The prognostic significance of PD-1 and its ligands in non-small cell lung cancer.

Background: In this study, we aimed to investigate the prognostic value of programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), and programmed cell death ligand 2 (PD-L2) expressions on immune and cancer cells in terms of survival in patients with lung adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Methods: Between January 2000 and December 2012, a total of 191 patients (172 males, 19 females; mean age: 60.3±8.4 years; range, 38 to 78 years) who were diagnosed with non-small cell lung cancer and underwent anatomic resection and mediastinal lymph node dissection were retrospectively analyzed. The patients were evaluated in three groups including lung squamous cell carcinoma (n=61), adenocarcinoma (n=66), and large-cell carcinoma (n=64). The survival rates of all three groups were compared in terms of immunohistochemical expression levels of PD-1, PD-L1, and PD-L2. Results: The mean follow-up was 71.8±47.9 months. In all histological subtypes, PD-1 expressions on tumor and immune cells were observed in 33% (61/191) and in 53.1% (102/191) of the patients, respectively. Higher expression levels of PD-L1 and PD-L2 at any intensity on tumor and immune cells were defined only in lung adenocarcinomas, and PD-L1 and PD-L2 values were detected in 36.4% (22/64) of these patients. The PD-L1 expressions on tumor and immune cells were observed in 41.7% (10/24) and 25% (6/24) of the patients, respectively. The PD-L2 expressions on tumor and immune cells were detected in 16.7% (4/24) and 8.4% (2/24) of the patients, respectively. Univariate and multivariate analyses revealed that PD-1 expression in tumor cells was an independent prognostic factor in all histological subtypes. Conclusion: Our study results suggest that PD-1 expression is a poor prognostic factor for overall survival in patients with completely resected adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.

Video-Assisted Thoracoscopic Surgery vs Thoracotomy for Non-Small Cell Lung Cancer Greater Than 5 cm: Is VATS a feasible approach for large tumors?

BACKGROUND: VATS lobectomy is a recommended surgical approach for patients with early-stage lung cancer. However, it is still controversial in locally advance disease. This study was conducted to compare intraoperative and postoperative results of VATS and thoracotomy in patients with tumors greater than 5 cm. METHODS: From January 2014 to December 2018, 849 patients underwent lobectomy or pneumonectomy for the treatment of non-small-cell lung cancer at our center. The inclusion criterion of this study was patients who underwent anatomic lung resection for lung cancer with tumors larger than 5 cm((≥ T3). The patients were divided into two groups: those who underwent video-assisted thoracoscopic surgery (n = 24) and those who underwent thoracotomy (n = 36). Patient characteristics, intraoperative and postoperative results were evaluated by review of the hospital records. RESULTS: In the VATS group, mean drainage time and postoperative length of hospital stay were significantly shorter than the thoracotomy group. Kaplan-Meier survival curves showed that overall and recurrence-free survival was longer in the VATS group and this result was statistically significant. CONCLUSIONS: According to the results of this study, we emphasize that VATS is a feasible surgical procedure for tumors larger than 5 cm.

Comparison of awake and intubated video-assisted thoracoscopic surgery in the diagnosis of pleural diseases: A prospective multicenter randomized trial.

BACKGROUND: This study aims to compare the safety and diagnostic accuracy of awake and intubated video-assisted thoracoscopic surgery in the diagnosis of pleural diseases. METHODS: This prospective randomized study was conducted between October 2016 and April 2018 and included 293 patients (201 males, 92 females; mean age 53.59 years; range, 18 to 90 years) from five medical centers experienced in video-assisted thoracoscopic surgery. The patients were randomized into two groups as awake video-assisted thoracoscopic surgery with sedoanalgesia (non-intubated) and video-assisted thoracoscopic surgery with general anesthesia (intubated). Patients with undiagnosed pleural effusions and pleural pathologies such as nodules and masses were included. Conditions such as pain, agitation, and hypoxia were indications for intubation. The groups were compared in terms of demographic data, postoperative pain, operative time, complications, diagnostic accuracy of the procedures, and cost. All patients completed a follow-up period of at least 12 months for samples that were non-specific, suspicious for malignancy or inadequate. RESULTS: Awake video-assisted thoracoscopic surgery was performed in 145 and intubated video-assisted thoracoscopic surgery was performed in 148 patients. Pleural disease was unilateral in 83% (243/293) and bilateral in 17% (50/293) of the patients. There was no difference between the groups in terms of presence of comorbidity (p=0.149). One patient in the awake video-assisted thoracoscopic surgery group (0.6%) was converted to general anesthesia due to refractory pain and agitation. As postoperative complications, fluid drainage and pneumonia were observed in one patient in the awake video-assisted thoracoscopic surgery group (0.6%) and fluid drainage was detected in one patient in the video-assisted thoracoscopic surgery group (0.6%). There were no differences in pain intensity measured with visual analog scale at postoperative 4, 8, 12, or 24 hours (p>0.05). Distribution and rates of postoperative pathological diagnoses were also similar (p=0.171). Both operative cost and total hospital cost were lower in the awake video-assisted thoracoscopic surgery group (p<0.001, p=0.001). CONCLUSION: Our study showed that awake video-assisted thoracoscopic surgery is safe, has similar reliability and diagnostic accuracy compared to video-assisted thoracoscopic surgery performed under general anesthesia, and is less costly. Awake video-assisted thoracoscopic surgery can be the first method of choice in all patients, not only in those with comorbidities.

Rare cause of superior vena cava syndrome: a giant bulla.

Superior vena cava syndrome (SVCS) is a group of symptoms caused by obstruction of superior vena cava. External compression caused by benign or malign processes is the most common physiopathology. We aim to present a 29-year-old man with non-productive cough, facial plethora and venous distention of the neck. Right apical tense bulla which was compress superior vena cava was detected and video-assisted thoracoscopic surgery applied. Our extensive search found out that only one report of SVCS secondary to bulla is available on Medline.

Atypical deep somatic soft-tissue leiomyoma of extrathoracic chest wall: first case of the literature.

Leiomyomas are benign soft-tissue tumours which take origin from the smooth muscles. Pleura and chest wall are uncommon location for such tumours. Here, we report a case of a 26-year-old female patient presented with 3 months history of chest pain. Chest X-ray and CT showed a calcified mass of 6×12 cm in size in the left lateral of the chest wall. After resection of the mass, pathological examination diagnosed it as atypical deep somatic soft-tissue leiomyoma of extrathoracic chest wall. No pathological finding was detected during follow-up.

Is endobronchial ultrasound-guided transbronchial needle aspiration an effective diagnostic procedure in restaging of non-small cell lung cancer patients?

BACKGROUND AND OBJECTIVES: Selecting the diagnostic procedure for mediastinal restaging after chemotherapy and/or radiotherapy in Stage IIIA-N2 non-small cell lung cancer (NSCLC) patients remains a problem. The aim of the study was to determine the efficacy of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the evaluation of mediastinal lymph nodes in the restaging of NSCLC patients. MATERIALS AND METHODS: The present multicentric study retrospectively analyzed the results of Stage IIIA-N2 NSCLC patients who had undergone EBUS for mediastinal restaging after preoperative chemotherapy or radiotherapy or both. RESULTS: In 44 patients with 73 N2 nodes, malignant cells were identified in EBUS-TBNA from 23 patients (57.5%) and 25 lymph nodes (34.2%). Twenty-one patients (42.5%) and 48 lymph nodes (65.8%) were negative for nodal metastasis. All of these patients with negative results subsequently underwent mediastinoscopy or surgery (n = 9 and n = 12, respectively). Metastasis was detected in 5 (23.8%) of 21 patients and 6 (12.5%) of 48 lymph nodes. The diagnostic sensitivity, specificity, positive predictive value, negative predicted value and accuracy of EBUS-TBNA based on number of patients were 82.1%, 100%, 100%, 76.2%, and 88.6%, respectively. CONCLUSIONS: EBUS-TBNA should be done before invasive procedures in restaging of the mediastinum in patients previously treated with neoadjuvant therapy because of high diagnostic accuracy rate. However, negative results should be confirmed with invasive procedures such as mediastinoscopy and thoracoscopy.

Is preoperative protein-rich nutrition effective on postoperative outcome in non-small cell lung cancer surgery? A prospective randomized study.

OBJECTIVE: Protein-rich nutrition is necessary for wound healing after surgery. In this study, the benefit of preoperative nutritional support was investigated for non-small cell lung cancer patients who underwent anatomic resection. METHODS: A prospective study was planned with the approval of our institutional review board. Fifty-eight patients who underwent anatomic resection in our department between January 2014 and December 2014 were randomized. Thirty-one patients were applied a preoperative nutrition program with immune modulating formulae (enriched with arginine, omega-3 fatty acids and nucleotides) for ten days. There were 27 patients in the control group who were fed with only normal diet. Patients who were malnourished, diabetic or who had undergone bronchoplastic procedures or neoadjuvant therapy were excluded from the study. Patients' baseline serum albumin levels, defined as the serum albumin level before any nutrition program, and the serum albumin levels on the postoperative third day were calculated and recorded with the other data. RESULTS: Anatomic resection was performed by thoracotomy in 20 patients, and 11 patients were operated by videothoracoscopy in the nutrition program group. On the other hand 16 patients were operated by thoracotomy and 11 patients were operated by videothoracoscopy in the control group. In the control group, the patients' albumin levels decreased to 25.71 % of the baseline on the postoperative third day, but this reduction was only 14.69 % for nutrition program group patients and the difference was statistically significant (p < 0.001). Complications developed in 12 patients (44.4 %) in the control group compared to 6 patients in the nutrition group (p = 0.049). The mean chest tube drainage time was 6 (1-42) days in the control group against 4 (2-15) days for the nutrition program group (p = 0.019). CONCLUSIONS: Our study showed that preoperative nutrition is beneficial in decreasing the complications and chest tube removal time in non-small cell lung cancer patients that were applied anatomic resection with a reduction of 25 % in the postoperative albumin levels of non-malnourished patients who underwent resection.

The clinical characteristics of sarcoid arthropathy based on a prospective cohort study.

BACKGROUND: Sarcoidosis is known as a Th1-mediated disease, which can mimic many primary rheumatologic diseases or sometimes co-exist with them. Clinical characteristics of sarcoid arthropathy are not well described and the studies reported in the literature so far are mostly based on data from referrals. The aim of this study was to evaluate the incidence and clinical characteristics of sarcoid arthropathy. METHODS: All our patients were prospectively evaluated in our rheumatology outpatient center from 2011 to 2015. A total of 114 (32 male) patients with sarcoidosis who were admitted to our clinic were included in the study. Clinical, demographical, laboratory, radiological and histological data of these patients obtained during 4-year follow-up and treatment period were compiled and analyzed. RESULTS: The mean patient age was 48.1 years (range, 20-82 years), and the mean disease duration was 40.5 months (range, 1-300 months). Sarcoid arthritis was observed in 71 (62.3%), and arthralgia in 106 (92.9%) patients. Out of the 71 patients with arthritis, 61 (85.9%) had involvement of ankle, 7 (9.8%) knee, 2 (2.8%) wrist, MCP and PIP joints, and 1 (1.4%) had shoulder periarthritis. Oligoarthritis (two to four joints) was the most common pattern followed by monoarthritis and polyarthritis. Arthritis and erytjhema nodosum and arthritis and female sex was found to be correlated (p = 0.03 and p = 0.001). Again, in patients with arthritis, even higher levels of CRP/ESR as well as ANA and RF positivity were observed (p = 0.03, p = 0.01, p = 0.01, and p = 0.02, respectively). A total of 11 patients had another rheumatic pathology concurrent with sarcoidosis. CONCLUSIONS: Inflammatory arthritis occurs in a majority of patients with sarcoidosis. Acute arthritis with bilateral ankle involvement is the most common pattern of sarcoid arthropathy. Sarcoidosis can mimic many primary rheumatic diseases or may coexist with them. Sarcoidosis should be considered not only as a mimicker but also as a Th1-mediated primary rheumatologic pathology.

Giant Cavernous Haemangioma of the Anterior Mediastinum.

Cavernous hemangiomas of the anterior mediastinum is rare. We present a case of a 56-year-old male patient with a giant cavernous hemangioma of the anterior mediastinum, 18 cm in diameters, approached by left posterolateral thoracotomy. To the best of our knowledge, such a unique case has not been previously presented in the literature.

Endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymphadenopathy: effect of the learning curve.

This study aimed to evaluate the learning curve and efficacy of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the examination of mediastinal or hilar lymph nodes suspected of having cancer or of benign disease such as sarcoidosis. A success-adjusted cumulative sum model was used to evaluate the learning curve for diagnostic rates and operation time. A total of 99 patients (77 men and 22 women) who underwent EBUS-TBNA from April 2011 to March 2012 in a single centre were analysed retrospectively. The quantity of lymph node sampling was deemed to be appropriate for histopathological examination in 97 of 99 patients (97%). Twenty-three cases (23%) were clearly diagnosed with neoplastic disease, 60 (60%) with reactive hyperplasia, 11 (11%) with granulomatosis and 3 (3%) histopathologically suspicious for lymph node metastasis. The sensitivity, specificity, and positive and negative predictive values and diagnostic accuracy for EBUS-TBNA were 80, 100, 100, 87.1 and 91.5%, respectively. According to the learning curve analysis, the ability to perform EBUS required performing approximately 37 procedures for the trials. In conclusion, more successful results are obtained after a certain learning curve, as is the case for every other invasive procedure.

Prognostic factors affecting survival in malignant pleural mesothelioma: analysis of 125 subjects.

AIM OF THE STUDY: Determining the pre-treatment prognostic factors in malignant pleural mesothelioma is important in terms of estimating the course of the disease and selecting patients who are candidate for multimodal therapy. The aim of the study was to determine the prognostic factors affecting survival in patients with malignant pleural mesothelioma. STUDY DESIGN: One hundred and twenty-five patients who had been diagnosed histologically as having malignant pleural mesothelioma over the past 5 years were evaluated retrospectively. Relationships of survival of the patients with their age, gender, exposure to asbestos, smoking history, platelet, hemoglobin, leukocyte (WBC) and serum LDH values, histology, performance score and stage of disease were examined. RESULTS: Advanced clinical stage, N2 nodal involvement and the presence of distant metastasis were found to be related to survival. Sarcomatous histology was found to be a poor prognostic factor independently of other factors. CONCLUSIONS: We showed that histological subtype and stage of disease were the most important parameters in planning the treatment, especially in determining the patients who were candidate for multimodal treatment and in estimating the prognosis.

The effect of preoperative albendazole treatment on the cuticular membranes of pulmonary hydatid cysts: should it be administered preoperatively?

THE AIM OF THIS STUDY: The aim of this study was to investigate the effects of preoperative albendazole treatment on the tensile strength of the cuticular membranes of pulmonary hydatid cysts. MATERIAL AND METHODS: A study including 44 patients operated on for pulmonary hydatid cysts was carried out between January 2009 and November 2010. The patients were divided into two groups according to their preoperative albendazole administration. Seventeen patients (with 20 cysts) in group A were operated on after three cycles of peroral 10 mg/kg/day albendazole treatment, whereas 27 patients (with 29 cysts) in group B underwent the operation without any preoperative administration of albendazole. Fresh tissue tensile stress tests were carried out on the cuticular membranes excised from both groups. RESULTS: The results of this study demonstrated that the tensile strength values of the cuticular membrane of the cysts excised from group A were lower than those obtained from group B, with a statistically significant difference. CONCLUSIONS: Albendazole treatment decreases the tensile strength of the cuticular membranes of pulmonary hydatid cysts, which may lead to their perforation. The patients should be operated on as soon as possible and without any preoperative medical treatment in order to prevent complications before the definitive surgical operation.

Neoadjuvant chemotherapy is a risk factor for bronchopleural fistula after pneumonectomy for non-small cell lung cancer.

INTRODUCTION: Performing pneumonectomy after neoadjuvant chemotherapy is still controversial. Bronchopleural fistula is a major complication after pneumonectomy. In this study the effect of neoadjuvant chemotherapy on postpneumonectomy bronchopleural fistula was investigated. MATERIAL AND METHODS: A retrospective review of patients who underwent pneumonectomy for non-small cell lung cancer from January 2005 to December 2011 was undertaken. The major complications and operative mortality were analyzed and compared between the patients having neoadjuvant chemotherapy and patients having surgery only. RESULTS: One hundred and seventy-seven pneumonectomies (77 right and 100 left) were performed during the study period and 49 of these patients (27.7%) received neoadjuvant chemotherapy. Median age was 60 years (range, 32 to 80). The bronchopleural fistula rate was 26.5% (13/49) in the neoadjuvant group versus 3.1% (4/128) in the surgery alone group (p = 0.029). The bronchopleural fistula rate was 16.9% (13/77) in the right pneumonectomy group vs. 4% (4/100) in the left pneumonectomy group (p = 0.004). Overall operative mortality was 5.6%. Mortality in the neoadjuvant group was 8.2% vs. 4.7% in the surgery only group (p = 0.37). CONCLUSIONS: Neoadjuvant chemotherapy and right pneumonectomy is a major risk factor for bronchopleural fistula. Especially right pneumonectomy should be avoided after induction therapy.

One-stoma carinoplasty: right upper sleeve lobectomy with hemicarinectomy for resection of right-tracheobronchial-angle tumors.

Tracheobronchial-angle tumors involve the right main bronchus, the right upper lobar bronchus, and the lateral wall of the lower trachea. Resecting these tumors is one of the most complex procedures in thoracic surgery. In cases of high-caliber mismatch, the selection of a suitable anastomotic technique can be challenging. We found that our use of a one-stoma carinoplasty technique overcame high-caliber mismatch after the resection of these tumors. From 2009 through 2012, 8 men (mean age, 59 ± 6.2 yr; range, 46-66 yr) underwent complete resection of non-small-cell right-tracheobronchial-angle tumors at our institution. In every case, right upper sleeve lobectomy, wedge carinal resection, and one-stoma carinoplasty were applied. After tumor resection, one patient with hemoptysis and bronchopleural fistula underwent a completion pneumonectomy and died 10 days postoperatively. Bronchoscopy was necessary in 2 patients who had atelectasis in the contralateral lung. At a mean follow-up duration of 19.43 ± 8.4 months (range, 0.2-27.1 mo), 6 patients were alive and free of disease. We conclude that our one-stoma carinoplasty technique enables the resection of tumors at the right tracheobronchial angle, with acceptable morbidity and mortality rates. This method saves the unaffected part of the ipsilateral lung and can overcome high-caliber mismatch. Because of these and other advantages, we suggest that using our method first might preclude having to perform a right carinal sleeve pneumonectomy or using Barclay's method.

Intraoperative management of tracheobronchial rupture after double-lumen tube intubation.

PURPOSE: Tracheobronchial rupture is an uncommon but potentially serious complication of endotracheal intubation. In this study, the diagnosis and treatment strategies of a specific group of ruptures caused by double-lumen tube intubation are herein presented. METHODS: The medical records of 18 patients diagnosed and treated for tracheobronchial rupture after undergoing double-lumen tube intubation between January 1999 and October 2010 are analyzed retrospectively. RESULTS: In all cases, the ruptures occurred in the membranous portion. The average length of laceration was 2.44 ± 1.78 cm. The most common site of rupture was in the lower third of the trachea (n = 7, 39 %) or the left mainstem bronchus (n = 7, 39 %). One patient was diagnosed before incision using fiberoptic bronchoscopy, and 17 patients were diagnosed using direct vision of the rupture intraoperatively. All patients were treated successfully with surgery. There were no morbidities or mortalities recorded in relation to tracheobronchial rupture. CONCLUSIONS: Thoracic surgeons must be alerted to the possibility for tracheobronchial rupture in patients intubated with double-lumen tubes, a procedure commonly used in thoracic surgery. Immediate repair must be performed for any laceration diagnosed intraoperatively.

Is Acrylate Co-monomer (Glubran-2) Useful in the Prevention of Prolonged Air Leaks After Pulmonary Lobectomy?

Many synthetic materials are being used in order to reduce the frequency of prolonged air leak (PAL) in thoracic surgical practice. This study presents our experience with the topical application of acrylate co-monomer (Glubran-2) as a synthetic tissue adhesive in an attempt to decrease troublesome postoperative air leaks in patients undergoing resection for non-small cell lung carcinoma. Of the 112 patients who had undergone resection for lung carcinoma, 69 patients having lobectomy or bilobectomy were included in this study. The application group (group A) consisted of 33 patients where a synthetic tissue adhesive (Glubran-2) was used and compared with the control group (group C, n = 36) retrospectively. There was no difference between the groups regarding demographic details and operative variables. Both groups were compared in view to PAL, chest tube duration, in-hospital stay and hospital costs. There was no significant difference between group A (n = 11, 33 %) and group C (n = 6, 17 %) for the development of PAL (P = 0.11). Hospital stay was 16.1 ± 6.7 days in group A and 15.3 ± 5.8 days in group C (P = 0.66). The surgical cost was significantly higher in group A (€806 ± 127) than the group C (€624 ± 94) (P < 0.001). There was no significant difference between the groups regarding overall hospital costs (P = 0.41). In this study, the use of Glubran-2 following lung resection for non-small cell lung carcinoma did not decrease the incidence of PAL. Neither did it have a favorable effect concerning in-hospital stay nor did it decrease overall hospital costs while increasing surgical costs as expected.

The effect of TTF-1 expression on ipsilateral mediastinal nodal (N2) metastases in primary adenocarcinoma of the lung.

AIM OF THE STUDY: To study the effect of thyroid transcription factor-1 (TTF-1) expression on ipsilateral mediastinal nodal (N2) metastases in primary adenocarcinoma of the lung. MATERIAL AND METHODS: The patients operated on with a diagnosis of primary adenocarcinoma of the lung were retrospectively analyzed and divided into two groups according to their TTF-1 expression. The relationship between TTF-1 expression and N2 metastases was evaluated. RESULTS: There were 73 patients (58 male, 15 female) with a mean age of 58.4 ±10.2 in the study group. Sixty-six lobectomies or pneumonectomies and mediastinal lymph node dissection, and seven mediastinoscopies were performed. Positivity of the TTF-1 protein expression detected by the immunohistochemical staining of the specimens was present in 33 patients (45.2%); these patients were classified as group A and the rest of the patients as group B. Eleven patients had N2 disease in group A versus five patients in group B and the difference between the two groups was statistically significant. CONCLUSIONS: Patients with primary adenocarcinoma of the lung having TTF-1 expression are more likely to have N2 disease. They might be considered as candidates for adjuvant therapy.

Surgical management of pulmonary hydatid cysts: is size an important prognostic indicator?

Giant hydatid cysts of the lung (diameter, ≥10 cm) are considered more difficult to treat surgically than are smaller cysts. We reviewed our experience with giant pulmonary hydatid cysts, focusing on clinical symptoms, cystic location, extent of surgery, and postoperative complications, according to age, long-term results, and comparison with non-giant cysts. From January 1988 to January 2008, 537 patients underwent surgery for pulmonary hydatid cysts. We separated patients into 2 groups: patients who had cysts <10 cm (group A) and those who had giant cysts (group B). Group B comprised 75 patients (14%). Giant cysts were more common in younger patients (mean age, 30 vs 32 yr; P=0.014). The most frequent complaints were cough, chest pain, and dyspnea. Patients with giant cysts were more often symptomatic at presentation (96% vs 88%; P=0.04). In both groups, lower-lobe locations predominated. Parenchyma-saving operations were almost uniformly performed for each group; however, a higher percentage of patients in group B required anatomic resection (4% vs 1%; P=0.038). Fifty-seven patients (10%) also underwent resection of concomitant liver cysts. Cystic rupture occurred more frequently in group B than in group A (27% vs 15%; P=0.01). There were no deaths in either group, nor were there significant differences in morbidity between groups.In summary, giant hydatid cysts of the lung occurred more often in younger patients and were more often symptomatic at presentation. Regardless of size, the cysts could usually be surgically treated without lung resection, and size did not appear to influence short-term perioperative outcomes.