Treatment selection pattern and prognostic factors in older patients with non-small cell lung cancer at recurrence: an observational study.

PURPOSE: Society is aging, and the proportion of older patients with lung cancer is increasing. However, the treatment choices and prognoses for older patients with cancer recurrence remain unclear. We retrospectively investigated the treatment choices and prognoses of older patients with recurrence. METHODS: We conducted a retrospective review of 1100 patients who underwent complete resection for non-small cell lung cancer at Kitasato University Hospital between 2004 and 2017. Patients of ≥75 years of age were defined as older patients, and the prognosis and prognostic factors of these patients upon recurrence were examined. RESULTS: Among the 290 patients who developed recurrence, 106 experienced recurrence at an older age. The factors associated with survival after recurrence included sex, time to recurrence, number of recurrences, performance status at recurrence, and active treatment. As the age at recurrence increased, the proportion of patients who did not receive active treatment increased, as did the proportion for whom the reason was the patient's and family's preferences. CONCLUSIONS: A considerable number of older patients who experience recurrence do not wish to receive active treatment. However, the prognosis can be improved by aggressive treatment for recurrence.

Prevalent and up-regulated vimentin expression in micropapillary components of lung adenocarcinomas and its adverse prognostic significance.

The factors conferring the increased malignancy on lung adenocarcinoma with micropapillary component (AC-MPC) remain to be elucidated. On proteomics based on 2-dimensional gel electrophoresis, 19 proteins differentially expressed by more than 1.5-fold between AC-MPC and conventional adenocarcinoma (CAC); in particular, vimentin, one of the proteins, was 3.5-fold up-regulated in AC-MPC. Subsequent semi-quantitative investigation by immunohistochemistry with large cohorts comprised 101 AC-MPC and 119 CAC, respectively, of different stages revealed that vimentin was expressed in MPC of 95 (94.1%) AC-MPC and the expression scores were higher than those of well- and moderately differentiated CAC, as well as the background non-MPC of the AC-MPC (P < 0.0001), but not significantly different from those of poorly differentiated CAC (P = 0.561). Even within the AC-MPC entity, higher vimentin expression was correlated with more frequent vascular invasion and more advanced node metastasis (P < 0.02), and multivariate analysis showed that high vimentin expression and worse node statuses were independent indicators of adverse prognosis (P < 0.048). In conclusion, vimentin expression is prevalent and markedly up-regulated in MPC, which might reflect the biological essence of poorer differentiation or dedifferentiation of MPC, and this might have a role in the acquisition and increase of invasiveness and consequent more malignant nature of MPC.

Clinical impact of lung age on postoperative complications in non-small cell lung cancer patients aged >70 y.

BACKGROUND: Surgery for elderly patients with primary lung neoplasms has become relatively common as populations age; however, the high frequency of postoperative complications has prevented its broad application. Recently, the Japanese Respiratory Society proposed lung age (LA) as an index of lung function, but reports on the association between LA and the risk factors for postoperative complications with non-small cell lung cancer (NSCLC) surgery have been limited. In this study, we analyzed the clinical applicability of LA for elderly patients with NSCLC. MATERIALS AND METHODS: We studied 320 patients aged >70 y underwent curative resections for NSCLC. LA was calculated based on the formula provided by the Japanese Respiratory Society, which depended on the patient's preoperative respiratory function and was divided into four age gap (AG) groups between the LA and the true age (TA). The categorical data were compared among the four groups. RESULTS: The numbers of patients in groups A, B, C, and D were 80, 77, 79, and 84, respectively. For the univariate analysis, the preoperative factors for postoperative complications were gender, AG, and smoking (P < 0.05). In a multivariate analysis, AG proved to be an independent factor. Although we found no significant differences, there was a tendency for the prognosis to worsen with an increase in the AG (P = 0.06). CONCLUSIONS: The AG was significantly associated with and an independent predictive factor for postoperative complications. We conclude that LA and AG are useful factors for predicting the risk of postoperative complications.

[Ultra powered stapling system for general lung surgery].

OBJECTIVE: Stapling systems can significantly improve lung tissue approximation during open and video-assisted thoracic surgery. We here evaluated an iDrive Ultra powered stapling system for lung resection. MATERIALS AND METHODS: The iDrive Ultra powered stapling system( Covidien) is the powered version of the EndoGIA stapling system. It comprises hand-held control unit combined with a loading unit,which is a powered EndoGIA- cartridges, for use in open and minimally invasive thoracic surgery. The mounted control unit has uses as follows:controlling the accurate placement of the cartridge by orientating the tip of the rigid shaft;and controlling the closure of the stapler and the firing. From April to July 2013, the system was used for a consecutive series of 15 patients during thoracic lung surgery. RESULTS: There were 6 women and 9 men, with a mean age of 62 years. The following procedures were performed:lobectomies, segmentectomies, and wedge resections. The system was used for stapling lung parenchyma for wedge resection(5 patients), segmentectomy( 2 patients), or fissure division (9 patients). There were no stapling failures and no complications related to use of the staplers. CONCLUSIONS: The new powered and handy stapling system is safe and efficient for lung resection.

Prognostic factors after radical local therapy for oligo-recurrence of non-small cell lung cancer.

OBJECTIVE: Oligo-recurrence refers to the presence of a limited number of metachronous recurrences that can be treated with radical local therapy, and most patients have a good prognosis. However, the clinical course after local therapy for oligo-recurrence of non-small cell lung cancer (NSCLC) varies, and the prognostic factors are unclear. The aim of this study was to elucidate the prognostic factors of patients with oligo-recurrence of NSCLC who underwent radical local therapy. METHODS: Between 2004 and 2015, 901 patients who underwent complete resection for NSCLC were included. We defined oligo-recurrence as two or fewer recurrences and retrospectively examined the factors that affected post-recurrence survival in patients who underwent radical local therapy for oligo-recurrence. RESULTS: Recurrence was confirmed in 267 patients, and among them, 125 experienced oligo-recurrence. Eighty-five patients with oligo-recurrence received local therapy, and their 5-year post-recurrence survival rate was 42.8%. Multivariable analysis of the prognostic factors of these patients revealed that single recurrence (hazard ratio = 2.19, P = 0.005) and systemic therapy (hazard ratio = 1.75, P = 0.043) were significant favorable prognostic factors associated with post-recurrence survival. However, the presence or absence of epidermal growth factor gene mutations, which is generally a prognostic factor for NSCLC recurrence, did not affect the prognosis of these patients. CONCLUSIONS: The number of recurrences and receiving systemic therapy are important prognostic factors for patients with oligo-recurrence who undergo radical local therapy, and these patients have a particularly favorable prognosis.

Insight into the significance of Foxp3 + tumor-infiltrating lymphocytes in squamous cell lung cancer.

PURPOSE: Although developing a better understanding of tumor-infiltrating Foxp3 + lymphocytes (Foxp3 + TILs) might provide essential knowledge to predict response to immunotherapy and prognosis, our current knowledge about Foxp3 + TILs is inadequate. This study investigated the prognostic significance of tumor-infiltrating Foxp3 + lymphocytes (Foxp3 + TILs) in squamous cell lung cancer (SQ-LC) objectively. METHODS: Among patients with SQ-LC surgically resected in our institution between 2011 and 2017, those with pathological stage IA3-IIIA were immunohistochemically studied to evaluate Foxp3 + TILs in their tumor stroma. The impact of Foxp3 + TILs on relapse-free survival (RFS) was analyzed with Kaplan-Meier survival analysis and multivariate analysis using a Cox proportional hazards model/Fine-Gray model. RESULTS: This study analyzed 100 patients. Multivariate analysis showed that a large number of Foxp3 + TILs in the stroma does not associate with a poor prognosis, rather that a large number of Foxp3 + TILs (≥ 64 cells) tend to be associated with a more favorable prognosis than a small number of Foxp3 + TILs (< 64 cells) (large vs small number: HR, 0.56; 95% CI, 0.17-1.83; P = 0.34). Exploratory analysis also showed that in the two populations divided by a difference in Foxp3 expression levels, similar trends to the main analysis were observed. CONCLUSION: Our results showed that a large number of Foxp3 + TILs in the stroma may not associate with a poor prognosis in SQ-LC. To use the seemingly complicated information of Foxp3 + TILs as biomarkers, better understanding the diversity and heterogeneity of Foxp3 + TILs and analyzing their subpopulations that increase in the TME may be needed.

Micropapillary and solid components as high-grade patterns in IASLC grading system of lung adenocarcinoma: Clinical implications and management.

OBJECTIVES: The grading system proposed by the International Association for the Study of Lung Cancer is based on a combination of predominant histologic subtypes and the proportion of high-grade components with a cutoff of 20%. We aimed to examine the clinical implications of the grading system beyond the discrimination of patient prognosis, while assessing the biological differences among high-grade subtypes. METHODS: We retrospectively reviewed 648 consecutive patients with resected lung adenocarcinomas and examined their clinicopathologic, genotypic, and immunophenotypic features and treatment outcomes. Besides the differences among grades, the clinical impact of different high-grade components: micropapillary (MIP) and solid (SOL) patterns, was individually evaluated. RESULTS: Survival outcomes were well-stratified according to the grading system. Grade 3 tumors exhibited aggressive clinicopathologic features, while being an independent prognostic factor in multivariable analysis. A small proportion (<20 %) of high-grade components in grade 2 had a negative prognostic impact. The prognostic difference bordering on the 20 % cutoff of the MIP proportion was validated; however, the proportion of SOL component did not affect prognosis. A survival benefit from adjuvant chemotherapy was observed in grade 3 tumors regardless of histologic subtype, but not in grade 1-2 tumors. The molecular and immunophenotypic features were different among grades, but still heterogeneous in grade 3, with MIP harboring frequent EGFR mutation and SOL exhibiting high PD-L1 expression. The treatment outcome after recurrence was worse in grade 3, but tumors with MIP pattern had an equivalent prognosis to that of grade 1-2 tumors, reflecting the high frequency of molecular targeted therapy. CONCLUSIONS: In addition to stratifying patient prognosis, the current grading system could discriminate clinical course, therapeutic effects of adjuvant chemotherapy, and molecular and immunophenotypic features. Further stratification based on biological heterogeneity in grade 3 remains necessary to enhance the role of the grading system in guiding patient management.

Insight into the significance of CD8+ tumor-infiltrating lymphocytes in squamous cell lung cancer.

BACKGROUND: Although there are great expectations regarding the use of tumor-infiltrating lymphocytes (TILs) to predict effects of immunotherapies and prognosis, knowledge about TILs remains insufficient for clinical application. METHODS: We objectively investigated the prognostic significance of tumor-infiltrating CD8 + lymphocytes (CD8 + TILs) in squamous cell lung cancer (SQ-LC). Among patients who underwent surgical resection of SQ-LC in 2011-2017, 100 patients with pathological stage IA3-III were immunohistochemically studied to evaluate CD8 + TILs in the tumor stroma and parenchyma. The impact of CD8 + TILs on relapse-free survival was analyzed using a Kaplan-Meier survival analysis and multivariate analyses using Fine-Gray and Cox proportional hazards models. RESULTS: The multivariate analysis showed that large and small numbers, but not intermediate numbers, of CD8 + TILs in the tumor stroma may be related to a more favorable prognosis (small vs. intermediate: HR, 0.64; 95% CI: 0.29-1.41, p = 0.27; large vs. intermediate: HR, 0.48; 95% CI: 0.21-1.09, p = 0.08). In contrast, a large number of CD8 + TILs in the tumor parenchyma was associated with a poor prognosis (HR, 2.60; 95% CI: 0.91-7.42, p = 0.075). An exploratory analysis showed a potentially strong association between an extremely large number of CD8 + TILs in the tumor parenchyma and a poor prognosis, even with a large number of CD8 + TILs in the tumor stroma. CONCLUSION: Our study provided partial but important information on the significance of CD8 + TILs in SQ-LC. To use CD8 + TILs as biomarkers, a better understanding of CD8 + TILs as well as other important components in the tumor microenvironment and the inflammatory phenotypes they form may be needed.

Examination of the effectiveness of local therapy for oligo-recurrence of EGFR-mutated NSCLC.

BACKGROUND: The effectiveness of local therapy has been reported in patients with oligo-recurrence of non-small cell lung cancer (NSCLC), a metachronous recurrence with a limited number of recurrences, which can be treated with local therapy. Conversely, remarkable progress has been made in systemic therapy for NSCLC with the advent of molecular targeted therapy. In particular, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are very effective in the treatment of EGFR-mutated NSCLC. There is currently no consensus on treatment for oligo-recurrence of EGFR-mutated NSCLC. METHODS: From 2004 to 2014, 811 patients underwent complete resection for NSCLC at Kitasato University Hospital and, of these, 244 patients developed recurrence. Oligo-recurrence was defined as the presence of two or less recurrent lesions, and 34 patients presented with EGFR-mutated oligo-recurrence. RESULTS: We retrospectively examined and compared the effects of EGFR-TKIs with those of radical local therapy in patients with oligo-recurrent EGFR-mutated NSCLC. The five-year post-recurrence survival (PRS) rates of patients with EGFR-mutated oligo-recurrence who received radical local therapy (n = 23) and those who did not (n = 11) were 59.4 and 45.5%, respectively (p = 0.777). Multivariate analysis revealed no favorable prognostic factors associated with prolonged PRS, and radical local therapies did not improve PRS in patients with oligo-recurrence (p = 0.551). CONCLUSION: Radical local therapy did not affect PRS in patients with oligo-recurrent EGFR-mutated NSCLC. Even in cases of oligo-recurrence, the administration of local therapy in patients with EGFR-mutated NSCLC might be carefully considered.

Prognostic implications of prostaglandin E-major urinary metabolite in resected non-small-cell lung cancer.

OBJECTIVES: Cyclooxygenase-2-derived prostaglandin E2 (PGE2) is highly involved in the promotion of cancer progression. The end product of this pathway, PGE-major urinary metabolite (PGE-MUM), is a stable metabolite of PGE2 that can be assessed non-invasively and repeatedly in urine samples. The aim of this study was to assess the dynamic changes in perioperative PGE-MUM levels and their prognostic significance in non-small-cell lung cancer (NSCLC). METHODS: Between December 2012 and March 2017, 211 patients who underwent complete resection for NSCLC were analysed prospectively. PGE-MUM levels in 2 spot urine samples taken 1 or 2 days preoperatively and 3-6 weeks postoperatively were measured using a radioimmunoassay kit. RESULTS: Elevated preoperative PGE-MUM levels were associated with tumour size, pleural invasion and advanced stage. Multivariable analysis revealed that age, pleural invasion, lymph node metastasis and postoperative PGE-MUM levels were independent prognostic factors. In matched pre- and postoperative urine samples obtained from patients who are eligible for adjuvant chemotherapy, an increase in PGE-MUM levels following resection was an independent prognostic factor (hazard ratio 3.017, P = 0.005). Adjuvant chemotherapy improved survival in patients with increased PGE-MUM levels after resection (5-year overall survival, 79.0 vs 50.4%, P = 0.027), whereas survival benefit was not observed in those with decreased PGE-MUM levels (5-year overall survival, 82.1 vs 82.3%, P = 0.442). CONCLUSIONS: Increased preoperative PGE-MUM levels can reflect tumour progression and postoperative PGE-MUM levels are a promising biomarker for survival after complete resection in patients with NSCLC. Perioperative changes in PGE-MUM levels may aid in determining the optimal eligibility for adjuvant chemotherapy.

Factors associated with lymph node metastasis upstage after resection for patients with micropapillary lung adenocarcinoma.

BACKGROUND: Micropapillary adenocarcinoma has a poor prognostic histological pattern. Additionally, preoperative detection of lymph node metastases by preoperative examination is difficult in some patients with micropapillary adenocarcinoma, and postoperative upstage may occur. However, clinicopathological features of patients with micropapillary adenocarcinoma with nodal upstage have not been established, therefore this study aimed to identify the factors associated with potential lymph node metastases during preoperative examination to ensure effective surgical procedures. METHODS: Between January 2011 and December 2020, 1029 patients received complete resection for primary non-small-cell lung cancer by lobectomy or more extensive resection with systematic lymph node dissection at this institution. One hundred and thirty-one patients diagnosed with adenocarcinoma with micropapillary component were included in this study. The clinicopathological features of patients with nodal upstage whose postoperative N stage was more advanced than the preoperative N stage were examined. RESULTS: Forty patients had nodal upstage after resection. 18 F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) revealed that a maximum standardized uptake value (SUVmax) ≥5 for the primary lesion was significantly associated with postoperative nodal upstage. There were no significant differences in terms of sex, age, smoking history, surgical procedure, and diabetes. Among 38 patients with nodal upstage, 23 patients had no significant preoperative lymphadenopathy and showed no abnormal FDG uptake in the lymph nodes on 18 F-FDG-PET-CT, respectively. CONCLUSIONS: Lymph node metastases were suspected in patients preoperatively diagnosed with micropapillary adenocarcinoma with FDG SUVmax ≥5 for the primary tumor. Therefore, standard surgical resection and careful lymph node dissection should be performed for such patients.

Impact of the first surge of the coronavirus disease pandemic on general thoracic surgery practices in Kanagawa: a questionnaire survey by the Kanagawa General Thoracic Surgical Study Group.

OBJECTIVES: The first surge in severe acute respiratory syndrome coronavirus 2 infection had a significant impact on health care institutions. Understanding how the pandemic affected general thoracic surgery would provide valuable data for establishing a health care protocol for upcoming surges. METHODS: A questionnaire survey on coronavirus disease-related patient statistics and health care was conducted between February 2020 and June 2020 across 14 facilities affiliated with the Kanagawa General Thoracic Surgery Study Group. RESULTS: The average number of newly referred patients from February to June 2020 was 65% of that during the same period in 2019. Six facilities placed restrictions on medical care services, among which four restricted surgeries. At all institutions and those placed on surgical restriction, the total number of surgeries under general anesthesia was 92% and 78%, the total number of primary lung cancers was 94% and 86%, and the total number of surgeries for pneumothorax was 71% and 77% of that in the preceding year, respectively. Infection control and insufficient resources of the medical material were the most influential factors impacting the medical institutions' decision to restrict the services provided. CONCLUSIONS: Restrictions on surgery had a significant impact on the care provided by general thoracic surgery departments. To avoid patient inconvenience, establishing a collaborative system that refers patients to operational medical institutions in case of medical treatment restrictions may be useful.

Selection of preoperative stress electrocardiography test for appropriate patients with non-small cell lung cancer.

OBJECTIVE: Lobectomy is an established surgical procedure for treating non-small cell lung cancer; however, it significantly impacts postoperative cardiac function. The stress electrocardiography test is relatively easy to perform and is used to confirm the presence of coronary artery stenotic lesions. However, it has a low pre-test probability and may yield many false positives. We examined the factors that would enable the appropriate selection of patients for stress electrocardiography as a preoperative cardiovascular examination preceding lobectomy for non-small cell lung cancer. METHODS: From June 2016 to July 2018, 240 patients at our institution who underwent stress electrocardiography before lobectomy for primary lung cancer were included in this study. Clinical information was extracted from electronic medical records and evaluated retrospectively. Smoking history, diabetes, hypertension, dyslipidemia, and ischemic heart disease were considered risk factors for coronary artery stenosis. We determined the coronary risk factors that were applicable to each participant and calculated the total number of coronary risk factors as a risk score. RESULTS: Patients with coronary risk factor scores of ≥ 3 were significantly more likely to have abnormal stress electrocardiography results. In addition, these patients also underwent more comprehensive examinations to identify coronary diseases. There were no patients with complications that could be attributed to ischemic heart disease. CONCLUSION: Stress electrocardiography may be more useful before lobectomy in non-small cell lung cancer patients if the patients are appropriately selected, with the test utilized mainly in patients with coronary risk factor scores of ≥ 3.

Subxiphoid dual-port thymectomy for thymoma in a patient with post-aortic left brachiocephalic vein.

Post-aortic left brachiocephalic vein (PALBV) is one of the rare congenital vessel abnormalities associated with congenital heart disease. As only a few reports of surgical treatment for thymic tumor in patients with PALBV are available, this study reports the case of a patient with PALBV who underwent surgical treatment for thymoma. In a 60-year old woman, a nodule in the anterior mediastinum was detected on chest computed tomography (CT) during examination for arrhythmia. Thymoma was suspected, and surgical resection was considered. PALBV was detected on a contrast CT scan before surgery. Video-assisted thoracoscopic surgery was used to perform thymectomy using the subxiphoid dual-port approach. This method provided an appropriate view of the operative field and made it easy to confirm the presence of PALBV and identify the thymic veins branching off from the internal thoracic vein.

Prognostic significance of galectin-3 expression in patients with resected NSCLC treated with platinum-based adjuvant chemotherapy.

BACKGROUND: Galectin-3 (GAL3), a protein encoded by the LGALS3 gene, plays diverse roles in cancer initiation, progression, and drug resistance. Accordingly, high GAL3 expression in tumor cells is associated with poor prognosis in non-small cell lung cancer (NSCLC). However, the prognostic impact of GAL3 expression on patients with resected NSCLC receiving platinum-based adjuvant chemotherapy (AC) remains unclear. This study aimed to determine the prognostic significance of GAL3 expression in NSCLC patients receiving platinum-based AC. METHODS: The study included 111 patients with completely resected stages II and IIIA NSCLC who were receiving platinum-based AC. GAL3 expression in cancer cells was evaluated immunohistochemically according to H-score ("histo score), with a score of ≥170 considered as high expression. The correlation of GAL3 expression with clinicopathological characteristics and survival was subsequently evaluated. RESULTS: In survival analysis, GAL3 expression was significantly associated with recurrence-free survival (RFS) and overall survival (OS). In multivariate analysis, GAL3 expression was an independent predictive factor of RFS rather than OS. CONCLUSIONS: GAL3 expression is a reliable biomarker to predict the prognosis of completely resected NSCLC patients receiving platinum-based AC.

Resection of intra-pulmonary endometriosis by video-assisted thoracoscopic surgery under pre-operative CT-guided marking synchronized with menstrual cycle.

A 37-year-old woman experienced repeated catamenial hemoptysis. She had a history of intrauterine curettage. Computed tomography (CT) showed ground glass opacity (GGO) in the right upper lung lobe. We suspected pulmonary endometriosis and scheduled surgery coincides with her menstrual cycle. Then she underwent surgical resection after pre-operative CT-guided marking of the pulmonary endometrial lesion. A yellowish change of the pleura was observed near the marking and the lesion was resected using video-assisted thoracoscopic surgery. Histopathologically, endometrial glands and intimal interstitium were evident. She has no symptoms 2.5 years after surgery. In this case, scheduling the surgery at the time of her menstrual period and video-assisted thoracoscopic surgery (VATS) after CT-guided marking facilitated effective resection.

Comparison between quantitative computed tomography, scintigraphy, and anatomical methods for prediction of postoperative FEV1 and DLCO: effects of chronic obstructive pulmonary disease status and resected lobes.

BACKGROUND: Postoperative assessment of pulmonary function is important for estimating the risk of thoracic surgery and long-term disability following pulmonary resection, including predicted postoperative (ppo) forced expiratory volume (FEV) in one second (ppoFEV1) and percent predicted lung diffusion capacity for carbon monoxide (ppo%DLCO) estimation. The ppo values were compared using four different estimation methods between chronic obstructive pulmonary disease (COPD) and non-COPD patients and according to the resected lobe. METHODS: This prospective study included 59 eligible patients requiring single lobectomy and succeeded in performing pulmonary function tests at 3 and 12 months after lobectomy. The ppoFEV1 and ppo%DLCO were compared with poFEV1 and po%DLCO obtained at 3 and 12 months after lobectomy. The ppo values were estimated using the four usual methods: the 19-segment anatomical technique (S), perfusion scintigraphy (Q), quantitative CT (CT), and quantitative CT with low attenuation volume (CTLAV) subtraction. RESULTS: For non-COPD and COPD patients, the smallest mean difference between ppo and po values was observed by S for FEV1 and %DLCO. Based on the resected lobe, the smallest mean difference was observed by (I) Q for right upper lobectomy (RUL) excluding %DLCO at 12 months by S, (II) S for left upper lobectomy (LUL), (III) CT and CTLAV for right lower lobectomy (RLL), and (IV) CT and CTLAV for left lower lobectomy (LLL) at 12 months. The ppo values calculated by S for RUL (FEV1 at 3 and 12 months and %DLCO at 3 months) and by all four methods for LLL (FEV1 and %DLCO at 3 months) were smaller than the po values. CONCLUSIONS: The S method is adequate for calculating ppoFEV1 and ppo%DLCO when patients are classified as non-COPD and COPD. However, S sometimes overestimates the ppoFEV1 and ppo%DLCO when patients are classified according to the resected lobe. The CTLAV method may be the method of choice instead of S for calculating ppoFEV1 and ppo%DLCO in patients who undergo lung lobectomy despite the presence or absence of airflow limitation.

EGFR mutation genotyping and ALK status determination in liquid-based cytology samples of non-small cell lung cancer.

Personalised medicine for primary lung cancers (PLCs) requires molecular analysis of cancer tissue or cells. The primary objective of the present prospective study was to assess the concordance between epidermal growth factor receptor (EGFR) gene mutation detection and echinoderm microtubule-associated protein-like (EML) 4-anaplastic lymphoma kinase protein (ALK) expression using liquid-based cytology (LBC) samples and matched histology samples of PLC patients. A total of 117 patients who underwent surgical resection of non-small cell PLC were enrolled. Cytological specimens scratched from the resected PLC lesion were fixed in CytoRich Red. DNA extracted from LBC samples was examined for EGFR gene mutations. Anaplastic lymphoma kinase arrangement was analysed by immunostaining and fluorescence in situ hybridisation. Our patient cohort comprised 93 cases of adenocarcinoma, 16 squamous cell carcinoma, three adenosquamous carcinoma, two large cell neuroendocrine carcinoma, one pleomorphic carcinoma and two other cases. Sixty-six (58.4%) LBC samples harboured EGFR gene mutations. The overall concordance rate in EGFR gene mutation status, including minor mutations, between histologic and paired LBC specimens (N = 105) was 100%. The overall concordance rate of EGFR gene mutation status, including minor mutations and ALK status according to immunostains between histologic and paired LBC specimens, was 100% (105/105) and 100% (48/48), respectively. Genotyping and protein expression studies can be reliably performed using LBC samples prepared with CytoRich Red. Analysis of such samples may guide individual therapy in PLC patients.

Sensitive and specific new enzyme-linked immunosorbent assay for N-ERC/mesothelin increases its potential as a useful serum tumor marker for mesothelioma.

BACKGROUND: Because mesothelioma initially progresses on the surface of the pleura and peritoneum without forming masses, it has been difficult to diagnose at an early stage. It would be very useful to identify a tumor marker that could be used for screening to enable more diagnoses to be made at an early, treatable stage. MATERIALS AND METHODS: We had previously identified N-ERC/mesothelin as a potential biomarker for mesothelioma. In the current work, we used a newly developed ELISA system to gain data on N-ERC/mesothelin levels in various clinical settings. A total of 102 healthy volunteers were recruited. In addition, 39 patients were diagnosed with mesothelioma, 53 patients were diagnosed with diseases that should be distinguished from mesothelioma, and 201 subjects were diagnosed with asbestos-related nonmalignant diseases (including simple exposure to asbestosis) who were treated at any of the cooperating hospitals were enrolled. RESULTS: Serum N-ERC/mesothelin levels measured by a new ELISA system showed that the median values from patients with mesothelioma were extremely high compared with levels obtained from other patients. Analysis in terms of histologic type showed that serum levels of N-ERC/mesothelin were elevated in epithelioid type mesothelioma, especially. In four important models of clinical settings, the sensitivity and specificity of N-ERC/mesothelin were about 71% to 90% and 88% to 93%, respectively. CONCLUSION: N-ERC/mesothelin is a very promising tumor marker for mesothelioma, especially epithelioid mesothelioma.