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.

[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.

[Doege-Potter syndrome with giant malignant solitary fibrous tumour of the pleura]. / Doege­Potter-szindróma a mellhártya óriás malignus szoliter fibrosus tumorával.

Infrequent solitary fibrous tumours of the pleura are associated with hypoglycaemia only in a few percent of the cases; this condition is called Doege-Potter syndrome, named after its first descriptors. Our 63 years old male patient has previously undergone clinical treatment for intrathoracic fluid accumulation on the left side caused by a giant tumour-like mass in the lower left lobe detected by CT scan. In the course of further investigations performed due to increasing load-induced dyspnoea, lung core biopsy verified low grade sarcoma in the tumour. Tumour board suggested surgery. The patient was transferred from the intensive care unit into the operation theater due to increasing dyspnoea and repeated hypoglycaemic periods in rapidly worsening general condition. Pneumonectomy and removal of the tumour was performed on the left side. Histology showed solitary fibrous tumour of the pleura corresponding to Doege-Potter syndrome. The patient was discharged without complications and underwent adjuvant chemotherapy due to pleural dissemination of the tumour observed intraoperatively. One year after surgery the patient underwent surgical removal of a locally recurrent tumour. In spite of repeated chemotherapy local and multiplex contralateral pulmonary progression was observed. Three-year survival was noted from the time of the first surgery. Orv Hetil. 2018; 159(41): 149-153.

A pleura óriás fibrosus tumora légzési elégtelenséggel szövodve.

Surgery of mostly benign giant tumours involving large part of the chest is a special surgical challenge. The problems comprise difficulties of surgical technique, management of the narcosis and postoperative intensive care. An additional peculiarity of our case is the extreme confliction of the otherwise presumably evident indication for surgery. Our 64-years-old male patient has been suffering from increasing dyspnoea on exercise for one and a half years. A chest X-ray performed for other reasons demonstrated a large, expansive structural change in the right thoracic cavity. Lung biopsy performed as part of respiratory investigations, which showed a solitaire fibrous tumour of the pleura. Oncological consultation suggested consideration of surgery. The general condition of the patient worsened rapidly in the course of preassessment; he had to be admitted to ICU due to dyspnoea and atrial fibrillation, where respiratory insufficiency developed and required respiratory therapy. Surgery was performed in this high anaesthetic risk patient, since removal of the tumour was the only chance for surviving. The patient left the hospital healthy after successful surgery and cumbersome postoperative period. He returned to his original job and no recurrence was detected one year after surgery.

Expression of proliferation markers Ki67, cyclin A, geminin and aurora-kinase A in primary breast carcinomas and corresponding distant metastases.

AIMS: To assess the expression of the following cell cycle regulatory proteins in primary metastatic breast carcinomas (MBCs) and on availability in matched distant metastases (DMs): Ki67, cyclin A, geminin and aurora-kinase A (aurkA); and to compare the expression of these markers in early MBC (EMBC) and late MBC separated into groups according to median time point on metastatic event occurred (28 months). METHODS: The expression of the above mentioned markers was analysed in a total of 47 primary MBCs and 59 DMs (out of which 37 were pairs) by immunohistochemistry. Fourteen breast carcinomas with no relapse over a 10-year follow-up period were utilised as control cases (CBC). RESULTS: Among the MBCs, 22 metastasised to the bone, 4 to the lung and 21 to the central nervous system (CNS). Geminin (p<0.001) and Ki67 (p=0.001) were increased in the MBCs while aurkA and cyclin A showed no difference when compared with CBCs. There were no differences between aurkA, cyclin A and geminin expression in MBCs and DMs in general. Expression of Ki67 was, however, elevated (p=0.027) in DMs. In CNS metastases all markers showed elevated expression as compared to MBCs. In bone metastases, geminin was lower (p<0.001) compared with primary MBCs. In the metastases of the lung, the evaluated markers did not show different expression. According to the median follow-up until the metastatic event, Ki67 was found to be significantly elevated in EMBC (p=0.018). CONCLUSIONS: Ki67 index and geminin distinguish a fraction of MBC with worse prognosis, showing increased levels in the latter in comparison to CBC being tumour-free over a 10-year follow-up period. Ki67 could possibly identify a group of MBCs that develop early DMs.

Relationship between TP53 tumour suppressor gene mutations and smoking-related bulky DNA adducts in a lung cancer study population from Hungary.

Lung cancer rate in Hungary is one of the highest in the world among men and also very high among women, for reasons not clearly understood yet. The aim of the study was to explore characteristics of DNA damage and TP53 gene mutations in lung cancer from Hungary. Tissue samples from 104 lung resections for lung cancer patients, both men and women, operated on for non-small cell lung cancer, specifically, primary squamous cell carcinoma or adenocarcinoma were studied. Of the cases, 37% smoked up to the surgery, 24% stopped smoking within 1 year before the surgery, 26% stopped smoking more than a year before the surgery and 13% never smoked. TP53 mutations were detected by denaturant gradient gel electrophoresis, automated capillary electrophoresis single-strand conformation polymorphism and sequencing. Bulky DNA adduct levels were determined by (32)P-post-labelling in non-tumorous lung tissue. In total, 45% (47/104) of the cases carried TP53 mutation. The prevalence of TP53 mutations was statistically significantly associated with duration of smoking, tumour histology and gender. Smokers had approximately twice as high bulky adduct level as the combined group of former- and never-smokers (10.9 +/- 6.5 versus 5.5 +/- 3.4 adducts/10(8) nucleotides). The common base change G --> T transversion (8/43; 19%) was detected exclusively in smokers. For the first time, we demonstrate that most carriers of G --> T transversions had also a high level of bulky DNA adducts in their non-tumourous lung tissue. Our study provides evidence for a high burden of molecular alterations occurring concurrently in the lung of lung cancer patients.

Primary pulmonary choriocarcinoma: a case report.

BACKGROUND: Primary pulmonary choriocarcinoma (PPC) is an extremely rare clinical entity. In contrast with gestational trophoblastic tumors that show an extreme sensitivity for chemotherapy, extragonadal choriocarcinomas are mostly unresponsive to surgical and chemotherapeutic treatment and are associated with poor prognosis. The reason non-gestational choriocarcinomas behave so differently from gestational tumors is unknown. CASE: In the present case we report a 30-year-old female patient with primary choriocarcinoma of lung localization who was successfully treated with surgical resection and multiple cycles of combination chemotherapy. During her recovery she was followed up by human chorionic gonadotropin (hCG) titer measurement, and after 1 year of close surveillance of beta-hCG levels her disease achieved complete remission. CONCLUSION: Because of the extreme rarity of this malignancy, there are no standardized therapeutic guidelines for treatment. The first choice in treatment of PPC is surgical resection. Postoperatively chemotherapy is indicated immediately, because definitive histologic diagnosis is not essential before chemotherapy since beta-hCG is a reliable tumor marker for choriocarcinoma.

Distinct claudin expression profile in histologic subtypes of lung cancer.

PURPOSE: Claudins are the main constituents of tight junctions. Little is known about their expression and localization in the normal bronchial epithelium and in lung cancer. PATIENTS AND METHODS: One hundred four lung cancer tissue blocks were studied including 46 adenocarcinomas (ADC), 30 squamous cell carcinomas (SCC), 15 small cell lung cancers (SCLC), 8 typical and 5 atypical carcinoids. All slides contained normal bronchial mucosa as well. Immunohistochemistry using antibodies against claudins-1, -2, -3, -4, and -7 proteins, as well as semi-quantitative estimation were performed. RT-PCR analysis was also carried out in 22 immunohistochemically representative tumor samples. RESULTS: Normal bronchial epithelial cells expressed all the examined claudin proteins. When compared, SCLCs and carcinoids showed striking differences in regard to claudins-1, -3, and -4 expressions (p<0.0001, p<0.0001, and p<0.0004, respectively), whereas ADCs and SCCs revealed significant differences in claudins-3, -4, and -7 expressions (p<0.0001, p<0.0001, and p<0.0053, respectively). However, comparison of ADCs with SCLCs revealed significant difference only in claudin-2 expression (p<0.0002). The comparison of ADCs and carcinoids resulted in significant differences regarding claudins-1, -3, and -4 expressions (p<0.0006, p<0.0001, and p<0.0001, respectively). SCCs and SCLCs varied in respect to claudin-2, -3, and -4 expressions (p<0.0009, p<0.0001, and p<0.0019, respectively), whereas SCCs and carcinoids showed different claudins-1 and -4 expressions (p<0.0076 and p<0.0045, respectively). RT-PCR analysis revealed parallel changes in the mRNA and protein expression of certain claudins. CONCLUSIONS: The observed distinct claudin expression profile within the non-small cell lung cancer group, further, the marked differences between SCLCs and carcinoids may have differential diagnostic impact, and the overexpression of certain claudins might have therapeutic implications.

No gender difference in development of obliterative airway disease in rat tracheal allografts.

The aim of this study was to test whether donor and recipient gender influence the development of obliterative airway disease in an established rat model of human bronchiolitis obliterans. Rat tracheas were transplanted from male and female Brown-Norway donors into male and female Lewis recipients. Grafts were harvested at days 7, 14 and 21 for morphometric studies and molecular analysis by real-time PCR. At each time point, both epithelial injury and the extent of luminal occlusion of the tracheal allografts were similar between the groups. Furthermore, intragraft mRNA expression for transforming growth factor (TGF)-beta1, interleukin (IL)-2 and interferon (INF)-gamma did not differ between the groups. Our data suggest that gender has no impact on the development of obliterative airway disease in this transplant model.

Lymphangiogenesis correlates with lymph node metastasis, prognosis, and angiogenic phenotype in human non-small cell lung cancer.

PURPOSE: Recent experimental studies have revealed that lymphangiogenesis plays an important role in cancer progression, but its clinical significance in the case of non-small cell lung cancer (NSCLC) remains unclear. Our aim was to assess the lymphangiogenesis of human NSCLC, and to correlate this with angiogenic phenotype (angiogenic versus nonangiogenic growth pattern) and clinical behavior. EXPERIMENTAL DESIGN: One hundred and three patients with NSCLC and complete follow-up information were included. Tumor samples were immunostained for vascular endothelial growth factor-C (VEGF-C), the lymphatic endothelial markers, LYVE-1 and D2-40/Podoplanin, and the panvascular marker, CD31. Lymphatic vessel density (LVD) and perimeters were evaluated within the tumor and peritumorally. RESULTS: LVDs at the tumor periphery were significantly higher in lymph node metastatic tumors (P < 0.005) and high LVDs correlated with poor overall survival (P < 0.001). However, this tendency proved to be significant only in the angiogenic tumor group (P < 0.001). Although 68% of the patients with nonangiogenic tumors had lymph node metastasis (P = 0.0048 versus angiogenic tumors), in the patient group with nonangiogenic NSCLCs, there was no information from the LVDs in any investigated tumor area (P > 0.05). In contrast to angiogenic tumors, which had actively sprouting lymphatics in all of the investigated tumor areas, nonangiogenic tumors showed no Ki67 staining intratumorally. CONCLUSIONS: Our results reveal tumor lymphangiogenesis as a novel prognostic indicator for the risk of lymph node metastasis in NSCLC. Moreover, it also provides the first evidence that nonangiogenic NSCLCs mainly co-opt host tissue lymphatics during their growth, in contrast to most of the angiogenic tumors, which expand with concomitant lymphangiogenesis.

DNA adducts in tumour, normal peripheral lung and bronchus, and peripheral blood lymphocytes from smoking and non-smoking lung cancer patients: correlations between tissues and detection by 32P-postlabelling and immunoassay.

Smoking is a major risk factor for lung cancer. This comparative study of smoking-related carcinogen-DNA adducts in pulmonary tissues and peripheral blood lymphocytes aims to further explore the primary DNA damaging processes by cigarette smoke in target and surrogate tissues. Samples of tumour and normal peripheral lung tissue, normal bronchial tissue and peripheral blood lymphocytes were obtained from a total of 85 lung cancer patients who underwent lung resection. Bulky DNA adducts were determined by 32P-postlabelling, and polycyclic aromatic hydrocarbon (PAH)-DNA adducts were detected by (+/-)-7beta, 8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene-DNA chemiluminescence immunoassay (BPDE-DNA CIA) in smaller subsets of tissue samples subject to availability of DNA. Bulky DNA adduct levels ranged between 0.3 and 27.8 adducts/10(8) nucleotides (nt) with mean adduct levels between 2.8 and 11.5 adducts/10(8) nt. Mean PAH-DNA adduct levels were 2.6-6.2 adducts/10(8) nt. Significantly higher bulky DNA adduct levels were detected in smokers' lungs as compared with non-smokers' (P < 0.02). PAH-DNA adduct levels appeared higher in the lungs of smokers compared with non-smokers but the difference was not significant. Lung tumour contained on average a 50% lower DNA adduct level compared with normal lung tissue. A statistically significant positive correlation was found between the DNA adduct levels of the corresponding tumour and normal lung tissue samples in both smokers and non-smokers using both methodologies. Bulky DNA adduct levels in normal lung and blood lymphocytes correlated significantly in non-smokers only (r = 0.55, P = 0.023). In lung tumour DNA samples there was a weak correlation between values obtained by 32P-postlabelling and by the BPDE-DNA immunoassay (r = 0.27, P = 0.054). However, with normal lung DNA samples, values obtained by the two assays did not correlate.