László Agócs

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.

The role of TTF-1 in differentiating primary and metastatic lung adenocarcinomas.

Thyroid transcription factor-1 (TTF-1) is a sensitive marker for pulmonary and thyroid adenocarcinomas. The aim of this work was to determine its usefulness in distinction between primary and metastatic lung adenocarcinomas. We have examined the expression of TTF-1 in 100 solitary pulmonary nodules. They included 50 stage I peripheral primary bronchial adenocarcinomas (30 men, 20 women, mean age: 60 years) and 50 metastatic pulmonary adenocarcinomas (21 men, 29 women, mean age: 57 years) of different origins, such as breast (13), colon (13), rectum (13), kidney (7), stomach (2), and thyroid gland (2). TTF-1 immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissues. In primary bronchial adenocarcinomas we found immunopositivity in 46/50 cases, among them 30 cases showed strong nuclear immunostaining. In four primary adenocarcinoma cases the observed immunopositivity was localized to the cytoplasm. Out of the metastatic adenocarcinomas all but the 2 thyroid cancers were negative. Both thyroid tumors showed strong immunopositivity. Our results confirm that TTF-1 immunohistochemistry is a very sensitive and highly specific method in the differential diagnosis of primary and metastatic lung adenocarcinomas and should be used in the everyday clinical practice.

P53 expression in stage I squamous cell lung cancer

P53 expression was studied using immunohistochemistry in patients (n=94) with pathologic stage I squamous cell lung cancer treated surgically between 1991-1992. The overall p53 positivity ratio was 48/94. 83 of the cases proved to be suitable for follow-up analysis carried out in November, 1995. 46/83 were p53 positive, and 25/46 patients were alive at the time of analysis. The patients who died (21/46) had a mean survival time of 17.5 months. In p53 negative cases (37/83), however, 29/37 patients were still alive at the time of follow-up, and 8/37 had died with a mean survival time of 23.1 months. A significant correlation could be found between p53 immunopositivity and reduced survival time (p=0.0125). Interestingly, out of 83 cases analyzed histologic evidence of tuberculous scar tissue was present in 9 tumors with a p53 positivity ratio of only 1/9. When flow cytometry was used to examine tumor samples from all subgroups mentioned above (n=32), no correlation was found between the p53 immunopositivity or the prognosis and the DNA content of tumor tissues. Our results suggest that in the early stage of squamous cell lung cancer the p53 positivity may be an indicator of a more aggressive tumor behavior and a shortened survival time.

Chemotherapy treatment is associated with altered PD-L1 expression in lung cancer patients

ObjectivesWhile the predictive value of programmed cell death ligand-1 (PD-L1) protein expression for immune checkpoint inhibitor therapy of lung cancer has been extensively studied, the impact of standard platinum-based chemotherapy on PD-L1 or programmed cell death-1 (PD-1) expression is unknown. The aim of this study was to determine the changes in PD-L1 expression of tumor cells (TC) and immune cells (IC), in PD-1 expression of IC, and in the amount of stromal mononuclear cell infiltration after platinum-based chemotherapy in patients with lung cancer.Materials and methodsWe determined the amount of stromal mononuclear cells and PD-L1/PD-1 expressions by immunohistochemistry in bronchoscopic biopsy samples including 20 adenocarcinomas (ADC), 15 squamous cell carcinomas (SCC), 2 other types of non-small cell lung cancer, and 4 small cell lung cancers together with their corresponding surgical resection tissues after platinum-based chemotherapy.ResultsPD-L1 expression of TC decreased in ten patients (24.4%) and increased in three patients (7.32%) after neoadjuvant chemotherapy (p = 0.051). The decrease in PD-L1 expression, however, was significant only in patients who received cisplatin–gemcitabine combination (p = 0.020), while in the carboplatin–paclitaxel group, no similar tendency could be observed (p = 0.432). There was no difference between ADC and SCC groups. Neither PD-1 expression nor the amount of stromal IC infiltration showed significant changes after chemotherapy.ConclusionsThis is the first study, in which both PD-L1 and PD-1 expression were analyzed together with the amount of stromal IC infiltration in different histological subtypes of lung cancer before and after platinum-based chemotherapy. Our results confirm that chemotherapy decreases PD-L1 expression of TC in a subset of patients, therefore, rebiopsy and re-evaluation of PD-L1 expression may be necessary for the indication of immune checkpoint inhibitor therapy.

Nem tapintható tüdőgócok drót- és izotópjelölés segítségével történő minimálinvazív műtéti eltávolítása

INTRODUCTION Nowadays ever smaller, sub-centimetre lung nodules are screened and diagnosed. For these, minimally invasive resection is strongly recommended both with diagnostic and therapeutic purpose. AIM Despite many advantages of minimally invasive thoracic surgery, thorough palpation of the lung lobes and thus the localization of lung nodules are still limited. There are several options to solve this problem. From the possibilities we have chosen and tried wire- and isotope-guided lung nodule localization. MATERIALS AND METHODS In 2017, at the Thoracic Surgery Department of the National Institute of Oncology we performed wire- and isotope-guided minimally invasive pulmonary nodule resection in five patients. The diameter of the lung nodules was between 0.5 and 1.2 cm. The age of the patients was between 44 and 65 years and none of them had severe comorbidities, which meant low risk for complications. RESULTS We successfully performed the minimally invasive atypical resection in all cases. After the wire and isotope placement we found a 2-3 mm pneumothorax in one patient that did not need urgent drainage. In another patient we found that high amount of intraparenchymal bleeding surrounded the channel of the wire. During the operation, two wires were displaced when the lung collapsed, and in another case the mentioned bleeding got into the thoracic cavity and made it difficult to detect the nodule. In one case we resected the wire-guided lung tissue, but the isotope-guided lung nodule was below the resection line. CONCLUSION Both techniques could help to localize the non-palpable lung nodules. Based on our initial experiences, the isotope-guided method provides more details to estimate the exact depth of the nodule from the visceral surface of the pleura and we can avoid the unpleasantness of wire displacement. On the other hand, the production of the isotope requires a more developed infrastructure and the exact timing of the operation after the isotope injection is more strict. Orv Hetil. 2018; 159(34): 1399-1404.INTRODUCTION Nowadays ever smaller, sub-centimetre lung nodules are screened and diagnosed. For these, minimally invasive resection is strongly recommended both with diagnostic and therapeutic purpose. AIM Despite many advantages of minimally invasive thoracic surgery, thorough palpation of the lung lobes and thus the localization of lung nodules are still limited. There are several options to solve this problem. From the possibilities we have chosen and tried wire- and isotope-guided lung nodule localization. MATERIALS AND METHODS In 2017, at the Thoracic Surgery Department of the National Institute of Oncology we performed wire- and isotope-guided minimally invasive pulmonary nodule resection in five patients. The diameter of the lung nodules was between 0.5 and 1.2 cm. The age of the patients was between 44 and 65 years and none of them had severe comorbidities, which meant low risk for complications. RESULTS We successfully performed the minimally invasive atypical resection in all cases. After the wire and isotope placement we found a 2-3 mm pneumothorax in one patient that did not need urgent drainage. In another patient we found that high amount of intraparenchymal bleeding surrounded the channel of the wire. During the operation, two wires were displaced when the lung collapsed, and in another case the mentioned bleeding got into the thoracic cavity and made it difficult to detect the nodule. In one case we resected the wire-guided lung tissue, but the isotope-guided lung nodule was below the resection line. CONCLUSION Both techniques could help to localize the non-palpable lung nodules. Based on our initial experiences, the isotope-guided method provides more details to estimate the exact depth of the nodule from the visceral surface of the pleura and we can avoid the unpleasantness of wire displacement. On the other hand, the production of the isotope requires a more developed infrastructure and the exact timing of the operation after the isotope injection is more strict. Orv Hetil. 2018; 159(34): 1399-1404.

A nagyméretű retrosternalis strumák műtéti megoldása – fej-nyak sebész és mellkassebész sikeres együttműködése

Absztrakt Bevezetes: A megnagyobbodott, akar a tracheat is komprimalo pajzsmirigy műteti kezelese legtobb esetben a totalis thyreoidectomia, amely mind a fej-nyak sebeszek, mind az altalanos sebeszek koreben ismert eljaras. A megnagyobbodott pajzsmirigy az esetek korulbelul 1–10%-aban a szegycsont moge er, ezaltal elterő műteti technikat igenyel az eltavolitasa. Betegek es modszerek: Munkacsoportunk 2000–2014-ig 182 substernalis struma miatt vegzett műtetet. Substernalisnak azon pajzsmirigylebenyeket tekintettuk, amelyek legalabb a jugulum szintje ala ertek. Retrospektive vizsgaltuk a 182 esetet, amelyek substernalisan elhelyezkedő pajzsmirigylebenyek miatt kerultek műtetre az elmult 14evben. Eredmenyek: Minden beteg panaszokkal erkezett, amelyek kozul a fulladas es nehezlegzes volt a leggyakoribb. A műtetet minden esetben megelőzte kepalkoto vizsgalat. 31 esetben praeoperativ nyaki ultrahang keszult, 13 esetben MR- es 138 esetben CT-vizsgalat jelentette a kepalkoto eljarast. 15 beteg eseteben tortent kor...

A transhiatalis sebészet járatlan ösvényei

Absztrakt A szerzők a transhiatalis műtetek ket uj, az irodalomban meg nem kozolt indikaciojat ismertetik. Recidiv bronchuscarcinoma miatti bal oldali pulmonectomiat kovető, jobb oldali spontan nyelőcsőrupturaban laparotomias transhiatalis megoldast vegeztek. A 2,5 cm-es repedest a szalagokkal lehuzott nyelőcsovon, a mediastinumban, csomos Vicryl-oltesekkel zartak es cseplesszel boritottak. A műtetet jobb mellűri es mediastinalis drenezessel, gastro- es jejunostomiaval fejeztek be. A masodik műtet soran also-hatso mediastinalis tumort (8×5 cm), incarceralt massziv hiatusherniat, megrovidult nyelőcsovet es a mediastinumba penetralo kisgorbuleti ulcust oldottak meg. Az időskor es rossz legzesfunkcio miatt, laparotomiat kovetően, a kiszelesitett hiatuson at, első lepesben a kornyezetevel szivosan osszetapadt hiatusservet es a megrovidult, perioesophagitises nyelőcsovet tettek szabadda. Ez utan a hatso mediastinumban, a gerincoszlop mellett magasra terjedő, kisgorbuletről kiindulo, okolnyi, jol kapszulalt kep...

Aspergillus empyema kezelése nyitott thoracostomiával és izomplasztikával, a tüdő funkciójának megőrzésével – esetismertetés

CASE REPORT Invasive aspergillosis is a life threatening complication in immune-compromised patients causing lung tissue destruction. Aspergillus empyema requires aggressive multimodality treatment. MATERIAL AND METHOD We present a case of Aspergillus empyema treated by thoracic and plastic surgery preserving the lung function in an 18 year-old male patient suffering dermatomyositis and treated with steroids for a long time. After open window thoracostomy (OWT) we used pedicled musculus latissimus dorsi (MLD) flap and mobilised the anterior serratus muscle to close the pleural cavity. CONCLUSION The intrathoracic use of muscle flaps after OWT in case of chronic Aspergillus empyema can preserve the underlying lung tissue. Cooperation of thoracic and plastic surgeons - as in the cases presented - provides an excellent opportunity to treat successfully of otherwise hopeless patients.

[Primary suppurative costochondritis--one of our successfully treated cases].

Secondary chest wall infections after previous surgical procedures are well known but the primary form of this is a relatively rare entity. We present a case of a 34-year-old man who suffered from primary suppurative costochondritis diagnosed by ultrasound and chest CT scan. The patient underwent a wide necrosectomy with a muscle flap reconstruction.