Comparative evaluation of staging algorithms proven N2 non-small cell lung cancer treated by lung resection after neoadjuvant therapy.

Background: In this study, we aimed to compare the performances of clinical methods, minimally invasive methods, mediastinoscopy, and re-mediastinoscopy used in the restaging of patients receiving neoadjuvant therapy for pathologically proven N2. Our secondary objective was to determine the most optimal algorithm for initial staging and restaging after neoadjuvant therapy. Methods: Between April 2003 and August 2017, a total of 105 patients (99 males, 6 females; mean age: 54.5±8.2 years; range, 27 to 73 years) who were diagnosed with pathologically proven Stage 3A-B N2 non-small cell lung cancer and received neoadjuvant therapy and subsequently lung resection were retrospectively analyzed. Staging algorithm groups (Group 1=first mediastinoscopy-second clinic, Group 2=first mediastinoscopy-second minimally invasive, Group 3=first mediastinoscopy-second re-mediastinoscopy, and Group 4=first minimally invasive-second mediastinoscopy) were created and compared. Results: In the first stage, N2 diagnosis was made in 90 patients by mediastinoscopy and in 15 patients by minimally invasive method. In the second stage, 44 patients were restaged by the clinical method, 23 by the minimally invasive method, 23 by re-mediastinoscopy, and 15 by mediastinoscopy. The false negativity rates of Groups 1, 2, 3, and 4 were 27.2%, 26.1%, 21.8%, and 13.3%, respectively. The most reliable staging algorithm was found to be the minimally invasive method in the first step and mediastinoscopy in the second step. The mean overall five-year survival rate was 46.3±4.4%, and downstaging in lymph node involvement was found to have a favorable effect on survival (54.3% vs. 21.8%, respectively; p=0.003). Conclusion: The staging method to be chosen before and after neoadjuvant therapy is critical in the treatment of Stage 3A-B N2 non-small cell lung cancer. In re-mediastinoscopy, the rate of false negativity increases due to technical difficulties and insufficient sampling. As the most optimal staging algorithm, the minimally invasive method is recommended in the first step and mediastinoscopy in the second step.

The prognostic impact of the mediastinal fat tissue invasion in patients with non-small cell lung cancer.

BACKGROUND: The prognosis of the mediastinal fat tissue invasion in non-small cell lung cancer (NSCLC) patients has not yet been clearly defined. The present study aimed to investigate the prognostic impact of the mediastinal fat tissue invasion in NSCLC patients. METHOD: We analyzed 36 patients who were found mediastinal fat tissue invasion by pathological evaluation (mediastinal fat group) and 248 patients who were classified as T4-NSCLC according to the 8th TNM classification (T4 group; invasion of other mediastinal structures in 78 patients, ipsilateral different lobe satellite pulmonary nodule in 32 patients, and tumor diameter > 7 cm in 138 patients). RESULT: Resection was regarded as complete (R0) in 255 patients (89.7%). Mediastinal fat group showed significantly higher incidence of incomplete resection (R1) and more left-sided tumors than the T4 group (p = 0.01, and p = 0.002, respectively). The survival was better in T4 group than mediastinal fat group (median 57 months versus 31 months), although it was not significant (p = 0.205). Even when only N0/1 or R0 patients were analyzed, the survival was not different between two groups (p = 0.420, and p = 0.418, respectively). 5-year survival rates for T4 subcategories (invasion of other structures, ipsilateral different lobe pulmonary nodule, and tumor diameter > 7 cm) were 39.4%, 41.9%, and 50.3%, respectively (p = 0.109). Multivariate analysis showed that age (p < 0.0001), nodal status (p = 0.0003), and complete resection (p < 0.0001) were independently influenced survival. CONCLUSION: There is no significant difference in the prognosis between mediastinal fat tissue invasion and T4 disease in NSCLC patients.

Prognostic Factors and Survival in Resected T4 Non-small Cell Lung Cancer: Is There Any Difference in the T4 Subgroups?

INTRODUCTION: The eighth edition of the TNM classification revised the subgroups of T4 non-small cell lung cancer (NSCLC). This study aimed to compare the T4-NSCLC subgroups that underwent surgical treatment in terms of mortality, morbidity, survival, and prognostic factors based on the new classification. MATERIALS AND METHODS: Between 2000 and 2014, a total of 284 T4-NSCLC patients who underwent lung resection (mediastinal organ invasion, n = 114; ipsilateral different lobe tumors, n = 32; and tumors larger than 7 cm, n = 138) were included in the present study. RESULTS: Surgical mortality and morbidity were 5.6% (n = 16) and 23.9% (n = 68), respectively. The 5-year survival rates were 46% for ipsilateral different lobe tumors, 45.4% for tumours larger than 7 cm, and 36.6% for mediastinal organ invasion (28% for patients with heart/atrium invasion, 43.3% for carina invasion, 37.5% for large vessel invasion) (p = 0.223). Age above 65 (p = 0.002, HR = 1.781), pN2 versus pN0/1 (p < 0.0001, HR = 2.564), incomplete resection (p = 0.003, HR = 2.297), and pneumonectomy (p = 0.02, HR = 1.524) were identified as poor prognostic survival factors. According to multivariate analysis, mediastinal lymph node metastasis (p = 0.001) and incomplete resection (p = 0.0026) were the independent negative risk factors for survival. CONCLUSION: According to the results of our study, surgical treatment is a good option in T4-NSCLC patients who have no mediastinal lymph node metastasis and are completely resectable. There is no difference in terms of survival among the T4 subgroups. The eighth edition of the TNM classification has a better prognostic definition than the previous version.

A Comparison of the Currently Used Nodal Stage Classification with the Number of Metastatic Lymph Nodes and the Number of Metastatic Lymph Node Stations for Non-Small Cell Lung Cancer; Which of These Is the Best Prognostic Factor?

OBJECTIVES: We aimed to compare the currently used nodal staging system (pN) with the number of metastatic lymph node (LN) stations (sN) and the number of metastatic LNs (nN) on survival in patients with NSCLC. METHODS: Between 2010 and 2017, 1038 patients resected for NSCLC were analyzed. We performed three-different stratifications of LN status assessment: pN-category (pN0, pN1 and pN2); sN-category (sN0, sN1; one station metastasis, sN2; two-three stations metastases, and sN3; ≥ 4 stations metastasis); nN-category (nN0, nN1; one-three LNs metastasis, nN2; four-six Lns metastasis, and nN3; ≥ 7 LNs metastasis). RESULTS: Five-year survival rate was 70.1% for N0 in all classifications. It was 54.3% for pN1, and 26.4% for pN2 (p < 0.0001). Five-year survival rates for N1, N2, and N3 categories were 54.1%, 42.4% and 16.1% according to sN, and 51.4%, 36.1%, and 7.9% according to nN, respectively (p < 0.0001). In multivariate analysis, sN and nN were independent risk factors such as pN (p < 0.0001). Hazard ratios versus N0 for N1, N2, and N3 were more significant for sN and nN than pN (1.597, 2.176, and, 3.883 for sN, 1.645, 2.658, and, 4.118 for nN, and 1.576, 3.222 for pN, respectively). When the subcategories of sN and nN were divided into pN1 and pN2 subgroups, the anatomic location of the LN involvement lost importance as tumor burden and tumor spreading increased. CONCLUSION: The number of metastatic LN stations and the number of metastatic LNs are better prognostic factors than currently used nodal classification in NSCLC.

Evaluation of anxiolytic effect and withdrawal anxiety in chronic intermittent diazepam treatment in rats.

This study evaluated the effect of intermittent administration in the development of dependence to diazepam in chronic use of the drug. Gabapentin was used to provide an anxiolytic effect on drug-free days. During a 28-day treatment schedule, rats were given diazepam (15 mg/kg) once daily continuously, or intermittently with saline or gabapentin (50 mg/kg) on days 5, 10, 15, 20, and 25. Anxiety-like behavior was assessed on days 10 and 30 using the elevated plus-maze test and novelty-induced grooming test. Contrary to continuous administration, intermittent diazepam did not provide anxiolytic-like activity on day 10; instead, it prevented withdrawal anxiety on day 30. Gabapentin produced anxiolytic-like effects during the withdrawal period, but not on day 10. These results suggest that intermittent administration of diazepam (given either alone or alternatively with a drug possessing anxiolytic activity) may be of value in preventing the development of physical dependence during the chronic use of the drug. However, further studies are needed to demonstrate that this protocol could effectively produce anxiolytic activity on diazepam-free days.

Silicosis in denim sandblasters.

BACKGROUND: During the past 2 decades, silica sand has been used widely in sandblasting denim in Turkey, which has resulted in an epidemic of silicosis. This study was conducted to summarize the clinical outcomes of formerly healthy young people who became disabled or died because of working in the textile industry. METHODS: The medical records of patients with silicosis due to denim sandblasting who were seen at our institution between 2001 and 2009 were reviewed. Follow-up data were assessed. Compensation and vital status of patients were determined, and survival analysis was performed. RESULTS: Thirty-two male patients diagnosed with silicosis due to denim sandblasting over an 8-year period were identified. Mean age was 31.5 years. They worked as denim sandblasters for a mean 66.4 h/wk for a median 28.5 months. Their mean cumulative exposure time to silica sand was 12,957 h. The median follow-up period was 29 months (range 3-101 months). The median latency period (time elapsed between initial exposure and diagnosis) was 5.5 years (range 2-14 years). Six of the followed patients (19%) died of progressive massive fibrosis. Nine of the patients (28%) were compensated because of silicosis. Just two patients with silicosis received compensation before they died. The mean survival rate was 78 months. The estimated 5-year survival rate was 69% for denim sandblasters with silicosis. CONCLUSIONS: Silicosis in young individuals after exposure in the textile sector suggests a lack of awareness of the hazards of silica outside of the traditional occupations associated with silicosis. Death from silicosis in young people suggests overexposure and unsafe working conditions as a result of a lack of control.

Scopolamine-induced convulsions in fasted mice after food intake: effects of glucose intake, antimuscarinic activity and anticonvulsant drugs.

The present study was performed to further evaluate the contribution of antimuscarinic activity and hypoglycaemia to the development of scopolamine-induced convulsions in fasted mice after food intake. The effects of anticonvulsant drugs on convulsions were also evaluated. Antimuscarinic drugs atropine (3 mg/kg) and biperiden (10 mg/kg) were given intraperitoneally (i.p) to animals fasted for 48 h. Like scopolamine, both drugs induced convulsions after animals were allowed to eat ad libitum. Another group of animals was given glucose (5%) in drinking water during fasting. These animals, although they had normoglycaemic blood levels after fasting, also developed convulsions after treated with scopolamine i.p. (3 mg/kg), atropine (3 mg/kg) or biperiden (10 mg/kg) and allowed to eat ad libitum. Among the drugs studied, only valproate (340 mg/kg), gabapentin (50 mg/kg) and diazepam (2.5 and 5 mg/kg) markedly reduced the incidence of scopolamine-induced convulsions. The present results indicate that antimuscarinic activity, but not hypoglycaemia, underlies these convulsions which do not respond to most of the conventional anticonvulsant drugs.