULTS: The present study included 24 patients who underwent segmentectomy and 21 who underwent lobectomy. There was no significant difference in the reduction of the median forced expiratory volume in 1 s (FEV1.0) after surgery. In the 6-min walk test, the increase in HR and RR after surgery has no significant differences between lobectomy and segmentectomy (HR: p = 0.372 and RR: p = 0.131). However, the two groups showed a significant difference in the reduction of SpO2 (p < 0.001). In addition, correlation analysis found that the more the number of resected segments, the more the reduction of SpO2 with a statistical significance (p = 0.002). CONCLUSIONS: Patients who received segmentectomy showed to suppress the reduction of SpO2 with a statistical difference after the 6-min walk test in comparison to those who received lobectomy. These results suggest that segmentectomy has less impact on the cardiopulmonary function and the 6-min walk test is useful for evaluating the postoperative cardiopulmonary function.

Return to work after surgical treatment for malignant pleural mesothelioma: report of a case.

We report the case of a 56-year-old woman who underwent pleural biopsy to identify the cause of the right pleural effusion. The pathological diagnosis was epithelial malignant pleural mesothelioma. The patient worked as a junior high school teacher and strongly hoped for continuing work. Thus, we performed pleurectomy/decortication (P/D) as a curative surgery. The operative findings showed pleural thickening that in the lower lobe of the lung. Thus, peeling of the lower lobe was performed. Pleural biopsy was only performed on the upper and middle lobes. As a result, the operation was limited P/D. The pathological findings showed a small number of mesothelioma cells in the upper and middle lobes. The patient received four courses of cisplatin plus pemetrexed systemic chemotherapy after surgery. Continuous maintenance chemotherapy using pemetrexed has been performed until the time of writing. At present, she has continued her work for 6 years after the operation and has extended her retirement age without recurrence.

Successful treatment of mucoepidermoid carcinoma in the left main bronchus.

Here, we report the successful treatment of a 40-year-old man with mucoepidermoid carcinoma that originated in the proximal end of the left main bronchus close to the carina. He underwent wide and deep airway wedge resection, including the distal trachea and part of the carina via left postero-lateral thoracotomy. He has demonstrated neither anatomic complications nor disease recurrence 2 years after the operation.

Is pneumonectomy using video-assisted thoracic surgery the way to go? Study of data from the Japanese Association for Thoracic Surgery.

BACKGROUND: The number of pneumonectomies performed has been decreasing every year. That decrease is the result of changes in distribution of histological type, stage, and tumor location. To investigate the results of pneumonectomies performed on lung cancer patients in Japan over a period of 15 years, data reported by the Japanese Association for Thoracic Surgery were analyzed. METHODS: All data shown in the table were derived from official records reported in Japan. Mortality refers to hospital death rather than 30-day death, to more precisely evaluate the safety of the operations. RESULTS: (1) The number of sleeve lobectomies did not increase. (2) The operative mortality rate with pneumonectomies did not fall. In 2011, the rate of hospital deaths among pneumonectomy patients rose to 3.9% and worsened to 5.3% in 2012, which was more than twice that of 30-day death, despite an improvement in results as a whole. (3) The incidence of lethal bronchopleural fistula showed very little improvement, declining from 11.7 to 9.6%. (4) In 2012, VATS was used in 13.1% of all pneumonectomy patients. That figure stood at only 0.5% in 1997. CONCLUSION: Regarding pneumonectomies performed in Japan during the period analyzed, use of the less-invasive approach increased but bronchopleural fistula was still a major complication. The rate of hospital deaths among pneumonectomy patients worsened 2 years in a row. What is of critical importance is not the choice of approach--VATS or open thoracotomy--but the surgeon's efforts to find a chance to perform lung-saving surgery.

Significant increase in circulating tumour cells in pulmonary venous blood during surgical manipulation in patients with primary lung cancer.

OBJECTIVES: Circulating tumour cells (CTCs) are tumour cells shed from a primary tumour and circulate in the peripheral blood after passing through the drainage vein. In previous studies, we showed that high numbers of CTCs were detected in the drainage pulmonary venous blood of most patients with resectable primary lung cancer, whereas only low numbers of CTCs were detected in the peripheral blood of some patients. Accordingly, this prospective study was conducted to assess changes in CTCs in the drainage pulmonary vein (PV) during lung cancer surgery. METHODS: A total of 30 consecutive peripheral-type primary lung cancer patients who underwent lobectomy (or right upper and middle bilobectomy) through open thoracotomy were included. For each patient, 2.5 ml of blood was sampled from the lobar PV of the primary tumour site before and after surgical manipulation for lobectomy. The CTCs were evaluated quantitatively with the CellSearch® system. RESULTS: Before surgical manipulation, CTCs were detected in PV blood in the majority of patients (22 of 30, 73.3%), although CTCs were detected in peripheral blood in only two patients (6.7%). The median number of CTCs in the PV (pvCTC-count) before surgical manipulation was 4.0 cells/2.5 ml, and there was no significant correlation between pvPV-count and any clinicopathological characteristic, including tumour size, progression and histological type. After surgical manipulation, at the time of completion of the lobectomy, the pvCTC-count significantly increased (median, 60.0 cells/2.5 ml; P = 0.001). The increase in pvCTC-count was significantly associated with microscopic lymphatic tumour invasion (ly); pvCTC-count significantly increased in ly-positive patients (pvCTC-count before and after surgical manipulation, 4.0 and 90.5 cells/2.5 ml, respectively; P = 0.006), but not in ly-negative patients (3.5 and 7.0 cells/2.5 ml, respectively; P = 0.153). The increase in pvCTC-count was not significantly associated with any other clinicopathological factor or with any surgical procedure, including the sequence of vessel interruption. CONCLUSIONS: We documented a significant increase in CTC count in drainage PV blood after surgical manipulation, especially in tumours with lymphatic invasion. We are awaiting survival data at 5 year follow-up examination, which may provide clinical significance of the pvCTC-count.

Circulating tumor cells (CTCs) in malignant pleural mesothelioma (MPM).

PURPOSE: To investigate the diagnostic and prognostic value of circulating tumor cells (CTCs), a potential surrogate of micrometastasis, in malignant pleural mesothelioma (MPM). METHODS: We prospectively evaluated CTCs in 7.5 mL of peripheral blood sampled from patients with a suspicion of MPM. A semiautomated system was used to capture CTCs with an antibody against the epithelial cell adhesion molecule. RESULTS: Of 136 eligible patients, 32 were finally diagnosed with nonmalignant diseases (NM), and 104 had MPM. CTCs were detected in 32.7 % (34 of 104) of MPM patients but in only 9.4 % (3 of 32) of NM patients (P = 0.011). The CTC count was significantly higher in MPM patients than in NM patients (P = 0.007), and a receiver operating characteristic (ROC) curve analysis showed an insufficient capability of the CTC test in discrimination between MPM and NM, with an area under ROC curve of 0.623 (95 % confidence interval, 0.523-0.723; P = 0.036). Among MPM patients, CTCs were more frequently detected in patients with epithelioid subtype (39.7 %, 31 of 78) than in those with nonepithelioid subtypes (11.5 %, 3 of 26; P = 0.016). Positive CTCs (CTC count ≥ 1) were a significant factor to predict a poor prognosis among epithelioid patients (median overall survival, 22.3 months for positive CTCs vs. 12.6 months for negative CTCs; P = 0.004) and not in nonepithelioid patients (P = 0.649). A multivariate analysis showed that positive CTCs were a significant and independent factor to predict a poor prognosis (hazard ratio, 2.904; 95 % confidence interval, 1.530-5.511; P = 0.001) for epithelioid MPM patients. CONCLUSIONS: CTC was a promising marker in diagnosis and prediction of prognosis in MPM, especially in epithelioid MPM.

Circulating endothelial cell (CEC) as a diagnostic and prognostic marker in malignant pleural mesothelioma (MPM).

BACKGROUND: The purpose of this study was to investigate the diagnostic and prognostic value of circulating endothelial cell (CEC), a potential surrogate of tumor angiogenesis, in malignant pleural mesothelioma (MPM). METHODS: We prospectively evaluated CEC count in 4.0 mL of peripheral blood sampled from patients with a suspicion of MPM. An automated system was used to capture CECs with an anti-CD146 antibody. RESULTS: Of 109 eligible patients, 30 were finally diagnosed with non-malignant diseases, and 79 were with MPM. CEC count was significantly higher in MPM patients than in NM patients (mean CEC count, 120.3 and 39.9, respectively; P = 0.001), and a receiver operating characteristic (ROC) curve analysis showed that CEC provided a significant diagnostic performance in discrimination between MPM and nonmalignant diseases with an area under curve (AUC-ROC) of 0.700 (95 % confidence interval [95 % CI], 0.595-0.806; P = 0.001). Among MPM patients, CEC count was positively correlated with intratumoral microvessel density (MVD), a measurement of tumor angiogenesis (Spearman correlation coefficiency [r] = 0.444; P = 0.001). Higher CEC count (>50) was significantly associated with a poor prognosis (median overall survival, 11.4 months [95 % CI, 7.6-15.2] for higher CEC count patients versus 20.1 months [95 % CI, 16.0-24.2] for lower CEC count patients; P = 0.028). A multivariate analysis showed that higher CEC count was a significant and independent factor to predict a poor prognosis (hazard ratio [HR], 2.24, [95 % CI, 1.24-4.43]; P = 0.009). CONCLUSIONS: CEC, as a surrogate of tumor angiogenesis, was a promising marker in diagnosis and prediction of prognosis in MPM.

Practical approaches to diagnose and treat for T0 malignant pleural mesothelioma: a proposal for diagnostic total parietal pleurectomy.

Malignant pleural mesothelioma (MPM) remains suffering poor prognosis in spite of recent diagnostic and therapeutic progress. Although there is currently no established evidence, early diagnosis and early intervention may play a key role to improve prognosis of MPM, similarly to other malignancies. As pleural effusion is usually the first clinical sign of MPM, pleural effusion cytology is often the first diagnostic examination to be carried out. Since the sensitivity of pleural effusion cytology is approximately 60%, however, false-negative diagnosis is given to almost half of true MPM patients at this clinical step. One practical way to reduce the number of misdiagnosed MPM is to encourage performing thoracoscopic pleural biopsy unless definitive diagnosis other than MPM is established. There still remain a considerable number of patients with radiological/thoracoscopic T0 MPM who are misdiagnosed with nonspecific pleuritis after a complete investigation including thoracoscopic biopsies. Such patients will turn out to be malignant during follow-up period, although they have the best opportunity for long-term survival if only early therapeutic intervention is given. Currently, we are performing diagnostic total parietal pleurectomy in highly selected patients, who are characterized with strong clinical suspicion, positive pleural effusion cytology but uncertain pathological diagnosis, excellent cardiopulmonary reserve, and with written informed consent for highly invasive diagnostic surgery for pathologically unproven disease.

XRCC3 gene polymorphism is associated with survival in Japanese lung cancer patients.

We focused on OGG1 Ser326Cys, MUTYH Gln324His, APEX1 Asp148Glu, XRCC1 Arg399Gln, and XRCC3 Thr241Met and examined the relationship between the different genotypes and survival of Japanese lung cancer patients. A total of 99 Japanese lung cancer patients were recruited into our study. Clinical data were collected, and genotypes of the target genes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Survival analysis to verify the impact of these gene polymorphisms on the clinical outcome of lung cancer showed that lung squamous cell carcinoma patients with the Thr/Met genotype at XRCC3 had a significantly shorter survival time than those with the Thr/Thr genotype (13 months versus 48 months; log-rank test, p < 0.0001). Cox regression analysis showed that the carriers of XRCC3 genotypes were at a significantly higher risk [adjusted hazard ratio (HR) = 9.35, 95% confidence interval (CI) = 2.52-34.68, p = 0.001; adjusted HR = 9.05, 95% CI = 1.89-44.39, p = 0.006]. Our results suggest that XRCC3 Thr241Met may act as a favorable prognostic indicator for lung squamous cell carcinoma patients.

Surgical treatment of clinical N1 non-small cell lung cancer: ongoing controversy over diagnosis and prognosis.

PURPOSE: The preoperative assessment of nodal status in lung cancer is complicated and problematic for physicians and surgeons. Although many patients with clinical N1 (cN1) non-small cell lung cancer (NSCLC) are candidates for surgical treatment, these patients represent a heterogeneous subgroup with unpredictable survival. We conducted this study to evaluate the surgical results of cN1 disease and to attempt to clarify the delicate issues surrounding its diagnosis and prognosis. METHODS: The subjects of this study were 187 consecutive patients with cN1 adenocarcinoma or squamous cell carcinoma of the lung, who underwent complete resection without induction therapy. RESULTS: Only 25% of the adenocarcinomas and 54% of the squamous cell carcinomas were correctly diagnosed as N1 disease preoperatively. Multiple logistic regression analyses revealed that adenocarcinoma (P = 0.0141) was a significant predictor of pN2. Multivariate analyses revealed that nodal metastasis (P < 0.0001), large tumor size (P = 0.0079), and high serum carcinoembryonic antigen value (P = 0.0096) were significantly poor prognostic factors in cN1 patients. CONCLUSIONS: It is difficult to diagnose nodal status in patients with cN1 disease, which requires various surgical procedures, including plasty, possibly with adjuvant therapy in a defined high-risk subgroup.

Impact of positive pleural lavage cytology on survival in patients having lung resection for non-small-cell lung cancer: An international individual patient data meta-analysis.

OBJECTIVES: Pleural lavage cytology is the microscopic study of cells obtained from saline instilled into and retrieved from the chest during surgery for non-small-cell lung cancer. The aims of this study were to collate multi-institutional individual patient data for meta-analysis to determine independence as a prognostic marker and to characterize the impact of positive results on stage-adjusted survival. METHODS: We identified 31 publications from 22 centers/research groups that performed pleural lavage cytology during surgery for non-small-cell lung cancer and invited submission of individual patient data. Actuarial survival was calculated using Kaplan-Meier methods, and comparisons were performed using the log-rank test. Cox proportional hazards regression was used to ascertain the covariates associated with survival. RESULTS: By January 1, 2008, submissions were received internationally from 11 centers with individual data from 8763 patients. In total, 511 (5.8%) patients had a positive pleural lavage cytology result, and this was shown to be an independent predictor of adverse survival associated with a hazard ratio of 1.465 (1.290-1.665; P < .001) compared with a reference hazard ratio of 1 for a negative result. On statistical modeling, the best adjustment for patients with a positive pleural lavage cytology result was a single increase in the T category assigned to the case, up to a maximum of T4. Correction for differences in survival were obtained in stages IB (P = .315) and IIB (P = .453), with a degree of correction in stage IIIA (P = .07). CONCLUSIONS: Pleural lavage cytology should be considered in all patients with non-small-cell lung cancer suitable for resection. A positive result is an independent predictor of adverse survival, and the impact on survival suggests that it may be appropriate to upstage patients by 1 T category.

APEX1 Asp148Glu gene polymorphism is a risk factor for lung cancer in relation to smoking in Japanese.

DNA repair enzymes play an important role in the development of various kinds of cancer. We here analyzed associations of XPD Lys751Gln, APEX1 Asp148Glu, XRCC1 Arg399Gln, and XRCC3 Thr241Met gene polymorphisms in DNA repair pathways in relation to the risk of lung cancer using PCR-RFLP. The study involved 104 lung cancer patients and 120 non-cancer controls divided into non-smokers and smokers. We found a statistically significant interaction between APEX1 Asp148Glu and the risk for lung cancer (adjusted OR 2.78, 95% CI 1.58-4.90, p=0.0004), of both adenocarcinoma (adjusted OR 2.24, 95%CI 1.18-4.25, p=0.014) and squamous cell carcinoma (adjusted OR 4.75, 95%CI 1.79-12.6, p=0.002) types. XRCC1 Arg399Gln showed a borderline significant association with adenocarcinoma (adjusted OR 1.89, 95%CI 1.00-3.57, p=0.051). The combined effect of smoking and presence of the APEX1 Asp148Glu demonstrated a significant association with risk of lung cancer (adjusted OR 3.61, 95% CI 1.74-7.50, p=0.001). The XPD Lys751Gln and XRCC3 Thr241Met genotypes displayed no statistically significant risk. Our findings suggest that the APEX1 Asp148Glu is associated with increased risk for primary lung cancer in Japanese individuals partaking in smoking.

Circulating tumor cell as a diagnostic marker in primary lung cancer.

PURPOSE: To investigate the diagnostic performance of circulating tumor cells (CTC) in discrimination between primary lung cancer and nonmalignant diseases as well as in prediction of distant metastasis. PATIENTS AND METHODS: We prospectively evaluated CTCs in 7.5-mL samples of peripheral blood sampled from patients with a suspicion or a diagnosis of primary lung cancer. A semiautomated system was used to capture CTCs with an antibody against epithelial cell adhesion molecule. RESULTS: Of 150 eligible patients, 25 were finally diagnosed as having nonmalignant disease, and 125 were diagnosed as having primary lung cancer with (n = 31) or without (n = 94) distant metastasis. CTCs were detected in 30.6% of lung cancer patients and in 12.0% of nonmalignant patients. CTC count was significantly higher in lung cancer patients than in nonmalignant patients, but a receiver operating characteristic (ROC) curve analysis showed an insufficient capability of the CTC test in discrimination between lung cancer and nonmalignant diseases with an area under ROC curve of 0.598 (95% confidence interval, 0.488-0.708; P = 0.122). Among lung cancer patients, CTC count significantly increased along with tumor progression, especially with development of distant metastasis. The area under ROC curve for CTC count in prediction of distant metastasis was 0.783 (95% confidence interval, 0.679-0.886; P < 0.001). When patients with one or more CTCs were judged as having metastatic disease, sensitivity and specificity of the CTC test were 71.0% and 83.0%, respectively. CONCLUSIONS: CTC is a useful surrogate marker of distant metastasis in primary lung cancer.

MUTYH Gln324His gene polymorphism and genetic susceptibility for lung cancer in a Japanese population.

BACKGROUND: Genetic polymorphisms of DNA repair enzymes in the base excision repair (BER) pathway, may lead to genetic instability and lung cancer carcinogenesis. We investigated the interactions among the gene polymorphisms in DNA repair genes and lung cancer. METHODS: We analyzed associations among OGG1 Ser326Cys and MUTYH Gln324His gene polymorphisms in relation to lung cancer risk using PCR-RFLP. The study involved 108 lung cancer patients and 121 non-cancer controls divided into non-smokers, smokers according to pack-years smoked in Japanese. RESULTS: The results showed that the MUTYH His/His genotype compared with Gln/Gln genotype showed an increased risk for lung cancer (adjusted odds ratio [OR] 3.03, confidence interval [95%CI], 1.31-7.00, p = 0.010), whereas there was no significant increase for the Gln/His genotype (adjusted OR 1.35, 95%CI 0.70-2.61, p = 0.376). The MUTYH His/His genotype was at a borderline increased risk for both adenocarcinoma and squamous cell carcinoma (adjusted OR 2.50, 95%CI 0.95-6.62, p = 0.065 for adenocarcinoma; adjusted OR 3.20, 95%CI 0.89-11.49, p = 0.075 for squamous cell carcinoma, respectively). However, the OGG1 Ser/Cys or Cys/Cys genotypes compared with the Ser/Ser genotype did not have significantly increased risk for lung cancer, containing either adenocarcinoma or squamous cell carcinoma. The joint effect of tobacco exposure and the MUTYH His/His genotype compared with the Gln/Gln genotype showed a significant association with lung cancer risk in smokers, and there was not significantly increased in non-smokers (adjusted OR 3.82, 95%CI 1.22-12.00, p = 0.022 for smokers; adjusted OR 2.60, 95%CI 0.60-11.25, p = 0.200 for non-smokers, respectively). The effect of tobacco exposure and the OGG1 Ser326Cys showed also no significant risk for lung cancer. CONCLUSION: Our findings suggest that the MUTYH Gln324His polymorphism appear to play an important role in modifying the risk for lung cancer in the Japanese population.

Radical surgery for malignant pleural mesothelioma: results and prognosis.

The role of surgical treatment for malignant pleural mesothelioma (MPM) continues to be controversial. We carried out a retrospective review of the prognosis in patients who had radical surgery for MPM. Of 87 consecutive patients on whom surgical exploration for biopsy-proven MPM was performed, 31 patients underwent extrapleural pneumonectomy (EPP) and 34 patients underwent pleurectomy/decortication (P/D). Sixty-five patients having EPP or P/D included 58 men (89%). The median age was 60 years (range 35-78) and the histologic type was epithelial in 48 patients (74%). IMIG staging classification was p-stage I disease in eight patients (12%), p-stage II in 13 (20%), p-stage III in 40 (62%) and p-stage IV in 4 (6%). Operative mortality was 3.2% for EPP and none for P/D. The median and 3-year survivals after EPP were 13 months and 33% whereas those after P/D were 17 months and 24%, respectively. A multivariate analysis demonstrated that older age (P=0.0467), non-epithelial histology (P=0.0057) and p-stage III-IV disease (P=0.0019), but not gender, side, surgical procedure, were significant independent negative prognostic factors. Although P/D appears to be acceptable in early stages, we encourage EPP, en bloc resection without entering the pleural cavity with intent for curability, which provides oncologically complete resection of all disease.

Pleomorphic carcinoma of the lung: a surgical outcome.

OBJECTIVES: Pleomorphic carcinoma of the lung, a rare malignant disease with a dual-cell component of spindle and/or giant cells, and of epithelial cells, was defined in the World Health Organization classification updated in 1999. Reported prognoses are heterogeneous, and optimal treatment remains undefined. METHODS: Data were retrospectively examined for 45 consecutive patients (41 men and 4 women) who had undergone surgical resection for pulmonary pleomorphic carcinoma. RESULTS: Sarcomatous elements were as follows: 23 spindle cell types (51.1%), 11 giant cell types (24.4%), and 11 combined spindle and giant cell types (24.4%). Epithelial components were adenocarcinoma in 25 (55.6%) patients, squamous cell carcinoma in 8 (17.8%) patients, and large call carcinoma in 12 (26.7%) patients. Nodal status was classified as pN0 disease in 28 (62.2%) patients, pN1 disease in 5 (11.1%) patients, and pN2 disease in 12 (26.7%) patients. Even patients with pN0 disease frequently manifested vascular invasion (16/28 [57.1%]). Five-year overall survival and disease-free survival were 39.2% and 47.1%, respectively. Although the subtype of epithelial components, as well as sarcomatous elements, did not affect prognosis, overall survival (P = .02) and disease-free survival (P = .002) in patients with pN1/N2 disease were significantly worse than those in patients with pN0 disease. Most recurrences occurred at distant sites (14/20 [70.0%]), and recurrence within 6 months after resection was found in 10 patients (10/20 [50.0%]). Moreover, median survival time after confirmation of initial relapse was 2.6 months. CONCLUSIONS: Pulmonary pleomorphic carcinoma, which often presented in symptomatic male smokers as a large peripheral lesion, carried a poor prognosis, even when early-stage disease was diagnosed and resected. Distant metastases occurred more frequently and earlier, and the survival after relapse was very short, suggesting that this entity should be considered to have a tremendously aggressive malignant behavior. Further investigation of biologic features of pulmonary pleomorphic carcinoma and therapeutic response is a high-priority issue, so that suitable treatment strategies can be planned.

NAT2 and CYP1A2 polymorphisms and lung cancer risk in relation to smoking status.

We investigated the associations between lung cancer and the gene polymorphisms of the drug metabolizing enzymes, containing cytochrome P450 1A1 (CYP1A1), cytochrome P450 1A2 (CYP1A2), glutathione S-transferase class mu (GSTM1), and N-acetyltransferase 2 (NAT2). The study involved 113 lung cancer patients and 121 non-cancer controls divided into never, light and heavy smokers according to pack-years of smoking in Japanese by using PCR-RFLP. For light smokers, the lung cancer risk of NAT2 intermediate-slow was significantly increased [the adjusted odds ratio (OR): 10.9, 95% confidence intervals (95%CI): 1.75-67.5, P-value: 0.010]. Moreover, never smokers having joint genotypes of NAT2 intermediate-slow and CYP1A2*1F A/A was also associated with increased the lung cancer risk (OR: 4.95, 95% CI: 1.19-20.6, P-value: 0.028). We suggested that light smokers with intermediate-slow NAT2 activity were at highest risk for lung cancer and the gene-gene interaction based on intermediate-slow NAT2 activity and high CYP1A2 activity would be increased a lung cancer risk among never smokers.

Novel marker D2-40, combined with calretinin, CEA, and TTF-1: an optimal set of immunodiagnostic markers for pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma is a challenging disease with regard to diagnosis and treatment; early and accurate diagnosis would lead to appropriate therapeutic strategies, including extrapleural pneumonectomy. Immunohistochemistry has proven valuable for the diagnosis of the most common epithelioid mesothelioma, although it is often difficult to differentiate it from pulmonary or metastatic adenocarcinoma with absolute certainty if a single antibody is employed. The current study was designed to identify an immunodiagnostic panel for pleural mesothelioma. METHODS: Large surgical specimens from 66 cases with pleural mesothelioma and 66 with lung adenocarcinoma were immunohistochemically reevaluated under uniform conditions. The antibodies examined were directed against the novel mesothelial marker D2-40, as well as calretinin, CEA, and TTF-1. RESULTS: For mesothelioma the sensitivities of D2-40 and calretinin were 84.8% and 87.9%, respectively, and their specificities were both 95.5%. For adenocarcinoma, the sensitivities of CEA and TTF-1 were 95.5% and 92.4%, respectively, and their specificities were both 100%. Immunoreactivity to D2-40 and calretinin was observed in most areas of epithelioid differentiation in mesothelioma. Western blots also showed higher levels of D2-40 antigen in pleura invaded by epithelioid mesothelioma as compared with unaffected pleura. CONCLUSIONS: These data strongly suggest the significant usefulness of D2-40 and calretinin as positive markers, and of CEA and TTF-1 as negative markers, for pleural mesothelioma. The 4-antibody immunohistochemical panel showed high sensitivity and specificity with regard to differentiation of epithelioid mesothelioma from lung adenocarcinoma.