Journal of Kidney Cancer and VHL最新文献

Immune checkpoint therapy (ICI) has enabled induction of remission in advanced renal cell carcinoma RCC. ICI toxicities can persist as chronic health conditions. We developed a patient survey to assess changes in medical comorbidities after ICI. The survey was developed by the Kidney Cancer Research Alliance (KCCure), with multidisciplinary representation from urologic surgeons, medical oncologists, and patient advocates. The survey was broadcast between July 2022 and September 2022 to patients via website, mailing lists, and social media platforms. Patient perspective on changes to any medical conditions were evaluated in the survey questionnaire. Of 1062 patients that responded, 399 were self-identified as being metastatic and 289 reported to be treated with ICI. Eighty-five percent of respondents were from the United States. The most common conditions noted were thyroid dysfunction in 80 patients, hypertension in 50 patients, chronic kidney disease in 23 patients, heart disease in 10 patients, and diabetes mellitus (DM) in 13 patients. Immune disorders developed in 26 (9%) patients. The limitations are the survey had minimal participation from minority populations. Multiple medical conditions were noted to either emerge or worsen as a result of ICI-based therapies in RCC. Awareness of this information as a starting point should stimulate the development of survivorship programs for renal cancer. A survey of patients with advanced kidney cancer showed that some medical conditions such as thyroid dysfunction, hypertension, heart and kidney disease, DM, and immune conditions were newly diagnosed and/or persisted after immune therapy.

We describe here an atypical case of pyonephrosis which on further evaluation turned out to be a renal cell carcinoma (RCC). The clinical presentation of the patient was that of an infective etiology. However, the renal mass associated with renal vein thrombus and lung metastasis was later diagnosed based on the clinical deterioration of the patient even after insertion of percutaneous nephrostomy. In this case, an underlying renal cancer was probably complicated secondarily leading to pyonephrosis which was the initial presenting manifestation which led to a delay in diagnosis. Pyonephrosis is usually associated with Xanthogranulomatous pyelonephritis. Association of RCC with pyonephrosis is extremely rare and hence seldom reported. Our patient later on underwent radical nephrectomy and the histopathology report was suggestive of RCC. We have described here the clinical manifestations and diagnostic issues of such a case. This case provides evidence that RCC should be kept as one of the differentials in such patients.

Robotic nephrectomy has become an increasingly preferred surgical technique for managing renal cell carcinoma (RCC). This review aims to systematically evaluate existing literature on the safety, efficacy, clinical outcomes, and associated costs of robotic nephrectomy, especially in relation to tumor dimensions and other pertinent patient factors. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed an extensive literature search across major databases (PubMed, Scopus, and Cochrane Library) from inception to October 2023. The inclusion criteria encompassed randomized controlled trials (RCTs), cohort studies, and case-control studies that compared robotic nephrectomy with open or laparoscopic nephrectomy. Outcomes analyzed included operative time, intraoperative blood loss, complication rates, length of hospital stay, oncological outcomes, and cost-effectiveness. The Egger test was used to assess publication bias. The review incorporated 30 studies involving 5,432 patients who underwent robotic nephrectomy. Key findings indicated that robotic nephrectomy resulted in significantly reduced intraoperative blood loss (mean difference of -85 mL; p < 0.001) and shorter hospital stays (mean difference of -1.3 days). Tumor size had a notable impact on surgical outcomes, with larger tumors (≥7 cm) being associated with prolonged operative times and slightly higher complication rates. Robotic nephrectomy was also associated with higher costs compared to conventional surgical techniques; however, reduced readmission rates offset some of these costs. Oncological outcomes for robotic nephrectomy were comparable to those of open nephrectomy. Robotic nephrectomy is a safe and effective approach for kidney cancer that demonstrates advantages in perioperative recovery and surgical precision, particularly for smaller tumors. While costs may be higher, the clinical benefits and potential long-term savings from decreased postoperative complications recommend its use. Further high-quality RCTs are essential to validate these findings.

We report a case of a pathogenic variant c.463+4C>G in the von Hippel-Lindau (VHL) gene identified in a patient presenting with bilateral adrenal tumors, including a histologically confirmed pheochromocytoma with no significant family history of VHL-associated tumors. This same variant was first reported as having pathogenic significance in an unrelated proband with a hemangioblastoma and a family history of pheochromocytoma. In our patient, next-generation sequencing and subsequent RNA (ribonucleic acid) analysis confirmed this mutation to be a pathogenic (class 4) variant in intron 2. The lack of family history of VHL-associated tumors correlated with the proband further suggests that this mutation may have reduced penetrance. This case confirms the pathogenicity of the same previously described variant in the VHL gene and underscores the utility of genetic testing in patients with atypical presentations of adrenal tumors, even in the absence of a relevant family history.

The prevalence of papillary renal cell carcinomas (PRCCs) is estimated to be between 10% and 15%. At present, there is no effective therapeutic approach available for patients with advanced PRCCs. The molecular biomarkers associated with PRCC diagnoses have been rarely studied compared to renal clear cell carcinomas; therefore, the necessity for the identification of novel molecular biomarkers to aid in the early identification of this disease. Bioinformatics and artificial intelligence technologies have become increasingly important in the search for diagnostic biomarkers for early cancer detection. In this study, three genes-BCL11A, NTN5, and OGN-were identified as diagnostic biomarkers using the Cancer Genome Atlas (TCGA) database and deep learning techniques. To identify the differential expression genes (DEGs), ribonucleic acid (RNA) expression profiles of PRCC patients were analyzed using a machine learning approach. A number of molecular pathways and coexpressions of DEGs have been analyzed and a correlation between DEGs and clinical data has been determined. Diagnostic markers were then determined via machine learning analysis. The 10 genes selected with the highest variable importance value (more than 0.9) were further investigated, with six upregulated (BCL11A, NTN5, SEL1L3, SKA3, TAPBP, SEMA6A) and four downregulated (OGN, ADCY4, SMOC2, CCL23). A combined receiver operating characteristic (ROC) curve analysis revealed that the BCL11A-NTN5-OGN genes, which have specificity and sensitivity values of 0.968 and 0.901, respectively, can be used as a diagnostic biomarker for PRCC. In general, the genes introduced in this study may be used as diagnostic biomarkers for the early diagnosis of PRCC, thus providing the possibility of early treatment and preventing the progression of the disease.

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare type of renal cell carcinoma (RCC) recognized as an independent entity in the latest WHO (World Health Organization) classification. We here report a case of a 51-year-old female patient with MTSCC, who presented with abdominal pain and left lower pole kidney lesion on the computed tomography scan. A robotic-assisted laparoscopic partial nephrectomy was performed. The diagnosis was confirmed on histopathological examination. MTSCC is rare and generally indolent. Either partial or radical nephrectomy is usually curative. The prognosis is usually favorable. However, occasionally, MTSCC could demonstrate aggressive features requiring systemic therapy. There are also several mimickers of MTSCC, which carry different prognostic and treatment profiles. Histological, immunohistochemical, and molecular genetic profile are useful in diagnosing the disease.

[This retracts the article DOI: 10.15586/jkcvhl.v10i1.232.].

Cutaneous leiomyomas (CLMs) are associated with Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) syndrome (Mendelian Inheritance in Man [MIM]: 150800)-a rare genodermatosis caused by a heterozygous pathogenic variant in the fumarate hydratase (FH) gene. It is characterized by a predisposition to develop cutaneous and/or uterine leiomyomas and an aggressive type of renal cell carcinoma (RCC). We describe a 27-year-old male who presented with a painful nodule on the left upper arm persisting for 5 years and the subsequent emergence of painless nodules in various parts of the body over the past two years. A family history of RCC prompted suspicion of the HLRCC syndrome. Cutaneous examination revealed erythematous subcutaneous nodules, with histological analysis confirming CLM. Genetic testing identified a pathogenic variant in the FH gene, confirming the diagnosis of HLRCC. Management involved surgical excision of the symptomatic nodules and genetic counselling/testing for the proband and his family members. The long-term follow-up plan includes dermatological and nephrological surveillance with annual renal magnetic resonance imaging (MRI) scans. This report aims to enhance the awareness of this disease and highlight the role of cutaneous lesions in facilitating early detection.

Central nervous system hemangioblastoma (CNS-HB) is the most common manifestation of von Hippel-Lindau disease (VHL). The main axis of the CNS-HB pathway is the VHL-HIF signaling pathway. Recently, we proposed an alternative VHL-JAK-STAT pathway in CNS-HB. In contrast, the VHL substrate transcription factor zinc fingers and homeoboxes 2 (ZHX2) have been identified as the oncogenic drivers in VHL-deficient clear cell renal cell carcinoma (RCC). However, ZHX2 expression in CNS-HB has not been previously reported. Furthermore, the VHL-ZXH2-NF-κB signaling pathway in CNS-HB remains unresolved. In this study, we aimed to investigate ZHX2 expression and VHL gene alteration in CNS-HB and propose the role of ZHX2 in CNS-HB. Using the MACS method, Scl+ hemangioblastoma-like cells were isolated from multipotent nestin-expressing stem cells. The ubiquitination of ZHX2 in these cells and the immunoprecipitation between ZHX2 and VHL were investigated. In addition, the VHL genes of patients with hemangioblastoma were analyzed. ZHX2 expression in CNS-HB tissues was examined by immunohistochemistry and western blotting. In addition, VHL gene mutations in CNS-HB were analyzed by sequencing. The association between ZHX2 expression and VHL gene mutation was analyzed. ZHX2 was ubiquitinated in Scl+hemangioblastoma-like cells after the transfer of the VHL expression vector into these cells. ZHX2 expression in these cells was well detected before transfer but disappeared after the transfer. ZHX2 expression was detected in 18 of the 21 CNS-HB tissues by immunoblotting and/or immunohistochemistry. Sporadic CNS-HB showed weak expression, whereas VHL-related CNS-HB showed moderate or strong expression. In particular, CNS-HB with severe VHL gene mutations, including large deletions, showed strong or moderate ZHX2 expression. The association between VHL gene mutation and ZHX2 expression revealed a significant correlation between VHL gene alteration severity and the level of immunoblotting (P < 0.05). In conclusion, the severity of VHL gene alteration correlates with the level of ZHX2 expression. ZHX2 is predominantly expressed in CNS-HB, especially in VHL-related cases with severe VHL gene alterations, suggesting a potential role in tumorigenesis and proliferation of CNS-HB.