Staging Of Renal Cell Carcinoma Research Articles

S3528 A Rare Presentation of Small Bowel Metastasis From Renal Cell Carcinoma: A Case Report and Review

Introduction: At the time of diagnosis, around 25–30% of patients with renal cell carcinoma (RCC) had metastatic disease. The most common locations for metastasis of renal cancer in order of frequency include lung, bone, liver, lymph nodes and brain. RCC metastases to the small intestine are extremely rare, with limited reports in the literature (Table). Case Description/Methods: A 20-year-old male presented with a 3-week history of dull epigastric pain, nausea, and vomiting. Past medical history was significant for iron deficiency anemia, and metastatic RCC was diagnosed in 2021 status post right open radical nephrectomy. The biopsy showed Xp11.2 translocation associated renal cell carcinoma WHO grade 4. The patient had lost follow-up previously. His laboratory workup this admission showed persistent iron deficiency anemia with mild leukocytosis and thrombocytosis and elevated liver enzymes. CT chest/abdomen/pelvis showed concern for intussusception in the distal jejunum causing an obstruction. Surgery team was consulted who took patient for diagnostic laparoscopy. Intraoperatively intussusception was partially reduced laparoscopically but could not be completely reduced since there was a big mass acting as a lead point. The decision was then made to convert to a mini-laparotomy. Small bowel resection with primary anastomosis was performed. Pathology from the specimen confirmed metastatic RCC. Oncology was consulted who plan to start pembrolizumab plus axitinib for systemic therapy. (Figure) Discussion: RCC intraluminal metastases in the small intestine are unusual reported as 2-4% incidence. Bowel metastases from RCC can manifest in several different forms including intussusception, bowel perforation, gastrointestinal bleeding and symptoms of intestinal obstruction due to the presence of a mass within the intestinal wall. This case presented a young male with metastatic RCC to small bowel which has not been reported so far. Clinicians should be aware that, in patients presenting with anemia, clinical symptoms of bowel obstruction and a history of RCC, intestinal tumor involvement should be considered. Metastasectomy may extend patient survival and surgical resection of the involved intestinal segment has been recommended as the treatment of choice.Figure 1.: A: Axial-enhanced CT scan of the abdomen showing Intussusception in the distal jejunum causing the obstruction. B: Intraoperative pictures of intussusception. C: A resected segment of the small intestine with a mass found at the lead point. Table 1. - Published reports of intussusception from renal cell carcinoma No. Author, Year No. of pts Stage of RCC (TNM) Gender Age (years) Histological subtype Outcome 1 Vani et al., 2017 2 NA M, F 65, 68 NA Pt. 1: Death 3 months after surgery. Pt. 2: Death 6 months after surgery. 2 Mishra et al., 2015 1 NA M 57 Clear cell NA 3 Wan Kyu Eo et al., 2008 1 pT1aN0M1 M 47 Clear cell NA 4 Venugopal et al.,2017 1 NA NA NA NA NA 5 Ekbote et al., 2015 1 NA M 52 Clear cell Alive after ten months 6 Bellio et al., 2016 1 pT1bN0 M 75 Clear cell NA 7 Deguchi et al., 2000 1 NA M 58 NA NA 8 Ogiso et al., 2005 1 pT1aN0M1 F 57 NA NA 9 Hegde R J et al., 2014 1 NA M 52 Clear cell NA 10 Budmiger et al., 2015 1 NA M 61 NA NA 11 Kerkeni B et al., 2013 1 pT2bNxM1 F 32 Clear cell Not interpretable 12 Khan AB et al., 1991 1 NA NA NA NA NA 13 Trojaneillo et al., 2017 1 NA M 75 NA Pt. died 9 months after surgery. 14 Tutar et al., 2008 1 NA M 59 Clear cell NA 15 Aissa et al., 2012 1 NA M 64 Tubulo- Papillary NA 16 Longo et al., 2013 1 NA F 52 Clear cell NA 17 Budmiger et al., 2015 1 NA M 61 Clear cell NA 18 Sasaki et al., 2006 1 NA M 64 Clear cell Pt died after few months after jejunal resection 19 Roviello et al., 2006 1 NA M 48 Clear cell Alive at follow up. 20 Rampersad et al., 2006 1 NA F 69 NA NA 21 Collet et al., 2001 1 NA F 77 NA NA Abbreviations: NA, not applicable; F, Female; M, Male.

Cost Effectiveness Analysis of Radiofrequency Ablation (RFA) Versus Stereotactic Body Radiotherapy (SBRT) for Early Stage Renal Cell Carcinoma (RCC).

To conduct a cost-effectiveness analysis of stereotactic body radiotherapy (SBRT) versus radiofrequency ablation (RFA) in the non-surgical management of early stage renal cell carcinoma (RCC) according to Consolidated Health Economic Evaluation Reporting Standards (CHEERS) criteria in the Canadian healthcare system. A Markov state transition model was constructed for initial local treatment with RFA or SBRT for early stage, kidney confined, medically inoperable RCC in a hypothetical cohort. Incremental cost effectiveness ratios (ICER) were then calculated to compare the two treatments. The analysis was conducted over 5-year time horizon from the perspective of a publicly funded health system in Canada. Secondary analyses were conducted to assess the effect of small versus large size (< 4 cm vs. > 4 cm) RCC on ICERs. Multiple one-way deterministic sensitivity analysis were conducted. Discounting of 1.5% per year was applied. Over 5 years, SBRT economically dominated RFA with a gain of 4.103 quality-adjusted life years (QALYs) and a cost of $16,097, compared with 3.607 QALYs at a cost of $18,324 for RFA. The ICER was $4490 CAD less per QALY for SBRT in the base case analysis (BCE). In patients with small tumors (T1a), SBRT compared with RFA was more effective and marginally more costly, resulting in an ICER of $2207 CAD per QALY gained, while for larger tumors (T1b), SBRT was less costly and more effective than RFA, resulting in an ICER of -$22904. Sensitivity analysis demonstrated significant variability in the cost-effectiveness of SBRT versus RFA when parameters were varied, with rates of distant metastasis following RFA or SBRT having the greatest implications on ICERs. Overall, SBRT used as a primary treatment for RCC shows promising effectiveness at an overall reduction in cost compared with RFA in the Canadian healthcare system. The use of SBRT appears to be cost-effective for larger tumors as well as smaller tumors. The validity of these conclusions are highly sensitive to the accuracy of local and distant progression rates reported in previous studies, and may be adjusted as the available data on SBRT and RFA continues to evolve and mature.

SC193 - The effect of age on cancer-specific mortality in T1a stage renal cell carcinoma patients: a population-based study across all treatment’s modalities

SC193 - The effect of age on cancer-specific mortality in T1a stage renal cell carcinoma patients: a population-based study across all treatment’s modalities

Preoperative neutrophil-lymphocyte ratio/platelet-lymphocyte ratio: A potential and economical marker for renal cell carcinoma.

Emerging evidences have elucidated the crucial role of inflammation in carcinogenesis and tumor progression. In the recent years, many inflammatory biomarkers showed promising prognostic factors in renal cell carcinoma (RCC). We intended to evaluate the significance of one such inflammatory factor which is potential, noninvasive, simple, as well as economical. The preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in RCC patients have shown favorable results. The objective was to assess the prognostic role of NLR/PLR in the advanced stage and high-grade RCC. This is a retrospective study. Ethical clearance was obtained from the institute ethics committee. One hundred and fifty histopathologically proven RCC cases during the period of January 2010-September 2018 were chosen from the pathology department and corresponding blood reports were obtained from the medical records department. We divided the cases based on their staging and grading. NLR/PLR values were calculated using formulas. Statistical analysis was done using R software. Data were expressed as mean ± standard deviation, median, and percentage. Independent t-test, Mann-Whitney test, and Chi-square test were used. P < 0.05 was considered statistically significant. The receiver operating characteristic curve (ROC) was plotted to assess the sensitivity of NLR/PLR. The elevated NLR/PLR values showed a significant relation with high-grade and advanced stage RCC. The ROC curve proved the accuracy of NLR/PLR in the advanced stage and high-grade RCC. A multicentric, prospective study can be planned in the future. Follow-up studies are needed to assess their prognostic role. NLR/PLR values can become part of routine investigations for all RCC patients. The values may help to estimate pathological outcomes, chance of recovery, recurrence, and survival rates.

Long-term outcomes of cryoablation for biopsy-proven T1 stage renal cell carcinoma

BackgroundTo summarize our clinical experience of cryoablation in renal cell carcinoma (RCC) of Chinese population and to evaluate the long-term outcomes of laparoendoscopic single-site (LESS) cryoablation (LCA) as well as percutaneous CT-guided cryoablation (PCA) for biopsy-proven T1a and T1b RCC.MethodsThis was a multi-center, retrospective study investigating T1 stage RCC patients from 2011 to 2021. The patients were treated by LCA or PCA according to individual situation. Overall survival (OS), cancer-related survival (CSS), and progression-free survival (PFS) were evaluated for oncological outcomes, and kidney function, complications, and hospital stay were used to estimate technical outcomes.ResultsA total of 163 consecutive patients were included. Among them, 59 cases were treated by LCA and PCA was performed in 104 cases. All operations were processed successfully. Mean diameter of the mass was (2.9±1.4) cm; median blood volume was 45ml (10~200 ml). The mean operation time was 84.0 ± 24.5 min. The median postoperative hospital stay was 3 days (1~6 days). Compared with LCA, procedure time of PCA was shortened, the volume of bleeding was reduced, and the hospital stay was decreased. The overall adverse events rate was 9.8% (16/163). The mean preoperative and postoperative eGFR of LCA were 77.6±15.3 ml/min and 75.6±17.4 ml/min, respectively. Analogously, the values of PCA were 78.7±12.9 ml/min and 76.7±14.3 ml/min. Mean follow-up time was 64.2 ± 30.2 months (range, 7–127 months). Local recurrence was observed in 13 patients (8.0%), 4 (6.8%) cases of LCA and 9 (8.7%) cases of PCA. PFS at 5 and 10 years were 95.5% and 69.2% for LCA and 96.7% and 62.8% for PCA. In total, 26 patients (16.0%) (11 patients from LCA and 15 from PCA) died throughout the follow-up period. OS at 5 and 10 years were 93.8% and 31.4% for LCA, and 97.4% and 52.7% for PCA. Six patients (3.7%) (3 cases from LCA and 3 from PCA) died of metastatic RCC. CCS for LCA were 98.0% and 82.8% at 5 and 10 years, while the data were 100% and 86.4% for PCA.ConclusionLCA and PCA for T1 stage RCC provides satisfactory long-term oncological and renal function preservation outcomes, with acceptable complication rates.

Renal cell carcinoma with tumour thrombus extending in duplicated inferior vena cava: A rarity with management conundrum

DIVC may play a role as a confounding factor in imaging diagnostic tests and also may represent a hazard for inadvertent injury and bleeding during surgery. Careful interpretation Radiological investigations help to define such anomalies and avoid significant morbidity during surgical exploration. We present a case of renal cell carcinoma involving Right kidney with tumor thrombus extending into both venae cava. Triphasic Contrast-Enhanced Computerized Tomography (CECT) scan of abdomen with three-dimensional reconstruction showed duplicated left sided IVC, Heterogeneously enhancing intraluminal soft tissue density filling defect was seen along the entire length of right renal vein, also crossing the midline to the left sided duplicated IVC -s/o tumour thrombus. Patient underwent right radical nephrectomy with tumour thrombectomy. Cavotomy was done at the junction of right renal vein and right IVC. Entire thrombus was delivered intact. Histopathological examination showed papillary renal cell carcinoma (type II) stage pT3bN1Mx. IVC thrombus showed clusters of malignant cells of same morphology as tumor entangled in thrombus. The patient is doing well at 3 months of follow-up.

Pan-keratin Immunostaining in Human Tumors: A Tissue Microarray Study of 15,940 Tumors.

To evaluate the efficiency of pan-keratin immunostaining, tissue microarrays of 13,501 tumor samples from 121 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. In normal tissues, strong pan-keratin immunostaining was seen in epithelial cells. Staining intensity was lower in hepatocytes, islets of Langerhans, and pneumocytes but markedly reduced in the adrenal cortex. Pan-keratin was positive in ≥98% of samples in 62 (83%) of 75 epithelial tumor entities, including almost all adenocarcinomas, squamous cell and urothelial carcinomas. Only 17 of 121 tumor entities (13%) had a pan-keratin positivity rate between 25% and 98%, including tumors with mixed differentiation, endocrine/neuroendocrine tumors, renal cell carcinomas, adrenocortical tumors, and particularly poorly differentiated carcinoma subtypes. The 15 entities with pan-keratin positivity in 0.9%-25% were mostly of mesenchymal origin. Reduced/absent pan-keratin immunostaining was associated with high UICC stage (p = 0.0001), high Thoenes grade (p = 0.0183), high Fuhrman grade (p = 0.0049), advanced tumor stage (p < 0.0001) and lymph node metastasis (p = 0.0114) in clear cell renal cell carcinoma, advanced pT stage (p = 0.0007) in papillary renal cell carcinoma, and with advanced stage (p = 0.0023), high grade (p = 0.0005) as well as loss of ER and PR expression (each p < 0.0001) in invasive breast carcinoma of no special type (NST). In summary, pan-keratin can consistently be detected in the vast majority of epithelial tumors, although pan-keratin can be negative a fraction of renal cell, adrenocortical and neuroendocrine neoplasms. The data also link reduced pan-keratin immunostaining to unfavorable tumor phenotype in in epithelial neoplasms.

Utilizing Computed Tomography to Analyze the Morphomic Change between Patients with Localized and Metastatic Renal Cell Carcinoma: Body Composition Varies According to Cancer Stage.

Background: This study aimed to elucidate the change of body composition in different clinical stages of renal cell carcinoma (RCC) by analyzing computed tomography (CT) images. Methods: We enrolled patients diagnosed with RCC in a tertiary medical center who did not mention body weight loss or symptoms of cachexia. We grouped patients into those with localized RCC and those with metastatic RCC. Analyses of the volume of skeletal muscles tissue (SMT), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) calculated based on CT images were performed and included subgroup analyses by sex and age. The correlation between tumor size and body composition in localized RCC was also examined. Results: A total of 188 patients were enrolled in this study. There was significantly lower VAT (p = 0.015) in the metastatic group than in the localized group. SAT, body weight, and body mass index (BMI) were not significantly different between these two groups. In the subgroup analysis, a significant difference in SMT and VAT was noted in the male and younger subgroups but not in the female and older subgroups. Regarding primary tumor size in localized RCC, VAT was significantly higher in patients with larger tumors (p = 0.003). Conclusions: In localized RCC, VAT volume was significantly larger in those with large primary tumor size. However, the VAT was significantly lower in those with metastatic status comparing to those with localized disease. The clinical course of cancers closely correlates with body composition.

Cancer-specific Mortality in T1a Renal Cell Carcinoma Treated with Local Tumor Destruction Versus Partial Nephrectomy

BackgroundLarge-scale analyses addressing cancer-specific mortality (CSM) in T1a renal cell carcinoma (RCC) patients treated with local tumor destruction (LTD), relative to partial nephrectomy (PN), are scarce. ObjectiveTo compare CSM after LTD versus PN. Design, setting, and participantsWithin the Surveillance, Epidemiology, and End Results (SEER) database (2004–2018), we identified patients with clinical T1a stage RCC treated with LTD or PN. Outcome measurements and statistical analysesAfter 1:1 ratio propensity score matching (PSM) between patients treated with LTD versus PN, competing risks regression (CRR) models addressed CSM, after adjustment for other-cause mortality (OCM) and other covariates (age, tumor size, tumor grade, and histological subtype). Results and limitationsRelative to the 35 984 PN patients, 5936 LTD patients were older and more frequently harbored unknown RCC histological subtype or unknown grade. After 1:1 PSM that resulted in 5352 LTD versus 5352 PN patients, the 10-yr CSM rate was 8.7% versus 5.5%. In multivariable CRR models, LTD was associated with higher CSM, relative to PN (hazard ratio [HR]: 1.58, p < 0.001). Subgroup analyses revealed invariably higher CSM after LTD versus PN in patients with tumor size ≤3 cm (10-yr CSM 7.2% vs 5.3%, multivariable HR: 1.47, p < 0.001) and in patients with tumor size 3.1–4 cm (10-yr CSM 11.4% vs 6.1%, multivariable HR: 1.72, p < 0.001). Lack of information regarding earlier cancer controls, retreatment, tumor location within the kidney, and type of surgery represented limitations. ConclusionsIn T1a RCC patients, LTD is invariably associated with higher CSM relative to PN, even after adjustment for OCM and all available patient and tumor characteristics, and regardless of tumor size considerations. However, the magnitude of CSM disadvantage was more pronounced in LTD patients with tumor size 3.1–4 cm than in those with tumor size ≤3 cm. Patient summaryIn patients with small renal masses, we observed higher cancer-specific death rates for local tumor destruction (LTD) than for partial nephrectomy. The LTD disadvantage was more pronounced for patients with tumor size 3.1–4 cm, but was also present in those with tumor size ≤3 cm.

Pan-Cancer Analysis Predicts the Immunological and Prognostic Role of ZC3H12C in KIRC.

ZC3H12C is an important member of the CCCH-zinc finger protein family and is mainly involved in host immune and inflammatory diseases. However, its abnormal expression and prognostic value in cancer have not yet been established. Through comparative analysis of the Cancer Genome Atlas (TCGA) database, we found that ZC3H12C is the most relevant to the prognosis, grade, and stage of renal clear cell carcinoma (ccRCC) across 33 cancers. With the help of patient transcription and clinical data from the TCGA and GEO (GSE53757, GSE36895) databases, we determined that in the immune environment of patients with ccRCC, ZC3H12C was clearly negatively correlated with Tregs and was significantly positively correlated with monocytes. In addition, protein phosphorylation and DNA methylation analysis also showed that ZC3H12C negatively regulates the role of cancer in ccRCC. Our research may provide new insights into ccRCC immunotherapy and bring forth novel biomarkers and therapeutic targets.

Variation in recurrence rate and overall survival (OS) outcomes by disease stage and incremental impact of time to recurrence on OS in localized renal cell carcinoma (RCC).

4543 Background: Prior research shows that post-nephrectomy recurrence is correlated with significantly increased mortality in patients (pts) with intermediate-high (int-high) risk and high risk RCC. However, no study has quantified the incremental OS associated with increased time to recurrence (ToR). Additionally, limited evidence is presented on the variation of recurrence rate and OS by stage of RCC. Methods: The SEER-Medicare database (2007–2016) was used in this retrospective observational study. Post-nephrectomy pts with newly diagnosed, int-high risk (pT2 N0 high grade, pT3 N0 any grade) or high-risk (pT4 N0 any grade, pT any N1 any grade) RCC were identified and stratified based on tumor stage and grade. Grade was defined based on Furhman grading system and was reported in SEER Registry. Post-nephrectomy recurrence free rates and OS by disease stage were described using Kaplan-Meier analyses. OS from nephrectomy in pts with recurrence vs pts without recurrence was compared by disease stage. Multivariable regression analysis was used to quantify the incremental OS associated with increased ToR post-nephrectomy in all pts with recurrence. Results: 643 pts met the inclusion criteria (269 with vs 374 without recurrence; median follow-up: 23 months). The mean age was 75.5 years (yrs), 61% male, and 86% white. Results presented in the table showed wide variance in 5-yr recurrence-free rate in int-high risk group (28%-63%) and indicated substantial risk of disease recurrence in all subgroups of int-high risk pts. Among those with T3 Grade 1-2, T3 Grade 3, and T3 Grade 4 disease, pts with recurrence had significantly higher risk of death than those without (all ps&lt;0.05;). Results for pts with T2 and T4 disease were not presented due to small sample size. Multivariable regression analysis indicated that 1 additional yr of ToR was associated with 0.73 additional yrs (8.8 additional months) of OS post nephrectomy (95% CI: 0.40, 1.05 yrs; p&lt;0.001). Conclusions: The non-trivial recurrence rates observed in pts with T3 Grade 1-2 and T3 Grade 3 RCC highlighted the substantial risk of recurrence and unmet needs in the int-high risk RCC patients. This study also confirms the incremental nature of the association of ToR and OS in patients with int-high and high risk localized RCC. These findings highlight the need for effective early intervention with adjuvant treatments in int-high and high risk post-nephrectomy RCC pts. [Table: see text]

Renal cell carcinoma in renal transplant recipients: Is there a role for screening?

10528 Background: Renal transplant (RT) recipients are at an increased risk of developing renal cell carcinoma (RCC), mainly due to iatrogenic immunosuppression and changes in immune surveillance. Most RCCs in RT recipients arises from the native kidney, but rarely may arise from the allograft. RCC post-RT can adversely affect allograft function and long-term survival. Screening for RCC in RT recipients is controversial and is not routinely done. Methods: We performed a retrospective chart review of RT recipients who underwent transplantation between January 1, 1999, and December 31, 2019. The following data were collected: Baseline demographic variables, cause of end-stage renal disease (ESRD), duration of dialysis prior to RT, type of RT (cadaveric vs. living donor), immunosuppressive regimen, site of RCC (native kidney vs transplanted kidney), time from RT to diagnosis of RCC, stage and Fuhrman grade, tumor histology, RCC treatment, and RCC-related mortality. RCC stage at diagnosis and survival were compared between patients who were screened versus those who were not. Results: Among 1998 RT recipients who underwent transplantation at Memorial Hermann Hospital (MHH) Texas Medical Center (TMC); 16 patients (0.8%) developed RCC. An additional 4 patients with RCC who underwent RT elsewhere but received follow up at MHH TMC were also included. Therefore, a total of 20 patients with post-RT RCC were identified, of whom 75% were men. Subject races included White (20%), Black (50%), Hispanic (20%), and Asian (10%). The median age was 56 years. Median duration of dialysis prior to RT was 36 months (range, 1–120). Median time to RCC diagnosis post-RT was 96 months (range, 16–312). Histologies included clear cell (75%), papillary (20%), and chromophobe (5%) RCC. RCC developed in the native kidney in 60% and in the allograft in 40% of the patients. Post-RT RCC patients were divided into those who underwent regular screening (n = 12) and no screening (n = 8). The regular screening group (n = 12) underwent ultrasound or computerized tomography annually or every 2 years. All of these patients had early-stage disease at presentation: stage I (n = 11) or II (n = 1). All patients who had RCC detected by screening were cured by nephrectomy (n = 10) or cryotherapy (n = 2). In patients who had no screening post RT, 37.5% had stage I, 25% had stage III, and 37.5% had stage IV RCC. Two patients with stage IV RCC died from metastatic disease. The RCC-related mortality was 0% in patients who were screened, compared to 25% in patients who had no screening. Conclusions: All RT recipients who had RCC diagnosed based on screening had an early diagnosis and no RCC-related mortality. Screening for RCC in RT recipients is an effective tool for early diagnosis and to reduce RCC-related mortality. Further research into the cost-effectiveness of screening is imperative.

Characterization of tumor thrombus in renal cell carcinoma with prostate specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT).

Venous tumor thrombus (TT) occurs as part of the natural history of renal cell carcinoma (RCC) local progression in a small minority of cases. MRI is currently the most accurate imaging modality for determining TT extent. PSMA PET/CT may improve RCC staging and IVC TT characterization. The objective of this study was to investigate the role of PSMA PET/CT in defining superior extent of TT in RCC and TT IVC tributary vessel spread, with comparative accuracy vs. MRI, to assess suitability for resection and inform preoperative surgical planning. Patients who underwent PSMA PET/CT for assessment of renal malignancy with TT from 2015 to 2020 at 3 tertiary hospitals in Brisbane, Australia, were retrospectively identified. TT extent was classified using Mayo Clinic levels and compared according to imaging modality. Fourteen patients were included, all of which were clear cell RCC. Ten patients also underwent MRI, 6 of which were concordant in extent according to MRI and PSMA PET. Discordant extent occurred in 4 patients, of which 2 patients had non-PSMA avid thrombus (Mayo level 0 and level 3 on MRI). Further discordance was seen in a patient with adrenal vein and lumbar vein TT only seen on MRI and PSMA PET/CT, respectively. Finally, discordant extent was seen in another patient with Mayo level 4 TT without lumbar vein involvement on MRI vs. level 3 on PSMA PET/CT with lumbar vein involvement. PSMA PET/CT can provide additional information about TT extent in RCC which may not be seen on MRI. Additional information from PSMA PET/CT in this setting may assist surgical planning, in addition to detection of metastatic disease.

Prognostic value of matrix metalloproteinases and transforming growth factor – β in kidney cancer

Purpose of the study. The study's objective is to investigate the expression level of tissue and serum markers of oncogenesis and nephrofibrosis transforming growth factor beta (TGF‑β) and matrix metalloproteinase‑9 (MMP‑9) in patients operated for various stages of renal cell carcinoma.Materials and methods. The study prospectively included medical data of 60 patients with kidney cancer with T1–3N0M0 who received surgical treatment in the Clinic of Urologynamed after S. R. Mirotvortsev of the State Medical University from 2016 to 2019. The patients were divided into 3 groups: Group 1 included 20 patients who underwent laparoscopic kidney resection; Group 2–20 patients who underwent laparoscopic nephrectomy; Group 3–20 patients who underwent open nephrectomy. The control group consisted of 15 healthy volunteers without chronic kidney diseases. All patients signed an informed consent to participate in the study. All patients at the preoperative stage, in the early (7–10 days) and remote postoperative periods (after 1 and 2 years) were tested by solid‑phase ELISA on a StatFax 4200 analyzer using eBiosence and Cloud‑Clone Corp reagent kits for the serum concentration of oncogenesis markers MMP‑9 and TGF‑β1.Results. Initial increase of MMP‑9 concentration was detected in all groups of PCC patients compared to the control group (p ≤ 0.05). According to the results of ROC analysis, this indicator has high specificity and sensitivity for prognosis of preoperative stage of renal cell carcinoma. The sensitivity and specificity of MMP‑9 were 87.5 % and 62 %, respectively, and the diagnostically significant level of MMP‑9 was 958 ng/ml. A comprehensive analysis of the content of MMP‑9 and TGF‑β1 oncogenesis markers in serum and tumor cells revealed the correlation of these indicators in various biological objects.Conclusion. Markers of oncogenesis and nephrofibrosis TGF‑β1 and MMP‑9 provide an opportunity for non‑invasive monitoring of tumor progression and probability of metastasis in the clinical setting. Serum MMP‑9 are a reliable predictor of tumor growth. Serum TGF‑β1 concentration isn't a sufficiently reliable marker of tumor progression.

MP24-11 IS PATHOLOGICAL UPSTAGING TO T3 RENAL CELL CARCINOMA ASSOCIATED WITH A SIMILAR PROGNOSIS TO NON-UPSTAGED PATHOLOGIC T3 DISEASE? A MULTICENTER ANALYSIS

You have accessJournal of UrologyCME1 May 2022MP24-11 IS PATHOLOGICAL UPSTAGING TO T3 RENAL CELL CARCINOMA ASSOCIATED WITH A SIMILAR PROGNOSIS TO NON-UPSTAGED PATHOLOGIC T3 DISEASE? A MULTICENTER ANALYSIS Ryan Nasseri, Kevin Hakimi, Ava Saidian, Riccardo Autorino, Brian Lane, Yasuha Fujii, Michele Marchioni, Hajime Tanaka, Dattatraya Patil, Francesco Porpiglia, Sabrina Noyes, Chandru Sundaram, James Porter, Andrea Minervini, Umberto Capitianio, Francesco Montorsi, Viraj Master, and Ithaar Derweesh Ryan NasseriRyan Nasseri More articles by this author , Kevin HakimiKevin Hakimi More articles by this author , Ava SaidianAva Saidian More articles by this author , Riccardo AutorinoRiccardo Autorino More articles by this author , Brian LaneBrian Lane More articles by this author , Yasuha FujiiYasuha Fujii More articles by this author , Michele MarchioniMichele Marchioni More articles by this author , Hajime TanakaHajime Tanaka More articles by this author , Dattatraya PatilDattatraya Patil More articles by this author , Francesco PorpigliaFrancesco Porpiglia More articles by this author , Sabrina NoyesSabrina Noyes More articles by this author , Chandru SundaramChandru Sundaram More articles by this author , James PorterJames Porter More articles by this author , Andrea MinerviniAndrea Minervini More articles by this author , Umberto CapitianioUmberto Capitianio More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Viraj MasterViraj Master More articles by this author , and Ithaar DerweeshIthaar Derweesh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002563.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Pathological upstaging to T3a disease may occur following radical (RN) or partial nephrectomy (PN) for patients with T1/T2 renal cell carcinoma (RCC). Follow up and perceived prognosis for these patients is similar to those who initially presented with clinical T3 RCC. We sought to compare survival outcomes in patients who underwent surgical therapy for upstaged versus non-upstaged pT3 RCC. METHODS: We conducted a retrospective analysis of a multi-institutional dataset of patients who underwent radical (RN) or partial nephrectomy (PN) with final pathologic stage of pT3. Patients were classified as being upstaged (US) from cT1 or cT2 or non-upstaged (NUS) with cT3 disease. Primary outcome was cancer specific survival (CSS)/cancer specific mortality (CSM), with secondary outcomes being Overall Survival (OS)/all-cause mortality (ACM) and Progression/progression-free survival (PFS). Multivariable Cox regression analysis (MVA) was conducted for predictors of mortality outcomes and Kaplan Meier Analyses (KMA) were conducted for survival outcomes comparing US and NUS groups. RESULTS: 1232 patients were analyzed (853 US/379 NUS; median follow up 46.2 months). MVA for CSM found that clear cell RCC (HR 2.1, p <0.001), positive surgical margin (HR 1.7, p=0.047), and NUS (HR 1.5, p=0.003) were independently associated with worsened CSM. MVA for ACM revealed age (HR 1.01, p=0.002), RN (HR 2.5, p <0.001), preoperative GFR <60 (HR 1.4, p=0.007), clear-cell RCC (HR 1.4, p=0.007), positive surgical margin (HR 2.2, p <0.001), and NUS (1.27, p=0.023) were independently associated with worsened ACM. MVA for Progression revealed Age (HR 1.01, p=0.022), positive margin (HR 1.9, p=0.016), and NUS (HR 1.67, p <0.001) to be predictive. Comparing NUS and US groups, KMA revealed worsened 5 year CSS (56% vs. 75%, p <0.001; Figure), 5 year OS (42% vs. 58%, p <0.001) and 5 year PFS (33% vs. 58%, p <0.001). CONCLUSIONS: Pathologic upstaging of clinical T1/T2 to T3 RCC was associated with improved survival outcomes when compared to non-upstaged pathologic T3 RCC. Such differences need to be taken into account when designing follow up protocols and for refinement of risk stratification in the T3 RCC stage group. Further investigation is requisite. Source of Funding: Stephen Weissman Kidney Cancer Research Fund © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e396 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ryan Nasseri More articles by this author Kevin Hakimi More articles by this author Ava Saidian More articles by this author Riccardo Autorino More articles by this author Brian Lane More articles by this author Yasuha Fujii More articles by this author Michele Marchioni More articles by this author Hajime Tanaka More articles by this author Dattatraya Patil More articles by this author Francesco Porpiglia More articles by this author Sabrina Noyes More articles by this author Chandru Sundaram More articles by this author James Porter More articles by this author Andrea Minervini More articles by this author Umberto Capitianio More articles by this author Francesco Montorsi More articles by this author Viraj Master More articles by this author Ithaar Derweesh More articles by this author Expand All Advertisement PDF DownloadLoading ...

Диагностическое значение иммунорегуляторных медиаторов в зависимости от степени распространенности опухолевого роста при почечно-клеточном раке

Introduction. In recent years, it has been established that the study of the content of molecular genetic biomarkers in blood serum, tissues characterizing the activity of tumor-infiltrating immune cells or tumor microenvironment makes it possible to evaluate the effectiveness of immunogenic effects of antitumor therapy, as well as to predict the development of its complications. The diagnostic value of immunoregulatory mediators in peripheral blood as prognostic biomarkers of immunotherapy in patients with renal cell carcinoma (RCC) has been confirmed by a small number of studies. This limits the further development of effective strategies for the treatment of patients with renal cell carcinoma. Additional research is needed to find molecular markers. The purpose of the study – to establish the diagnostic value of changes in the serum content of tumor microenvironment mediators from the stage of the disease in patients with RCC. Material and methods. The study included 66 patients with RCC and 30 practically healthy individuals who made up the control group. Additionally, by the method of solid-phase enzyme immunoassay, the serum content of seven mediators produced by tumor microenvironment cells was determined: proinflammatory cytokines – TNFa, INFy; chemokine – MCP1; colony-stimulating factors – G- CSF GM- CSF; growth factors – VEGF, TGF-β1. Results. It was found that at the 1st and 2nd stages of the disease, the level of cytokines/chemokines and colony-stimulating factors in the blood serum increases in comparison with the group of conditionally healthy individuals, with the exception of the content of INFy. With the progression of tumor growth in patients with stages 3 and 4 of the disease, a statistically significant high content of cytokines/chemokines and colony-stimulating factors remains in the blood serum, the level of INFy decreases and the concentration of growth factors (VEGF, TGF-β1) increases. The calculated AUC data showed a good quality of the prediction model, which gives reason to consider the increase in the serum content of mediators of the tumor microenvironment of RCC as an indicator of the stage of the disease and the prevalence of tumor growth, as well as a promising laboratory marker for predicting the effectiveness of immunotherapy treatment technologies. Conclusions. The growth of tumor cells in the initial stages of RCC is accompanied by a significant increase in the content of pro-inflammatory cytokines/chemokines and colony-stimulating factors in the blood serum. During the progression of tumor growth in patients with RCC, there is an activation of the release of growth factors such as TGF-β1 and VEGF into the bloodstream. Mediators of the tumor microenvironment entering the peripheral bloodstream (cytokines/chemokines, colony-stimulating and growth factors) are prognostic indicators for evaluating the effectiveness of immunotherapy technologies for the treatment of tumor diseases.

PSMA PET/CT in Renal Cell Carcinoma: An Overview of Current Literature.

Although the vast majority of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging occurs in the field of prostate cancer, PSMA is also highly expressed on the cell surface of the microvasculature of several other solid tumors, including renal cell carcinoma (RCC). This makes it a potentially interesting imaging target for the staging and monitoring of RCC. The objective of this review is to provide an overview of the current evidence regarding the use of PSMA PET/Computed Tomography in RCC patients.

Grade-dependent changes in sphingolipid metabolism in clear cell renal cell carcinoma.

There is a host of evidence for the role of bioactive sphingolipids in cancer biology, and dysregulated sphingolipid metabolism was observed in many malignant tumors. The aim of the present study was to provide more detailed data on sphingolipid metabolism in different stages of clear cell renal cell carcinoma (ccRCC). Samples of the tumor and noncancerous fragments of the same kidney were collected from patients who underwent a radical nephrectomy. The subjects were stratified according to the degree of malignancy of the tumor (n = 14 for G2, 12 for G3, and 9 for G4). The content of bioactive sphingolipids/glycosphingolipids was measured with an HPLC and HPTLC method, and the mRNA and protein expression of sphingolipid transporters and metabolizing enzymes was evaluated using real-time polymerase chain reaction (PCR) and Western blot, respectively. Compared to healthy kidney tissue, ccRCC was characterized by accumulation of sphingosine, sphingosine-1-phosphate (S1P), ceramide, dihydrosphingosine, and dihydroceramide. However, in the case of the latter two, the accumulation was limited to higher malignancy grades. In addition, compared to the healthy tissue, the content of gangliosides in the tumor was increased at the expense of globosides. We also found profound grade-dependent changes in the mRNA level of S1P-metabolizing enzymes, and spinster homolog 2. In general, their expression was much higher in G2 tumors compared to higher malignancy grades. We conclude that ccRCC is characterized by profound and multilevel alterations in sphingolipid metabolism, which to a large extent are grade-dependent. We hypothesize that dysregulation of sphingolipid metabolism contributes to the progression of ccRCC.

The role of dual tracer PSMA and FDG PET/CT in renal cell carcinoma (RCC) compared to conventional imaging: A multi-institutional case series with intra-individual comparison.

The objective of this study was to perform an intra-individual dual tracer comparison of Fluorodeoxyglucose (FDG) and Prostate Specific Membrane Antigen (PSMA) computed tomography (CT)/Positron Emission Tomography (PET) against standard of care (SOC) imaging for the characterisation, staging and restaging of renal cell carcinoma (RCC). A multicentre retrospective cohort study was performed at 3 major tertiary referral institutions in Brisbane, Australia between 2015 and 2020. All patients who underwent both PSMA and FDG PET/CT following SOC imaging for investigation of RCC were identified. Clinical details, imaging characteristics and histopathology were collected prior to univariate statistical analysis. Eleven patients who underwent dual tracer PET/CT were included. Mean age was 65.5 years (SD 8.8). Most patients were male (64%) with clear cell morphology (91%). The indication for dual tracer PET was staging (36%) and restaging after radical/partial nephrectomy (64%). Primary tumour assessment showed mixed avidity patterns (concordant 40%, discordant favouring PSMA 20%, and FDG 40%). Metastatic disease assessment showed concordant avidity in 6 patients (55%), concordant negative in 3 (27%), and discordant uptake favouring PSMA. PET outperformed SOC imaging for assessment of metastatic disease in 5 patients (45%) and equivalent for the remainder. A change in management was noted in three cases (27%). Dual tracer FDG and PSMA PET/CT for assessment of primary and metastatic RCC were mostly concordant. PET imaging outperformed conventional imaging and led to a change in management for 1 in 4 patients. Further studies with larger samples sizes are required to validate these findings and identify characteristics to guide patient selection for selective or dual tracer use.

A0063 - The effect of age on cancer-specifc mortality in T1a stage renal cell carcinoma patients: A population-based study across all treatment’s modalities

A0063 - The effect of age on cancer-specifc mortality in T1a stage renal cell carcinoma patients: A population-based study across all treatment’s modalities