Search

Renal and cardiovascular disorders are very prevalent and associated with significant morbidity and mortality. Among diverse pathogenic mechanisms, the dysregulation of immune and inflammatory responses plays an essential role in such disorders. Consequently, the discovery of Annexin A1, as a glucocorticoid-inducible anti-inflammatory protein, has fueled investigation of its role in renal and cardiovascular pathologies. Indeed, with respect to the kidney, its role has been examined in diverse renal pathologies, including acute kidney injury, diabetic nephropathy, immune-mediated nephropathy, drug-induced kidney injury, kidney stone formation, and renal cancer. Regarding the cardiovascular system, major areas of investigation include the role of Annexin A1 in vascular abnormalities, atherosclerosis, and myocardial infarction. Thus, this review briefly describes major structural and functional features of Annexin A1 followed by a review of its role in pathologies of the kidney and the cardiovascular system, as well as the therapeutic potential of its modulation for such disorders.

Purpose: The role of non-tumour renal biopsy in predicting renal function after surgery for renal cell carcinoma (RCC) is poorly investigated. The aim of the study was to assess the impact of renal parenchymal histology on renal function after radical nephrectomy in a cohort of patients with RCC., Methods: This cohort study included 171 patients with RCC submitted to radical nephrectomy between 2006 and 2018. Two biopsy samples from normal parenchyma were collected at nephrectomy and renal parenchyma damage (RPD) was scored on histologic samples according to validated methodology. The outcomes were eGFR after surgery and its reduction > 25% relative to baseline at maximum 12 months' follow-up. Linear and logistic multivariable regression were used, adjusting for age at surgery, presence of hypertension, diabetes, clinical tumour size, time from surgery and basal eGFR., Results: 171 patients were enrolled and RPD was demonstrated in 64 (37%). Patients with RPD had more comorbidities (CCI > 2 in 25 vs. 9%, p < 0.001), in particular hypertension (70 vs. 53%; p = 0.03), diabetes with (5% vs. 0%, p = 0.007) or without (31 vs. 18%; p = 0.007) organ damage, cerebrovascular disease (19 vs. 5%; p = 0.006) and nephropathy (20 vs. 3%; p = 0.0004). At multivariable analyses, RPD was associated with lower eGFR (Est. - 5.48; 95% CI - 9.27: - 1.7; p = 0.005) and with clinically significant reduction of eGFR after surgery (OR 3.06; 95% CI 1.17: 8.49; p = 0.026)., Conclusions: Presence of RPD in non-tumour renal tissue is an independent predictor of functional impairment in patients with RCC. Such preliminary finding supports the use of parenchyma biopsy during clinical decision making., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Objective: To evaluate the quality of the contrast images obtained with a Primovist® (gadoxetate disodium) Magnetic Resonance Image in order to diagnose benign, malignant and malformations in the urinary tract., Material and Methods: A retrospective image and diagnosis review of Primovist® MRI studies performed in liver insufficient patients without apparent renal abnormalities was done, in order to evaluate the urinary tract for irregularities., Results: A total of 117 Primovist® MRI studies performed between july 2014 and November 2018 were reviewed, 5 were excluded because they were incomplete. The average age was 59.6 ± 16.6 years old. The following diagnosis were encountered: 36 simple cysts, 6 perirenal fibrosis after pyelonephritis, 1 renal cancer, 1 renal atrophy, 1 proximal uretheric flexure, 1 bilateral hydronephrosis due to lower urinary obstruction because of benign prostatic hyperplasia and 1 complex cyst. No MRI study was indicated with suspicions of renal abnormalities. Relevant images are included that demonstrate the capability of Primovist® MRI to diagnose renal abnormalities., Conclusion: Even though none of the Primovist® MRI studies was done with suspicious of renal abnormalities it was possible to diagnose incidental benign, malignant and malformations of the urinary tract. This study shows how Primovist® MRI can be useful contrast study for urinary tract irregularities.

A novel analytical approach is proposed to discriminate between solid biopsies of chromophobe renal cell carcinoma (chRCC) and renal oncocytoma (RO). The method comprises the following steps: (i) ultrasonic extraction of proteins from solid biopsies, (ii) protein depletion with acetonitrile, (iii) ultrasonic assisted in-solution digestion using magnetic nanoparticle with immobilized trypsin, (iv) C18 tip-based preconcentration of peptides, (v) sequential extraction of the peptides with ACN, (vi) MALDI-snapshot of the extracts and (vii) investigation of the extract containing the most discriminating features using high resolution mass spectrometry. With this approach we have been able to differentially cluster renal oncocytoma and chromophobe renal cell carcinoma and identified 18 proteins specific to chromophobe and seven unique to renal oncocytoma. Chromophobes express proteins associated with ATP function (ATP5I & 5E; VATE1 & G2; ADT2), glycolysis (PGK1) and neuromedin whilst oncocytomas express ATP5H, ATPA, DEPD7 and TRIPB thyroid receptor interacting protein., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Renal cryoablation has become accepted as treatment for small renal tumors as an alternative to surgery. However, parallel with the increase in the use of this therapy, there also has been increases in the number of reports of complications related to renal cryoablation. One potential complication is injury to important non-renal structures adjacent to the ablated renal tumor, such as the colon, duodenum, ureter, psoas muscle and so on. To prevent injury of adjacent organs, separating organs from the tumor is desirable. Over the past 15 years, several techniques have been developed to protect against injury of organs adjacent to renal tumors that are targets of cryoablation. The most commonly used technique for this purpose has been hydrodissection. Others include dissection with gas, balloon dissection and probe traction. To avoid injury of a ureter running near the renal tumor, pyeloperfusion is known to be useful. The rate of cases necessitating avoidance of organ injury by using these techniques is relatively high. In some cases, more than two techniques are combined. In the present review, we provided an overview of techniques currently available to protect against organ injuries, and discussed the advantages and disadvantages of each technique., (© 2019 The Japanese Urological Association.)

Purpose: Imaging plays a key role throughout the renal cell carcinoma (RCC) patient pathway, from diagnosis and staging of the disease, to the assessment of response to therapy. This review aims to summarise current knowledge with regard to imaging in the RCC patient pathway, highlighting recent advances and challenges., Methods: A literature review was performed using Medline. Particular focus was paid to RCC imaging in the diagnosis, staging and response assessment following therapy., Results: Characterisation of small renal masses (SRM) remains a diagnostic conundrum. Contrast-enhanced ultrasound (CEUS) has been increasingly applied in this field, as have emerging technologies such as multiparametric MRI, radiomics and molecular imaging with 99m technetium-sestamibi single photon emission computed tomography/CT. CT remains the first-line modality for staging of locoregional and suspected metastatic disease. Although the staging accuracy of CT is good, limitations in determining nodal status persist. Response assessment following ablative therapies remains challenging, as reduction in tumour size may not occur. The pattern of enhancement on CT may be a more reliable indicator of treatment success. CEUS may also have a role in monitoring response following ablation. Response assessments following anti-angiogenic and immunotherapies in advanced RCC is an evolving field, with a number of alternative response criteria being proposed. Tumour response patterns may vary between different immunotherapy agents and tumour types; thus, future response criteria modifications may be inevitable., Conclusion: The diagnosis and characterisation of SRM and response assessment following targeted therapy for advanced RCC are key challenges which warrant further research.

In the interest of renal functional preservation, partial nephrectomy has supplanted radical nephrectomy as the preferred treatment for T1 renal masses. This procedure usually involves the induction of renal warm ischemia by clamping the hilar vessels prior to tumor excision. Performing robot-assisted partial nephrectomy (RAPN) "off-clamp" can theoretically prevent renal functional loss associated with warm ischemia. We describe our institutional experience and compare perioperative and renal functional outcomes using a propensity score matched cohort. We conducted a retrospective comparison from a prospectively maintained database of all patients who underwent RAPN from 2009 to 2015. Of those patients, 143 underwent off-clamp RAPN. Fifty off-clamp RAPN patients were propensity score matched with fifty clamped RAPN patients based on renal function, tumor size, and R.E.N.A.L. nephrometry score. The cohorts were compared across demographics, operative information, perioperative outcomes, and renal functional outcomes. For all off-clamp RAPN patients, mean nephrometry score was 7.1, mean estimated blood loss (EBL) was 236.9 mL, perioperative complication rate was 7.7%, and mean decrease in estimated glomerular filtration rate (eGFR) was 7.1% at a median follow-up of 9.2 months. In the propensity score matched cohorts, off-clamp RAPN resulted in a shorter mean operative time (172.0 versus 196.0 min, p = 0.025) and a lower mean EBL (179.7 versus 283.2 mL, p = 0.046). A lower complication rate of 6.0% in the off-clamp group compared with 20.0% in the clamped group approached significance (p = 0.071). Mean preoperative eGFR was similar in both cohorts. Importantly, there was no significant difference in decrease in eGFR between the clamped cohort (9.8%) and off-clamp cohort (11.9%) at a median follow-up of 9.0 months (p = 0.620). Off-clamp RAPN did not result in improved renal functional preservation in our experience. Surprisingly, the off-clamp cohort experienced lower intraoperative blood loss, shorter operative times, and fewer complications.

Objectives: To assess the correlation of the resected and ischaemic volume (RAIV), which is a preoperatively calculated volume of nephron loss, with the amount of postoperative renal function (PRF) decline after minimally invasive partial nephrectomy (PN) in a multi-institutional dataset., Patients and Methods: We identified 348 patients from March 2005 to December 2013 at six institutions. Data on all cases of laparoscopic (n = 85) and robot-assisted PN (n = 263) performed were retrospectively gathered. Univariable and multivariable linear regression analyses were used to identify the associations between various time points of PRF and the RAIV, as a continuous variable., Results: The mean (sd) RAIV was 24.2 (29.2) cm 3 . The mean preoperative estimated glomerular filtration rate (eGFR) and the eGFRs at postoperative day 1, 6 and 36 months after PN were 91.0 and 76.8, 80.2 and 87.7 mL/min/1.73 m 2 , respectively. In multivariable linear regression analysis, the amount of decline in PRF at follow-up was significantly correlated with the RAIV (β 0.261, 0.165, 0.260 at postoperative day 1, 6 and 36 months after PN, respectively). This study has the limitation of its retrospective nature., Conclusion: Preoperatively calculated RAIV significantly correlates with the amount of decline in PRF during long-term follow-up. The RAIV could lead our research to the level of prediction of the amount of PRF decline after PN and thus would be appropriate for assessing the technical advantages of emerging techniques., (© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.)

A hypodermic needle has been introduced incorporating an electrical impedance spectroscopy (EIS) sensor, called micro-EIS-on-a-needle for depth profiling (μEoN-DP). The μEoN-DP can locate endophytic renal tumors as well as determine tumor margins by detecting the impedance difference between normal and cancer tissues. To evaluate the μEoN-DP as a novel tool to determine the optimal surgical margin during partial nephrectomy (PN), the electrical impedance differences between renal parenchymal tissues and renal cell carcinoma (RCC) tumors are investigated with regard to the distance from the tumors. Optimal frequencies at which the discrimination extent is maximized are suggested based on the discrimination index. The resistance and capacitance of normal and cancer tissues are extracted using electrical equivalent circuit by excluding the influences of other electrical components on the sensor output. The extracted resistance and capacitance of cancer tissues are 37.8% larger and 25.7% smaller than that of normal tissues, respectively. Additionally, high sensitivity and specificity are obtained by using extracted resistance and capacitance, thus implying that the μEoN-DP shows promise as a supplementary tool for PN margin evaluation and decreasing the prevalence of positive surgical margins while maximizing parenchymal preservation., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: The minimally invasive treatment of small renal masses with cryoablation has become increasingly widespread during the past 15 years. Studies with long-term follow-up are beginning to emerge, showing good oncological control, however, tumors with a central and endophytic location seem to possess an increased risk of treatment failure. Such tumors are likely to be subjected to a high volume of blood giving thermal protection to the cancerous cells. Arterial clamping during freezing might reduce this effect but at the same time subject the kidney to ischemia. The aim of this study was to evaluate the effect of renal artery clamping during cryoablation in a porcine survival model., Methods: Ten Danish Landrace pigs (approximately 40 kg) underwent bilateral laparoscopic cryoablation with clamping of the right renal artery during freezing. The cryoablation consisted of a standard double-freeze cycle of 10-minute freeze followed by 8 minutes of thaw. Arterial clamping subjected the right kidney to 2 cycles of ischemia (10 minutes) with perfusion in between. After surgery, the animals were housed for 14 days prior to computed tomography perfusions scans, radioisotope renography, and bilateral nephrectomy., Results: No perioperative or postoperative complications were experienced. Mean differential renal function was 44% (95% confidence interval: 42-46) in the clamped right kidney group and 56% (95% confidence interval: 54-58) in the nonclamped left kidney group, P < .05. The ±5% technical inaccuracy is not accounted for in the results. Mean maximum temperature between freeze cycles was 5.13°C (95% confidence interval: -0.1 to 10.3) in the clamped right kidney group and 22.7°C (95% confidence interval: -16.6 to 28.8) in the nonclamped left kidney group, P < .05. Mean cryolesion volume, estimated on computed tomography perfusion, was 12.4 mL (95% confidence interval: 10.35-14.4) in the clamped right kidney group and 6.85 mL (95% confidence interval: 5.57-8.14) in the nonclamped left kidney group, P < .05. Pathological examination shows a higher degree of vital cells in the intermediate zone of the cryolesions in the nonclamped left kidneys when compared with the clamped right kidneys., Conclusion: Arterial clamping increases cryolesion size by approximately 80%, and pathologic examinations suggest a decreased risk of vital cells in the intermediate zone. The clamped kidneys showed no sign of injury from the limited ischemic insult. This study was limited by being a nontumor model.

Objective: To evaluate a recently published volume-based renal function prediction calculator intended to be used in small renal mass surgical counseling., Methods: Retrospective data collection included three-dimensional calculation of renal mass and parenchyma of patients who have undergone extirpative therapy. The predicted glomerular filtration rate (GFR) was calculated using the online calculator. The predicted GFR was compared with the actual 6-month GFR. The Pearson correlation coefficient, paired t test and root-mean-square error (RMSE) are utilized for statistical analysis., Results: After institutional review board approval, three institutions provided data for analysis. After patients with renal mass size >300 cc, renal size >400 cc or preoperative CKD ≥stage 3 had been excluded, we retrospectively analyzed data from 136 patients. The median mass volume was 22.2 cc (IQR 7-49). In multiple linear regression analysis, the most significant variables predicting postoperative GFR were partial versus radical nephrectomy and preoperative GFR with an overall R 2 of .68 (F = 26.13, P < .001). The predicted GFR was 75.4 mL/min/1.73 m 2 compared to an actual GFR of 70.7 mL/min/1.73 m 2 (P < .001, paired t test). The predicted GFR was highly correlated with the actual postoperative GFR at 6 months (Pearson correlation, r = .65, P < .001). RMSE of the validation cohort was 16.87., Conclusions: The predictive tool to determine renal function benefit of nephron sparing surgery compared to radical nephrectomy online calculator effectively predicts GFR and could potentially be used to help urologists and patients discuss renal function prior to extirpative renal surgery.

Globally, renal cell carcinomas (RCCs) represent a major portion of patients suffering from cancer. Temsirolimus is an anti-renal cancer drug that has already been approved in poor-risk metastatic RCC (mRCC) patients. In our present study, we have evaluated the in vitro effect of varying concentrations of temsirolimus on cancerous rat kidney cystatin; renal cancer was induced in rats making use of dimethylnitrosamine (DMN). It has already been reported that cancerous rat kidney cystatin performs its activity in an efficacious manner as compared to normal rat kidney cystatin, so here an attempt was made to see the effect of temsirolimus on this increased activity of cystatin in renal cancers. Anti-papain activity assay was utilized to see this effect and it was found that temsirolimus reduces the increased activity of cancerous rat kidney cystatin similar to that of normal rat kidney cystatin. Further, to have an insight into temsirolimus induced structural alterations in cancerous rat kidney cystatin; various spectroscopic assays viz. UV, Fluorescence, Circular dichroism (CD) and FTIR spectroscopy were employed. UV and Fluorescence spectroscopy shows cancerous rat kidney cystatin transformation to normal form in the presence of temsirolimus. FTIR and CD spectroscopy confirmed the complete structural reversion of cancerous rat kidney cystatin to normal form in the presence of 40μM temsirolimus. Thus, it can said that temsirolimus causes renal cystatin to revert to normal form; the increased activity of renal cystatin observed in incidences of renal cancer is restored back to normal thereby halting the progression of renal cancer., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose: To compare diameter as a continuous variable with categorical R.E.N.A.L. nephrometry score (RNS) in predicting surgical outcomes of robotic partial nephrectomy (RPN)., Methods: We retrospectively reviewed consecutive patients receiving RPN at our institution between July 2007 and June 2014 (n = 286). Three separate multivariate analyses were performed to assess the relationship between RNS components (R = radius, E = endophyticity, N = nearness to collecting system, L = location relative to polar lines), total RNS, and diameter as a continuous variable with operating time, warm ischemia time (WIT), and estimated blood loss (EBL). Each linear regression model's quality of fit to the data was assessed with coefficients of determination (R 2 )., Results: Continuous tumor diameter and total RNS were each significantly correlated to operative time, EBL, and WIT (p < 0.001). Categorical R related to operative time (R = 2 vs. R = 1, p = 0.001; R = 3 vs. R = 1, p = 0.001) and WIT (R = 2 vs. R = 1, p = 0.003; R = 3 vs. R = 1, p = 0.016), but not to EBL. For each of these outcomes, diameter outperformed both R and total RNS, as assessed by R 2 . Age, body mass index, Charlson Comorbidity Index, and anterior versus posterior location did not correlate with surgical outcomes., Conclusions: In this series of RPN from a high-volume center, surgical outcomes more closely related to tumor diameter than RNS. While RNS provides surgeons a standardized tool for preoperative planning of renal masses, tumor size may be employed as a more familiar measurement when counseling patients on potential outcomes.

Purpose: Partial nephrectomy (PN) for early stage renal cancer preserves renal function better than radical nephrectomy (RN) and is generally considered oncologically similar. The Intergroup European Organisation for Research and Treatment of Cancer trial comparing outcomes after PN vs. RN, however, showed reduced overall survival in the PN group. Our aim was to evaluate recurrence, death, and renal function after PN vs. RN for T1 tumors in a Canadian population., Materials and Methods: From 2000 to 2015, 2,358 patients with a first occurrence of a clinical T1 renal cancer who underwent PN or RN were identified from the Canadian Kidney Cancer Information System. Clinical, surgical, and pathologic parameters were analyzed. Time to progression was compared after PN vs. RN using a Cox proportional hazards model, adjusted for pertinent variables., Results: Inclusion criteria were met in 1,615 PN and 743 RN. Preoperative characteristics appeared similar in both groups. Time to progression was not different after PN vs. RN, adjusted for potential confounders (hazard ratio = 1.17 [95% CI: 0.8-1.72, P = 0.42]). Postoperative estimated glomerular filtration rate at 1 and 3 years was significantly greater for PN vs. RN in a linear regression model, accounting for preoperative estimated glomerular filtration rate., Conclusions: These results suggest that progression-free survival after PN and RN in patients with T1 renal cancer was similar, but that there was better preservation of renal function after PN. This suggests that both PN and RN have similar oncological efficiency, and that selection of surgical approach should be based on other factors such as technical feasibility, potential complications, and preservation of renal function., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To investigate if IgG can be expressed in clear cell renal cell carcinoma (cRCC) , and the expression of IgG is involved in the cancer progression. If IgG expression can serve as a potential target in cancer therapies and be used for judging the prognosis., Materials and Methods: By immunohistochemistry, we detected IgG in cRCC tissues(75 cRCC tissues and75 adjacent normal kidney tissues). Immunofluorescence and Western blot was used to detect the IgG in cRCC cell lines (786-0, ACHN and CAKI-I). By RT-PCR, the functional transcript of IgG heavy chain was detected. Knockdown of IgG was to analyze the proliferation, migration and invasion ability by CCK8, Transwell and Matrigel and apoptosis in cRCC cell lines., Results: By immunohistochemistry, we found strong staining of IgG in 66 cases of 75 cRCC tissues and 63 cases of 75 adjacent normal kidney tissues. Immunofluorescence and Western blot was found IgG in cRCC cell lines. Knock-down IgG in cRCC cell lines resulted in significant inhibition of cell proliferation, migration and invasion, and the induction of apoptosis of the 786-0 cells. The immunohistochemistry analysis showed that high IgG expression significantly correlated with the poor differentiation and advanced stage of cRCC., Conclusion: IgG was over expressed in cRCC and was involved in the proliferation, migration and invasion of cancer cells. IgG expression may serve as a potential target in cancer therapies and could be used for judging the prognosis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background and Aims: Dysfunction of kidney mitochondria plays a critical role in the pathogenesis of a number of renal diseases. Proteomics represents an untargeted attempt to reveal the remodeling of mitochondrial proteins during disease. Combination of separation methods and mass spectrometry allows identification and quantitative analysis of mitochondrial proteins including protein complexes. The aim of this review is to summarize the methods and applications of proteomics to renal mitochondria., Methods: Using keywords "mitochondria", "kidney", "proteomics", scientific databases (PubMed and Web of knowledge) were searched from 2000 to August 2015 for articles describing methods and applications of proteomics to analysis of mitochondrial proteins in kidney. Included were publications on mitochondrial proteins in kidneys of humans and animal model in health and disease., Results and Conclusion: Proteomics of renal mitochondria has been/is mostly used in diabetes, hypertension, acidosis, nephrotoxicity and renal cancer. Integration of proteomics with other methods for examining protein activity is promising for insight into the role of renal mitochondria in pathological states. Several challenges were identified: selection of appropriate model organism, sensitivity of analytical methods and analysis of mitochondrial proteome in different renal zones/biopsies in the course of various kidney disorders.

Purpose: To assess the impact of 3D printed models of renal tumor on patient's understanding of their conditions. Patient understanding of their medical condition and treatment satisfaction has gained increasing attention in medicine. Novel technologies such as additive manufacturing [also termed three-dimensional (3D) printing] may play a role in patient education., Methods: A prospective pilot study was conducted, and seven patients with a primary diagnosis of kidney tumor who were being considered for partial nephrectomy were included after informed consent. All patients underwent four-phase multi-detector computerized tomography (MDCT) scanning from which renal volume data were extracted to create life-size patient-specific 3D printed models. Patient knowledge and understanding were evaluated before and after 3D model presentation. Patients' satisfaction with their specific 3D printed model was also assessed through a visual scale., Results: After viewing their personal 3D kidney model, patients demonstrated an improvement in understanding of basic kidney physiology by 16.7 % (p = 0.018), kidney anatomy by 50 % (p = 0.026), tumor characteristics by 39.3 % (p = 0.068) and the planned surgical procedure by 44.6 % (p = 0.026)., Conclusion: Presented herein is the initial clinical experience with 3D printing to facilitate patient's pre-surgical understanding of their kidney tumor and surgery.

To explore the relationship between Mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3(MEKK3) and cell apoptosis, clinicopathology, and prognosis, we characterize the expression of MEKK3, survivin and stat3 in renal clear cell carcinoma (RCCC). The expressions were measured by RT-PCR and Western blot from 15 cases of RCCC and 15 cases of control group (CG). Protein expression was detected by tissue microarray and immunochemistry in 98 cases of RCCC, 28 cases of CG. Expression patterns were analyzed for their association with pathological factors, correlation and prognosis in RCCC. Expression of MEKK3, survivin and stat3 mRNA was significantly higher in RCCC than in CG (P < 0.01). MEKK3, survivin and stat3 expression differed significantly between pathological grade (P < 0.05) and clinical stage (P < 0.05). MEKK3 expression was positively correlated with survivin and stat3 (P < 0.01). Furthermore, we investigated the role of MEKK3 in RCCC using the technique of RNA silencing via small interfering (siRNA) in ACHN cells. The results indicated that the targeted depletion of MEKK3 caused a dramatic massive apoptotic cell death. Kaplan-Meier survival analysis showed that MEKK3 and survivin expression, pathological grade, and clinical stage reduced cumulative survival. Cox multivariate regression analysis showed that MEKK3, survivin, and clinical staging were independent prognostic factors in renal cancer (P < 0.05). MEKK3 can be used as an important marker of prognostic evaluation in RCCC. The mechanism may be closely related to cell apoptosis. Targeted therapy of MEKK3 may provide a new strategy for treatment of chemotherapeutic-resistant tumors., (© 2014 Wiley Periodicals, Inc.)

Purpose: To evaluate the clinical value of different magnetic resonance imaging (MRI) sequences for a real-time thermo-monitoring during laser-induced thermotherapy (LITT) in kidneys., Methods: Twenty-eight ex vivo pig kidneys were treated with laser ablation under MR guidance in a high-field MR scanner (Magnetom Espree or Avanto Fit, Siemens, Germany). For the thermal ablation of the kidney, a neodymium yttrium-aluminum-garnet (Nd:YAG) laser was used in combination with a special protective catheter (length 43 cm, 4 French) which is sealed at the distal end. First, ablation was performed for 7, 10, and 13 minutes using FLASH sequences for investigation of time-dependent growth of lesion size. In the second step, we evaluated the optimal imaging sequence during a 7 minutes ablation of the kidney and after cooling using four different MR sequences (Haste, FLASH, radial VIBE, and Caipirinha DIXON)., Results: Macroscopic lesion volume increased from 3,784 ± 1,525 mm(3) to 7,683 ± 5,756 mm(3) after the ablation from 7 to 13 minutes and MR volume ranged from 2,107 ± 1,674 mm(3) to 2,934 ± 1,549 mm(3) after the ablation from 7 to 13 minutes. During ablation, FLASH (132 ± 34%) and radial VIBE (120 ± 43%) sequences displayed lesion volumes most efficiently with a trend to overestimation. The Caipirinha DIXON (323 ± 24%) sequence overestimated the volumes significantly during real-time monitoring. The volumes measured by MRI with FLASH (61 ± 30%), Haste (67 ± 28%), or radial VIBE (48 ± 14%) sequences after cooling of the kidney after ablation were always underestimated. The Caipirinha DIXON (142 ± 2%) sequence still overestimated the lesion volume after cooling of the kidney., Conclusion: LITT is a feasible ablation modality in kidney tissue. Moreover, macroscopic and MR lesion volume increases time-dependently. For online monitoring, radial VIBE and FLASH sequences seem to be most efficient., (© 2014 Wiley Periodicals, Inc.)

Although radical nephrectomy is still practiced in many patients with large renal tumors, oncology and nephrology arguments for kidney-sparing approach for small renal masses has taken over this first. Indeed, partial nephrectomy provides equivalent oncologic results while preserving renal function and thereby limit morbidity and cardiovascular mortality related to chronic kidney disease. In addition, patients who develop kidney cancer often have medical comorbidities that may affect renal function, such as diabetes and hypertension. Histological examination of renal tissue adjacent to the tumor showed significant pathological changes in the majority of patients. For elderly patients or patients with comorbidities, active surveillance allows kidney-sparing approach with extremely low rates of progression and metastasis of cancer disease. Despite these significant advances in understanding for the treatment of small renal masses, partial nephrectomy remains underused. Better management must take into account the preservation of renal function in order to increase overall survival. A strategy for the systematic evaluation of renal function in patients with CR, with multidisciplinary staff (nephrologist urologist and oncologist), is therefore highly desirable.

Mannitol has been administered during partial nephrectomy as a renal protective agent for ischemic damage. However, we do not have any high-level clinical evidence of its effectiveness. The aim of the present study was to evaluate the effect of mannitol during open partial nephrectomy by comparing the postoperative renal function of patients who received it and those who did not. We retrospectively reviewed the records of 55 patients who underwent open partial nephrectomy for renal cancer in a solitary kidney from January 1990 to December 2012, and who were followed up postoperatively for at least 6 months. Of the 55 patients, mannitol was given to 20 patients (group M+) and not to the other 35 patients (group M-). We compared not only the postoperative estimated glomerular filtration rate, but also its decrease rate and the incidence of acute kidney injury requiring dialysis in the two groups. There were no significant differences in perioperative patient characteristics between the two groups. Mannitol made no significant difference in both the postoperative estimated glomerular filtration rate and its decrease rate at any point within 6 months of the postoperative period. The incidence of acute kidney injury requiring dialysis was one (5.0%) in group M+ and two (5.7%) in group M-. These findings suggest that there might be no advantage from the administration of mannitol during open partial nephrectomy., (© 2013 The Japanese Urological Association.)

High-intensity focused ultrasound (HIFU) is an attractive therapy for kidney cancer, but its efficacy can be limited by heat deposition in the pre-focal tissues, notably in fat around the kidney (peri-nephric fat), the acoustic properties of which have not been well characterized. Measurements of attenuation were made using a modified insertion-loss technique on fresh, unfixed peri-nephric fat obtained from patients undergoing kidney surgery for cancer. The de-focusing effect of changing the position of the fat layers was also investigated using fresh subcutaneous fat from euthanized pigs. The mean attenuation of human peri-nephric fat was found to be 11.9 ± 0.9 Np/m (n = 10) at 0.8 MHz, the frequency typically used for HIFU ablation of kidney tumors, with a frequency dependence of f(1.2). A typical 2- to 4-cm thickness of peri-nephric fat would result in a de-rated intensity of 3% - 62% at 0.8 MHz compared with a hypothetical patient with no peri-nephric fat. Through the use of freshly excised porcine subcutaneous fat, the presence of fat 100 mm in front of the focus was found to have a de-focusing effect of approximately 1 mm in both transverse directions, which corresponds to a full HIFU beam width off-target. Peri-nephric fat may significantly affect both the intensity and accuracy of HIFU fields used for the ablation of kidney cancer., (2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved)

The three most common kinds of urologic malignancies are prostate, bladder, and kidney cancer, which typically cause substantial morbidity and mortality. Early detection and effective treatment are essential due to their high fatality rates. As a result, there is an urgent need for innovative research to improve the clinical management of patients with urologic cancers. A type of small noncoding RNAs of 22 nucleotides, microRNAs (miRNAs) are well-known for their important roles in a variety of developmental processes. Among these, microRNA-21 (miR-21) stands out as a commonly studied miRNA with implications in tumorigenesis and cancer development, particularly in urological tumors. Recent research has shed light on the dysregulation of miR-21 in urological tumors, offering insights into its potential as a prognostic, diagnostic, and therapeutic tool. This review delves into the pathogenesis of miR-21 in prostate, bladder, and renal cancers, its utility as a cancer biomarker, and the therapeutic possibilities of targeting miR-21. [ABSTRACT FROM AUTHOR]

Background: In Japan, comprehensive cancer statistics are collected through cancer registries. However, data on urological cancers are rarely summarized or published in research papers. Methods: This retrospective study was performed using publicly available statistical data on urological cancers (prostate cancer [PCa], bladder cancer [BCa], and cancers of kidney and urinary tract [except urinary bladder]) in Japan, including a summary of the Ministry's mortality statistics, cancer incidence statistics from the Regional Cancer Registries through 2015, and the National Cancer Registry statistics from 2016. We examined the incidence and mortality rates of urological cancers stratified by age groups. Results: The number of new cases of PCa, BCa, and cancers of kidney and urinary tract (except urinary bladder) in 2019 was 94,748, 23,383, and 30,458, respectively, and the number of deaths in 2022 was 13,439, 9,598, and 9,795, respectively. The incidence and mortality rates of urological cancers have consistently increased. Since 2000, there has been a noteworthy increase in the mortality rate of urological cancers among individuals aged > 85 years. The incidence and mortality rates of BCa and cancers of kidney and urinary tract (except urinary bladder) were significantly higher in males than in females. Conclusions: Urological cancers in very elderly patients (> 85 years) will become increasingly important in the future. [ABSTRACT FROM AUTHOR]

Copyright of Türk Radyoloji Seminerleri is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Capsaicin, the organic compound which attributes the spicy flavor and taste of red peppers and chili peppers, has been extensively studied for centuries as a potential natural remedy for the treatment of several illnesses. Indeed, this compound exerts well-known systemic pleiotropic effects and may thus bring important benefits against various pathological conditions like neuropathic pain, rhinitis, itching, or chronic inflammation. Yet, little is known about the possible biological activity of capsaicin at the kidney level, as this aspect has only been addressed by sparse experimental investigations. In this paper, we aimed to review the available evidence focusing specifically on the effects of capsaicin on renal physiology, as well as its potential benefits for the treatment of various kidney disorders. Capsaicin may indeed modulate various aspects of renal function and renal nervous activity. On the other hand, the observed experimental benefits in preventing acute kidney injury, slowing down the progression of diabetic and chronic kidney disease, ameliorating hypertension, and even delaying renal cancer growth may set the stage for future human trials of capsaicin administration as an adjuvant or preventive therapy for different, difficult-to-treat renal diseases. [ABSTRACT FROM AUTHOR]

Background: Renal cell carcinoma accounts for 2–3% of all malignant cancers in adults and is characterized by the potential development of venous tumor thrombus. Case presentation: We present a rare case of a 62-year-old Caucasian man who arrived in the emergency department for monosymptomatic hematuria. Further investigation revealed a right renal cell carcinoma with 16 cm intravascular extension through the renal vein into the inferior vena cava and right atrium associated with significant coronary artery disease based on the computed tomography scan and coronary angiography. To the best of our knowledge, after an extensive literature review, only one similar case has been reported with involvement of the contralateral kidney. Therefore, there are no applicable management recommendations. After performing coronary artery bypass graft surgery, we proceeded with an open right radical nephrectomy and inferior vena cava and right atrium thrombectomy under cardiopulmonary bypass and while the patient's heart was still beating. The postoperative course went without complications, and the patient was discharged from the hospital on the 10th postoperative day. Conclusions: Radical nephrectomy and thrombectomy with reconstruction of the inferior vena cava combined with coronary artery bypass graft can be performed safely and effectively in selected patients with renal cell carcinoma and significant coronary artery disease. Multidisciplinary teamwork and careful patient selection are essential for optimal outcomes. [ABSTRACT FROM AUTHOR]

It is quite unusual to have numerous primary malignant tumors at the same time in the same patient. These cancers are classified as metachronous or synchronous. The occurrence of synchronous urologic tumors poses diagnostic and treatment challenges and has always been a subject of controversy in the clinical decision-making process. Unfortunately, no clear standardized management protocols for these patients exist. Therefore, diagnosis and treatment may be difficult, especially with few resources. We present a 75-year-old man with simultaneous prostate and kidney cancers successfully treated at our center. This is one of the rare cases in the English literature with two primary urologic cancers. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate AT1-R expression in normal and cancerous human kidneys, how these expressions are modified, and AT1-R functionality. AT-1R mRNA expression, determined by real-time PCR, was detected in all samples. AT-1R mRNA increased in well-differentiated cancer (G1, p < 0.01) and decreased 2.9-fold in undifferentiated cancer (G4, p < 0.001) compared with normal kidney tissues. Immunocytochemistry analysis showed that the AT-1R was expressed in the normal tubular epithelium. The glomerulus was also immunoreactive, and as expected, the smooth muscle cells of the vessel walls also expressed the receptor. A total of 35 out of 42 tumors were AT-1R positive, with the cell tumors showing varying numbers of immunoreactive cells, which were stained in a diffuse cytoplasmic and membranous pattern. Computer-assisted counting of the stained tumor cells showed that the number of AT-1R-positive cells increased in the well-differentiated cancers. The functionality of AT-1R was assessed in primary cultures of kidney epithelial cells obtained from three G3 kidney cancer tissues and corresponding histologically proven non-malignant tissue adjacent to the tumor. Indeed, Ang II stimulated, in a dose-dependent manner, the 24 h proliferation of normal kidney cells and cancer cells in the primary culture and phosphorylated extracellular regulated kinases 1 and 2. In conclusion, Ang II may be involved in the growth or function of neoplastic kidney tissue. [ABSTRACT FROM AUTHOR]

Capsaicin, the organic compound which attributes the spicy flavor and taste of red peppers and chili peppers, has been extensively studied for centuries as a potential natural remedy for the treatment of several illnesses. Indeed, this compound exerts well-known systemic pleiotropic effects and may thus bring important benefits against various pathological conditions like neuropathic pain, rhinitis, itching, or chronic inflammation. Yet, little is known about the possible biological activity of capsaicin at the kidney level, as this aspect has only been addressed by sparse experimental investigations. In this paper, we aimed to review the available evidence focusing specifically on the effects of capsaicin on renal physiology, as well as its potential benefits for the treatment of various kidney disorders. Capsaicin may indeed modulate various aspects of renal function and renal nervous activity. On the other hand, the observed experimental benefits in preventing acute kidney injury, slowing down the progression of diabetic and chronic kidney disease, ameliorating hypertension, and even delaying renal cancer growth may set the stage for future human trials of capsaicin administration as an adjuvant or preventive therapy for different, difficult-to-treat renal diseases.

Problem: There remains uncertainty around cancer risk at lower levels of arsenic in drinking water. This study updates evidence from our previous review on the relationship between arsenic in drinking water and urinary bladder and kidney cancers (updated search January 2013 to February 2023). Method: Thirty-four studies were retained for review; six met criteria for inclusion in meta-analysis. Risk estimates for bladder and kidney cancer incidence and mortality were analyzed separately using Bayesian multilevel linear models. Results: For bladder cancer incidence, the estimated posterior mean relative risks (RRs) were 1.25 (0.92–1.73), 2.11 (1.18–4.22) and 3.01 (1.31–8.17) at arsenic concentrations of 10, 50 and 150 μg/L, respectively, with posterior probabilities of 92%, 99% and 100%, respectively, for the RRs to be >1. The corresponding RRs for kidney cancer were 1.37 (1.07–1.77), 1.95 (1.44–2.65) and 2.47 (1.74–3.52), with posterior probabilities of 100%. For bladder cancer, the posterior mean mortality ratios were 1.36 (0.35–6.39), 2.92 (1.24–7.82) and 4.88 (2.83–9.03) with posterior probabilities of 72%, 99% and 100%, respectively. Conclusions: The findings show increased bladder and kidney cancer risks at lower levels of arsenic in drinking water. Given that many people worldwide are exposed to lower levels of arsenic in drinking water, the public health impacts are substantial. [ABSTRACT FROM AUTHOR]

Objectives: Cancer metastasis to the kidney is a rare event. We retrospectively analyzed clinicopathologic characteristics in 6 cases of diagnosed renal metastases from primary lung cancer. We also provide clinical follow-up data and brief review of the literature. Methods: Immunohistochemistry was used to evaluate the expression of TTF-1, NapsinA, CK7, CK(AE1/AE3), P63, P40, CgA, PAX-8, GATA3 and Ki-67 in primary tumor and metastases. Additionally, the clinical characteristics, imaging features, diagnosis, and treatment were analyzed. Results: With the help of immunohistochemistry and combined clinical history, we found four cases were lung adenocarcinomas, one case was lung squamous cell carcinoma, and the other case was lung small cell carcinoma metastases to the kidney.The patients were all male by gender and had a mean age of 62 years, and metastasis to the left kidney were more universal. Most of the tumors histological grade originating from the lung were poorly-moderately differentiated, and the time to metastasis to the kidney was relatively short for squamous lung cancer and small cell lung cancer, while the time to metastasis for lung adenocarcinoma was related to its degree of differentiation. Overall, we found the prognosis of lung cancer patients with renal metastases were poor especially with multi-site metastases. Conclusions: Distinguishing primary and secondary tumors of the kidney is essential to guide treatment and prevent unnecessary surgery, so clinical information, radiology, histological correlation of the primary tumor, and immunohistochemical findings help the pathologist determine correct diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the study was to investigate trends of FT for in-patient treatment of renal RCC in the USA and Germany. Methods: We analyzed the SEER database for the USA and the nationwide German hospital billing database each from 2006 to 2019 for a RCC diagnosis in combination with FT, radical nephrectomy, and partial nephrectomy. FT was defined as radiofrequency ablation (RFA) or cryotherapy. Linear regression analysis was performed to detect changes over time. Results: For the USA, we included 7,318 FT cases. The share of FT increased from 2.4% in 2006 to 6.4% in 2019 (p < 0.001). For Germany, we identified 2,920 FT cases. The share of FT increased from 0.7% in 2006 to 2.0% in 2019 (p < 0.001). The number of RFAs in the USA steadily increased by 227% from a total of 93 in 2006 to 304 in 2019 while the number of cryotherapies in the USA steadily increased by 289% from a total of 127 in 2006 to 494 in 2019 (p < 0.001). The number of RFAs in Germany increased by 344% from a total of 59 in 2006 to 262 in 2019 (p < 0.001) while the number of cryotherapies steadily increased by 43% from a total of 54 in 2006 to 77 in 2019 (p < 0.001). In Germany, RFA is significantly more performed than cryotherapy while in the USA cryotherapy is more frequently applied. Conclusion: We observed a constant increase of FT in the USA and Germany for RCC in-patient treatment with a higher share in the USA. [ABSTRACT FROM AUTHOR]

Purpose: To systematically review studies focused on screening programs for renal cell carcinoma (RCC) and provide an exhaustive overview on their clinical impact, potential benefits, and harms. Methods: A systematic review of the recent English-language literature was conducted according to the European Association of Urology guidelines and the PRISMA statement recommendations (PROSPERO ID: CRD42021283136) using the MEDLINE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases. Risk-of-bias assessment was performed according to the QUality In Prognosis Studies (QUIPS) tool. Results: Overall, nine studies and one clinical trials were included. Eight studies reported results from RCC screening programs involving a total of 159 136 patients and four studies reported screening cost-analysis. The prevalence of RCC ranged between 0.02 and 0.22% and it was associated with the socio-demographic characteristics of the subjects; selection of the target population decreased, overall, the screening cost per diagnosis. Conclusions: Despite an increasing interest in RCC screening programs from patients and clinicians there is a relative lack of studies reporting the efficacy, cost-effectiveness, and the optimal modality for RCC screening. Targeting high-risk individuals and/or combining detection of RCC with other health checks represent pragmatic options to improve the cost-effectiveness and reduce the potential harms of RCC screening. [ABSTRACT FROM AUTHOR]

Renal cancer is one of the most common malignancies, and its incidence is increasing year by year, second only to prostate and bladder cancers. Therefore, early screening is of great significance to prevent and improve the prognosis of patients with renal cancer. Therefore, this study intends to observe the early diagnostic value of miR-15b-5p combined with Colour ultrasound imaging in renal cell carcinoma. In this study, the clinical samples of 76 patients with renal cell carcinoma diagnosed by pathology in our hospital from April 2020 to June 2022 were retrospectively collected as the research objects. Another 100 healthy people who underwent general physical examination in our hospital during the same period were selected to detect the expression level of miR-15b-5 in serum by RT-PCR together with the 76 experimental samples. Colour ultrasound imaging was used to detect the blood flow distribution around and inside the kidney of the patients with renal cancer, and the parameters were measured and compared with the gold standard for statistical analysis. The expression level of miR-15b-5 in renal cell carcinoma group was significantly higher than that in control group. Most of them showed renal hamartoma (40.79%). Benign renal tumors were mainly characterized by type I and II blood flow, while malignant renal tumors were characterized by type III and IV blood flow. Compared with the pathological gold standard, the diagnostic accuracy of ultrasound imaging was founded to be about 81.25%. Further ROC analysis showed that ultrasound imaging combined with miR-15b-5 detection could effectively improve the early screening value of renal cell carcinoma. We observed that miR-15b-5 has a specific expression level in the serum of patients with renal cell carcinoma, and its combination with ultrasound imaging can significantly improve the early detection of renal cell carcinoma. This approach is envisaged to be highly useful for, early diagnosis, intervention and management of patients with renal cell carcinoma. [ABSTRACT FROM AUTHOR]

To analyze the factors and costs associated with 30-day readmissions for patients undergoing radical nephrectomy. We used the 2014 Nationwide Readmission Database to identify adults who underwent radical nephrectomy for renal cancer, stratified by surgical approach. We determined patient factors associated with readmission rates, diagnoses, and costs using multivariate logistic regression. Among 19,523 individuals, the 30-day readmission rate was 7.7% (n = 1,506). On multivariate regression, odds of readmission were significantly increased with age ≥75 in those who underwent open nephrectomy (OR: 1.35; 95%CI: 1.03–1.78). Subjects with a Charlson comorbidity score ≥3 had significantly higher rates of readmission regardless of surgical approach (Open RN – OR: 1.85; 95%CI: 1.33–2.56; Lap RN – OR: 1.99; 95%CI 1.10–3.59; Robotic RN – OR: 2.18; 95%CI: 1.23–3.86). Common reasons for readmission were gastrointestinal, cardiovascular, urinary tract infections, and wound complications across all surgical approaches. The mean cost per readmission was as high as 126% ($20,357) of the mean index admission cost. One in 13 adults undergoing radical nephrectomy is readmitted within 30 days of discharge. Associated readmission cost is up to 1.26 times the cost of index admission. Our findings may inform efforts aiming to reduce hospital readmissions and curtail healthcare costs. [ABSTRACT FROM AUTHOR]

Background: Cryoablation is a promising minimally invasive, nephron-sparing treatment of small renal carcinoma (RCC) in co-morbid patients. Purpose: To assess the safety, efficacy, and cancer-specific outcomes of computed tomography (CT)-guided cryoablation of stage T1 (RCC). Material and Methods: A retrospective evaluation of 122 consecutive patients with 128 tumors treated with cryoablation during 2016–2017. All patients had biopsy-verified T1 RCC. Results: Median age was 69 years (IQR=59–76); 69% were male. Median tumor size was 26 mm (± 20–33); 9% were stage T1b. Mean follow-up time was 36.3±12.0 months. In total, 14 (11%) procedures led to complications, of which 4 (3%) were intraoperative, 5 (4%) appeared ≤30 days and 5 (4%) >30 days after treatment. Major complications arose after 4 (3%) procedures. Statistically significant associations were found between major complications and stage T1b (P = 0.039), RENAL score (P = 0.010), and number of needles used in cryoablation (P = 0.004). Residual tumor was detected after 4 (3%) procedures and 5 (4%) tumors had local tumor progression. Of 122 patients, 3 (2%) advanced to metastatic disease. Significant statistical associations were found between local tumor progression and T1b stage tumors and number of needles used in cryoablation (P = 0.05 and P = 0.004, respectively). For patients with T1a tumors, the one- and three-year disease-free survival was 98% and 95%, respectively, and for T1b 100% after one year and 75% after three years. Conclusions: This study showed that cryoablation is a safe and effective treatment of stage T1 RCC and suggests that in selecting candidates for cryoablation of RCC, the tumor characteristics are more critical than patients' baseline health status. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to compare oncological outcomes in the two rare subtypes, unclassified renal cell cancer (un-RCC) and translocation RCC (tRCC), vs clear cell RCC (ccRCC). Materials and Methods: Between 2004 and 2019, from Turkish Urooncology Society Database, we identified 2324 patients for histological subtypes including 80 unRCC (3.4%), 19 tRCC (0.8%) and 2225 ccRCC (95.8%). Results: The overall (15.8%) and cancer-specific mortalities (11.1%) were found to be higher in tRCC group and the recurrence free mortality (13.8%) was found to be higher in unRCC group. Larger pathological tumor size (p = 0.012) and advanced pathological T stage (p = 0.042) were independent predictive factors on overall mortality in patients with unRCC tumors. Conclusion: The oncological outcomes of the unRCC and tRCC are worse than ccRCC and pathological tumor size and pathological stage are predictive factors for mortality in the unRCC. [ABSTRACT FROM AUTHOR]

It is estimated that 5–8% of renal tumours are hereditary in nature, with many inherited as autosomal‐dominant. These tumours carry a unique spectrum of pathological and molecular alterations, the knowledge of which has expanded in recent years. Due to this knowledge, many advances in the treatment of these tumours have been achieved. In this review, we summarize the current understanding of the genetic renal neoplasia syndromes, clinical and pathological presentations, molecular pathogenesis, advances in therapeutic implications and targeted therapy. [ABSTRACT FROM AUTHOR]

Normal processes of embryonic development and abnormal transformation to cancer have many parallels, and in fact many aberrant cancer cell capabilities are embryonic traits restored in a distorted, unorganized way. Some of these capabilities are cell autonomous, such as proliferation and resisting apoptosis, while others involve a complex interplay with other cells that drives significant changes in neighboring cells. The correlation between embryonic development and cancer is driven by shared proteins. Some embryonic proteins disappear after embryogenesis in adult differentiated cells and are restored in cancer, while others are retained in adult cells, acquiring new functions upon transformation to cancer. Many embryonic factors embraced by cancer cells are transcription factors; some are master regulators that play a major role in determining cell fate. The paired box (PAX) domain family of developmental transcription factors includes nine members involved in differentiation of various organs. All paired box domain proteins are involved in different cancer types carrying pro-tumorigenic or anti-tumorigenic roles. This review focuses on PAX8, a master regulator of transcription in embryonic development of the thyroid, kidney, and male and female genital tracts. We detail the role of PAX8 in each of these organ systems, describe its role during development and in the adult if known, and highlight its pro-tumorigenic role in cancers that emerge from PAX8 expressing organs. [ABSTRACT FROM AUTHOR]

The National Research Council's vision of using adverse outcome pathways (AOPs) as a framework to assist with toxicity assessment for regulatory requirements of chemical assessment has continued to gain traction since its release in 2007. The need to expand the AOP knowledge base has gained urgency, with the U.S. Environmental Protection Agency's directive to eliminate reliance on animal toxicity testing by 2035. To meet these needs, our goal was to elucidate the AOP for male-rat-specific kidney cancer. Male-rat-specific kidney tumors occur through the ability of structurally diverse substances to induce α2u-globulin nephropathy (α2u-N), a well-studied mode of action (MoA) not relevant in humans that results in kidney tumor formation in male rats. An accepted AOP may help facilitate the differentiation from other kidney tumors MoAs. Following identification and review of relevant in vitro and in vivo literature, both the MIE and subsequent KEs were identified. Based on the weight of evidence from the various resources, the confidence in this AOP is high. Uses of this AOP include hazard identification, development of in vitro assays to determine if the MoA is through α2u-N and not relevant to humans resulting in decreased use of animals, and regulatory applications. [ABSTRACT FROM AUTHOR]

Background: Recent advances in genomic and genetic technologies have facilitated better health outcomes for urologic cancer patients. Genomic and genetic heterogeneity may contribute to differences in tumor biology and urologic cancer burden across various populations.Objective: To examine how emerging genomic and genetic biomarkers, self-reported race, and ancestry-informative markers are associated with kidney, prostate, and bladder cancer outcomes.Results: Genomic and genetic alterations found in African American kidney cancer patients included distinct somatic mutations, somatic copy number alterations, chromosomal instability, germ-line risk alleles, and germ-line genetic variants. These changes correlated with improved risk prediction, prognosis, and survival; and a predicted decrease in response to targeted therapies. SNP risk alleles and ancestry-informative markers were associated with improved risk prediction in prostate cancer patients of both African and European descent. AKT activation suggest differential response to AKT-targeted therapies in African American, Asian American, and Tunisian bladder cancer patients. Both self-reported race and genetic ancestry predicted urologic cancer risk prediction.Conclusion: Precision medicine approaches that integrate population-specific genomic and genetic information with other known urologic cancer-specific characteristics can improve outcomes and be leveraged to reduce cancer health disparities. Further investigations are necessary to identify novel genomic biomarkers with clinical utility. [ABSTRACT FROM AUTHOR]

Mallinckrodt Chemical Works (MCW) was the earliest uranium processing facility in the United States, and in 1942 produced the uranium oxide used for the first sustained and controlled nuclear fission chain-reaction at the University of Chicago. A second follow-up through 2012 was conducted of 2514 White male workers employed 1942–1966 at the MCW for dose-response analyses for selected causes of death. Organ/tissue-specific dose reconstruction included both external (12,686 MCW film badge records, 210 other facility film badge records, and 31,297 occupational chest x-rays) and internal sources of uranium and radium (39,451 urine bioassays, 2341 breath radon measurements, and 6846 ambient radon measurements). Dust measurements from pitchblende facilitated quantitative risk estimates for non-radiogenic effects on the lung and kidney. Vital status was determined from multiple sources including the National Death Index and the Social Security Administration. Cox regression models were used for dose response analyses. Vital status was determined for 99% of the workers, of whom 75% had died. The mean lung dose from all sources of external and internal radiation combined was 69.9 mGy (maximum 885 mGy; percent workers >100 mGy, 10%) and there was no evidence for a dose response for lung cancer (Hazard Ratio (HR) of 0.95 (95% CI = 0.81–1.12) at 100 mGy). A significant association with radiation was found for kidney cancer (HR of 1.73 (95% CI = 1.04–2.79) at 100 mGy) and suggested for nonmalignant kidney diseases (HR of 1.30 (95% CI = 0.96–1.76) at 100 mGy). A non-radiation etiology could not be discounted, however, because of the possible renal toxicities of uranium, a heavy metal, and silica, a component of pitchblende dust. Non-significant HRs at 100 mGy for other sites of a priori interest were 0.36 (0.06–2.03) for leukemia other than CLL, 0.68 (0.17–2.77) for liver cancer, and 1.23 (0.79–1.90) for non-Hodgkin lymphoma. The HR at 100 mGy was 1.09 (0.99–1.20) for ischemic heart disease. An association was seen between dust and combined malignant and non-malignant lung disease, HR at 10 mgm−3year−1 of 1.01 (1.00–1.02). A positive radiation dose response was observed for malignant and non-malignant kidney disease, and a negative dose response for malignant and non-malignant lung disease. Cumulative measures of dust were significantly associated with malignant and non-malignant lung disease and suggested for malignant and non-malignant kidney disease. Small numbers preclude definitive interpretations which will await the combination with similar studies of early uranium processing workers. [ABSTRACT FROM AUTHOR]