Description of an activity-based enzyme biosensor for lung cancer detection.

BACKGROUND: Lung cancer is associated with the greatest cancer mortality as it typically presents with incurable distributed disease. Biomarkers relevant to risk assessment for the detection of lung cancer continue to be a challenge because they are often not detectable during the asymptomatic curable stage of the disease. A solution to population-scale testing for lung cancer will require a combination of performance, scalability, cost-effectiveness, and simplicity. METHODS: One solution is to measure the activity of serum available enzymes that contribute to the transformation process rather than counting biomarkers. Protease enzymes modify the environment during tumor growth and present an attractive target for detection. An activity based sensor platform sensitive to active protease enzymes is presented. A panel of 18 sensors was used to measure 750 sera samples from participants at increased risk for lung cancer with or without the disease. RESULTS: A machine learning approach is applied to generate algorithms that detect 90% of cancer patients overall with a specificity of 82% including 90% sensitivity in Stage I when disease intervention is most effective and detection more challenging. CONCLUSION: This approach is promising as a scalable, clinically useful platform to help detect patients who have lung cancer using a simple blood sample. The performance and cost profile is being pursued in studies as a platform for population wide screening.

Lung cancer is responsible for more deaths worldwide than all other cancers. It is often detected with the appearance of symptoms when treatment is limited and outcomes for the patient are much worse. While imaging chest scans can detect disease, they are poorly used even in the United States where it is an approved screening method. When cancer is present, protease enzymes are responsible for making space and modifying the lung tissue for the growing tumor. This report describes a panel of 18 sensors that release a fluorescent signal when these enzymes are present in a blood sample. The signal acts like a fingerprint of activity that can be used to identify people with lung cancer. This sensor platform can detect patients with curable lung cancer and could provide a platform for screening very large populations of at-risk individuals.

The role of adjuvant chemotherapy in resected stage I non - small cell lung cancer: A Turkish Oncology Group Study.

PURPOSE: The benefit of adjuvant chemotherapy for tumors smaller than 4 cm is not clear. We aimed to evaluate the prognostic impact of adjuvant platin-based chemotherapy in high-risk stage I patients with non-small cell lung cancer (NSCLC). METHODS: This cooperative group study included 232 NSCLC patients who underwent curative surgery for stage I disease with tumor size 2-4 cm. Re ults: Median age at presentation was 63 years (range 18-90). The mean tumor size was 29.6 ± 7.3 mm. The frequency of patients with specified risk factors were: visceral pleural effusion (VPI): n: 82 (36.6%); lymphovascular invasion (LVI): n: 86 (39.1%); Grade 3: n: 48 (32.7%); Solid micropapillary pattern (SMP): n: 70 (48.3%). Adjuvant platin-based chemotherapy was administered to 51 patients. During a median follow-up period of 50.5 months 68 patients (29.3%) developed recurrence, 54 (23.3%) died from any cause and 38 (16.4%) of them died of lung cancer. Patients who received chemotherapy compared with the non-chemotherapy group had a longer 5-years relapse-free survival (RFS) (84.5 vs 61.1%). Also on multivariate analysis, adjuvant chemotherapy was a significant independent prognostic factor for RFS. CONCLUSION: Adjuvant platin-based chemotherapy should be considered for patients with small tumors with adverse risk factors. Key words: adjuvant chemotherapy, lung cancer, oncology, lymphovascular invasion, solid-micropapillary pattern, platinum-based therapy.

Differences in PET/CT standardized uptake values involvement and survival compared to histologic subtypes of lung adenocarcinoma.

PURPOSE: Lung adenocarcinoma is histologically diverse but has distinct histologic growth patterns. There is no consensus on the clinical benefit of this histologic model. We aimed to evaluate the differences in the distribution of the preoperative primary tumor positron emission tomography (PET)/computed tomography (CT) standardized uptake values (SUVs) and survival in the lung adenocarcinoma subtypes. METHODS: We retrospectively evaluated the data of 107 patients with resected lung adenocarcinoma who had preoperative PET/CT between 2005 and 2017 in a single center. Patients had lepidic, acinar, papillary, micropapillary, and solid histologic subtypes. We compared fluorodeoxyglucose SUVs and survival data of histologic subtypes. RESULTS: The median age of the patients was 62 years (40-75), 76.4% were male, the median SUVmax was 9.4 (1-36.7), and the median follow-up time was 29 months (3-135 months). The median overall survival (OS) was 71 months and the median progression-free survival (PFS) was 33 months. SUVmax was significantly different in histologic subtypes: values for papillary, micropapillary, solid, acinar, and lepidic subtypes were 9.7, 8, 12, 9.1, and 3.9, respectively (p = 0.000). Solid predominant adenocarcinoma had significantly higher SUVmax than the other subtypes (p = 0.001). Lepidic predominant adenocarcinoma had significantly lower SUVmax than the other subtypes (p = 0.000). There was no significant difference in OS between histologic subtypes (p = 0.66), but PFS was significantly different between the groups (p = 0.017), and the solid subtype had a shorter PFS than the other histologic subtypes. CONCLUSION: Lung adenocarcinoma consists of a diverse group of diseases. Different SUVmax values are seen in different histologic subtypes of nonmetastatic lung adenocarcinoma. Solid predominant types have high SUVmax values while lepidic predominant types have lower SUVmax values. The solid subtype had a shorter PFS than the other histologic subtypes.

Evaluation of Cytotoxicity and Mutagenicity of Wastewater from Istanbul: Data from Hospitals and Advanced Wastewater Treatment Plant.

Wastewater (WW) carry considerable amount of chemicals that could have mutagenic or cytotoxic effect from hospital discharges to aquatic environment. Our objective was to determinate the possible mutagenic and toxic effects of hospital originated WWs and effectiveness of the wastewater treatment plants (WTP) functions. In the study the mutagenic and cytotoxic potential of three hospitals and influent/effluent of a treatment plant WW collected in Istanbul and was examined using AMES, XTT, and lactate dehydrogenase (LDH) assays. Mutagenic effects were detected at both hospital discharges and advanced biological wastewater plant. We observed no cytotoxic effect in fibroblasts for LDH and XTT assays whereas high cytotoxicity for all samples was found in hepatocytes by XTT assay. According to the results even if advanced technology is used for treatment of WW, mutagenic and cytotoxic effects still remain, and the present technologies need to be further improved.

Variations in pulmonary fissural anatomy: a medicolegal autopsy study of 256 cases.

BACKGROUND: We aimed to document the anatomical variations of pulmonary fissures found during routine forensic autopsies. METHODS: A total of 256 pairs of lungs were investigated. Presence of any variant and accessory fissures was noted. RESULTS: Seventy-seven percent of the lungs had anatomical variations. In about 2/3 of the cases, oblique fissures were incomplete on both sides. The horizontal fissure was incomplete in 68.4%, and absent in 4.3% of the lungs. Twelve left lungs (4.7%) had a horizontal fissure. Accessory fissures were observed in 35 lungs (13.7%). Azygos lobe variations were detected in 1.7% of the lungs. A superior accessory fissure was present in 6.2% and 2% of right and left lungs, respectively. CONCLUSION: This and previous similar studies demonstrate the existence of several different anatomical fissural variations in the lungs. Clinicians, radiologists and surgeons should keep these in mind to better evaluate and treat their patients.

Macroscopic complete resection is not associated with improved survival in patients with malignant pleural mesothelioma.

OBJECTIVE: Macroscopic complete resection (MCR) is the recommended surgical strategy in malignant pleural mesothelioma. Our objective was to analyze whether MCR influences survival in malignant pleural mesothelioma. METHODS: Between 2002 and 2016, 154 patients underwent pleurectomy decortication (n = 90), extrapleural pneumonectomy (n = 42), or exploratory/diagnostic procedures (n = 22) in a single institution. Patient data were recorded in a prospective database. Patients who underwent surgical resection (n = 132) were analyzed according to MCR as a whole group and after propensity score matching based on gender, age, histology, clinical T and N status, adjuvant chemotherapy, and trimodality treatment. Kaplan-Meier survival and univariate and multivariate analyses were performed. RESULTS: Median age was 56 years (range, 26 to 80 years) and 62 were women. One hundred ten had epithelioid histology. MCR was achieved in 75 patients (49%). In-hospital mortality was seen in 7 patients (4.5%). Preoperative chemotherapy was applied in 32 patients. One hundred thirty-three patients underwent adjuvant treatment (45 had chemoradiation). Mean follow-up was 21 ± 19 months. Overall median survival, 2-year, and 5-year survivals were 18.1 months, 36%, and 16%, respectively. There was no difference in median survival between patients who underwent MCR (21.4 months) and who did not (16.3 months) (P = .6). Following propensity score matching (23 patients in each group), median survivals were similar (13.3 vs 14.2 months; P = .63). CONCLUSIONS: MCR was not associated with improved survival in malignant pleural mesothelioma. We need to clearly define MCR and identify subgroups of patients who would benefit from this principle because minimal versus extensive and location of gross residual disease may have different influences on survival.

Minimally Invasive Repair of Pectus Carinatum.

BACKGROUND: The second most common deformity of the anterior chest wall, pectus carinatum, is a diverse deformity that has been largely managed using open techniques. This study reviews clinical experience with a newly designed bar for minimally invasive repair of pectus carinatum. METHODS: We reviewed the records of all patients recorded in our Chest Wall Deformities Clinical Database. Between January 2006 and November 2016, minimally invasive repair of pectus carinatum was performed in 172 patients. All met the criteria of a "compression test" of 10 to 25 kg/cm2. The mean age was 17.3 years, and 22.7% had a positive family history of a congenital chest wall deformity. Symmetric and asymmetric deformities were treated. During our study period, we designed 4 different bar configurations and their related stabilizers. All patients are assessed every 3 to 6 months. After 2 to 3 years of follow-up, the bar and the stabilizers are removed. RESULTS: Of 172 patients, 97.1% tolerated the procedure very well. The operation was a mean length 76.6 minutes. Average blood loss was 40 mL. Mean hospital length of stay was 3.7 days. Complications included pneumothorax, wire breakdown/rib cut, wound infection, severe pain, skin hyperpigmentation, nickel allergy, and overcorrection leading to excavatum. Patients returned to routine activity in 10 to 14 days. With a mean follow-up of 29.8 months in bar removal patients, 130 of 172 (93.8%) reported excellent results. CONCLUSIONS: Minimally invasive repair of pectus carinatum with the technically modified fourth-generation bar and its securing system has advantages of low morbidity, short hospital stay, and excellent cosmetic results, even in asymmetric cases.

Protective effect of cysteinyl leukotriene receptor antagonist montelukast in bleomycin-induced pulmonary fibrosis.

BACKGROUND: This study aims to investigate the early- and late-term effects of pharmacological inhibition of cysteinyl leukotriene activity by using montelukast in bleomycin-induced inflammatory and oxidative lung injury in an animal model. METHODS: The study included 48 male Wistar albino rats (weighing 250 g to 300 g). Rats were administered intratracheal bleomycin or saline and assigned into groups to receive montelukast or saline. Bronchoalveolar lavage fluid and lung tissue samples were collected four and 15 days after bleomycin administration. RESULTS: Bleomycin resulted in significant increases in tumor necrosis factor-alpha levels (4.0±1.4 pg/mL in controls vs. 44.1±14.5 pg/mL in early-term vs. 30.3±5.7 pg/mL in late-term, p<0.001 and p<0.001, respectively), transforming growth factor beta 1 levels (28.6±6.6 pg/mL vs. 82.3±14.1 pg/mL in early-term vs. 60.1±2.9 pg/mL in late-term, p<0.001 and p<0.001, respectively), and fibrosis score (1.85±0.89 in early-term vs. 5.60±1.14 in late-term, p<0.001 and p<0.01, respectively). In bleomycin exposed rats, collagen content increased only in the late-term (15.3±3.0 ?g/mg in controls vs. 29.6±9.1 ?g/mg in late-term, p<0.001). Montelukast treatment reversed all these biochemical indices as well as histopathological alterations induced by bleomycin. CONCLUSION: Montelukast attenuates bleomycin-induced inflammatory and oxidative lung injury and prevents lung collagen deposition and fibrotic response. Thus, cysteinyl leukotriene receptor antagonists might be regarded as new therapeutic agents for idiopathic pulmonary fibrosis.

No Adverse Outcomes of Video-Assisted Thoracoscopic Surgery Resection of cT2 Non-Small Cell Lung Cancer during the Learning Curve Period.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) anatomic lung resections are gradually becoming the standard surgical approach in early-stage non-small cell lung cancer (NSCLC). The technique is being applied in cases of larger tumors depending on the experience of the surgical team. The objective of this study was to compare early surgical and survival outcomes in patients undergoing anatomic pulmonary resections using VATS and thoracotomy techniques for clinical T2 NSCLC during the adaptation period of the surgical team to the VATS approach. METHODS: The data of all patients who underwent anatomic pulmonary resection for NSCLC using VATS and open techniques since April 2012 were recorded to create a prospective lung cancer database. Clinical T2 NSCLC patients who underwent VATS anatomic lung resection were identified and compared with cT2 patients who underwent open resection. RESULTS: Between April 2012 and August 2014, 269 anatomical resections for NSCLC were performed (80 VATS and 189 thoracotomy). Thirty-four VATS patients who had clinical T2 disease were identified and stage-matched to thoracotomy patients. The average tumor diameter was comparable (34.2±11.1×29.8±10.1 mm vs. 32.3±9.8×32.5±12.2 mm, p=0.4). Major complications were higher in the thoracotomy group (n=0 vs. n=5, p=0.053). There was no 30-day mortality, and the 2-year survival rate was 91% for VATS and 82% for thoracotomy patients (p=0.4). CONCLUSION: VATS anatomic resections in clinical T2 NSCLC tumors are safe and have perioperative and pathologic outcomes similar to those of thoracotomy, while remaining within the learning curve.

Risk of serious perioperative complications with removal of double bars following the Nuss procedure.

Objectives: The aim of this study is to present our experience with Nuss bar removal and evaluate potential risk factors. The Nuss procedure requires an operation to remove the bar 2-3 years after the initial correction. Although removal of the bar is generally believed to be safe, perioperative complications including major bleeding can occur. Methods: All cases involving removal of the Nuss bar done since April 2007 were recorded in a prospective database. Data were collected on the amount of blood loss, the number of diagnostic interventions, operative management and postoperative course. Results: Of a total of 246 (162 with single bars, 80 with double bars, 4 with triple bars) cases, 43 patients (17.5%) experienced perioperative complications. Five patients underwent secondary postoperative interventions; one patient required same-session emergency video-assisted thoracic surgery (VATS) due to major bleeding. Patients who had complications were significantly older than patients with no complications (20.5 ± 6.5 years vs 17.2 ± 5.9 years, P = 0.002). People having double bars removed were significantly more likely to have perioperative complications (12% vs 27%, P = 0.03) and complications requiring secondary interventions (n = 1 for a single bar, n = 5 for double bars, P = 0.01). Conclusions: Major complications after removal of the Nuss bar occur with some frequency. Although the double-bar removals in our cohort were associated with major complications, the reasons are poorly understood. Immediate management of the complications may require multidisciplinary care. Multicentric pooling of cases is needed for better risk stratification.

Video-assisted minimally invasive diaphragmatic plication: feasibility of a recognized procedure through an uncharacteristic hybrid approach.

BACKGROUND: Diaphragmatic plication is an approved surgical procedure for treatment of symptomatic diaphragmatic paralysis and eventration. We aim to define our minimally invasive technique of plication and objectively assess our surgical outcomes of the largest series reported in the literature so far, using pulmonary function tests. METHODS: Symptomatic patients whom were planned to undergo plication using video-assisted mini-thoracotomy between December 2009 and December 2015 were the cohort of this retrospective study. Single camera port and a utility incision (3-4 cm) were used for access. Data of patient demographics with preoperative and postoperative spirometric results were collected for statistical comparison. RESULTS: Procedure (30 left, 7 right) was completed in 37 (27 male, 10 female) patients. One patient was excluded because of insufficient objective postoperative comparison criteria due to previous permanent tracheostomy. Mean length of surgery was 48.8 ± 19.7 (range: 30-70) min. Postoperative overall morbidity was 8.3 %, with no mortality. The mean length of hospital stay was 3.1 ± 1.7 days. All patients except one (97.3 %) were asymptomatic on discharge and on follow-ups. Significant improvement in measurements of forced expiratory volume in 1st second was observed on postoperative measurements (P < 0.001), with a mean overall increase of 13 % in whole cohort. No recurrence was detected throughout a mean follow-up of 19 months. CONCLUSIONS: Diaphragmatic plication via video-assisted mini-thoracotomy is an effective and curative surgical procedure which can be performed successfully with low morbidity rates. As it combines the rapidity and economical benefits of open thoracotomy with the advantages of video thoracoscopic procedures such as fast recovery and short postoperative hospital stay, it can be preferred as a safe and effective alternative hybrid method compared to standard open or closed techniques, for symptomatic patients with non-functional hemidiaphragm.

Previously Complicated Nuss Procedure Does Not Preclude Blind Removal of the Bar.

BACKGROUND: Nuss procedure has become the procedure of choice for well-selected patients with pectus excavatum. Perioperative complications may pose difficulty during the subsequent bar removal due to adhesions and tissue plane disruptions during the initial surgery and repair. This report describes bar removal experience in patients whose Nuss procedures were complicated by cardiac injury, pericardial breach, and lung parenchyma/diaphragm injury during the initial procedure. METHODS: A total of 529 patients who underwent Nuss procedure between 2007 and 2014 were recorded in a prospective database. Twenty patients with complications (cardiac injury [n = 1], pericardial breach [n = 3], and lung parenchyma/diaphragm injury [n = 16]) were identified. All bars were removed via subcutaneous tissue dissection, without intrathoracic visualization. RESULTS: Average duration of bars was 36 months (±16 months). All bar removal procedures were completed without any need for extra interventions with negligible blood loss. Eighteen patients were able to be discharged within 2 postoperative days. CONCLUSION: Blind bar removal in patients with previously complicated Nuss procedure seems safe and no other interventions (videothoracoscopy, subxiphoid incision, etc.) during bar removal seem to be necessary.

Is Video-Assisted Thoracoscopic Surgery Adequate in Treatment of Pulmonary Hydatidosis?

BACKGROUND: Surgical management of pulmonary hydatid cyst disease has been well established. However, there are still limited data on the role of video-assisted thoracoscopic surgery in treatment of this disease. The aim of this study is to identify the advantages and disadvantages of minimally invasive surgery and compare the outcomes with patients undergoing thoracotomy in this parasitic disease. METHODS: The medical records of 77 patients (53 male, 24 female) undergoing surgery for pulmonary hydatid cyst disease between January 2011 and January 2014 were reviewed. Removal of the hydatid cyst was completed using video-assisted thoracoscopic surgery in 39% (n = 30) of the patients, whereas open thoracotomy was used in 61% (n = 47). Conversion rate was 21%. Statistical analysis was used to assess differences in drainage amount, time to drain removal, length of surgery, length of hospital stay, and pain scores. Probability values of less than 0.05 were considered significant. RESULTS: The drainage amount, time to drain removal, length of surgery, duration of narcotic analgesics usage, and visual analog scale scores in the thoracotomy group were significantly longer than those of the thoracoscopy group. Postoperative complications occurred in 4.3% of thoracotomy and in 13.3% of thoracoscopy patients. There was no mortality in either group. During the follow-up period, no recurrence was detected. CONCLUSIONS: Video-assisted thoracoscopy for surgery of pulmonary hydatid cyst disease is superior to open thoracotomy causing less postoperative pain, a better cosmetic result, a shorter surgical time, a lower drainage volume, and a shorter time to drain removal in a selected group of patients. The fear of recurrence because of incomplete isolation of the cyst during removal was not a concern regarding our technique.

Pulmonary resection in the treatment of life-threatening hemoptysis.

PURPOSE: Massive hemoptysis is a life threatening situation with high mortality rates. Surgery is effective, however generally an avoided treatment. We report our experience with patients undergoing lung resection for life-threatening hemoptysis. METHODS: Records of all surgically treated patients for hemoptysis between June 2009 and June 2012 were reviewed and analyzed retrospectively. RESULTS: Anatomical resection was performed on 31 (15.3%) patients out of 203 patients referred to our intensive care unit for life-threatening hemoptysis. 25 (80.6%) were male and six (19.4%) were female; with mean age of 46.4 ± 13.7 (21-77). Pneumonectomy was performed in four (12.9%), lobectomy in 24 (77.4%), segmentectomy in two (6.5%) and bilobectomy in one case. Postoperative complications developed in eight (25.8%), and mortality was observed in two (6.5%) patients. Etiology was bronchiectasis in 13 (42.0%), tuberculosis in eight (25.8%), carcinoma in four (12.9%), aspergilloma in four (12.9%), hydatid cyst in one (3.2%) and lung abscess in one (3.2%) of the cases. CONCLUSIONS: Although lung resection in the treatment of massive hemoptysis is accompanied with high morbidity and mortality rates, surgery is the only permanent curative modality. Acceptable results can be achived in the company of a multidisciplinary approach, through avoidance of pneumonectomy and urgent surgery.

A comparative cost analysis study of lobectomy performed via video-assisted thoracic surgery versus thoracotomy in Turkey.

INTRODUCTION: Cost analysis studies performed in western countries report that the overall cost of lobectomies performed via video-assisted thoracic surgery is similar to or less than those performed via thoracotomy. The situation may be different in a developing country. AIM: We evaluated the cost differences of these two surgical methods. MATERIAL AND METHODS: We retrospectively reviewed the hospital records of 81 patients who underwent lobectomy either via video-assisted thoracic surgery (n = 32) or via thoracotomy (n = 49). Patient characteristics, pathology, perioperative complications, additional surgical procedures, length of hospital and intensive care unit stay, and outcomes of both groups were recorded. Detailed cost data for medications, anesthesia, laboratory, surgical instruments, disposable instruments and surgery cost itself were also documented. Statistical analyses were performed to compare the groups. RESULTS: The two groups were homogeneous in regard to age, sex, pathology and perioperative morbidity. The mean duration of hospitalization in the video-assisted thoracic surgery group was significantly shorter than that of the thoracotomy group (7.78 ±5.11 days vs. 10.65 ±6.57 days, p < 0.05). Overall final mean cost in the video-assisted thoracic surgery group was significantly higher than that of the thoracotomy group ($3970 ±1873 vs. $3083 ±1013, p = 0.002). This significant difference relies mostly on the cost of disposable surgical instruments, which were used much more in the video-assisted thoracic surgery group than the thoracotomy group ($2252 ±1856 vs. $427 ±47, p < 0.05). CONCLUSIONS: In contrast to western countries, a video-assisted thoracic surgical lobectomy may cost more than a lobectomy via thoracotomy in a developing country. More expensive disposable surgical instruments and cheaper hospital stay charges lead to higher overall costs in video-assisted thoracic surgical lobectomy patients.