Increased level of TXNIP and nuclear translocation of TXN is associated with end stage renal disease and development of multiplex renal tumours.

BACKGROUND: End-stage and acquired cystic renal disease (ESRD/ACRD) kidneys are characterized by inflammatory remodelling and multiplex renal cell carcinomas (RCC). Eosinophilic vacuolated tumour (EVT) occurs exclusively in ACRD. The aim of this study was to identify the involvement of thioredoxin-interacting protein (TXNIP) and thioredoxin (TXN) in ESRD/ACRD pathology. METHODS: Expression of TXNIP and TXN was examined in histological slides of 6 ESRD and 6 ACRD kidneys, precursor lesions and associated tumours as well as of RCCs from the general population by immunohistochemistry. RESULTS: Strong TXNIP expression was seen in epithelial cells, myo-fibroblasts and endothelial cells and weak TXN expression in ESRD/ACRD kidneys and tumours. In ACRD specific EVT and its precursors TXN were translocated into nuclei. CONCLUSION: The impaired TXNIP/TXN redox homeostasis might be associated with development of multiplex cancer especially of EVT in ESRD/ACRD kidney.

End-stage kidney disease: a never healing wound leading to another never healing wound, renal cancer.

BACKGROUND: End-stage kidney disease and acquired cystic kidney disease are the final stages of chronic kidney disease, leading to loss of kidney function and frequent development of tumours. It has been suggested that an inflammatory microenvironment may be responsible for the progressive kidney remodelling and cancer development. METHODS: Our aim was to analyse gene expression suggested to be involved in the remodelling of kidneys in end-stage kidney disease, and in the development of preneoplastic lesions and tumours. Immunohistochemistry was employed to assess the cellular localisation of different genes involved in these pathways on representative tissue sections. RESULTS: Cellular (αSMA positive naïve activated fibroblasts, endothelial cells, macrophages) and non-cellular components (cytokines IL6, TGFß, IL1ß, CSF2, fibronectin, laminin, and matrix modifier proteases MMP9 and MMP12) of the inflammatory microenvironment were expressed in the kidneys of patients with end-stage kidney disease. IL6 and FN1 expressing naïve activated fibroblasts and recruited inflammatory cells were the most abundant cellular components of the inflammatory microenvironment. CONCLUSION: The progressive inflammatory and fibrotic processes in end-stage kidney disease have features recalling those of  a never healing wound and may explain the frequent development of kidney cancer.

Our experience with cytoreductive radical prostatectomy in patients with oligometastatic prostate cancer / Cytoreductiv radikális prostatectomiával szerzett tapasztalataink oligometastaticus prosztatadaganatok esetében.

Összefoglaló. Bevezetés: Az utóbbi években az oligometastaticus prosztatadaganatok kezelése során a szisztémás kezelés mellett egyre gyakrabban végzik a primer tumor lokális kezelését is. Célkituzés: A szerzok a tanulmányban a cytoreductiv radikális prostatectomia szerepét vizsgálták az oligometastaticus prosztatadaganatok kezelése során. Módszer: 2012. 01. 01. és 2019. 01. 01. között összesen hét betegben végeztek cytoreductiv radikális prostatectomiát oligometastaticus prosztatadaganat esetében. A betegek átlagos életkora 64 év, az átlagos PSA-koncentráció 43 ng/ml volt. Az áttétek száma minden beteg vonatkozásában maximum három volt, és valamennyi esetben csontáttét volt jelen. A betegek androgéndeprivatiós hormonkezelést kaptak, és közülük négy esetben már a mutét elott elkezdték a hormonterápiát. Négy betegnél a csontmetastasisok miatt az áttétek sugárkezelése is megtörtént. Eredmények: A cytoreductiv prostatectomia szövettana öt esetben igazolt lokálisan elorehaladott (pT3) daganatot, és két alkalommal marginpozitivitás volt jelen. Emiatt öt beteg kapott adjuváns lokális irradiációt a metastasisok besugárzásán kívül. A mutétet követoen biokémiai progresszió egy esetben jelentkezett. Ennek oka lokális recidíva volt, mely miatt a beteg 'salvage' irradiációt kapott. Az átlagosan 38 hónapos utánkövetés során új metastasist nem diagnosztizáltak, és tumor okozta halálozás nem fordult elo. Következtetés: A cytoreductiv prostatectomia oligometastaticus prosztatarákos betegek kezelésében - válogatott beteganyagon - megvalósítható lehetoség. Ugyanakkor a cytoreductiv prostatectomia elonyei a tumorprogresszió szempontjából még nem egyértelmuek, ennek eldöntéséhez további vizsgálatok szükségesek. Orv Hetil. 2021; 162(13): 483-487. INTRODUCTION: In recent years, in addition to systemic therapy, local treatment of primary tumor has become increasingly common in the treatment of oligometastatic prostate cancers. Objectve: The authors measured the role of cytoreductive radical prostatectomy in the treatment of oligometastatic prostate carcinoma. METHODS: From Janury 2012 to January 2019, they performed cytoreductive radical prostatectomy in seven patients with oligometastatic prostate cancer. The mean age of the patients was 64 years, and the mean PSA value was 43 ng/ml. The patients had maximum three distant metastases and all metastases were localized to the bones. The patients received androgene deprivation therapy and this treatment was started before the surgery in four cases. Irradiation of the bone metastasis was performed in four cases. RESULTS: The histology of the cytoreductive radical prostatectomy showed locally advanced tumor (pT3) in five patients and margin-positive status was present in two cases. Hence, adjuvant irradiation was administered locally in five patients in addition to the irradiation of bone metastases. Biochemical progression was detected in one patient during the follow-up period. It was caused by local recurrence of the tumor and the patient was treated with salvage irradiation. During the 38 months follow-up period neither new distant metastasis nor cancer-related mortality was detected. CONCLUSION: The cytoreductive radical prostatectomy is a feasible option in selected cases with oligometastatic prostate cancer. However, the benefits of cytoreductive radical prostatectomy regarding tumor progression are not clear yet and further studies are required. Orv Hetil. 2021; 162(13): 483-487.

Impaired Vitamin D Signaling Is Associated With Frequent Development of Renal Cell Tumor in End-stage Kidney Disease.

BACKGROUND/AIM: End-stage kidney disease is characterized by chronic inflammation and frequent development of cancer. The level of circulating vitamin D is generally low in patients with end-stage renal disease (ESRD). Experimental studies have implicated the role of dysfunctional vitamin D metabolism in tumorigenesis. PATIENTS AND METHODS: We analyzed the expression of vitamin D receptor (VDR), cytochrome P450 family 27 subfamily B member 1 (CYP27B1) and cytochrome P450 family 24 subfamily A member 1 (CYP24A1), the key genes involved in vitamin D signaling, in kidneys from patients with ESRD, tissue microarrays containing ESRD-associated renal cell tumors, as well as in their precursor lesions by immunohistochemistry. RESULTS: Kidneys from patients with ESRD showed strong structural rearrangement with only few tubules and epithelial cell groups embedded in fibrotic-inflammatory stroma. Only an estimated 1-3% of the epithelial cells showed positive staining with antibodies to VDR, CYP27B1 and CYP24A1, which contrasted with the 100%, 40-50% and 40-50% of positively stained cells, respectively, found in normal kidneys. Down-regulation of the vitamin D signaling proteins was found in patients with renal cancer, with the exception of tumors and their precursors occurring exclusively in ESRD. CONCLUSION: The significantly reduced activity of CYP27B1 in kidney from patients with ESRD explains the low level of circulating vitamin D. We suggest that the lack of anti-tumorigenic effect of vitamin D is a crucial factor in the frequent development of unique types of renal cell cancer in in patients with ESRD.