Tüdőtranszplantáció magyar betegek számára

When conservative treatment fails, lung transplantation often remains the only therapeutic option for patients with end stage parenchymal or vascular lung diseases. According to the statistics of the International Society for Heart and Lung Transplantation, in 2010 more than 3500 lung transplantations have been performed worldwide. The Department of Thoracic Surgery at the University of Vienna is considered to be one of the world's leading lung transplantation centres; in the last year 115, since 1989 more than 1500 lung transplantation procedures under the supervision of Prof. Dr. Walter Klepetko. Similar to other Central-European countries, lung transplantation procedures of Hungarian patients have also been performed in Vienna whithin the framework of a twinning aggreement. However, many crucial tasks in the process, such indication and patient selection preoperative rehabilitation organ procurement and long term follow-up care have been stepwise taken over by the Hungarian team. Although the surgery itself is still preformed in Vienna, professional experience is already available in Hungary, since the majority of Hungarian recipients have been transplanted by hungarian surgeons who are authors of this article the professional and personal requirements of performing lung transplantations are already available in Hungary. The demand of performing lung transplantation in Hungary has been raising since 1999 and it soon reaches the extent which justifies launching of an individual national program. Providing the technical requirements is a financial an organisational issue. In order to proceed, a health policy decision has to be made

Venovenosus extrakorporális membránoxigenizációval (ECMO) végzett mellkassebészeti műtétek tapasztalatai Magyarországon. Retrospektív klinikai tanulmány = Experiences with venovenous extracorporeal membrane oxygenation (ECMO) support for thoracic surgery in Hungary. Retrospective clinical study

Absztrakt: Bevezetés: A modern mellkassebészeti műtétek nagy része féloldali tüdőlélegeztetéssel és az operált oldal nyugalomba helyezésével történik úgy, hogy a sebészi feltárás és a beteg oxigenizációja egyaránt megfelelő legyen. A beavatkozás technikai korlátja, ha az intraoperatív gázcsere nem biztosítható: nincs elérhető légút, vagy nincsen elegendő gázcserét biztosító tüdőparenchyma. A lélegeztetés alternatíváját kezdetben a cardiopulmonalis bypass jelentette, napjainkban az extrakorporális membránoxigenizáció (ECMO) használata került előtérbe. Célkitűzés: Az elektív, intraoperatív, venovenosus (VV-) ECMO-val végzett mellkassebészeti műtéteink indikációinak, biztonságosságának, a perioperatív morbiditásra és mortalitásra gyakorolt hatásának retrospektív vizsgálata. Betegek és módszer: A 2014. 04. 28. és a 2018. 04. 30. közötti időszakra vonatkozóan az Országos Onkológiai Intézet számítógépes adatbázisából megállapítottuk, hogy 12 beteg műtéténél használtunk intraoperatív VV-ECMO-t. Eredmények: A betegek átlagéletkora 45 év volt, alapbetegségük 2 esetben benignus, 10 esetben malignus daganat. Az ECMO indikációját 3 esetben extrém súlyos légcsőszűkület jelentette, 4 betegnél korábbi tüdőreszekció miatt az intraoperatív gázcseréhez elégtelen tüdőállomány. 5 beteg esetében mind a légút, mind a parenchyma hiánya képezte az ECMO indikációját. Az apnoe (átlagosan 142 perc) megszakítására nem volt szükség. A VV-ECMO-kezeléssel összefüggő szövődményt nem észleltünk. Intraoperatív halálozás nem történt, a 30 napos perioperatív halálozás 8,33% volt. Következtetés: Technikai inoperabilitás esetén, ha nincs az intraoperatív lélegeztetéshez használható légút, vagy nem áll rendelkezésre elegendő tüdőparenchyma a gázcseréhez, és a kis vérköri vérkeringés fenntartásához elegendő a pulmonalis érmeder, valamint nincs szükség a nagyerek reszekciójára, a VV-ECMO biztonságosan, a vérzésveszély fokozódása nélkül, több órán keresztül pótolja a teljes pulmonalis gázcserefunkciót. A VV-ECMO alkalmazása nem növelte a perioperatív morbiditást és mortalitást. A VV-ECMO alkalmazásával inoperábilis betegek válnak operálhatóvá. Orv Hetil. 2019; 160(42): 1655–1662. | Abstract: Introduction: Most modern thoracic operations are performed with single-lung ventilation balancing between convenient surgical approach and adequate gas exchange. The technical limitations include difficult airways or insufficient parenchyma for the intraoperative single-lung ventilation. Earlier, cardiopulmonary bypass was the only solution, however, today the extracorporeal membrane oxygenation is in the forefront. Aim: We retrospectively analysed our elective operations by use of venovenous ECMO to assess the indication, safety, perioperative morbidity and mortality. Patients and method: 12 patients were operated using venovenous (VV-) ECMO between 28 April 2014 and 30 April 2018 in the National Institute of Oncology. The main clinicopathological characteristics, data regarding the operation, the use of ECMO and survival were collected. Results: The mean age was 45 years, 2 patients had benign and 10 had malignant diseases. Extreme tracheal stricture was the indication for ECMO in 3 cases, while 4 patients had previous lung resection and lacked enough parenchyma for single-lung ventilation. 5 patients had both airway and parenchymal insufficiency. The average time of apnoea was 142 minutes without interruption in any of the cases. We did not experience any ECMO-related complication. We had no intraoperative death and 30-day mortality was 8.33%. Conclusion: In case of technical inoperability, when there is no airway or insufficient parenchyma for gas exchange, but pulmonary vascular bed is enough and there is no need for great-vessel resection, VV-ECMO can safely replace the complete gas exchange without further risk of bleeding. The use of VV-ECMO did not increase the perioperative morbidity and mortality. Previously inoperable patients can be operated with VV-ECMO. Orv Hetil. 2019; 160(42): 1655–1662

Mechanisms of vascularization in murine models of primary and metastatic tumor growth

Directed capillary ingrowth has long been considered synonymous with tumor vascularization. However, the vasculature of primary tumors and metastases is not necessarily formed by endothelial cell sprouting; instead, malignant tumors can acquire blood vessels via alternative vascularization mechanisms, such as intussusceptive microvascular growth, vessel co-option, and glomeruloid angiogenesis. Importantly, in response to anti-angiogenic therapies, malignant tumors can switch from one vascularization mechanism to another. In this article, we briefly review the biological features of these mechanisms and discuss on their significance in medical oncology

Current therapy of KRAS-mutant lung cancer

KRAS mutations are the most frequent gain-of-function alterations in patients with lung adenocarcinoma (LADC) in the Western world. Although they have been identified decades ago, prior efforts to target KRAS signaling with single-agent therapeutic approaches such as farnesyl transferase inhibitors, prenylation inhibition, impairment of KRAS downstream signaling, and synthetic lethality screens have been unsuccessful. Moreover, the role of KRAS oncogene in LADC is still not fully understood, and its prognostic and predictive impact with regards to the standard of care therapy remains controversial. Of note, KRAS-related studies that included general non-small cell lung cancer (NSCLC) population instead of LADC patients should be very carefully evaluated. Recently, however, comprehensive genomic profiling and wide-spectrum analysis of other co-occurring genetic alterations have identified unique therapeutic vulnerabilities. Novel targeted agents such as the covalent KRAS G12C inhibitors or the recently proposed combinatory approaches are some examples which may allow a tailored treatment for LADC patients harboring KRAS mutations. This review summarizes the current knowledge about the therapeutic approaches of KRAS-mutated LADC and provides an update on the most recent advances in KRAS-targeted anti-cancer strategies, with a focus on potential clinical implications

Circulating endothelial cells, bone marrow-derived endothelial progenitor cells and proangiogenic haematopoietic cells in cancer: From biology to therapy

Vascularization, a hallmark of tumorigenesis, is classically thought to occur exclusively through angiogenesis (i.e. endothelial sprouting). However, there is a growing body of evidence that endothelial progenitor cells (EPCs) and proangiogenic hematopoietic cells (HCs) are able to support the vascularization of tumors and may therefore play a synergistic role with angiogenesis. An additional cell type being studied in the field of tumor vascularization is the circulating endothelial cell (CEC), whose presence in elevated numbers reflects vascular injury. Levels of EPCs and CECs are reported to correlate with tumor stage and have been evaluated as biomarkers of the efficacy of anticancer/antiangiogenic treatments. Furthermore, because EPCs and subtypes of proangiogenic HCs are actively participating in capillary growth, these cells are attractive potential vehicles for delivering therapeutic molecules. The current paper provides an update on the biology of CECs, EPCs and proangiogenic HCs, and explores the utility of these cell populations for clinical oncology

Sleeve lobectomy in patients with non-small-cell lung cancer: a report from the European Society of Thoracic Surgery database 2021

OBJECTIVES: For centrally located lung tumours, sleeve lobectomy is preferred over pneumectomy. We report on the surgical practices and perioperative outcomes of sleeve resections based on data from the European Society of Thoracic Surgeons database. METHODS: We retrieved data of patients undergoing sleeve lobectomy or bilobectomy from 2007 to 2021. We evaluated baseline characteristics, surgical approach, neoadjuvant treatments, morbidity and postoperative outcomes of open and video-assisted thoracoscopic surgery (VATS) procedures. RESULTS: In total, 1652 patients (median age: 63 years; females/males: 446/1206) underwent sleeve lobectomy (n = 1536) or bilobectomy (n = 116) by open thoracotomy (n = 1491; 90.2%) or VATS (n = 161; 9.8%) with a thoracotomy conversion rate of 21.1% (n = 34); 398 (24.1%) patients received neoadjuvant treatment. Overall morbidity and 30-day mortality were 40.6% and 2.2%, respectively. Bronchial anastomotic complications occurred in 29 patients (1.8%) with conservative treatment in 6 cases (20.7%) and operative management in 23 (79.3%). On multivariable analysis, factors related to the elevated risk of cardiopulmonary complications were body mass index < 20 [odds ratio (OR): 2.26; P < 0.001] and bilobectomy (OR : 2.28, P < 0.001). Age <60 years (OR: 0.71, P = 0.013), female sex (OR: 0.54, P < 0.001) and VATS (0.64, P < 0.001) were associated with decreased risk. Neoadjuvant treatment was not associated with increased risks of cardiopulmonary complications (OR: 1.05; P = 0.664). Compared to open thoracotomy, VATS was associated with significantly decreased overall morbidity (30.4% vs 41.7%, P = 0.006) and length of stay (median: 5 days vs 8 days; P < 0.001). CONCLUSIONS: Sleeve lobectomies can be safely performed after neoadjuvant treatment. The VATS approach fosters shorter length of stay and decreased morbidity.status: publishe

Szemelvények a Semmelweis Egyetem, az Országos Onkológiai Intézet és az Országos Korányi Tbc és Pulmonológiai Intézet együttműködésén alapuló tüdőrák-kutatási programból

Lung cancer places a significant socio-economic burden on the Hungarian population. This overview summarizes the findings of collaborative translational lung cancer research efforts of three Hungarian flagship academic institutions, the Semmelweis University, the National Institute of Oncology and the National Koranyi Institute of TB and Pulmonology. With regards to the molecular factors regulating tumor angiogenesis, we identified the prognostic significance of apelin and erythropoietin receptor (EPOR) expression in non-small cell lung cancer (NSCLC). Furthermore, the impact of KRAS mutation subtypes and ERCC1 (excision repair cross-complementation group 1) expression on the response to platinum-based chemotherapy have been studied. We also described the epidemiology and predictive power of rare EGFR (epidermal growth factor receptor) mutations in a large Hungarian patient cohort. Lastly, the expression of molecular factors associated with NSCLC progression was studied specifically in brain metastatic matched cases series. These preclinical and clinical studies provide clinically relevant information that hopefully will contribute to the improvement of lung cancer patient care

Erythropoietin receptor expression is a potential prognostic factor in human lung adenocarcinoma

Recombinant human erythropoietins (rHuEPOs) are used to treat cancer-related anemia. Recent preclinical studies and clinical trials, however, have raised concerns about the potential tumor-promoting effects of these drugs. Because the clinical significance of erythropoietin receptor (EPOR) signaling in human non-small cell lung cancer (NSCLC) also remains controversial, our aim was to study whether EPO treatment modifies tumor growth and if EPOR expression has an impact on the clinical behavior of this malignancy. A total of 43 patients with stage III-IV adenocarcinoma (ADC) and complete clinicopathological data were included. EPOR expression in human ADC samples and cell lines was measured by quantitative real-time polymerase chain reaction. Effects of exogenous rHuEPOalpha were studied on human lung ADC cell lines in vitro. In vivo growth of human ADC xenografts treated with rHuEPOalpha with or without chemotherapy was also assessed. In vivo tumor and endothelial cell (EC) proliferation was determined by 5-bromo-2'-deoxy-uridine (BrdU) incorporation and immunofluorescent labeling. Although EPOR mRNA was expressed in all of the three investigated ADC cell lines, rHuEPOalpha treatment (either alone or in combination with gemcitabine) did not alter ADC cell proliferation in vitro. However, rHuEPOalpha significantly decreased tumor cell proliferation and growth of human H1975 lung ADC xenografts. At the same time, rHuEPOalpha treatment of H1975 tumors resulted in accelerated tumor endothelial cell proliferation. Moreover, in patients with advanced stage lung ADC, high intratumoral EPOR mRNA levels were associated with significantly increased overall survival. This study reveals high EPOR level as a potential novel positive prognostic marker in human lung ADC

Apelin promotes lymphangiogenesis and lymph node metastasis

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Apelin promotes lymphangiogenesis and lymph node metastasis

Whereas the role of the G-protein-coupled APJ receptor and its ligand, apelin, in angiogenesis has been well documented, the ability of the apelin/APJ system to induce lymphangiogenesis and lymphatic metastasis has been largely unexplored. To this end, we first show that APJ is expressed in lymphatic endothelial cells (LECs) and, moreover, that it responds to apelin by activating the apelinergic signaling cascade. We find that although apelin treatment does not influence the proliferation of LECs in vitro, it enhances their migration, protects them against UV irradiation-induced apoptosis, increases their spheroid numbers in 3D culture, stimulates their in vitro capillary-like tube formation and, furthermore, promotes the invasive growth of lymphatic microvessels in vivo in the matrigel plug assay. We also demonstrate that apelin overexpression in malignant cells is associated with accelerated in vivo tumor growth and with increased intratumoral lymphangiogenesis and lymph node metastasis. These results indicate that apelin induces lymphangiogenesis and, accordingly, plays an important role in lymphatic tumor progression. Our study does not only reveal apelin as a novel lymphangiogenic factor but might also open the door for the development of novel anticancer therapies targeting lymphangiogenesis