Claudin expression in pulmonary adenoid cystic carcinoma and mucoepidermoid carcinoma.

Background: Although the expression of tight junction protein claudins (CLDNs) is well known in common histological subtypes of lung cancer, it has not been investigated in rare lung cancers. The aim of our study was to examine the expression of different CLDNs in pulmonary salivary gland tumors. Methods: 35 rare lung cancers including pathologically confirmed 12 adenoid cystic carcinomas (ACCs) and 23 mucoepidermoid carcinomas (MECs) were collected retrospectively. Immunohistochemical (IHC) staining was performed on formalin fixed paraffin embedded (FFPE) tumor tissues, and CLDN1, -2, -3, -4, -5, -7, and -18 protein expressions were analyzed. The levels of immunopositivity were determined with H-score. Certain pathological characteristics of ACC and MEC samples (tumor grade, presence of necrosis, presence of blood vessel infiltration, and degree of lymphoid infiltration) were also analyzed. Results: CLDN overexpression was observed in both tumor types, especially in CLDN2, -7, and -18 IHC. Markedly different patterns of CLDN expression were found for ACC and MEC tumors, especially for CLDN1, -2, -4, and -7, although none of these trends remained significant after correction for multiple testing. Positive correlations between expressions of CLDN2 and -5, CLDN3 and -4, and CLDN5 and -18 were also demonstrated. Tumors of never-smokers presented lower levels of CLDN18 than tumors of current smokers (p-value: 0.003). Conclusion: This is the first study to comprehensively describe the expression of different CLDNs in lung ACC and MEC. Overexpression of certain CLDNs may pave the way for targeted anti-claudin therapy in these rare histological subtypes of lung cancer.

PD-1 and PD-L1 expression in rare lung tumors.

Background: Our knowledge is still limited about the characteristics and treatment of rare lung tumors. The aim of our study was to determine programmed cell death ligand-1 (PD-L1) and programmed cell death-1 (PD-1) expression in rare pulmonary tumors to assess the potential role of immunotherapy. Methods: 66 pathologically confirmed rare lung tumors including 26 mucoepidermoid carcinomas (MECs), 27 adenoid cystic carcinomas (ACCs), and 13 tracheobronchial papillomas (TBPs) were collected retrospectively. Immunohistochemical (IHC) staining was performed on formalin fixed paraffin embedded (FFPE) tumor tissues, and PD-L1 expression on tumor cells (TCs) and immune cells (ICs), and PD-1 expression on ICs were determined. The cut off value for positive immunostaining was set at 1% for all markers. Results: PD-L1 expression on TCs was observed in two cases of MEC (7.7%), one case of ACC (3.7%), and was absent in TBP samples. PD-L1 expression on ICs could be demonstrated in nine cases of MEC (34.6%), four cases of ACC (14.8%), and was absent in TBPs. All PD-L1 TC positive tumors were also PD-L1 IC positive. Higher expression level than 5% of PD-L1 TC and/or IC was observed only in one ACC and in two MEC patients. Among them, strong PD-L1 immunopositivity of >50% on TCs and of >10% on ICs could be demonstrated in one MEC sample. PD-L1 expression of ≥1% on ICs was significantly more common in MEC, than in TBP (p < 0.001). In MEC ≥1% PD-L1 TC or IC expressions were significantly more common in patients aged 55 or older, than in younger patients (p = 0.046, and p = 0.01, respectively). PD-1 expression on ICs was found in five cases of MEC (19.2%), four cases of ACC (14.8%), and in two cases of TBP (15.4%). Only one MEC case showed a higher than 5% expression level of PD-1 on ICs. Conclusion: This retrospective study comprehensively demonstrated the rare expression of PD-L1 and PD-1 in pulmonary MEC, ACC, and TBP. However, we found very strong PD-L1 immunopositivity on both TCs and ICs in one MEC sample, which warrants further investigations in a larger cohort.

Unilateral video-assisted thoracoscopic thymoma resection ­ Indications, early and mid-term results / Az unilateralis videoasszisztált torakoszkópos thymomaeltávolítás javallata, korai és középtávú eredményei

Introduction. Thymoma is the most common tumour of the anterior mediastinum. Video-Assisted Thoracic Surgery technique of thymoma resection is spreading world-wide, but the thoracoscopic method is still contentious in many ways. Authors evaluate the early and mid-term results of a 17 years period of VATS unilateral approach at 2 Hungarian thoracic surgical centers. Method. Depending on the anatomical situation of the thymoma, we performed thymectomy, or partial thymectomy (thymomectomy) for the Masaoka­Koga I­II­III stage thymoma from the right or left side through 2 or 3 intercostal ports. We managed the operations with ultrasonic dissector and electrocauter. By using international standards we evaluated perioperative morbidity, mid-term oncological results and clinical symptoms of myasthenia. Results. 23 of the 54 patients were man, 31 were woman, the average age was 58 (26­79) years, 23 of them had myasthenia. The conversion rate was 11,5% (7/61). The average operation time was 84 (39­150) minutes. The average hospitalisation time was 5.5 (3­19) days. The average size of the thymomas was 46 (18­90) mm. The histology resulted thymoma type A in 2 cases, AB in 19 cases, B1/2/3 in 11/11/1 cases, mixed B in 10 cases. The examination of the resection line was R0/1/2 in 42/11/1 cases. The Masaoka­Koga stages were: I (17), IIA (28), IIB (2), III (7). There was 25 thymomectomies, and 29 thymectomies. In seven cases there were extension of the operation to the pericardium (2), to the lung (2), to the phrenic nerve (6), and to innominate vein (1). The in-hospital mortality over 30 day was in 1 case (1.85%). The morbidity was 11/54 (20.4%). The average follow-up time was 62.56 (5­198) months. In the group with myasthenia the effectivity of the operation was 18/21 (85.7%), including complete remission of 5/21 (23.8%). Post-thymectomy myasthenia gravis developed in 2/31 cases (6.5%). The average 5 years survival was 100%, tumour-free 5 years survival was 96%. Conclusions. The higher proportion of the thymomectomy in the early results, higher conversion rate and lower R0 proportion might be in connection with the attitude of the surgeons, with the learning curve and with the limitations of the unilateral method. After a longer follow-up time late results may become more real and comparable. Instead of unilateral VATS technique we have changed to the subxyphoideal approach of VATS because of its better visualisation.

Application of video-assisted thoracoscopy in the surgical treatment of myasthenia gravis in adults without thymoma / Jobb oldali videoasszisztált thoracoscopos thymectomia a thymoma nélküli, felnottkori myasthenia gravis sebészi kezelésében

Introduction: Surgical technique of thymectomy performed for treatment of myasthenia gravis has considerably changed in the last almost 30 years. In addition to standard interventions ­ transsternal and transcervical thymectomy ­, video-assisted thoracoscopic interventions (VATS), later on robotic surgery came into general use. In our two institutions, we apply VATS thymectomy since 2011. Methods: There are several different surgical techniques for this purpose; we approached the mediastinum through the right thoracic cavity. We prepared initially 3, later on 2 perimammal ports for the access of the thymus; the patients were in supine position during surgery. We used an ultrasonic cutting device in all cases. In order to perform extended thymectomy, we removed the fatty tissue around the thymus and opened widely the left thoracic cavity, too. During patient enrollment, we preferred patients with normal or lower body weight. Results: During 8 years and 4 months, we operated on 92 patients using this method for myasthenia gravis without thymoma; there were 20 male and 72 female patients at the age of 33 years on average (19­75 years). Duration of surgery was 35­160 minutes, 82.3 minutes on average. The bulky fatty tissue around the thymus made the orientation and the complete removal more difficult in a few patients. We experienced vascular injury in 4 cases and injury of the contralateral lung in 3 cases. Conversion was necessary in 2 cases (1 sternotomy and 1 thoracotomy), there were no nerve injuries. Assisted ventilation was necessary in case of ten patients in the postoperative period for a few hours; all other patients were extubated on the operating table. There was no need for repeated intubation and tracheostomy; there was no respiratory insufficiency and perioperative mortality. Duration of ICU care was 1.1 days on the average (0­11 days), that of the total hospital care 4.8 days on average (3­15 days). Duration of thoracic drainage was 1.16 days on average (1­4 days). Two patients (2.41%) died within one and five years after surgery. During 12­108 months (48 months on average) follow-up of 81 patients, 21 patients (25.3%) suffering from myasthenia total recovery was observed, pharmacologic remission was achieved in 4 patients (5.3%), minimal manifestation remained in 23 patients (24.1%), while in 28 patients (33.73%) other improvement was observed. The status of 4 patients (4.82%) remained unchanged and that of 4 patients (5.3%) worsened. Conclusion: VATS thymectomy represents a completely new surgical method for surgeons having experience in transsternal surgical technique. Bulky mediastinal fatty tissue makes surgery very difficult. The perioperative period is advantageous for the patients and also the long term follow-up results are acceptable. It is questionable that the thymus can be completely removed with this method in all cases.

[Indications and perioperative results of completion pneumonectomy]. / A komplettáló pneumonectomia javallatai és perioperatív eredményei.

Introduction: Completion pneumonectomy (CP) means the removal of the entire residual lung tissue after previously performed lung resection. Mortality and morbidity of CP are higher when compared to those of standard pneumonectomy. In this article, we give an overview on indications and perioperative results of CP. Method: We analysed the perioperative results of CP performed during a period of 15 years in a retrospective manner, based on the patients' medical records, descriptions of surgeries and histological findings. We divided the indications into three groups: rescue surgery for complications in the early postoperative period (rescue: rCP), incomplete resection verified by histological results (pathological: pCP) and conventional surgeries performed in the late postoperative period (conventional: cCP). We classified the complications according to an international scale. Results: The overall surgery-related morbidity of 102 patients was 70.5% (minor: 36.27%, major: 34.23%), the mortality was 16.6%. There were no lethal complications during the surgical procedures. rCP: 24 patients (18 men, 6 women, 46-77 years, average 61.7 years). Intervals between operations: 10.87 days (0-32 days). Indications: necrosis or abscess formation (8 cases), bronchial fistula (5 cases), insufficient or blocked anastomosis (3 cases), massive haemoptysis (3 cases), intrathoracic bleeding (2 cases), non-expanding lung (3 cases). Overall morbidity: 79.19%. Nine patients died (37.5%). pCP: 7 patients (5 men, 2 women), 45-66 years (average: 56.3 years). Primary surgery: 6 lobectomies, 1 bilobectomy. Intervals between operations: 1-5 months (average: 2.84 months). Three patients did not develop complications, four had anaemia requiring blood transfusion, one empyema requiring fenestration, one died (14.28%) due to intrathoracic bleeding. There were no tumours in the removed lung tissues in cases of four patients. cCP: 71 patients (22 women, 44 men, 29-79 years (average: 60.3 years). Intervals between operations: 34 days - 40 years (average: 6.7 years). Histological findings of the previous surgeries: primary lung tumour (64 patients), metastases of tumours in other organs (1 patient), bronchiectasia (1 patient) and tuberculosis (5 patients). Indications of cCP: late bronchial fistula (2 patients), verified or suspected tumour (65 patients), other (4 patients). Histological findings with primary lung tumour in the patient's history: 32 new tumours, 15 local recurrences, 9 metastases, 2 metastases or recurrences, 7 non-malignant. Histological findings without malignancy in the patient's history: 3 new tumours, 1 tuberculosis and 2 chronic inflammations. Overall morbidity was 76.2%, mortality within 30 days or in the hospital 9.8%. Conclusions: Morbidity and mortality are the highest after rCP, but these patients usually do not have any other chance for healing. We have not performed repeat surgery for incomplete tumour resection in the last 10 years. Comparing our results to the international data, the morbidity after cCP is high, the mortality is similar.

[Treatment of adult intrapulmonary sequestration with video-assisted thoracoscopic lobectomy]. / Felnottkori intrapulmonalis sequestratio kezelése videothoracoscopos lobectomiával.

INTRODUCTION: Surgical removal is the gold standard method for the treatment of pulmonary sequestration (PS); nowadays, video-assisted thoracoscopic lobectomy (VATS) is more frequently applied in the surgical treatment of malignant pulmonary tumours and appears to be suitable also in case of benign pulmonary diseases. We are the first in Hungary, who report three, radiologically identified intralobar PS treated with VATS. METHOD: Surgeries were performed in general anaesthesia with double-lumen separated ventilation in lateral decubitus position through two ports (1.5 cm camera port and 5-6 cm axillary working port, protected by a plastic ring). Results and cases: Two of the patients presented with the symptoms of haemoptysis and pneumonia, and the third patient after radiological screening (one 37 years old woman and 2 men, 39 and 46 years old). The nutritive artery was identified on the CT scans in all cases. We removed the right lower lobe in two cases and the left lower lobe in one case without major complications. CONCLUSION: We recommend the video-thoracoscopic lobectomy for the treatment of PS as a suitable treatment option.