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Az Írottkő–Geschriebenstein Natúrpark esettanulmányon keresztül – amely az osztrák–magyar határon terül el – megválaszoljuk, hogy a határon átnyúló védett területek milyen mértékben alkalmasak regionális fejlesztésre. A cikk elején a védett területek koncepcióit és lehetséges megközelítéseit mutatjuk be a határon átnyúló összefüggésben. Nemzetközi összehasonlításban is elemezzük a határon átnyúló védett területek fejlődéstörténetét, valamint különleges helyzetüket a Vasfüggöny „kelet– nyugati” határa mentén. Az Írottkő–Geschriebenstein Natúrpark példáján a regionális kormányzás szemléletéből elemezzük a határon átnyúló kooperáció lehetőségeit és korlátait, az Európai Területi Együttműködés keretei között támogatott projektben. Megemlítjük, hogy a határon átnyúló együttműködés tartalmi összefüggésében – mint például a turizmusban – sok egysége jött létre az együttműködésnek. Szintén fontos a kommunikációs és kooperációs feltételeket erősíteni a kétoldalú, határon átnyúló együttműködésben. Az EU-s programok bürokráciája, valamint egyes sikeres modellek kiterjeszthetőségének hiánya a regionális fejlesztésben és együttműködésben továbbra is akadályokat jelent.

Abstract Background Chromophobe renal cell carcinoma (chRCC) and renal oncocytoma are two distinct but closely related entities with strong morphologic and genetic similarities. While chRCC is a malignant tumor, oncocytoma is usually regarded as a benign entity. The overlapping characteristics are best explained by a common cellular origin, and the biologic differences between chRCC and oncocytoma are therefore of considerable interest in terms of carcinogenesis, diagnosis and clinical management. Previous studies have been relatively limited in terms of examining the differences between oncocytoma and chromophobe RCC. Methods Gene expression profiling using the Affymetrix HGU133Plus2 platform was applied on chRCC (n = 15) and oncocytoma specimens (n = 15). Supervised analysis was applied to identify a discriminatory gene signature, as well as differentially expressed genes. High throughput single-nucleotide polymorphism (SNP) genotyping was performed on independent samples (n = 14) using Affymetrix GeneChip Mapping 100 K arrays to assess correlation between expression and gene copy number. Immunohistochemical validation was performed in an independent set of tumors. Results A novel 14 probe-set signature was developed to classify the tumors internally with 93% accuracy, and this was successfully validated on an external data-set with 94% accuracy. Pathway analysis highlighted clinically relevant dysregulated pathways of c-erbB2 and mammalian target of rapamycin (mTOR) signaling in chRCC, but no significant differences in p-AKT or extracellular HER2 expression was identified on immunohistochemistry. Loss of chromosome 1p, reflected in both cytogenetic and expression analysis, is common to both entities, implying this may be an early event in histogenesis. Multiple regional areas of cytogenetic alterations and corresponding expression biases differentiating the two entities were identified. Parafibromin, aquaporin 6, and synaptogyrin 3 were novel immunohistochemical markers effectively discriminating the two pathologic entities. Conclusions Gene expression profiles, high-throughput SNP genotyping, and pathway analysis effectively distinguish chRCC from oncocytoma. We have generated a novel transcript predictor that is able to discriminate between the two entities accurately, and which has been validated both in an internal and an independent data-set, implying generalizability. A cytogenetic alteration, loss of chromosome 1p, common to renal oncocytoma and chRCC has been identified, providing the opportunities for identifying novel tumor suppressor genes and we have identified a series of immunohistochemical markers that are clinically useful in discriminating chRCC and oncocytoma.

Background: Chromophobe renal cell carcinoma (chRCC) and renal oncocytoma are two distinct but closely related entities with strong morphologic and genetic similarities. While chRCC is a malignant tumor, oncocytoma is usually regarded as a benign entity. The overlapping characteristics are best explained by a common cellular origin, and the biologic differences between chRCC and oncocytoma are therefore of considerable interest in terms of carcinogenesis, diagnosis and clinical management. Previous studies have been relatively limited in terms of examining the differences between oncocytoma and chromophobe RCC., Methods: Gene expression profiling using the Affymetrix HGU133Plus2 platform was applied on chRCC (n = 15) and oncocytoma specimens (n = 15). Supervised analysis was applied to identify a discriminatory gene signature, as well as differentially expressed genes. High throughput single-nucleotide polymorphism (SNP) genotyping was performed on independent samples (n = 14) using Affymetrix GeneChip Mapping 100 K arrays to assess correlation between expression and gene copy number. Immunohistochemical validation was performed in an independent set of tumors., Results: A novel 14 probe-set signature was developed to classify the tumors internally with 93% accuracy, and this was successfully validated on an external data-set with 94% accuracy. Pathway analysis highlighted clinically relevant dysregulated pathways of c-erbB2 and mammalian target of rapamycin (mTOR) signaling in chRCC, but no significant differences in p-AKT or extracellular HER2 expression was identified on immunohistochemistry. Loss of chromosome 1p, reflected in both cytogenetic and expression analysis, is common to both entities, implying this may be an early event in histogenesis. Multiple regional areas of cytogenetic alterations and corresponding expression biases differentiating the two entities were identified. Parafibromin, aquaporin 6, and synaptogyrin 3 were novel immunohistochemical markers effectively discriminating the two pathologic entities., Conclusions: Gene expression profiles, high-throughput SNP genotyping, and pathway analysis effectively distinguish chRCC from oncocytoma. We have generated a novel transcript predictor that is able to discriminate between the two entities accurately, and which has been validated both in an internal and an independent data-set, implying generalizability. A cytogenetic alteration, loss of chromosome 1p, common to renal oncocytoma and chRCC has been identified, providing the opportunities for identifying novel tumor suppressor genes and we have identified a series of immunohistochemical markers that are clinically useful in discriminating chRCC and oncocytoma.

Radical cystectomy is the standard treatment for muscle-invasive bladder cancer. Today, most patients can undergo substitution enteroplasty following cystectomy. Recto-colic urinary diversions and cutaneous ureterostomy are now uncommon. An ileal conduit (Bricker) may be proposed to patients with urethral involvement, as well as to elderly patients and to women who are at a high risk of severe urine leakage following enteroplasty. Thanks to progress in anesthesia, surgical techniques and intensive care, cystectomy with substitution enteroplasty is now a routine procedure. For localized bladder cancer (pT2N0M0 stage), this intervention is associated with a 10-year survival rate of about 80%. The mean length of stay in the intensive care unit varies between 1 and 7 days, and the mean total hospital stay ranges from 10 to 13 days. Early complications, which occur in less than 30% of cases, are mainly medical; the most common are cardiovascular complications, pulmonary embolism, disorientation and urinary tract and pulmonary infections. Late complications are less common and are mainly surgical; they include uretero-ileal stenoses (-10% of cases), uretero-ileal stenosis (4%), and intestinal obstruction (4%). Urinary and sexual disorders are frequent after radical cystectomy and substitution enteroplasty. Early postoperative incontinence occurs in more than 50% of cases but often responds to physiotherapy. In contrast, most male patients remain impotent. Simple transurethral resection of the prostate with cystectomy may be used instead of radical cystoprostatectomy in order to reduce the risks of incontinence and impotence, but this approach is controversial, as some authors have reported an increased risk of recurrence and metastasis.

Over the last two decades, several improvements have been made in the diagnosis and treatment of renal carcinoma. In the past, renal cancer was usually discovered after hematuria, pain, or palpation of a lumbar mass, and required total nephrectomy. Today, about 40% of renal tumors are discovered incidentally by ultrasonography or computed tomography. Therefore, the majority of renal carcinomas are discovered at an early stage. Partial nephrectomy has been developed for polar and small tumors. This surgery can now be performed using a laparoscopic approach, thereby decreasing morbidity and shortening the hospital stay.