Attila Szendrői

Urinary matrix metalloproteinase-7 level is associated with the presence of metastasis in bladder cancer

Study Type – Therapy (case series)
Level of Evidence 4

Identifying Resistance Mechanisms against Five Tyrosine Kinase Inhibitors Targeting the ERBB/RAS Pathway in 45 Cancer Cell Lines

Because of the low overall response rates of 10–47% to targeted cancer therapeutics, there is an increasing need for predictive biomarkers. We aimed to identify genes predicting response to five already approved tyrosine kinase inhibitors. We tested 45 cancer cell lines for sensitivity to sunitinib, erlotinib, lapatinib, sorafenib and gefitinib at the clinically administered doses. A resistance matrix was determined, and gene expression profiles of the subsets of resistant vs. sensitive cell lines were compared. Triplicate gene expression signatures were obtained from the caArray project. Significance analysis of microarrays and rank products were applied for feature selection. Ninety-five genes were also measured by RT-PCR. In case of four sunitinib resistance associated genes, the results were validated in clinical samples by immunohistochemistry. A list of 63 top genes associated with resistance against the five tyrosine kinase inhibitors was identified. Quantitative RT-PCR analysis confirmed 45 of 63 genes identified by microarray analysis. Only two genes (ANXA3 and RAB25) were related to sensitivity against more than three inhibitors. The immunohistochemical analysis of sunitinib-treated metastatic renal cell carcinomas confirmed the correlation between RAB17, LGALS8, and EPCAM and overall survival. In summary, we determined predictive biomarkers for five tyrosine kinase inhibitors, and validated sunitinib resistance biomarkers by immunohistochemistry in an independent patient cohort.

Opposite prognostic roles of HIF1α and HIF2α expressions in bone metastatic clear cell renal cell cancer

BACKGROUND Prognostic markers of bone metastatic clear cell renal cell cancer (ccRCC) are poorly established. We tested prognostic value of HIF1α/HIF2α and their selected target genes in primary tumors and corresponding bone metastases. RESULTS Expression of HIF2α was lower in mRCC both at mRNA and protein levels (p/mRNA/=0.011, p/protein/=0.001) while HIF1α was similar to nmRCC. At the protein level, CAIX, GAPDH and GLUT1 were increased in mRCC. In all primary RCCs, low HIF2α and high HIF1α as well as CAIX, GAPDH and GLUT1 expressions correlated with adverse prognosis, while VEGFR2 and EPOR gene expressions were associated with favorable prognosis. Multivariate analysis confirmed high HIF2α protein expression as an independent risk factor. Prognostic validation of HIFs, LDH, EPOR and VEGFR2 in RNA-Seq data confirmed higher HIF1α gene expression in primary RCC as an adverse (p=0.07), whereas higher HIF2α and VEGFR2 expressions as favorable prognostic factors. HIF1α/HIF2α-index (HIF-index) proved to be an independent prognostic factor in both the discovery and the TCGA cohort. PATIENTS AND METHODS Expressions of HIF1α and HIF2α as well as their 7 target genes were analysed on the mRNA and protein level in 59 non-metastatic ccRCCs (nmRCC), 40 bone metastatic primary ccRCCs (mRCC) and 55 corresponding bone metastases. Results were validated in 399 ccRCCs from the TCGA project. CONCLUSIONS We identified HIF2α protein as an independent marker of the metastatic potential of ccRCC, however, unlike HIF1α, increased HIF2α expression is a favorable prognostic factor. The HIF-index incorporated these two markers into a strong prognostic biomarker of ccRCC.

Diagnostic algorithm, prognostic factors and surgical treatment of metastatic cancer diseases of the long bones and spine

Oncological management of skeletal metastases has changed dramatically in the last few decades. A significant number of patients survive for many years with their metastases. Surgeons are more active and the technical repertoire is broader, from plates to intramedullary devices to (tumour) endoprostheses. The philosophy of treatment should be different in the case of a trauma-related fracture and a pathological fracture. A proper algorithm for establishing a diagnosis and evaluation of prognostic factors helps in planning the surgical intervention. The aim of palliative surgery is usually to eliminate pain and to allow the patient to regain his/her mobility as well as to improve the quality of life through minimally invasive techniques using life-long durable devices. In a selected group of patients with an oncologically controlled primary tumour site and a solitary bone metastasis with positive prognostic factors, which meet the criteria for radical excision (approximately 10% to 15% of the cases), a promising three to five years of survival may be achieved, especially in cases of metastases from breast and kidney cancer. Spinal metastases require meticulous evaluation because decisions on treatment mostly depend on the tumour type, segmental stability, the patient’s symptoms and general state of health. Advanced radiotherapy combined with minimally invasive surgical techniques (minimally invasive stabilisation and separation surgery) provides durable local control with a low complication rate in a number of patients. Cite this article: EFORT Open Rev 2017;2:372-381.

Mucoepidermoid Lung Tumor Appearing as an Abscess on the Scrotum

The authors present the case of a 52-year-old man who had recurring scrotal abscesses resulting in oncotomy being carried out seven times within 2 years. Eventually, it was dissected out totally. Histology proved anaplastic cancer metastasis. The primary tumor was detected in the bronchia; moreover, metastases were found in other organs as well. The patient died 6 weeks after the first diagnosis. We intended to draw attention to frequently occurring scrotal inflammation and thus the underlying diseases. We emphasize the importance of histology examinations.

Pathogenic and targetable genetic alterations in 70 urachal adenocarcinomas: Genetic alterations in 70 urachal adenocarcinomas

Urachal cancer (UrC) is a rare but aggressive malignancy often diagnosed in advanced stages requiring systemic treatment. Although cytotoxic chemotherapy is of limited effectiveness, prospective clinical studies can hardly be conducted. Targeted therapeutic treatment approaches and potentially immunotherapy based on a biological rationale may provide an alternative strategy. We therefore subjected 70 urachal adenocarcinomas to targeted next‐generation sequencing, conducted in situ and immunohistochemical analyses (including PD‐L1 and DNA mismatch repair proteins [MMR]) and evaluated the microsatellite instability (MSI) status. The analytical findings were correlated with clinicopathological and outcome data and Kaplan‐Meier and univariable/multivariable Cox regression analyses were performed. The patients had a mean age of 50 years, 66% were male and a 5‐year overall survival (OS) of 58% and recurrence‐free survival (RFS) of 45% was detected. Sequence variations were observed in TP53 (66%), KRAS (21%), BRAF (4%), PIK3CA (4%), FGFR1 (1%), MET (1%), NRAS (1%), and PDGFRA (1%). Gene amplifications were found in EGFR (5%), ERBB2 (2%), and MET (2%). We detected no evidence of MMR‐deficiency (MMR‐d)/MSI‐high (MSI‐h), whereas 10 of 63 cases (16%) expressed PD‐L1. Therefore, anti‐PD‐1/PD‐L1 immunotherapy approaches might be tested in UrC. Importantly, we found aberrations in intracellular signal transduction pathways (RAS/RAF/PI3K) in 31% of UrCs with potential implications for anti‐EGFR therapy. Less frequent potentially actionable genetic alterations were additionally detected in ERBB2 (HER2), MET, FGFR1, and PDGFRA. The molecular profile strengthens the notion that UrC is a distinct entity on the genomic level with closer resemblance to colorectal than to bladder cancer.

Az étrend szerepe a húgyúti kövek kialakulásában és megelőzésében

In Hungary and in the developed countries urinary stones occur more often due to nutritional habits, obesity and sedentary lifestyle beside the endocrine and metabolic causes. In the daily urological and family doctor practice prevention should have an important role. Prevention is based not only on body weight control, physical exercise and medical treatment, but on proper diet as well. The nutritional components can change the consistence of urine, causing supersaturation, which is essential in stone formation. Specific nutritional components can either prevent stone formation (increased fluid intake, citrate, magnesium, fruits and vegetables) or either increase stone formation (decreased fluid intake, proteins, carbohydrates, oxalate, salt, increased calcium intake, ascorbic-acid etc). We summarized evidence-based practical dietary suggestions on the primary and secondary prevention of urinary stones. Orv Hetil. 2017; 158(22): 851-855.

Paradigmaváltás a csontmetasztázisok sebészetében. I. Végtagi és medencelokalizációjú áttétek

Absztrakt: Rakregiszterek statisztikai szerint mig a rak incidenciaja az elmult evtizedben is folyamatosan nőtt, az ujabb hatasos multimodalitasu kezelesek eredmenyekeppen a mortalitasa alig emelkedett. Osszefoglalo kozlemenyunk celja annak bemutatasa, hogy ujabb irodalmi adatok alapjan hogyan valtozott a csontmetasztazisos betegek tulelese, milyen prognosztikai faktorok befolyasoljak a betegek eselyeit. A jobb eredmenyek aktivabb sebeszi beavatkozast eredmenyeztek a vegtagi es a csigolyaattetek kezeleseben egyarant. Bemutatjuk a sebeszi rekonstrukcios eljarasok algoritmusat, targyaljuk a kulonboző megoldasok előnyeit, hatranyait, szovődmenyeit. Megallapithato, hogy a patologias/fenyegető patologias toresektől eltekintve nem a sebeszi az első korben valasztando eljaras, es ez is rendszerint palliativ cellal tortenik. Celja, hogy a beteg fajdalmait csokkentsuk, mobilitasat visszaadjuk, eletminőseget javitsuk, lehetőleg olyan kevesse megterhelő eljarasokkal (minimalisan invaziv), amelyek gyors rehabilitacio...

The Cradle of the Journal of International Urology and Nephrology: Foundations of Our Journal

The history of urology as an independent discipline in Hungary dates back to the second half of the nineteenth century. Géza Antal (1847–1889) was the first Professor and Chair of the first urological department in Hungary, Our journal celebrates its 45th anniversary this year. The first issue was called as Urology and Nephrology—An International Quarterly. It is important to look back to evaluate the past to energize and motivate ourselves to keep us on the right track and to get inspired for further development. The history of the Journal of International Urology and Nephrology is closely related to the history of the Hungarian urology and also the name of Professor Zoltán Szendrői.

Less invasive treatment option for renal carcinoma with venous tumor thrombus

Aim To retrospectively analyze patients treated by renal tumor and venous tumor thrombus (VTT) removal and to introduce a less stressful and safer surgical method without thoracotomy in Neves level 3 cases. Methods From 2002 to 2011, 33 patients underwent surgery for renal cell cancer combined with tumor thrombus of the inferior vena cava. Preoperative symptoms, tumor-node-metastasis classification of tumors, thrombus extension classified by Neves and Zincke system, types of surgical interventions, complications, postoperative management, and survival results were analyzed. Results Ten patients had level 1, 17 had level 2, and 6 had level 3 thrombi according to Neves and Zincke. In 5 patients with level 3 thrombi, the liver was mobilized without thoracotomy and in 1 patient endoluminal occlusion was utilized. There was no intraoperative mortality. The median survival time of 10 patients who died during follow-up period was 36.6 months (range, 1-116 months). Conclusion Renal cell cancer complicated with tumor thrombus without metastasis can be curable by performing a complete resection. The thrombus level determines the surgical approach and method. Our results confirm that level 3 caval vein tumor thrombus can be safely surgically treated by laparotomy with liver mobilization. Thoracotomy, use of cardiopulmonary bypass, and hypothermic circulatory arrest can be avoided with adequate liver- and vascular surgery methods.