Renal Malignancy Research Articles

(524) Adolescent Varicocelectomy: Long-term Follow-up of Clinical Outcomes and Patient Satisfaction

Abstract Introduction Worldwide 10–15% of male adolescents have a varicocele, which is the most common surgically correctable cause of male subfertility. In young adult men, varicocele can be associated with smaller testis volume and abnormal semen parameters. However, there is still controversy in whether surgical repair has better long-term outcomes than just active surveillance. Objective To evaluate satisfaction, symptoms improvement, hypogonadism, and paternity in patients who underwent varicocelectomy when they were adolescents. Methods We performed a retrospective chart review of adolescents undergoing varicocelectomy from 2011-2021. Inclusion criteria were having primary varicocele, having 12-21 years at time of surgery, having had the varicocelectomy >1-year ago, ≥1 postoperative visits, and having answered the questionnaire. Exclusion criteria were having a diagnosis of secondary varicocele (renal malignancy or venous abnormality) and incomplete records. Data about clinical, surgical, and postoperative outcomes were gathered. Patients were contacted by phone and were asked about orchialgia, paternity, varicocele recurrence, diagnosis and treatment for hypogonadism, and satisfaction after surgery. Descriptive analysis and paired t-test were used, statistical significance was assessed at p<0.05. Results From a total of 50 patients meeting the inclusion criteria, we were able to contact 23 patients. The mean age at varicocele diagnosis was 17.43±2.52 years. Varicocele was grade 3 in 16 (69.6%) patients and left-sided in 17 (73.9%) patients. Eight (34.8%) patients had a preoperative testicular ultrasound, that in 2(25%) patients showed testicular volume discrepancy >20%. At the physical exam, 6(26.1%) patients were found to have asymmetric testicles. Overall, 2(8.7%) patients had a previous varicocele repair and 7(30.4%) had a preoperative abnormal semen analysis. Mean age at surgery was 18.78±2.02 years. Microscopic varicocelectomy was performed in 22 (95.7%) patients, mainly in the left-side (78.3%). Pre- and postoperative FSH and T levels were done in 10 patients, without any significant difference after surgery (p=0.074 and p=0.069, respectively). Pre- and postoperative semen analysis were performed in 12 patients and showed a significant improvement in motility after varicocelectomy (p=0.022). Mean follow-up after surgery was 1.42±1.40 months. The questionnaire was performed in a mean of 3.43±2.55 months after varicocelectomy and the mean age of the responders was 22.3±3.11 years. Orchialgia persisted in 7 patients (30.4%), predominately in the left side (71.4%). None of the patients had been diagnosed with varicocele recurrence nor had required a surgical reintervention. Twenty-one (86.9%) patients were not actively trying to achieve a natural conception nor had been involved in a pregnancy after varicocelectomy. Two patients (8.7%), with a preoperative abnormal semen analysis, were able to conceive. None of the patients referred to have hypogonadism nor being under testosterone therapy. The majority of patients (86.9%) referred to be satisfied with the postoperative results. Conclusions Our results suggested that long-term outcomes of varicocelectomy in adolescents would show high patient satisfaction, low rate of recurrence, no association with hypogonadism, and a significant persistence of testicular pain. Although male fertility after varicocelectomy demonstrated promising results, a longer follow-up assessment should be done when patients are actively trying to conceive, to have a more representative sample size. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Acerus, Boston Scientific, Endo Pharmaceuticals and Coloplast

A Single Center Experience With Bilateral Wilms Tumor.

Wilms tumor (WT) is the most common pediatric renal malignancy and bilateral disease (BWT) occurs in 5% of cases and is associated with poor outcomes. Management of BWT includes chemotherapy and oncologic resection while preserving renal function. Previous literature has demonstrated variable approaches in BWT treatment. The aim of this study was to examine a single institution experience and outcomes with BWT. A retrospective chart review was performed for all patients with WT treated at a free-standing tertiary children's hospital between 1998 and 2018. Patients with BWT were identified and treatment courses were compared. Outcomes of interest included need for dialysis post-operatively, need for renal transplantation post-operatively, disease recurrence, and overall survival. Of 120 children with WT, 9 children (6F:3M) of median age 32months (IQR: 24-50months) and median weight 13.7kg (IQR: 10.9-16.2kg) were diagnosed with and treated for BWT. Pre-operative biopsies were obtained in 4/9 patients, 3 of whom received neoadjuvant chemotherapy and 1 who underwent radical nephrectomy. Of the 5 patients who did not undergo biopsy, 4/5 were treated with neoadjuvant chemotherapy, and 1/5 underwent upfront nephrectomy. Post-operatively, 4/9 children required dialysis, of whom 2 subsequently underwent renal transplantation. Two patients were lost to follow-up, and of the remaining 7 patients, disease recurrence occurred in 5/7 children and overall survival was 71% (n=5). Management of BWT varies regarding the use of pre-operative biopsy, neoadjuvant chemotherapy, and extent of disease resection. Further guidelines on treatment protocols may optimize outcomes in children with BWT.

Stage Migration in Renal Malignancies in COVID Era: A Single-Center Analysis.

The COVID-19 disease, caused by SARS-CoV-2 virus, attained the status of a pandemic by March 2020. There was apprehension among patients suffering from renal malignancies about balancing cancer treatment and preventing COVID-19 infection transmission. We analyzed 184 patients with renal malignancies retrospectively, who presented to our institute over 2 years: 91 patients of renal malignancies in pre-COVID era (March 2019-Feb 2020) and 93 patients in COVID era (March 2020-Feb 2021). The parameters analyzed were age, tumor size, clinical presentation, clinical stage, pathological stage, nuclear grade, and presence of metastasis. Level of significance was kept at 95%, and p value <0.05 was considered significant. The age of patients was comparable in both groups (p: 0.381). Clinical presentation was also similar in both groups whereas there were more cases diagnosed during routine evaluation in pre-COVID era (p: 0.022). Tumor size was 5.84 ± 3.03cm vs. 7.10±3.83cm (p: 0.017) in pre-COVID vs. COVID era, respectively. Patients in COVID era had significantly higher clinical stage (p = 0.041), pathological stage (p =0.027), nuclear grade (p = 0.007), and presence of metastasis (p = 0.005) as compared to pre-COVID era. Patients, who underwent Nephron-sparing surgery, also had higher pathological stage in COVID era. COVID overshadowed the management of renal malignancies. There was a clear shift and stage migration in patients of renal malignancies in COVID era as compared to pre-COVID era, probably because of less routine health check-ups and patients deferring hospital visits due to fear of contracting COVID infection.

Alterations of miRNA Expression in Diffuse Hyperplastic Perilobar Nephroblastomatosis: Mapping the Way to Understanding Wilms' Tumor Development and Differential Diagnosis.

Wilms' tumor (WT) is the most common renal malignancy in children. In diffuse hyperplastic perilobar nephroblastomatosis (DHPLN), nephrogenic rests result in a bulky enlargement of the kidney, a condition considered as a premalignant state before WT. Despite relevant clinical differences between WT and DHPLN, they are often challenging to distinguish based on histology. Molecular markers would improve differential diagnosis, but none are available at present. In our study, we investigated the potential of microRNAs (miRNAs) as such biomarkers, also aiming to shed light on the chronological order of expression changes. Formalin-fixed, paraffin-embedded (FFPE) samples from four DHPLN cases and adjacent healthy tissues were tested using a PCR array containing primers for 84 miRNAs implicated in genitourinary cancer. Expression in DHPLN was compared to WT data available in dbDEMC. Let-7, miR-135, miR-146a-5p, miR-182-5p, miR-183-5p, miR-20b-3p, miR-29b-3p, miR-195-5p and miR-17-5p showed potential to be used as biomarkers to distinguish WT and DHPLN in cases when traditional differential diagnosis is inconclusive. Our study also revealed miRNAs which may play a role in the initial steps of the pathogenesis (at a precancerous stage) and ones which become deregulated later in WT. More experiments are needed to confirm our observations and find new candidate markers.

Suburothelial hemorrhage masquerading as renal neoplasms: a case report of antopol Goldman lesion

Renal cell carcinoma (RCC), which accounts for 2-3% of all adult malignancies, is one of the most lethal urologic cancers. They are sporadic in the majority of cases with 4-6% being familial. They are adenocarcinomas arising from renal tubular epithelial cells. They can present with symptoms of loin pain, palpable mass and haematuria. Another rare presentation is spontaneous perirenal haemorrhage which can be seen in up to 50% of these patients. These patients are also predisposed to increased risk of deep vein thrombosis (DVT) due to prevailing pro-thrombogenic state. Management requires radical nephrectomy for localised disease, targeted therapy and cytoreductive nephrectomy for metastatic RCC. Our patient is adult female who was referred to surgical OPD given her history of gross haematuria and right flank pain for 6 days. She is a known case of DVT on treatment with Warfarin for 4 years. A diagnosis of renal malignancy was made, contrast CT was suggestive of solid mass lesion of the upper pole of calyx likely transitional cell carcinoma (TCC)/papillary RCC. She underwent an urgent radical nephrectomy which showed a hard 5×5 cm lump in the upper pole of the kidney, revealing a clot on the cut section. Post-op HPE showed a large subcapsular hematoma in the upper pole with microscopy showing large areas of haemorrhage surrounded by chronic inflammatory infiltrate, likely Antopol Goldman lesion notorious for its similarity to renal malignancy.

Glaucoma and Systemic Disease.

Glaucoma is the leading cause of irreversible blindness in the world. Due to its potential to cause permanent vision loss, it is important to understand how systemic conditions and their respective treatments can be associated with or increase the risk for developing glaucoma. In this review, we examined the literature for up-to-date discussions and provided commentary on glaucoma, its pathophysiology, and associated risk factors. We discuss systemic diseases and the impact, risk, and mechanism for developing glaucoma, including pharmacologically induced glaucoma; inflammatory and auto-immune conditions; infectious, dermatologic, cardiovascular, pulmonary, renal, urologic, neurologic, psychiatric and systemic malignancies: intraocular tumors; as well as pediatric, and genetic conditions. The goal of our discussion of systemic conditions including their commonality, mechanisms, treatments, and associations with developing glaucoma is to emphasize the importance of ocular examinations and follow-up with the multidisciplinary teams involved in the care of each patient to prevent unnecessary vision-loss.

Abstract LB005: Insights of renal cell carcinoma from multiomic perspective

Abstract Introduction: Clear cell renal carcinoma is the most frequent form of renal malignancy, with an increasing incidence rate worldwide. In this study we used a multi-omic approach to differentiate normal and tumor tissues in clear cell Renal Cell Carcinoma (ccRCC). Methods: Using transcriptomic data of patients with malignant and adjacent normal tissue samples from gene chip and RNA-Seq cohorts, we identified the top genes over-expressed in ccRCC. We collected surgically resected ccRCC specimens to further investigate the transcriptomic results on the proteome level. The differential protein abundance was evaluated using targeted mass spectrometry (MS). Results: We assembled a database of more than 600 renal tissue samples from NCBI GEO and TCGA and used these to uncover the top genes with higher expression in ccRCC. For protein level analysis 162 malignant and normal kidney tissue samples have been acquired. The most consistently upregulated genes were IGFBP3, PLIN2, PLOD2, PFKP, VEGFA, and CCND1 (p&amp;lt;1E-05 for each gene). Mass spectrometry further validated the differential protein abundance of these genes (IGFBP3, p = 7.53E-18; PLIN2, p = 3.9E-39; PLOD2, p = 6.51E-36; PFKP, p = 1.01E-47; VEGFA, p = 1.40E-22; CCND1, p= 1.04E-24). We also identified proteins correlating with overall survival. Conclusions: We used transcriptomic and proteomic data to identify a minimal panel of proteins highly specific for clear cell renal carcinoma tissues. The introduced gene panel could be used as a promising tool in the clinical setting. Citation Format: Aron Bartha, Zsuzsanna Darula, Gyongyi Munkacsy, Eva Klement, David Fenyo, Peter Nyirady, Balazs Gyorffy. Insights of renal cell carcinoma from multiomic perspective [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB005.

V05-07 ROBOTIC-ASSISTED LEFT RADICAL NEPHRECTOMY AND IVC THROMBECTOMY IN CROSS-FUSED RENAL ECTOPIA

You have accessJournal of UrologyCME1 Apr 2023V05-07 ROBOTIC-ASSISTED LEFT RADICAL NEPHRECTOMY AND IVC THROMBECTOMY IN CROSS-FUSED RENAL ECTOPIA Hannah Pham, Raj Satkunasivam, Brian Miles, Wesley Ekeruo, Mark Sultenfuss, Michael Brooks, and Monty Aghazadeh Hannah PhamHannah Pham More articles by this author , Raj SatkunasivamRaj Satkunasivam More articles by this author , Brian MilesBrian Miles More articles by this author , Wesley EkeruoWesley Ekeruo More articles by this author , Mark SultenfussMark Sultenfuss More articles by this author , Michael BrooksMichael Brooks More articles by this author , and Monty AghazadehMonty Aghazadeh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003263.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Crossed fused renal ectopia is a relatively rare entity with an estimated prevalence of 1 in 2000 births (Tsuboi et al). Renal cell carcinoma (RCC) in this setting is even more rare and there are no previous reports of associated inferior vena cava (IVC) tumor thrombi. Renal malignancy involving crossed fused ectopia presents a unique, complex surgical challenge and, therefore, there a few reports of minimally invasive surgical management. Herein, we describe a successful robotic resection of a large left renal mass with IVC thrombus involving a crossed fused ectopic right kidney. METHODS: We performed a transperitoneal robotic nephrectomy and caval thrombectomy on a 68-year-old male with an 11cm left renal mass and level 1 IVC thrombus, in the setting of a crossed fused ectopic right kidney. A two-position approach - modified left flank, followed by modified right flank - was employed to safely complete the procedure. Critical procedure steps included: 1) Pre-operative left renal artery embolization, 2) IVC control, cavotomy, and thrombectomy, 3) Left radical nephrectomy, and 4) Partial nephrectomy of the ectopic right kidney. The use of intraoperative ultrasound, Firefly technology, and indocyanine green were also fundamental adjuncts to the procedure. Perioperative outcomes are reported along with associated contemporary comparisons. RESULTS: The total operative time was five hours and thirty-one minutes, which included re-positioning and re-docking time. Estimated blood loss was 300cc without the need for perioperative transfusion. The postoperative course was uncomplicated, and the patient was discharged on postoperative day 4. There were no major perioperative complications. Pre- and postoperative estimated glomerular filtration rate was 86 and 52, respectively. Final pathology showed pT3b, N1, and clear cell RCC. Margins were negative. CONCLUSIONS: We demonstrate robotic resection of RCC with IVC thrombus in the setting of crossed fused renal ectopia, which is, to our knowledge, the first reported description of this entity and this approach. Success was predicated on strict adherence to standard oncologic and operative principles for minimally invasive IVC thrombectomy, radical nephrectomy, and partial nephrectomy. Source of Funding: None. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e426 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hannah Pham More articles by this author Raj Satkunasivam More articles by this author Brian Miles More articles by this author Wesley Ekeruo More articles by this author Mark Sultenfuss More articles by this author Michael Brooks More articles by this author Monty Aghazadeh More articles by this author Expand All Advertisement PDF downloadLoading ...

Clinical relevance of BCOR internal tandem duplication and TP53 aberration in clear cell sarcoma of the kidney.

Clear cell sarcoma of the kidney (CCSK) is the second most common pediatric renal malignancy, characterized by BCOR internal tandem duplication (ITD), YWHAE rearrangement, BCOR-CCNB3 fusion, and lack of other consistent structural alteration. We accidentally identified TP53 deletion in CCSK, which was often associated with adverse clinical outcomes. In this study, we assessed the incidence as well as the clinical relevance of these molecules in CCSK patients. BCOR ITD, YWHAE rearrangement, BCOR-CCNB3 fusion and TP53 status were examined by polymerase chain reaction, fluorescence in situ hybridization, or Sanger sequencing in a cohort of 39 patients with CCSK. Among them, 34 cases (87.18%) had BCOR ITD, 1 (2.56%) had YWHAE rearrangement, and 1 (2.56%) had BCOR-CCNB3 gene fusion. The remaining 3 (7.69%) harbored none of these aberrations. BCOR ITD, YWHAE rearrangement and BCOR-CCNB3 were mutually exclusive. Furthermore, 25.64% of the cohort acquired TP53 aberration (10/39, 3 with both copy number deletion and point mutation, 6 with deletion only, and 1 with mutation only), all of which were associated with BCOR ITD. Patients with or without BCOR ITD or TP53 aberration did not differ in demographic characteristics such as sex, onset age, or tumor stage at diagnosis. However, the overall survival rates and progression-free survival rates of BCOR ITD or TP53 deletion groups showed obvious downward trends, albeit not all reaching statistical significance. Patients with both BCOR ITD and TP53 deletion had the poorest prognosis.

Sicca symptoms and sialoadenitis as immune-related adverse events of nivolumab treatment in renal malignancy

Sicca symptoms and sialoadenitis as immune-related adverse events of nivolumab treatment in renal malignancy

Association between dietary 3-monochloropropane-1,2-diol esters (3-MCPDE) and renal cancer in Peninsular Malaysia: exposure assessment and matched case-control study

3-Monochloropropane-1,2-diol esters (3-MCPDE) are food contaminants commonly found in refined vegetable oils and fats, which have possible carcinogenic implications in humans. To investigate this clinically, we conducted an occurrence level analysis on eight categories of retail and cooked food commonly consumed in Malaysia. This was used to estimate the daily exposure level, through a questionnaire-based case-control study involving 77 subjects with renal cancer, with 80 matching controls. Adjusted Odds Ratio (AOR) was calculated using the multiple logistic regression model adjusted for confounding factors. A pooled estimate of total 3-MCPDE intake per day was compared between both groups, to assess exposure and disease outcome. Among the food categories analysed, vegetable fats and oils recorded the highest occurrence levels (mean: 1.91 ± 1.90 mg/kg), significantly more than all other food categories (p < .05). Risk estimation found the Chinese ethnic group to be five times more likely to develop renal cancer compared to Malays (AOR = 5.15, p = .001). However, an inverse association was observed as the 3-MCPDE exposure among the Malays (median: 0.162 ± 0.229 mg/day/person) were found to be significantly higher than the Chinese (p = .001). There was no significant difference (p = .405) in 3-MCPDE intake between the cases (median: 0.115 ± 0.137 mg/day/person) and controls (median: 0.105 ± 0.151 mg/day/person), with no association between high intake of 3-MCPDE and the development of renal cancer (OR = 1.41, 95% CI: 0.5091–2.5553). Thus, there was insufficient clinical evidence to suggest that this contaminant contributes to the development of renal malignancies in humans through dietary consumption. Further research is necessary to support these findings, which could have significant public health ramifications for the improvement of dietary practices and food safety measures.

Diagnostic value of pseudocapsule ring hyperenhancement in contrast-enhanced ultrasound in renal focal lesions.

To investigate the diagnostic value of pseudocapsule ring hyperenhancement in contrast-enhanced ultrasound (CEUS) of focal renal lesions. Ninety eligible patients admitted were selected as the study subjects. The incidence rate of annular hyperenhancement in different benign and malignant focal lesions during angiography and the shape of annular enhancement were counted. The correlation between the occurrence of benign and malignant renal tumors and annular hyperenhancement and unenhanced areas was also analyzed. Capsule enhancement was observed in 56 cases, including 50 cases of malignant tumors (89.3%, 50/56) and 6 cases of benign tumors (10.7%, 6/56). Pearson correlation analysis showed that renal malignancy was positively associated with the occurrence of pseudocapsule ring hyperenhancement (γ = 0.489, P < 0.001). Benign and malignant renal tumors were positively correlated with the occurrence of non-enhancing areas (γ = 0.215, P = 0.042). The thickness and peak intensity of pseudocapsule ring enhancement in renal malignant tumors were significantly higher than those in benign tumors (all P < 0.001), while the time to peak was significantly lower than that in benign tumors (P < 0.001). The results of receiver operating characteristic (ROC) curve showed that the ring enhancement thickness, time to peak, and area under ROC curve of peak intensity of tumor reached more than 0.9. In CEUS, the pseudocapsule of focal renal lesions is a characteristic feature of renal malignant tumors, which can be used as a differential basis for benign and malignant tumors to improve the accuracy of benign and malignant renal tumors.

The emerging role of long non-coding RNAs in renal cell carcinoma progression and clinical therapy via targeting metabolic regulation.

Renal cell carcinoma (RCC) is the most frequent renal malignancy in the world, and its incidence is increasing year by year. RCC is a well-known drug resistant tumor, and the treatment methods are limited. Most patients with RCC are discovered at the advanced stage, and thus have poor prognosis even after treatment. Therefore, it is very urgent to find new markers for the diagnosis and treatment of RCC. Accumulating evidence shows that lncRNAs participate in the occurrence and progression of RCC, which is achieved by the lncRNA-miRNA-mRNA axis. It is widely known that metabolic defect is an essential pathogenesis in RCC. As is the case with other tumors, RCC can satisfy the demands of cancerous cells for uncontrolled proliferation through aerobic glycolysis. However, whether lncRNAs can modulate RCC progression through metabolic pathway is still not clarified. Taken together, this review mainly summarized the metabolic regulatory mechanisms of lncRNAs in RCC progression, especially their roles in glucose metabolism, lipid metabolism, amino acid metabolism and mitochondrial dynamics, as well as the clinical applications of lncRNAs via targeting metabolism in RCC therapy. It will provide the new targets and approaches for early clinical diagnosis, treatment and prognosis of RCC.

Risk of Surgical Intervention in Children with Diagnoses of Cancer and Preoperative Malnutrition: A National Analysis

Perioperative nutrition is a critical component of appropriate healing and recovery after surgery. We sought to identify perioperative risk in children with cancer and low preoperative hypoalbuminemia undergoing surgical intervention. We queried the 2015-2019 NSQIP-Peds datasets for children with a primary diagnosis of renal or hepatic malignancy undergoing surgical resection. Postoperative outcomes were evaluated for comparative risk between patients with low albumin (albumin<3.0g/dL) and normal albumin within 30 days of their surgical procedure. Univariate analysis and multivariable logistic regression were conducted to identify perioperative risk in patients with hypoalbuminemia. We identified 360 children with primary diagnosis of hepatic malignancy and 896 children with renal malignancy undergoing surgical resection. Of these, 77 children had hypoalbuminemia. Patients with renal or hepatic malignancy diagnosis and low albumin levels were more likely to experience postoperative dehiscence, need for TPN at discharge, postoperative bleeding or transfusion, unplanned reoperation, and unplanned readmission, based on univariate analysis (all P>0.05). Postoperative bleeding, need for nutritional support at discharge, and unplanned readmission were each associated with hypoalbuminemia. We demonstrate that low preoperative albumin is associated with significant perioperative risk. More attention should focus on perioperative nutritional status of children with cancer who are undergoing major resections.

Imaging case series of melioidosis: the great masquerader

BackgroundMelioidosis is an infectious disease caused by Gram-negative bacterium Burkholderia pseudomallei. It is endemic to Southeast Asia. Inhalation, inoculation and ingestion are major routes of transmission. Increased risk of infection is seen in patients with diabetes, alcoholism, chronic renal and liver failure and malignancy. The aim of the present case series is to describe the varied imaging manifestations of melioidosis.Case presentationThis is a retrospective review of imaging findings in eight patients with culture-proven B. pseudomallei infections diagnosed in our institute from September 2019 to September 2021. A total of eight culture-proven melioidosis cases were reported from our institute. All of them had multiorgan involvement and predisposing conditions or risk factors, most common being diabetes mellitus and alcoholism. Lung was the most common organ involved showing nodules and consolidations followed by liver and spleen demonstrating multiple ‘honeycomb’-like abscesses. Musculoskeletal manifestations included osteomyelitis and intramuscular abscess. Cerebral abscess, cerebral infarcts, prostatic abscess, abdominal aortic mycotic aneurysm with periaortic hematoma and splenic vein thrombosis with splenic infarcts were a few other manifestations.ConclusionsMelioidosis is a great mimicker with acute, subacute or chronic clinical course involving multiple organs and resembling other common infections. Hence, it should be considered as a possible etiological agent when evaluating patients with risk factors and multiorgan involvement.

Downstream Targets of VHL/HIF-α Signaling in Renal Clear Cell Carcinoma Progression: Mechanisms and Therapeutic Relevance.

The clear cell variant of renal cell carcinoma (ccRCC) is the most common renal epithelial malignancy and responsible for most of the deaths from kidney cancer. Patients carrying inactivating mutations in the Von Hippel-Lindau (VHL) gene have an increased proclivity to develop several types of tumors including ccRCC. Normally, the Hypoxia Inducible Factor alpha (HIF-α) subunits of the HIF heterodimeric transcription factor complex are regulated by oxygen-dependent prolyl-hydroxylation, VHL-mediated ubiquitination and proteasomal degradation. Loss of pVHL function results in elevated levels of HIF-α due to increased stability, leading to RCC progression. While HIF-1α acts as a tumor suppressor, HIF-2α promotes oncogenic potential by driving tumor progression and metastasis through activation of hypoxia-sensitive signaling pathways and overexpression of HIF-2α target genes. One strategy to suppress ccRCC aggressiveness is directed at inhibition of HIF-2α and the associated molecular pathways leading to cell proliferation, angiogenesis, and metastasis. Indeed, clinical and pre-clinical data demonstrated the effectiveness of HIF-2α targeted therapy in attenuating ccRCC progression. This review focuses on the signaling pathways and the involved genes (cyclin D, c-Myc, VEGF-a, EGFR, TGF-α, GLUT-1) that confer oncogenic potential downstream of the VHL-HIF-2α signaling axis in ccRCC. Discussed as well are current treatment options (including receptor tyrosine kinase inhibitors such as sunitinib), the medical challenges (high prevalence of metastasis at the time of diagnosis, refractory nature of advanced disease to current treatment options), scientific challenges and future directions.

Outcomes of Radiofrequency Ablation for Solitary T1a Renal Cell Carcinoma: A 20-Year Tertiary Cancer Center Experience.

The aim is to determine the long-term oncologic and survival outcomes of the radiofrequency ablation (RFA) of solitary de novo T1a renal cell carcinoma (RCC). We retrospectively reviewed our renal ablation registry and included only patients with new solitary, biopsy-proven T1a RCC (<4 cm) who underwent RFA from January 2001 through December 2020. We collected patient and tumor characteristics. Survival rates were estimated using the Kaplan-Meier method. Of the 243 patients who met our inclusion criteria (160 male and 83 female, median age 68 years), 128 (52.6%) had another primary malignancy other than renal malignancy. Two-hundred forty-three RFA procedures were performed for 243 renal tumors of a median tumor size of 2.5 cm. The median follow-up period was 3.7 years. Most tumors (68.6%) were clear cell RCC. Ten patients (4.1%) experienced Clavien-Dindo Grade III complications. Seven patients(3.1%) developed recurrence at the ablation zone, and 11 (4.5%) developed recurrence elsewhere in the kidney. The 15-year local-recurrence- and disease-free survival were 96.5% and 88.6%, respectively. The 15-year metastasis-free survival and cancer-specific survival were 100%. RFA is a highly effective modality for the management of T1a RCC, with low complication and recurrence rates. Long-term data revealed favorable oncologic and survival outcomes.

Trauma-related falls in an urban geriatric population: predictive risk factors for poorer clinical outcomes

BackgroundThe aim of this study was to elucidate associations between polypharmacy, types of medications, and geriatric comorbidities to identify predictive risk factors for poorer clinical outcomes following trauma-related falls in the geriatric population. Nearly 80% of trauma-related hospital admissions in the older adult population are secondary to falls, accounting for 3 million emergency department visits annually. Numerous studies have demonstrated associations between falls, polypharmacy, and other geriatric comorbidities, but studies outlining predictive risk factors for poor clinical outcomes are lacking.MethodsA retrospective cohort study of 1087 patients ≥ 65 years old who presented to Level 1 Trauma Center after a trauma-related fall. Comorbidities, current medication, demographic information, and clinical outcomes were identified to ascertain predictive risk factors for poorer clinical outcomes. Variables were assessed for statistical significance on unadjusted analysis. Variables found to be significant were entered into a multivariable logistic regression model to test for adjusted associations, with p < 0.05 as statistically significant, and presented as adjusted odds ratios with 95% confidence intervals.ResultsPolypharmacy ≥ 4 medications (aOR 2.38 (1.10–5.15), p < .028) was an independent predictor of hospital readmission within 30 days. Chronic kidney disease, male gender, and Asian race had an increased association with ICU admission. History of malignancy (aOR 3.65 (1.62–8.19), p < .002) and chronic kidney disease (aOR 2.56 (1.11–5.96), p < .027) were independent predictors of 30-day mortality.ConclusionsPolypharmacy, chronic renal disease, malignancy history, male gender, and Asian race had an increased association of adverse clinical outcomes after falls in the geriatric population. Critical evaluation of patients with these risk factors may be needed to mitigate risk in this population.

TRIM21 attenuates renal carcinoma lipogenesis and malignancy by regulating SREBF1 protein stability

BackgroundMetabolic reprogramming is a hallmark of various cancers. Targeting metabolic processes is a very attractive treatment for cancer. Renal cell carcinoma (RCC) is a type of metabolic disease, and the lipidomic profile of RCC is significantly altered compared with that of healthy tissue. However, the molecular mechanism underlying lipid metabolism regulation in RCC is not clear.MethodsThe XF long-chain fatty acid oxidative stress test kits were used to assess the dependence on long-chain fatty acids and mitochondrial function after knockdown TRIM21 in RCC cells. The effect of TRIM21 on the lipid content in RCC cells was determined by metabolomics analysis, Oil Red O staining, and cellular Nile red staining. qRT-PCR and western blot were used to explore the relationship between TRIM21 and lipogenesis, and then the key molecule sterol regulatory element binding transcription factor 1 (SREBF1) was identified to interact with TRIM21 by immunoprecipitation, which was also identified in an orthotopic model. Subsequently, the relevance and clinical significance of TRIM21 and SREBF1 were analyzed by The Cancer Genome Atlas (TCGA) database, and 239 tissues were collected from RCC patients.ResultsTRIM21 silencing attenuated the dependence of RCC cells on fatty acids, and enhanced lipid accumulation in RCC cells. TRIM21 overexpression significantly decreased lipid contents by decreasing the expression of lipogenic enzymes via ubiquitination-mediated degradation of SREBF1. SREBF1 is critical for TRIM21-mediated lipogenesis inhibition in vitro and in vivo. Moreover, TRIM21 expression is negatively correlated with SREBF1 expression, and TRIM21-SREBF1 is a reliable combinational biomarker for RCC prognosis.ConclusionThe findings from this study reveal a novel pathway through which TRIM21 inhibits the lipid metabolism process of RCC and shed light on the development of targeted metabolic treatment and prognosis diagnosis of RCC.

Diagnostic Accuracy Of Contrast Enhanced Ct For Detection Of Renal Cell Carcinoma Taking Histopathology As Gold Standard.

Renal cell carcinoma being the commonest primary renal malignancy of adulthood accounts for approximately 80-90% renal malignant lesions. The purpose of radiological imaging modalities when devising the treatment options for renal masses is crucial as it significantly influence the clinical outcome and prognosis of the disease. Subjective impression by a radiologist for diagnosing a mass lesion is known to be critical and its precision is improved by contrast enhanced CT as demonstrated by certain retrospective analyses. We aimed to ascertain the diagnostic accuracy of contrast enhanced computed tomography to diagnose renal cell cancers by verifying through histopathology reported diagnoses. This Cross-sectional (validation) study was carried out in Radiology and Urology departments of Ayub Teaching Hospital; Abbottabad, from 1st November 2020 to 30th April 2022. The study population included all admitted symptomatic patients with age range 18-70 years of either gender. The patients were subjected to detailed clinical examination and history and an ultrasound and contrast enhanced CT abdomen and pelvis. CT scans were reported under supervision of single consultant radiologist. Data was analysed in SPSS version 20.0. Mean age of the patients was 38.88±11.62 years ranging from 18-70 years and mean duration of symptoms was 54.64±49.171 ranging from 3-180 days. All of the total 113 patients underwent contrast enhanced CT scan and later operated to confirm the diagnoses by histopathology. The comparison yielded true positive (TP) cases to be 67, True Negative (TN) 16, False Positive (FP) 26, and 4 False Negative (FN) as per CT scan diagnoses. CT scan had a diagnostic Accuracy of 73.45% with 94.37% sensitivity and 38.10% specificity. Contrast-enhanced CT has a high sensitivity for making the diagnosis of renal cell carcinoma; however, its specificity is low. A multidisciplinary approach is necessary to overcome the low specificity. Therefore, collaboration between radiologists and urologic oncologists should be considered while devising treatment plan for patients.