Benign Pulmonary Diseases Research Articles

Short-Term Outcome of Three-Dimensional Versus Two-Dimensional Video-Assisted Thoracic Surgery for Benign Pulmonary Diseases

It is unclear whether three-dimensional (3D) video-assisted thoracic surgery (VATS) pulmonary resections are comparable to two-dimensional (2D) VATS pulmonary resections in patients with potentially operable benign pulmonary diseases. We analyzed the clinical data of patients who underwent 2D and 3D VATS pulmonary resections for benign diseases in our hospital from November 2013 to August 2014. Perioperative factors (estimated blood loss and operative time) and postoperative factors (postoperative hospital length of stay, postoperative complications, and duration of chest tube drainage) were evaluated. VATS was performed in 278 patients during the 10-month study period. The 2D VATS system was used in 142 patients (51.08%), and the 3D VATS system was used in 136 (48.92%). Operative time was significantly different between the two groups (p = 0.007). However, no significant differences were found in estimated blood loss (p = 0.75), chest drainage tube placement time (p = 0.852), rate of postoperative complications (p = 0.566), or postoperative hospital length of stay (p = 0.951). The use of 3D VATS appears to facilitate precise execution of surgical techniques in specific operative tasks and, as a result, reduces lung resection performance time in patients with benign pulmonary diseases.

Surgical resection of the benign pulmonary diseases presented with hemoptysis

Role of lung resection for benign pulmonary diseases presented with hemoptysis is still controversial. Weretrospectively reviewed the patients’ records with significant hemoptysis that underwent anatomic pulmonary resectionfrom 2009 to 2015. Among ten patients (male 9, female 1, mean age 52.3 years), eight patients had inflammatorydiseases including aspergilloma or bronchiectasis and nine patients underwent lobectomy or pneumonectomy. Therewas no postoperative mortality and recurrence of hemoptysis. Lung resection is still one of the effective treatmentoptions for benign lung diseases presented with hemoptysis although the number of included patients was small.

Chirurgie thoracique vidéo assistée dans le cancer bronchique non à petites cellules

IntroductionThoracotomy has been considered as the gold standard approach for lobectomy. However, the number of procedures performed by video-assisted approach (VATS) has steadily increased during the recent years.State of the art: VATS approach for lobectomy is so far validated for stage I lung cancer. VATS lobectomies are associated with less post-operative morbidity, lower hospital stay, allowing their integration into “fast track” recovery programs. VATS complies to oncologic resection rules, allowing a complete lymphadenectomy. Furthermore, it seems that VATS lobectomies are linked to better overall survival and recurrence free survival. PerspectivesOwing to its many advantages, VATS pulmonary resections could be extended in the future to more advanced stages, benign pulmonary diseases, as well as lung metastasectomy. ConclusionBecause of its many advantages, VATS lobectomy can be regarded as the gold standard approach for stage I lung cancer surgery.

NLK functions to maintain proliferation and stemness of NSCLC and is a target of metformin.

ObjectiveNemo-like kinase (NLK) is an evolutionarily conserved serine/threonine kinase that regulates the activity of a wide range of signal transduction pathways. Metformin, an oral antidiabetic drug, is used for cancer prevention. However, the significance and underlying mechanism of NLK and metformin in oncogenesis has not been fully elucidated. Here, we investigate a novel role of NLK and metformin in human non-small cell lung cancer (NSCLC).Materials and methodsNLK expression was analyzed in 121 NSCLCs and 92 normal lung tissue samples from benign pulmonary disease. Lentivirus vectors with NLK-shRNA were used to examine the effect of NLK on cell proliferation and tumorigenesis in vitro. Then, tumor xenograft mouse models revealed that NLK knockdown cells had a reduced ability for tumor formation compared with the control group in vivo. Multiple cell cycle regulator expression patterns induced by NLK silencing were examined by western blots in A549 cells. We also employed metformin to study its anti-cancer effects and mechanisms. Cancer stem cell property was checked by tumor sphere formation and markers including CD133, Nanog, c-Myc, and TLF4.ResultsImmunohistochemical (IHC) analysis revealed that NLK expression was up-regulated in NSCLC cases (p < 0.001) and correlated with tumor T stage (p < 0.05). Silencing of NLK suppressed cell proliferation and tumorigenicity significantly in vitro and in vivo, which might be modulated by JUN family proteins. Furthermore, metformin selectively inhibits NLK expression and proliferation in NSCLC cells, but not immortalized noncancerous lung bronchial epithelial cells. In addition, both NLK knockdown and metformin treatment reduced the tumor sphere formation capacity and percentage of CD133+ cells. Accordingly, the expression level of stem cell markers (Nanog, c-Myc, and TLF4) were decreased significantly.ConclusionNLK is critical for cancer cell cycle progression, and tumorigenesis in NSCLC, NLK knockdown, and metformin treatment inhibit cancer cell proliferation and stemness. Metformin inhibits NLK expression and might be a potential treatment strategy for NSCLC.

The correlation of peripheral blood lymphocyte subsets with prognosis in lung cancer patients

Objective: To study the relationship of lymphocyte subsets with prognosis and clinico-pathologic features in lung can- cer patients. Methods: Flow cytometry was used to analyze the distribution of T-lymphocyte subsets and natural killer cells in the pe- ripheral blood of lung cancer patients, patients with benign pulmonary diseases, and healthy controls. The peripheral-blood lymphocyte levels of the subjects were compared. Clinical data obtained from 102 lung cancer cases were reviewed retrospectively, and the relation- ship of lymphocyte subsets with prognosis and clinico-pathologic features was analyzed. Results: The level of CD4+ T cells was lower in the peripheral blood of lung cancer patients than that of the healthy controls (P 0.05). However, the abnormal distribution of lympho- cyte subsets was related to lymphatic metastasis, TNM stage, and tumorigenesis P<0.05). Conclusion: The distribution of T-lympho- cyte subsets and natural killer cells was abnormal in the peripheral blood of lung cancer patients, and the dynamic changes in distribu- tion can help assess the immune functions of lung cancer patients. Cellular immune function can act as a prognostic indicator in lung cancer patients.

Serum HE4: An Independent Prognostic Factor in Non-Small Cell Lung Cancer.

Human epididymis secretory protein 4 (HE4) is a secreted glycosylated protein encoded by the WAP four-disulfide core domain 2 (WFDC2) gene, located on a chromosome 20 segment that is frequently amplified in many cancers. This study aimed at determining serum HE4 prognostic value in non-small cell lung cancer (NSCLC), following the REMARK guidelines. Serum samples from 346 consecutive patients with histologically proven and previously untreated NSCLC and 41 patients with benign pulmonary disease were collected at the Montpellier-Nimes Academic Hospital. Work-up investigations performed to determine the disease characteristics and treatment algorithms were congruent with international guidelines. HE4 levels in serum were measured with an ELISA test (Fujirebio Diagnostics) that uses two monoclonal antibodies, 2H5 and 3D8, against the C-WFDC domain of HE4. The area under the ROC curve (i.e., overall ability of HE4 to discriminate between controls and patients) was 0.78 (95% confidence interval [CI], 0.738–0.821; z test P <0.0001). Serum HE4 levels were significantly higher in patients with worse performance status, advanced TNM stage and positive nodal status. In the Cox model, overall survival was shorter in patients with high pretreatment serum HE4 (above 140 pmol/L) than in patients with serum H4 level ≤ 140 pmol/L [median survival: 17.7 weeks (95% CI, 11.9 to 24.9) and 46.4 weeks (95% CI, 38.6 to 56.3), respectively; hazard ratio: 1.48 (95% CI, 1.12 to 1.95) for high HE4; adjusted P = 0.0057]. High serum HE4 level at diagnosis is an independent determinant of poor prognosis in NSCLC.

Single incision thoracoscopic lobectomy through a 2.5 cm skin incision.

Single incision thoracoscopic surgery (SITS) involves only one intercostal space with minimal skin incision, which means it can be the most minimally invasive technique up to date. We minimized the skin incision to a length of 2.5 cm to achieve the less chest wall trauma and the more cosmesis during SITS lobectomy for benign pulmonary disease. Four patients who had bronchiectasis [left lower lobe (LLL)], congenital lobar emphysema [left upper lobe (LUL)], aspergilloma [right upper lobe (RUL)], and hamartoma (RUL) were planned to undergo 2.5 cm SITS lobectomy. There were no conversion cases to multi-port video-assisted thoracic surgery (VATS) or thoracotomy. The mean operation time was 182±25 minutes. Chest drains were removed on postoperative day (POD) 2 in all patients. Three patients discharged on POD 3. One patient who discharged on POD 5 readmitted for delayed pleural effusion and treated with mini-tube insertion. There were no late complications or symptom relapses during the median follow-up of 13.5 months. A 2.5 cm SITS lobectomy can be alternative option for relatively young patients with benign lung disease.

Detection of CK19, LUNX, and KS1/4 mRNA expression in the peripheral blood for diagnosis of micrometastases in patients with non-small cell lung cancer and their clinical implications.

The expression of CK19, LUNX, and KS1/4 mRNA biomarkers was detected in the peripheral blood of non-small cell lung cancer (NSCLC) patients to investigate the feasibility of indicating lung cancer micrometastases. Micrometastases were identified in the peripheral blood of 32 NSCLC patients, 15 benign pulmonary disease (BPD) patients, and 10 healthy volunteers by reverse transcriptase-polymerase chain reaction. The detection rates of CK19, LUNX, and KS1/4 mRNA-positive cells in the peripheral blood obtained from the NSCLC group were 34.4% (11/32), 37.5% (12/32), and 25% (8/32), respectively. CK19, LUNX, and KS1/4 mRNA-positive cells were detected in 6.6% (1/15), 0.0% (0/15), and 13.3% (2/15) of the patients with BPD, respectively. However, the healthy group did not express any of the three markers. The expression of CK19, LUNX, and KS1/4 mRNA was significantly higher in the NSCLC group than that in the healthy and BPD groups (P < 0.05). CK19 and LUNX mRNA may be ideal biomarkers indicating micrometastases in patients with NSCLC; however, the diagnostic applicability of KS1/4 mRNA remains uncertain. The rate of expression of CK19 was not correlated with the clinicopathological characteristics (P > 0.05). The rate of expression of LUNX and KS1/4 was closely related to the clinical stage (P < 0.05), and not related to the clinical characteristics of the disease (age, gender, smoking history, pathological type, histologic classification, and differentiation; P > 0.05).

Expression of miR-148/152 family as potential biomarkers in non-small-cell lung cancer.

BackgroundAltered miR-148/152 family expression contributes to human carcinogenesis. This study was designed to detect the potential for using miR-148/152 family as biomarkers for NSCLC patients.Material/MethodsThe relative expression levels of miR-148/152 family (miR-148a, miR-148b, and miR-152) in serum of 36 non-small-cell lung carcinoma (NSCLC) patients, 20 patients with benign pulmonary diseases (BPD), and 10 healthy individuals were assessed by real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR).ResultsThe expression of all three miRNAs were significantly lower in the serum of NSCLC than that of BPD and healthy controls (all p<0.01), and their expression levels were strongly correlated with each other (r=0.781, 0.720, and 0.645, respectively). Downregulation of miR-148/152 family was found to be corrected with more aggressive tumors. The area under the receiver operating characteristic curves (AUCs) for miR-148a, miR-148b, and miR-152 discriminating NSCLC from BPD were 0.775, 0.725, and 0.774, respectively, all higher than that of CEA (0.506). Combining the three miRNAs increased the discrimination performance, yielding an AUC of 0.789 (95% confidence interval, 0.643 to 0.895), with a sensitivity of 72.2% and a specificity of 90.0%.ConclusionsThe results of present study suggest that the expression levels of circulating miR-148/152 family may serve as biomarkers for NSCLC.

The Clinical Research of Serum VEGF, TGF-β1, and Endostatin in Non-small Cell Lung Cancer.

The aim of the study was to analyze the expressions of vascular endothelial growth factor (VEGF), transforming growth factor β1 (TGF-β1) and endostatin in non-small cell lung caner (NSCLC), and to explore their correlations with NSCLC. 80 NSCLC patients during January 2013 to June 2014 were selected. The expression levels of VEGF, TGF-β1, and endostatin before surgeries were detected, and compared with 40 healthy individuals and 40 patients with benign pulmonary diseases. Serum VEGF, TGF-β1, and endostatin levels were (573.6 ± 25.4) pg/mL, (36.2 ± 10.5) ng/mL, and (20.3 ± 7.8) ng/mL, respectively, in NSCLC group, which were obviously higher than those in healthy individuals and patients with benign pulmonary diseases, and the difference was statistically significant (p < 0.05); there was no statistical difference of the VEGF, TGF-β1, and endostatin levels between the healthy individuals and patients with benign pulmonary diseases (p > 0.05), or among patients with different physiological characteristics such as gender, age, and smoking history in NSCLC group (p > 0.05). Serum VEGF, TGF-β1, and endostatin levels also showed no statistical difference among patients with different pathological characteristics such as histological types, with or without lymphatic metastasis (p > 0.05). However, the three indicators were significantly different among patients with different TNM stages, with or without distant metastasis and different cell differentiation degrees (p < 0.05). Serum VEGF and TGF-β1 were positively related (r = 0.479, p < 0.05), endostatin was negatively related to both VEGF and TGF-β1 (r = -0.392, -0.354, p < 0.05 in both comparisons). The expression levels of VEGF, TGF-β1, and endostatin significantly contributed to the poor cell differentiation in NSCLC. They had important effects on the occurrence, development, and metastasis of NSCLC, which could be applied as the indicators to predict the malignancy of NSCLC.

S74 Circulating Tumour Cells In Peripheral And Pulmonary Venous Blood Predict Poor Long-term Survival In Surgically Resected Non-small Cell Lung Cancer Patients

Background We tested the hypothesis that the circulating tumour cells (CTCs) in preoperative peripheralblood (PPB) and intraoperative pulmonary venous blood (IPVB) could predict poor long term survival in surgically resected NSCLC patients. Method CTCs were separated from the blood using magnetic beads coated by antibody against epithelial-cell adhesion molecule (EpCAM) through magnetic activated cell sorting (MACS). The CTCs were quantified with fluorescence labelled antibodies against pan-cytokeratin through flow cytometry. CTCs were prospectively quantified in PPB and IPVB in 23 consecutive stage I-IIIA patients with surgically resected NSCLC. Association between CTCs and prognosis of these patients was evaluated after 5-year follow-up. Results In the NSCLC patients, outcomes were assessed according to levels of CTCs at surgery, and compared with CTCs detected in benign pulmonary diseases, and healthy volunteers, wherethe mean and 95% CI of CTCs counts were all 5 CTCs/15 mL in PPB and >50 CTCs/15 mL in IPVB. Univariate Cox proportional-hazards regression analysis showed that CTCs count in PPB or IPVB was an independent risk factor for tumour-free and overall survivals. The high risk group of patients had a shorter median tumour-free survival (22 months vs. >60.0 months, P 60 months, P Conclusions CTCs countin PPBand IPVB was an independent risk factor for tumour-free and overall survivalin surgically resected NSCLC patients.

Differentially expressed glycosylated patterns of α-1-antitrypsin as serum biomarkers for the diagnosis of lung cancer.

Lung cancer is the most common malignancy worldwide. Thus, there is a critical need for diagnostic biomarkers with adequate sensitivity and specificity for lung cancer detection. Glycans in glycoproteins are significantly altered in cancer, and may serve as a tool for identifying potential diagnostic biomarkers. Recent studies have reported changes in α-1-antitrypsin (A1AT) glycosylation in lung cancer serum, tissue and cell lines. In this study, a lectin microarray was used to detect glycosylation changes in serum A1AT from patients with lung adenocarcinoma (ADC), squamous cell lung cancer, small-cell lung cancer (SCLC) and benign pulmonary diseases. Differentially expressed glycosylated patterns of A1AT were identified by lectin arrays and were confirmed by lectin-based enzyme-linked immunosorbent assay (ELISA). We found that galactosylated A1AT could distinguish non-small-cell lung cancer (NSCLC) from benign pulmonary diseases (AUC = 0.834); fucosylated A1AT showed exceptional capability in distinguishing ADC from benign diseases (AUC = 0.919) or other lung cancer subtypes (AUC = 0.844), and A1AT containing poly-LacNAc could detect SCLC from benign diseases (AUC = 0.905) or NSCLC (AUC = 0.707). The present study indicates that glycosylated patterns of A1AT may serve as potential biomarkers for detection of lung cancer. Further studies in larger sample sizes are necessary to validate the clinical utility of these markers.

Optimal cut-off values for CYFRA 21-1 expression in NSCLC patients depend on the presence of benign pulmonary diseases

BackgroundSerum cytokeratin fragment 21-1 (CYFRA 21-1) expression levels are reported to be useful in the diagnosis of lung cancer, especially non-small cell lung cancer (NSCLC). However, the clinical value of CYFRA 21-1 as a tumor marker remains unclear, and no optimal cut-off value has been determined thus far. The purpose of this study was to establish a potential clinical cut-off value for serum CYFRA 21-1 as a diagnostic marker in patients with NSCLC. MethodsA total of 90 patients with NSCLC, 237 patients with benign pulmonary disease (BPD), and 1296 healthy controls were enrolled in this study. Among BPD there are 84 with chronic obstructive pulmonary disease (COPD), 81 with pneumonia, 38 with tuberculosis and 34 with chronic bronchitis. CYFRA 21-1 was measured in sera with an electrochemiluminescence (ECL) E170 analyzer. Comparisons were conducted using the chi-squared test and the Mann–Whitney test (two-sided). A receiver operating characteristic (ROC) curve was constructed to investigate the diagnostic power of CYFRA 21-1 expression, and the recommended cut-off value was chosen to calculate its sensitivity and specificity. ResultsThe cut-off values of CYFRA 21-1 in NSCLC by the ROC curve were 4.70ng/mL when compared with COPD, which was obviously greater than that found with pneumonia (2.79ng/mL) (P<0.05), tuberculosis (2.66ng/mL) (P<0.05), and chronic bronchitis (3.94ng/mL) (P<0.05) patients. Therefore, a cut-off value of 4.24ng/mL in NSCLC was suggested. ConclusionsThe presence of various BPDs may be one of the main reasons that no optimal cut-off value for CYFRA 21-1 expression in NSCLC has been determined previously.

Abstract LB-293: Circulating tumor cells in peripheral and pulmonary venous blood predict poor long-term survival in surgical resected non-small cell lung cancer patients

Abstract Background: We tested the hypothesis that the circulating tumor cells (CTCs) in preoperative peripheral blood (PPB) and intraoperative pulmonary venous blood (IPVB) could predict poor long term survival in surgically resected NSCLC patients. Methods: CTCs were separated from the blood using magnetic beads coated by antibody against epithelial-cell adhesion molecule (EpCAM) through magnetic activated cell sorting (MACS). The CTCs were quantified with fluorescence labeled antibodies against pan-cytokeratin through flow cytometry. CTCs were prospectively quantified in PPB and IPVB in 23 consecutive stage I-IIIA patients with surgically resected NSCLC. Association between CTCs and prognosis of these patients was evaluated after 5-year follow-up. Results: In the NSCLC patients, outcomes were assessed according to levels of CTCs at surgery, and compared with CTCs detected in benign pulmonary diseases, and healthy volunteers, where the mean and 95%CI of CTCs counts were all 5 CTCs/15mL in PPB and &amp;gt;50 CTCs/15mL in IPVB. Univariate Cox proportional-hazards regression analysis showed that CTCs count in PPB or IPVB was an independent risk factor for tumor-free and overall survivals. The high risk group of patients had a shorter median tumor-free survival (22 months vs. &amp;gt;60.0 months, P60 months, P&amp;lt;0.0015). Conclusions: CTCs count in PPB and IPVB was an independent risk factor for tumor-free and overall survival in surgically resected NSCLC patients. Citation Format: Zhidong Liu, Yunsong Li, Chongyu Su, Yi Han, Shaofa Xu. Circulating tumor cells in peripheral and pulmonary venous blood predict poor long-term survival in surgical resected non-small cell lung cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-293. doi:10.1158/1538-7445.AM2014-LB-293

Is video-assisted thoracic surgery lobectomy in benign disease practical and effective?

The aim of this study was to analyze the surgical outcomes of video-assisted thoracic surgery (VATS) lobectomy for benign pulmonary disease and to propose surgical guidelines based on the retrospective cohort study. From January 2004 to December 2009, all lobectomies performed in a university-based tertiary care hospital were analyzed. The inclusion criteria were as follows: (I) VATS lobectomy for benign disease; (II) thoracotomy conversion cases initially approached by VATS lobectomy. All malignant cases were excluded. Electronic medical records were retrospectively analyzed and patients were divided into two groups: with infection and without infection. The primary outcomes were the thoracotomy conversion rate, length of hospital stay, period of thoracic drainage and complications. VATS was performed in 163 (42%) of 385 patients who underwent lobectomy for benign disease. There were 68 in the infection group and 95 in the group without infection. VATS lobectomy was successful in 157 (96%) patients while 6 were converted into thoracotomy. The mean operation time and blood loss were 160 minutes and 326 mL. Comparing two groups, operation time and blood loss were not statistically different (P value =0.92, 0.63). Moreover conversion rate, length of hospital stay, period of thoracic drainage and complications (P value =0.67, 0.18, 0.25, and 0.50) were not different. VATS lobectomy for benign disease is practical and effective in selected cases regardless of the presence of infection. However, because various technical obstacles may be encountered during the procedure, therefore, careful patient selection is needed.

Circulating Tumor Cells in Peripheral and Pulmonary Venous Blood Predict Poor Long-Term Survival in Surgically Resected Non-Small Cell Lung Cancer Patients

ABSTRACT Aim: We tested the hypothesis that the circulating tumor cells (CTCs) in preoperative peripheral blood (PPB) and intraoperative pulmonary venous blood (IPVB) could predict poor long-term survival in surgically resected NSCLC patients. Methods: CTCs were separated from the blood using magnetic beads coated with antibody against epithelial-cell adhesion molecule (EpCAM) through magnetic activated cell sorting (MACS). The CTCs were quantified with fluorescence-labeled antibodies against pan-cytokeratin through flow cytometry. CTCs were prospectively quantified in PPB and IPVB in 23 consecutive stage I-IIIA patients with surgically resected NSCLC. Association between CTCs and prognosis of these patients was evaluated after 5-year follow-up. Results: In the NSCLC patients, outcomes were assessed according to levels of CTCs at surgery, and compared with CTCs detected in benign pulmonary diseases, and healthy volunteers, where the mean and 95% CI of CTCs counts were all 5 CTCs/15mL in PPB and >50 CTCs/15mL in IPVB. Univariate Cox proportional-hazards regression analysis showed that CTCs count in PPB or IPVB was an independent risk factor for tumor-free and overall survivals. The high risk group of patients had a shorter median tumor-free survival (22 months vs. >60.0 months, P 60 months, P Conclusions: CTCs count in PPB and IPVB was an independent risk factor for tumor-free and overall survival in surgically resected NSCLC patients. Disclosure: All authors have declared no conflicts of interest.

Immediate and Long-term Results of Bronchial Artery Embolization for Hemoptysis Due to Benign Versus Malignant Pulmonary Diseases

BackgroundBronchial artery embolization (BAE) is widely used for the treatment of hemoptysis. The immediate and long-term results of BAE for hemoptysis in patients with benign and malignant pulmonary diseases were inconsistent in previous studies and were thus investigated. MethodsThis was a retrospective review of the clinical records of 154 patients (108 with benign disease and 46 with malignant disease) who received BAE for hemoptysis from January 2005 to June 2011 at the Chinese People's Liberation Army General Hospital. ResultsImmediate cessation of hemoptysis was achieved in 98 patients with benign disease (90.7%) and 42 patients with malignancy (91.3%). The long-term control rate of hemoptysis in patients with benign disease was 74.3% (80/108) at 1 year, significantly higher than in patients with cancer (16/46, 35.5%, P<0.01). The worst outcomes in the benign and malignant groups were observed in patients with aspergilloma and squamous cell lung cancer, respectively. The average number of abnormal vessels on bronchial arteriography was higher in the benign group than in the malignant group (3±1.3 versus 2±1.1, respectively, P<0.01). Moreover, recurrent hemoptysis was independently associated with the presence of massive hemoptysis and bronchial-pulmonary artery shunt in both groups (P<0.05). ConclusionsBAE is a relatively safe procedure for patients with hemoptysis. immediate control of hemoptysis with BAE is achieved in most cases, but the long-term hemoptysis control rate is worse in malignant lung diseases than in benign conditions, especially among patients with squamous cell lung cancer.

Serum cytokeratin 19 fragment, CK19-2G2, as a newly identified biomarker for lung cancer.

BackgroundCK19-2G2, a new fragment of cytokeratin 19, is a potential tumor marker for diagnosing lung cancer. The preoperative level of serum CK19-2G2 has been demonstrated to be associated with tumor metastasis and survival of breast cancer patients. This study investigated the postoperative dynamic changes in serum CK19-2G2 levels and its clinical significance in lung cancer patients.Materials and MethodsPreoperative serum CK19-2G2 levels were measured in 630 lung cancer patients and were compared with individuals with benign pulmonary diseases (n = 134) and healthy volunteers (n = 263). In 352 cases, the patients underwent surgery. In these patients, in addition to preoperative assays, serum CK19-2G2 was also monitored at 1 week and 1 month after the operation.ResultsThe preoperative baseline levels of serum CK19-2G2 was significantly higher in lung cancer patients than patients with benign diseases and healthy controls (P<0.001). The postoperative levels of CK19-2G2 declined significantly within 1 week after tumor resection. Hereafter, a further decrease was observed in the patients who underwent palliative operations, while for the patients in the radical resection group, their CK19-2G2 levels stabilized.ConclusionCK19-2G2 may be a candidate marker for diagnosing and monitoring a patient's response to lung cancer treatment. In addition, CK19-2G2 may be an indicator for micrometastases in lung cancer patients.

94 th Annual Meeting of the American Association for Thoracic Surgery (AATS) seen through thoracic surgical glasses

The 94th Annual Meeting of the American Association for Thoracic Surgery (AATS) was held from Saturday, April 26 till Wednesday, April 30 in Toronto, Ontario, Canada, home of a world renowned department of general thoracic surgery and lung transplantation where one of our junior colleagues is currently performing a fellowship to obtain more experience with complex thoracic surgical interventions. The AATS congress was very well organized, smoothly running and providing an outstanding scientific program addressing all major thoracic topics. My main interests for this congress were lung cancer, mesothelioma, quality improvement, transplantation and basic research. The general thoracic symposium was entitled ‘Becoming a master thoracic surgeon’. Timely subjects were chosen which were of major interest to our specialty. Regarding lung cancer the topics ranged from the smallest lesions to large cancers invading the spine, aorta or main carina. Scientific updates and technical aspects were thoroughly discussed. Alternative techniques to surgery were put into perspective as brachytherapy and stereotactic radiotherapy. There is clearly a need for more prospective randomized trials and the difficulties of performing such trials including financial and regulatory issues seem to be universal! Interesting debates were presented on pulmonary metastasectomy and stage IIIA lung cancer for which the role of surgery remains highly controversial. Multimodality treatment clearly presents the way to move forward and improve overall survival results. The non-oncological procedures, lung volume reduction surgery and endobronchial valves continue to be debatable interventions. Very interesting was the presentation on ex vivo lung perfusion allowing marginal donor lungs to recover and subsequently to be used for lung transplantation. The presidential address of Dr. D. Sugarbaker was centered around “focused attention” which is essential to obtain excellence in our specialty. Disturbing circumstances should be avoided as much as possible in order to stay focused especially in the operating room when performing technically challenging procedures. In the scientific sessions highly selected abstracts were presented and most of them were of high quality giving rise to vivid discussions. Also the pro-con debates e.g., on robotic surgery were animated and certainly, technology is advancing in a fast way. Concerning quality control and improvement, it is obvious that specific indicators are being developed and will be introduced in daily clinical practice to benchmark the results of different thoracic centers. A minimal surgeon and hospital volume is required to obtain the best postoperative results. There were also quite a lot of interesting posters often presented by junior staff and fellows. I particularly liked the poster discussions with the authors which enables them to interact with senior colleagues. Current guidelines which are of special interest to cardiothoracic surgeons were included in the program as e.g., on the prevention and management of atrial fibrillation in thoracic surgical procedures. Atrial fibrillation remains a major postoperative complication in general thoracic surgery. Treatment should be tailored to specific patients’ characteristics. Late-breaking clinical trials brought interesting and stimulating subjects to our attention as the analysis of exhaled carbonyl compounds to differentiate between benign and malignant pulmonary disease. Image-guided video-assisted thoracic surgery seems a promising technique to adequately remove pulmonary nodules with safe margins. Invited speakers were scheduled within scientific sessions and the ‘Evolution of staging in lung cancer’ presented by Dr. Peter Goldstraw brought a refreshing and enlighting historical overview of the different versions of the tumour-node-metastasis (TNM) classification of lung cancer. In general, the AATS annual meeting was extremely valuable in providing a summary and update of general thoracic surgery at the same time offering a lot of opportunities to interact and discuss not only with colleagues of North America but in fact of large parts of the world, making it a real international conference.

Quantitative analysis of exhaled carbonyl compounds distinguishes benign from malignant pulmonary disease

The analysis of exhaled breath is a promising noninvasive tool for the diagnosis of lung cancer, but its clinical relevance has yet to be established. We report the analysis of exhaled volatile carbonyl compounds for the identification of specific carbonyl cancer markers to differentiate benign pulmonary disease from early-stage lung cancer and to compare its diagnostic accuracy with positron emission tomography (PET) scans. Aminooxy-coated silicon microchips were used for the selective capture of exhaled carbonyls by an oximation reaction. Breath samples were collected then directed through the silicon chips by applying a vacuum. Carbonyl adducts were analyzed by Fourier transform mass spectrometry. Eighty-eight control subjects, 107 patients with lung cancer (64 stage 0, I, or II), 40 patients with benign pulmonary disease, and 7 patients with a solitary pulmonary metastasis participated. Analysis of cancer markers was performed blinded to the pathologic results. Four carbonyls were defined as cancer markers with significantly higher concentrations in patients with lung cancer. The number of increased cancer markers distinguished benign disease from both early and stage III and IV lung cancer. For early-stage disease, defining greater than 2 increased markers as diagnostic of lung cancer resulted in 83% sensitivity and 74% specificity. PET scans for this same cohort resulted in 90% sensitivity but only 39% specificity. Markers normalized for 3 of the 4 markers after resection of the lung cancer. Analysis of specific exhaled carbonyls can differentiate early lung cancer from benign pulmonary disease. Breath analysis was more specific than PET for a lung cancer diagnosis. Judicious use of these data may expedite the care of patients with lung cancer.