Post Nephrectomy Research Articles

Incidental renal cell carcinoma post bilateral nephrectomy in autosomal dominant polycystic kidney disease.

Renal cell carcinoma (RCC) is more common in patients with autosomal dominant polycystic kidney disease (ADPKD) than in the general population. Diagnosing RCC in ADPKD is challenging due to the presence of multiple renal cysts, often leading to delays and difficulties in distinguishing RCC from cyst infection or hemorrhage. To analyze the prevalence and characterize the clinical features of RCC in patients with ADPKD undergoing simultaneous bilateral native nephrectomy. Between May 2017 and April 2024, 19 ADPKD patients undergoing hemodialysis and awaiting kidney transplantation due to end-stage renal disease (ESRD) underwent bilateral nephrectomies in a single center. Parameters such as patient characteristics, intraoperative blood loss, blood transfusion volume, length of hospital stay, and postoperative complications were documented. Pathological findings for RCC were reviewed. A total of 38 kidneys were excised from 19 patients, with a mean age of 56.8 years and an average hemodialysis duration of 84.2 months. Eight patients underwent open nephrectomies, and 11 underwent hand-assisted laparoscopic nephrectomies. RCC was detected in 15.8% of kidneys, affecting 21.1% of patients. Two patients had multifocal RCC in both kidneys. All RCC cases were pT1 stage, with the largest lesion averaging 16.5 mm in diameter. The average operative duration was 120 minutes, with intraoperative blood loss averaging 184.2 mL. Five patients required blood transfusions. Postoperative complications occurred in five patients, with a mean hospital stay of 17.1 days. The mean follow-up period was 28.1 months. The prevalence of RCC is higher in patients with ADPKD with ESRD than in those with ESRD alone. Thus, clinicians should be cautious and implement surveillance programs to monitor the development of RCC in patients with ADPKD, particularly those on dialysis.

6937 A Rare Case of Pembrolizumab-induced Multiple Endocrinopathies Presenting with Acute Adrenal Crisis Secondary to Isolated ACTH Deficiency - A Case Report

Abstract Disclosure: R. Abdelmasih: None. W. Pan: None. Introduction: Pembrolizumab is an immune checkpoint inhibitor (ICI) that blocks programmed cell death receptor 1 (PD-1) which took a massive leap in the oncology world. However, we are still understanding more about its immune-related adverse events (irAEs). Here we report a case of adrenal crisis due to pembrolizumab-induced hypophysitis and adrenalitis. Case Description: A 74-year-old male with a history of left renal cell carcinoma post left nephrectomy 5 years ago, complicated with lung metastasis for which Pembrolizumab was started. 5 months after, patient developed hypothyroidism and was started on Levothyroxine. 3 months later, Patient presented with lethargy and hypotension. Physical exam revealed hypotension (MAP of 55), fever, and acute encephalopathy. AM cortisol 4.2 ug/dL, Patient was started on IV pressors and a stress dose of Hydrocortisone. Hemodynamics improved, and Hydrocortisone was tapered down. ACTH stimulation test revealed a subnormal response of cortisol 0.2, 1.7, and 2.7 ug/dL at 0, 30, and 60 minutes respectively in the setting of very low ACTH of < 1.5 pg/ml, other pituitary hormones were checked, revealing normal insulin-like growth factor was 116 ng/mL, LH 15.29 mIU/mL, and FSH 27.45 mIU/mL. TSH was high 15 mIU/mL and free T4 was 1.4 ng/dl, levothyroxine dose was increased, and hydrocortisone was maintained at 10 in am and 5 in pm with excellent response. Discussion:ICIs inhibit the immunological pathways that control T-cell activation, leading to multiple immune-related endocrinopathies. Thyroiditis is the most reported one (30%), though anti-PD1-induced hypophysitis is exceptionally rare (< 1%). To date, the pathophysiology of pembrolizumab-induced central AI is not clearly understood, it’s presumed that it causes lymphocytic hypophysitis often presenting with isolated ACTH deficiency. Also, Pembrolizumab-induced primary adrenal insufficiency has seldom been reported and not yet understood, interestingly, anti-steroidogenic enzyme antibodies were absent in those few most reported cases which suggests a different mechanism compared to traditional primary AI. We suggest that our patient had combined primary and secondary adrenal insufficiency based on ACTH stim test result with very low cortisol responses in the setting of very low ACTH, which we believe is what led to such severe presentation of adrenal crisis. Diagnosis of PD1-induced AI can be challenging due to the overlapping of advanced malignancy and AI presentation. A higher level of suspicion is prompted especially in patients who experienced other endocrine irAEs (as our patient who had PDL-1-induced hypothyroidism). We present this case to shed light on this rare yet potentially fatal endocrine adverse event that can be reversed by prompt diagnosis and timely management due to the increasing use of pembrolizumab. More cases are needed for a better understanding of such a rare adverse event. Presentation: 6/2/2024

Concomitant Wilms tumor and autosomal dominant polycystic kidney disease.

Concomitant Wilms tumor (WT) and autosomal dominant polycystic kidney disease (ADPKD) is exceedingly rare, presenting a diagnostic and technical challenge to pediatric surgical oncologists. The simultaneous workup and management of these disease processes are incompletely described. We performed a retrospective analysis of patients treated at our institution with concomitant diagnoses of WT and ADPKD. We also review the literature on the underlying biology and management principles of these conditions. We present three diverse cases of concomitant unilateral WT and ADPKD who underwent nephrectomy. One patient had preoperative imaging consistent with ADPKD with confirmatory testing postoperatively, one was found to have contralateral renal cysts intraoperatively with confirmatory imaging post nephrectomy, and one was diagnosed in childhood post nephrectomy. All patients are alive at last follow-up, and the patient with longest follow-up has progressed to end-stage kidney failure requiring transplantation and dialysis in adulthood. All patients underwent germline testing and were found to have no cancer predisposition syndrome or pathogenic or likely pathogenic variants for WT. Concomitant inheritance of ADPKD and development of WT are extremely rare, and manifestations of ADPKD may not present until late childhood or adulthood. ADPKD is not a known predisposing condition for WT. When ADPKD diagnosis is made by family history, imaging, and/or genetic testing before WT diagnosis and treatment, the need for extensive preoperative characterization of cystic kidney lesions in children and increased risk of post-nephrectomy kidney failure warrant further discussion of surgical approach and perioperative management strategies.

A Case of an Adult Complicated Left Diaphragmatic Hernia: Case Report and Literature Review

Introduction: Diaphragmatic hernia by definition is the protrusion of abdominal structures into the thoracic cavity. Classified as either congenital or acquired, adult diaphragmatic hernia without a history of trauma is rare, and iatrogenic diaphragmatic hernia is rarer. The array of symptoms may be acute or latent and will depend on the herniated organ, which certainly makes this pathology a challenge at the level of diagnosis and subsequent management. Case Report: Here we present the case of a 73-year-old male patient who presented one year post left nephrectomy complicated by splenectomy (post splenic injury), with two weeks history of diffuse abdominal pain, non-bilious vomiting, and shortness of breath. Workup done revealed a left diaphragmatic hernia containing necrotic-perforated small bowel loops. A laparotomy with intestinal resection, loop ileostomy along with a primary repair of the diaphragmatic defect were performed. Conclusion: Although a great portion of acquired diaphragmatic hernias remain asymptomatic, they may be presenting with severe symptomatology and aggravating complications. At the level of clinical manifestation, suspicion of diaphragmatic hernia ascends the ladder of differential diagnosis in a patient with combined respiratory and gastrointestinal symptoms and hence is essential to avoid delayed treatment and superimposing lethal complications. Definitive treatment of diaphragmatic hernia is surgical repair given the high morbidity and mortality associated with such injury.

Circulating kidney injury molecule-1 (KIM-1) biomarker analysis in IMmotion010: A randomized phase 3 study of adjuvant (adj) atezolizumab (atezo) vs placebo (pbo) in patients (pts) with renal cell carcinoma (RCC) at increased risk of recurrence after resection.

4506 Background: In IMmotion010, adj atezo did not prolong investigator-assessed disease-free survival (DFS; primary endpoint) vs pbo after resection in pts with RCC (HR: 0.93, 95% CI: 0.75, 1.15; P=0.50; Pal Lancet 2023). This exploratory analysis of circulating protein biomarkers was performed to identify high-risk pts with minimal residual disease (MRD) who may show differential benefit from treatment (tx) with atezo. Methods: Pts with RCC with clear-cell or sarcomatoid component and increased recurrence risk post nephrectomy were randomized 1:1 to atezo 1200 mg or pbo IV q3w for 16 cycles or 1 year. A retrospective proteomics analysis was done with an affinity-based proximity extension assay (PEA) panel of ≈3000 analytes to identify circulating proteins with differential abundance patterns in matched serum samples (baseline vs at recurrence). A high sensitivity electrochemiluminescence (ECL) assay was then used to evaluate levels of KIM-1, a membrane glycoprotein overexpressed in clear-cell and papillary RCC, in all available baseline and post-tx serum samples. Outcomes in pts with KIM-1 high (≥86 pg/mL) vs low status at baseline were analyzed. Results: In pts with matched PEA samples (n=73), circulating KIM-1 was identified as the most significantly enriched protein at recurrence vs baseline. Of 778 pts enrolled in IMmotion010, 752 (97%) had baseline KIM-1 data (high: 300 [40%]; low: 452 [60%]). KIM-1–high status was associated with reduced DFS, and pts with KIM-1 high had better DFS with atezo vs pbo (Table). Longitudinal analysis of matched samples showed that in KIM-1–high pts, 9% (12/138) and 26% (36/141) of pts had a ≥30% increase from baseline in KIM-1 levels at Cycle 4 Day 1 with atezo vs pbo, compared with 16% (34/213) and 12% (25/207) in KIM-1-low pts, respectively. A ≥30% KIM-1 increase was associated with worse DFS in both KIM-1–high (atezo HR: 1.68, 95% CI: 0.77, 3.69; pbo HR: 3.53, 95% CI: 2.24, 5.58) and KIM-1–low (atezo HR: 3.56, 95% CI 2.21, 5.75; pbo HR: 3.22, 95% CI: 1.81, 5.70) subgroups. In pts with matched ECL samples (n=103), median KIM-1 levels were higher ( P<0.001) at recurrence (172 pg/mL) than at baseline (79 pg/mL). Conclusions: In IMmotion010, high baseline serum KIM-1 levels were associated with poorer prognosis but improved clinical outcomes with atezo vs pbo. Increased post-tx KIM-1 was associated with worse DFS. These data suggest that circulating KIM-1 may be a non-invasive marker of MRD and disease recurrence and be associated with benefit from atezo in adj RCC. Further investigation of KIM-1 in adj RCC is warranted. Clinical trial information: NCT03024996 . [Table: see text]

Post-unilateral Nephrectomy Administration of Alcohol Escalates Kidney Oxidative Stress of Male Wistar Rats

Alcohol has been used in folk medicine to potentiate some health benefits. Although, alcohol was reported to induce renal dysfunction, its activity on kidney tissues is not fully elucidated. However, whether or not alcohol could be beneficial after unilateral nephrectomy is unknown; thus, the objective of this study was to investigate the impact of post-unilateral nephrectomy administration of alcohol on kidney oxidative stress of male Wistar rats with 150 – 210 g-body weight, randomly grouped into four groups and the oxidative stress biomarkers such as lipid peroxidation (MDA), superoxide dismutase (SOD), Catalase (CAT) and glutathione peroxidase (GPx) determined using kidney tissue homogenates. Nephrectomy and alcohol significantly increased MDA and significantly decreased SOD, CAT and GPx; furthermore, post unilateral nephrectomy administration of alcohol caused advanced significant elevation of MDA as well as advanced significant depletion of SOD, CAT, and GPx of the kidney tissue. This study demonstrated for the first time that post-unilateral nephrectomy intake of alcohol enhances kidney oxidative stress by increasing kidney lipid peroxidation (MDA) and inhibiting its antioxidants (SOD, CAT, GPx); forming basis for campaigning against alcohol intake after unilateral nephrectomy as well as folk treatment with alcohol which may involve an individual that underwent nephrectomy.

FRI224 A Rare Case Of Recurrent Paraganglioma Presented With Liver Metastasis

Abstract Disclosure: E. Gupta: None. M. Al Mushref: None. Malignant Paragangliomas (PGLs) and Pheochromocytomas (PCC) are extremely rare. Approximately 10% of PCCs and 25% of PGLs are metastatic. Metastatic PGLs typically occur in patients with predisposing genetic mutations. We present a case of recurrent metastatic PGL in a young female with no known genetic predisposition to metastatic disease occurring after surgical resection. Our patient is a 28-year-old female with a history of PGL status post left adrenalectomy and nephrectomy two and a half years prior who presented to the ED for abdominal pain. She was first diagnosed after being admitted for hypertensive emergency. During time of diagnosis, plasma and urinary metanephrines were significantly elevated at 1.13 nmol/L and 907 ug/gCr respectively and plasma and urinary normetanephrines were elevated at 80.2 nmol/L and 52043 ug/gCr respectively. MRI showed a 16 cm left retroperitoneal mass and MIBG scan showed increased uptake in the mass however no evidence of metastatic disease was noted then. The patient had immigrated from Haiti. Her mother had passed away at age 20 of unknown cause and her father has no known history. Genetic testing was negative for hereditary gene mutations including multiple SDHDs, VHL, NF1, MEN1 and MAX. Surgical exploration showed a giant left retroperitoneal neoplasm involving the left kidney and left adrenal and both organs were resected. Pathology revealed PGL, focally extending to peripheral specimen margin and benign retroperitoneal lymph nodes and soft tissues. Post-resection meta- and normetanephrines levels were normal. Unfortunately, the patient was lost to follow up after surgery. On this admission, she endorsed right lower quadrant abdominal pain. Plasma normetanephrine was 1.72 nmol/L, metanephrine was normal, and chromogranin A level was elevated at 545 ng/mL. CT scan revealed multiple hepatic lesions and MIBG scan further showed new increased uptake suggesting metastasis. The patient was asymptomatic and blood pressure remained normal during her hospitalization. Due to concerns of recurrent PGL with metastasis, she established care with Oncology for initiation of treatment. PGL is an extremely rare neuroendocrine tumor and is closely related to PCC. Sympathetic PGLs cause catecholamine surge symptoms but low volume disease may remain asymptomatic. Genetic predisposition is common in malignant PGL particularly succinate dehydrogenase mutation subunit B. Patients should be closely followed up to screen for recurrence and genetic testing should also be done. In our patient’s case, despite surgical resection and negative genetic testing, she developed recurrence of the PGL with new metastasis emphasizing the importance of close surveillance in the case of PGL to monitor for recurrence. Presentation: Friday, June 16, 2023

THU540 Cribriform Morular Thyroid Carcinoma In A Young Female With Prior Exposure To Whole-Body Radiation For Metastatic Wilms’ Tumor

Abstract Disclosure: D. Caesario: None. M.S. Richardson: None. D. Carneiro-Pla: None. J.K. Fernandes: None. Introduction: Cribriform morular thyroid carcinoma (CMTC) is a rare thyroid cancer that is classically associated with familial adenomatous polyposis (FAP), but can also occur sporadically. We report a case of CMTC in a young female with history of whole-body radiation therapy (WBRT). Case Report: A 19-year-old female with past medical history of Wilms’ tumor (WT) with lung metastasis status post left nephrectomy and WBRT at the age of 6 was seen for newly diagnosed thyroid nodules. Physical exam was remarkable for thyromegaly. Thyroid function tests were normal. Thyroid ultrasound revealed 2 dominant TI-RADS 4 nodules measuring 1.9 x 1.7 x 2.1 cm on the left lobe and 0.9 x 0.8 x 0.8 cm on the right lobe. No suspicious lymphadenopathy. Fine needle aspiration biopsy on both nodules showed findings consistent with papillary thyroid carcinoma (PTC). No family history of thyroid disorders, malignancies, or FAP. She underwent total thyroidectomy with central neck node sampling. Thyroid gland surgical pathology result revealed CMTC positive for thyroid transcription factor-1 (TTF-1), β-catenin, and cytokeratins 5 and 6. It was negative for calcitonin. There was no evidence of invasion, extension, or lymph node metastasis. Genetic tests are currently pending. Discussion: CMTC was previously considered a variant of PTC, accounting for 0.2 to 6% of PTC cases. However, recent observations have challenged this view, and latest WHO update reclassified it as a distinct form of thyroid cancer. It is associated with an indolent clinical course and good prognosis. It almost exclusively affects young women. Both familial and sporadic cases are associated with mutations in the adenomatous polyposis coli (APC) gene. The APC protein is a negative regulator that controls β-catenin concentrations, which is involved in cell adhesion. Mutations in the APC gene may result in FAP and colorectal cancers. In cases associated with FAP, the tumors are usually multifocal and/or bilateral, while sporadic cases usually appear as single nodule. Tumor cells are always positive for TTF-1 and negative for calcitonin. They can also be positive for multiple cytokeratins, but strong nuclear and cytoplasmic staining for β-catenin is the hallmark of this tumor type. The case above occurred in a young female with no significant family history, but who underwent WBRT for WT as a child. Radiation is a known predisposing factor for thyroid cancer, and limited studies on early exposure to radiation revealed higher incidence of sporadic CMTC. However, even among FAP associated cases, CMTC diagnosis preceded that of FAP in up to 40% of the cases. Additionally, up to 20% of WT cases have mutations of the WT1 gene, and among these, at least half also carry acquired somatic mutations in CTNNB1, the gene encoding β-catenin. So far, there has been no reported case of CMTC in the background of WT. It will be interesting to see if she has these underlying mutations. Presentation: Thursday, June 15, 2023

#5026 ESTIMATED PROXIMAL TUBULE FLUID PHOSPHATE CONCENTRATION AS AN ELEMENT OF DECREASED RENAL FUNCTION IN PATIENTS UNDERGOING UNILATERAL NEPHRECTOMY

Abstract Background and Aims Patients with chronic renal failure (CRF) develop early alterations in mineral metabolism called Chronic Kidney Diseases Mineral Bone Disorders (CKD-MBD), detectable with the available markers (PTH, Ca, Ps) only in the most advanced stages of disease. Recent evidence suggests that the early development of CKD-MBD is related to the nutritional phosphorus intake and the reduction of the number of nephrons (renal functional reserve). Infact with the reduction in the nephrons number, compensation systems must be activated for the maintenance of the phosphoric balance with an increase in urinary phosphate and in the concentration of phosphorus in the single nephron (ePTFp). Therefore, the measurement of ePTFp has been proposed as a new early marker of CKD-MBD and effective renal functional reserve. Threshold values of ePTFp (2.2 mg/dl) have been identified to indicate patients with reduced renal functional reserve and therefore at increased risk of progression of renal damage. The measurement of residual renal function with ePTFp may be a useful parameter to be evaluated in patients who undergo unilateral nephrectomy due to renal neoplasia. In fact, post-nephrectomy some patients have a high reduction of the renal function not identified by preoperative GFR assessment or other risk factors. In these patients, ePTFp could represent a measure of pre nephrectomy kidney functional reserve and thus indicate the risk of reduce renal function after nephrectomy. The aim of the study was to evaluate the relationship between pre-operative ePTFp and renal function after nephrectomy. Methods This is a transversal monocentric observational study. From January 2022 to November 2022, we enrolled patients diagnosed with renal cell carcinoma for which has been indicated unilateral nephrectomy surgery. In all patients we evaluated pre nephrectomy and three months after surgery, renal function, and ePTFP with the formula [ePTFp = (Phosphaturia / creati-ninuria) x creatininemia x 3,33]. 30 subjects with normal renal function (eGFR 100±10 ml/min, no proteinuria) were evaluated for the ePTFp reference values. Results We evaluated 13 patients: age 57.5 ± 13.6; Cr 1.48±0.7 mg/dl; eGFR 58.5 ± 23.3, mil/min; Pi, mg/dl 3.2± 0.6; Ca 9.9± 0.6 mg/dl,PTH 58,8± 41 pg/ml FA 176,7± 108 IU/L, proteinuria 500±150 mg 24H. Compared to the control population (GFR 100 ml/min) the 24-hour phosphaturia was no different while ePTFp was increased 2.1± 0.9 vs 1.2±0.2 mg/dl; p: 0.05. In the post-nephrectomy assessment, creatinine and GFR were stable (Cr 1.48±0.7 vs 1.5 ±0.7 mg/dl; p: n.s; eGFR 58.5 ± 23.3, vs 56.5 ± 22.3, mil/min; p: n.s), while ePTFp was increased (ePTFp pre 2.1± 0.9 vs ePTFp post 3.3± 2.7; p<0.01). Patients with pre-nephrectomy ePTFP ≥ 2.2 mg/dl (n. 6, eGFR 56.5 ± 20.3, proteinuria 550±100 mg/24h) had a greater renal function reduction post nephrectomy (mean GFR delta -9.5±2 ml/min) respect to patients with pre-nephrectomy ePTFP <2.2 mg/dl (n. 7, eGFR 59.7 ± 24.3, proteinuria 500±200 mg/24h; mean GFR delta -0.5±2 ml/min; p: 0.05). In all the population there was direct correlation between ePTFp and the reduction of GFR post nephrectomy (r: 0.667; p: 0.05). Conclusion In our patients ePTFp was higher than the control group and correlate with the entity of the GFR reduction post nephrectomy. The group with a preoperatory ePTFp ≥ 2,2 mg/dl had a higher post nephrectomy GFR reduction. These results suggest that ePTFp identify the pre nephrectomy kidney functional reserve. In particular and ePTFp higher than limits highlighted in the literature (2.2 mg/dl) pre nephrectomy identify a greater risk of kidney function reduction post nephrectomy. ePTFp may be proposed as a parameter to identify patients with higher risk of decreased renal function post nephrectomy.

MP19-15 EXPLORING PERCEPTIONS OF THE RISK OF RECURRENCE IN RENAL CELL CARCINOMA: EVIDENCE FROM A SURVEY OF PRACTICING PHYSICIANS

You have accessJournal of UrologyCME1 Apr 2023MP19-15 EXPLORING PERCEPTIONS OF THE RISK OF RECURRENCE IN RENAL CELL CARCINOMA: EVIDENCE FROM A SURVEY OF PRACTICING PHYSICIANS Rituparna Bhattacharya, Caroline Vass, Cathy Anne Pinto, Kelley Myers, Kentaro Imai, Cooper Bussberg, Shawna R. Calhoun, and Christine Poulos Rituparna BhattacharyaRituparna Bhattacharya More articles by this author , Caroline VassCaroline Vass More articles by this author , Cathy Anne PintoCathy Anne Pinto More articles by this author , Kelley MyersKelley Myers More articles by this author , Kentaro ImaiKentaro Imai More articles by this author , Cooper BussbergCooper Bussberg More articles by this author , Shawna R. CalhounShawna R. Calhoun More articles by this author , and Christine PoulosChristine Poulos More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003244.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The treatment landscape for early-stage renal cell carcinoma (RCC) following nephrectomy is rapidly evolving, especially with the approval of pembrolizumab adjuvant therapy in the United States. Exploratory survey questions aimed to quantify qualitative descriptors of the level of risk of recurrence and to examine physicians’ perceptions of risk and its determinants. METHODS: The survey questions were included in a survey completed by physicians experienced with treating nonmetastatic RCC in the United States. Physicians were asked to (1) assign each of four categories of the risk of post nephrectomy disease recurrence (low, intermediate-low [int-low], intermediate-high [int-high], and high) to selected risk ranges; (2) categorize the risk of recurrence for three patient vignettes; and (3) assign an expected time until disease recurrence for two additional vignettes. Descriptive statistics were used. RESULTS: 250 physicians (64% oncologists, 36% urologists) completed the survey. The median risk levels assigned by oncologists were <20% for low, 21%-50% for int-low, 51%-80% for int-high, and 51-80% for high risk. Urologists’ median risk levels were identical to those of oncologists in the sample, except for the int-high level, which urologists assigned 21%-50%. On average, physicians perceived an individual with pT3, Fuhrman Grade 3, N0, M0 tumor and ECOG Performance status (PS)=1 as int-low risk. Int-high risk was the median perceived risk level assessed for the following two vignettes: pT2, N0, M0, Fuhrman grade 4 tumor with sarcomatoid feature and ECOG PS 0; and pT3, N1, M0, Fuhrman grade 3 tumor and ECOG PS 1. More than one-third of physicians expected a patient with pT3 tumor to remain disease free for 2-3 years post nephrectomy (n=95; 38%) if N0 M0, and 1-2 years (n=92; 36.8%) if N1 M0. CONCLUSIONS: Physicians’ perception of risk of recurrence post nephrectomy is critical when evaluating patient eligibility for and choosing to recommend adjuvant therapy. This exploratory analysis provides insights into risk perceptions among oncologists and urologists. Source of Funding: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e271 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rituparna Bhattacharya More articles by this author Caroline Vass More articles by this author Cathy Anne Pinto More articles by this author Kelley Myers More articles by this author Kentaro Imai More articles by this author Cooper Bussberg More articles by this author Shawna R. Calhoun More articles by this author Christine Poulos More articles by this author Expand All Advertisement PDF downloadLoading ...

PD17-11 MOLECULAR PROFILING REVEALS IMMUNOSUPPRESSIVE TUMOR IMMUNE MICROENVIRONMENT IN PRIMARY VERSUS PAIRED ASYNCHRONOUS METASTATIC CLEAR CELL RENAL CELL CARCINOMA

You have accessJournal of UrologyCME1 Apr 2023PD17-11 MOLECULAR PROFILING REVEALS IMMUNOSUPPRESSIVE TUMOR IMMUNE MICROENVIRONMENT IN PRIMARY VERSUS PAIRED ASYNCHRONOUS METASTATIC CLEAR CELL RENAL CELL CARCINOMA Brittney Cotta, Srinivas Nallandhighal, Daniel Triner, Nathan Graham, Rohit Mehra, Marcin Cieslik, Amy Kasputis, Todd Morgan, and Simpa Salami Brittney CottaBrittney Cotta More articles by this author , Srinivas NallandhighalSrinivas Nallandhighal More articles by this author , Daniel TrinerDaniel Triner More articles by this author , Nathan GrahamNathan Graham More articles by this author , Rohit MehraRohit Mehra More articles by this author , Marcin CieslikMarcin Cieslik More articles by this author , Amy KasputisAmy Kasputis More articles by this author , Todd MorganTodd Morgan More articles by this author , and Simpa SalamiSimpa Salami More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003272.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Clear cell renal cell carcinoma (ccRCC) is a highly immune infiltrated cancer, but how the tumor immune microenvironment (TIME) evolves during disease progression is unknown. Insights into heterogeneity within primary ccRCC raise questions about potential heterogeneity between primary and paired metastatic tumors. This information may improve understanding of immune evasion leading to metastatic disease and response to immunotherapy. In this study, we characterize and compare the TIME of primary ccRCC with paired asynchronous metastases. METHODS: Analysis of ccRCC patients who developed recurrence post radical nephrectomy and had both primary and metastatic tissue available. Whole-transcriptome sequencing was performed on formalin-fixed paraffin-embedded (FFPE) specimens using the illumina platform. Differential expression gene (DEG) analysis was performed using R package edgeR. Gene set enrichment analyses (GSEA) to identify hallmark pathway enrichment was performed using R package fgsea. TIME deconvolution was quantified using CIBEROSRT, an in silico flow cytometry tool. RESULTS: 42 tumor samples from 19 patients (19 primary tumors with 23 matched metastases) were analyzed. Metastasis sites included lung (n=6), bone (n=6), adrenal (n=4), liver (n=2), lymph node (n= 2), and soft tissue (n=3). Angiogenesis and epithelial to mesenchymal transition (EMT) were the most significantly enriched pathways in metastases compared to primary tumors (FDR < 5%). The primary tumors displayed a more immunosuppressive TIME than their matched metastases when comparing immune cell types. (Figure 1). The higher proportion of T regulatory cells (Tregs) in primary tumors was consistent compared against all metastasis tissue types. Metastasis samples displayed higher proportion of M2 macrophages (p=0.003), with the highest proportion in bone and soft tissue. Bone metastases also appeared to be more immunosuppressive in their TIME when compared to lung metastases, with greater Tregs and a lower immune content score. CONCLUSIONS: We demonstrate higher infiltration of immunosuppressive cells in the TIME of primary ccRCC compared with metastatic sites. Further studies are necessary to determine the prognostic and therapeutic significance of these findings. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e500 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Brittney Cotta More articles by this author Srinivas Nallandhighal More articles by this author Daniel Triner More articles by this author Nathan Graham More articles by this author Rohit Mehra More articles by this author Marcin Cieslik More articles by this author Amy Kasputis More articles by this author Todd Morgan More articles by this author Simpa Salami More articles by this author Expand All Advertisement PDF downloadLoading ...

MP04-19 IMPACT OF SURGERY ON CYTOTOXIC ACTIVITY OF PATIENT-DRIVEN CD8 T CELL

You have accessJournal of UrologyCME1 Apr 2023MP04-19 IMPACT OF SURGERY ON CYTOTOXIC ACTIVITY OF PATIENT-DRIVEN CD8 T CELL Reza Nabavizadeh, Rodrigo Rodrigues Pessoa, Zesheng An, Joanina Gicobi, Susan Harrington, Henan Zhang, Tianxiao Xu, Jacob Hirdler, Christine Lohse, Bradley Leibovich, Haidong Dong, and Fabrice Lucien Reza NabavizadehReza Nabavizadeh More articles by this author , Rodrigo Rodrigues PessoaRodrigo Rodrigues Pessoa More articles by this author , Zesheng AnZesheng An More articles by this author , Joanina GicobiJoanina Gicobi More articles by this author , Susan HarringtonSusan Harrington More articles by this author , Henan ZhangHenan Zhang More articles by this author , Tianxiao XuTianxiao Xu More articles by this author , Jacob HirdlerJacob Hirdler More articles by this author , Christine LohseChristine Lohse More articles by this author , Bradley LeibovichBradley Leibovich More articles by this author , Haidong DongHaidong Dong More articles by this author , and Fabrice LucienFabrice Lucien More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003215.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Renal cell carcinoma (RCC) elicits immune dysfunction through infiltration of immunosuppressive cells and expression of immuno-inhibitory molecules such as PD-L1. The impact of removing primary malignancy on boosting systemic antitumor immunity remains unclear. Here, we investigated the impact of nephrectomy on cytotoxic activity of patient-driven CD8 T cells. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from 11 prospectively enrolled patients before and at 3-month post nephrectomy for clear cell RCC. Human 786-O ccRCC cells was used as target cells and killing rates were measured by calcein release assay. Wilcoxon paired t test and Mann Whitney test were used for analysis. RESULTS: Five patients showed detectable patient-derived CD8 T cells killing at baseline and this number increased to 7 at 3 months. Four patients showed no T-cell killing at both baseline and 3 months. The killing rate was 1.9 higher at 3-month compared to baseline, 21.4% (range 0%-52.5%) versus 11.4% (range 4.0% to 32.5%), respectively (p=0.0245). Level of tumor-reactive CD11ahighCD8 T cells at 3 months was increased in 7 patients compared to baseline while 2 patients showed decreased and another 2 had unchanged levels. For T cells positive for CX3CR1 and GZMB, 6 patients showed increased levels at 3 months, 2 decreased and 3 had unchanged levels. At 3 months, patients that had T cell cytotoxic activity had higher levels of CD11a (mean 10.27% vs 7.7%, p=0.20) and CX3CR1 and GZMB (mean 9.62% vs 19.6%, p=0.11), two marker of enhanced cytotoxicity. There were lower levels of tumor-reactive effector CD8 T cells in patients with blood concentrations of PD-L1>1 ng/ml compared to patients with ≤1 ng/ml (mean 6.146 ng/ml vs 0.121 ng/ml; p=0.032) (Figure 1). CONCLUSIONS: Nephrectomy is associated with an increase rate and enhanced tumor cell killing ability of peripheral CD8 T cells. Higher levels of CD11a, CX3CR1 and GZMB CD8 T cells as well as lower PD-L1 serum levels after surgery were associated with higher cytotoxic activity of patient-derived tumor-reactive effector CD8 T cells. Source of Funding: This work was supported by NIH R01CA256927 and R01AI095239 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e41 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Reza Nabavizadeh More articles by this author Rodrigo Rodrigues Pessoa More articles by this author Zesheng An More articles by this author Joanina Gicobi More articles by this author Susan Harrington More articles by this author Henan Zhang More articles by this author Tianxiao Xu More articles by this author Jacob Hirdler More articles by this author Christine Lohse More articles by this author Bradley Leibovich More articles by this author Haidong Dong More articles by this author Fabrice Lucien More articles by this author Expand All Advertisement PDF downloadLoading ...

Prediction of overall survival (OS) prognosis for chromophobe renal cell carcinoma of post nephrectomy patients: A SEER database study

Prediction of overall survival (OS) prognosis for chromophobe renal cell carcinoma of post nephrectomy patients: A SEER database study

Evaluating the clinical utility of circulating tumor cells (CTC) profiling to predict selection of preferred therapeutic regimens in newly diagnosed or pretreated refractory renal cell carcinomas (RCC).

717 Background: There is an unmet need for biomarkers enabling therapeutic selection and prediction of clinical outcomes in kidney cancer . We evaluated the feasibility and utility of profiling of circulating tumor cells (CTCs) via multiplexed fluorescence immunocytochemistry (ICC) to identify liquid biopsy biomarkers linked to treatment response (or resistance) in advanced RCC patients. In addition, transcriptome analysis for 20802 genes from exosomal RNA is planned to evaluate novel prognostic and predictive signatures. Methods: Patients with either untreated or pretreated advanced RCC were eligible prior to starting a new systemic therapy regimen. IRB approved written informed consent was obtained. Serial blood samples were collected at baseline, and at 3, 6, 12 and 24 months. Primary endpoint of the study was to detect the proportion of patients with RCC in whom CTCs can be detected and profiled. Secondary endpoints are to correlate the profiling and changes in CTC with response and clinical outcomes. The study will meet its primary endpoint if the assay provides adequate detection and profiling for at least 12 patients. With an overall sample size of 50 the width of a 95% confidence interval for the rate of providing a therapeutic intervention is guaranteed to be less than 26%. Results: 44 evaluable patients have been enrolled; 11 females, 33 males. Median age was 64 years (range 40-85 years). 38 white patients, 2 black patients and 4 of other ethnicity have been enrolled.16 patients were untreated, 22 were pretreated and 6 were undergoing adjuvant therapy post nephrectomy. 37 patients had clear cell histology, 4 non clear cell and 3 unclassified histology. 42 of the 44 (95.5%) patients had detectable CTCs in the baseline sample. 21 on treatment samples have been collected to date, with detectable CTCs in all except one sample. 53 of 65 samples (81.5%) demonstrated detection of at least one biomarker by ICC. VEGFA expression was the most commonly detected biomarker on ICC (detected in 28 of 63 samples). Conclusions: The primary endpoint was met, and feasibility of the test was demonstrated with 95% of the baseline samples showing CTC detection and 81.5% showing biomarker expression. This blood-based, non-invasive liquid biopsy demonstrated high sensitivity for detection of cancer cells, and presents a potential opportunity for biomarker profiling to predict therapeutic efficacy of conventional RCC therapeutic agents. Correlation of longitudinal CTC with clinical outcomes will be reported. Transcriptome analysis is under evaluation for novel prognostic and predictive signatures and will be reported.

Detection of hypermethylated SHOX2 in circulating cell-free DNA post nephrectomy identifies patients with renal cell carcinoma at highest risk for disease recurrence independent of TNM

Detection of hypermethylated SHOX2 in circulating cell-free DNA post nephrectomy identifies patients with renal cell carcinoma at highest risk for disease recurrence independent of TNM

TRU-CUT ISOLATED PAROTID METASTASIS FROM RENAL CELL CARCINOMA: AN UNUSUAL PRESENTATION AND REVIEW OF LITERATURE

Background: Renal cell carcinoma with isolated metastasis to the parotid gland is extremely rare. Slow growth, low level of suspicion and negative Fine needle aspiration cytology (FNAC) often delay the diagnosis. A high level of suspicion of metastatic disease from a specic site is important, otherwise can be missed for a benign swelling leading to delayed treatment and poorer prognosis. A 59-year-old Case presentation: male presented with a swelling in the right preauricular area 5 years post right radical nephrectomy for right renal cell carcinoma (RCC). The examination was suggestive of a benign swelling. FNAC was done twice, which was inconclusive. A Tru-cut biopsy of the lesion revealed metastatic RCC. MRI revealed a dumbbell type of tumor extending deep into the gland and encasing vessels. PET-CT was negative for metastasis to the rest of the body. The patient received targeted therapy followed by radiation therapy with imaging showing non-progression of the disease. Conclusion: Metastatic disease should be considered whenever a parotid mass is detected in patients with an RCC history. Examination ndings can be misleading; hence dedicated imaging is critical. Small parotid metastasis can be cured with surgery. A combination of chemotherapy and radiation therapy can palliate the unresectable disease.

PS-R07-6: RENOVASCULAR HYPERTENSION SECONDARY TO MASSIVE ILIOPSOAS HEMATOMA

An 81-year-old female with stage G3 chronic kidney disease and post left nephrectomy for upper tract urothelial carcinoma 20 years ago, was admitted to our hospital for heart failure. She acutely developed right thigh pain, and contrast-enhanced computed tomography (CT) revealed an idiopathic iliopsoas hematoma for which transcatheter arterial embolization (TAE) was performed. Subsequently, her hypertension worsened despite multiple antihypertensive medications (Nifedipine, Carvedilol, Doxazosin, Spironolactone), remained uncontrolled over one month. At this point, plasma renin activity and plasma aldosterone concentration were both elevated on taking carvedilol and spironolactone. An angiotensin II receptor blocker (ARB, Olmesartan) was additionally started for refractory hypertension. Oliguric acute kidney injury (AKI) developed on the day following ARB administration, and her serum creatinine increased from 0.98 to 2.0 mg/dL. After stopping the ARB, the kidney function immediately recovered to the previous level. On review of the previously performed contrast CT, the remnant (right) kidney was ventrally displaced, and the right renal artery was kinked by the massive iliopsoas hematoma (Figure 1a and 1b). Three months after TAE, the hematoma completely disappeared, and the right kidney and renal artery returned to their original positions. Renal Doppler ultrasonography before the appearance, and after the disappearance of hematoma, demonstrated no abnormalities indicative of renal artery stenosis. Furthermore, hypertension also improved over the three months after TAE. Renal artery stenosis is primarily caused by atherosclerosis, fibromuscular dysplasia, and rarely external compression. We report a rare case of renovascular hypertension which would be induced by renal artery kinking due to massive iliopsoas hematoma. JOURNAL/jhype/04.03/00004872-202301001-01329/figure1/v/2023-10-24T163949Z/r/image-jpeg

NCMP-17. PLASMA EXCHANGE FOR IMMUNE CHECKPOINT INHIBITOR INDUCED ACUTE DEMYELINATING POLYNEUROPATHY REFRACTORY TO IVIG

Abstract The use of immune checkpoint inhibitors in the treatment of cancer has gained prominence due to their effectiveness. Unfortunately, neurological immune-related adverse events represent a growing problem in neuro-oncology practice. Many of these cases are rare and their diagnoses and management can be challenging. We present a case of a 69-year-old male with urothelial carcinoma status post left nephrectomy who developed bilateral lower extremity weakness that began following his first dose of Atezolizumab. After three doses, his lower extremity weakness worsened to the point where he could not walk. A NCV study was performed and was consistent with acute demyelinating polyneuropathy. A cervical MRI (Magnetic Resonance Imaging) showed an enhancing lesion at C6-C8. He was treated with three days of intravenous methylprednisolone every six hours for three days followed by three days of 0.4gm/kg IVIG. He regained his ability to walk after IVIG treatment. The enhancing lesion noted on MRI remained. Three weeks after the first IVIG treatment, he declined significantly, redeveloping symptoms where he could not ambulate and required assistance to use the toilet. He had no lower extremity reflexes and had loss of proprioception of his hands. He was scheduled for another IVIG infusion at .4gm/kg followed by a dose of IVIG .6gm/kg the next day, and then four more days of IVIG .25gm/kg. His lower extremity weakness and difficulty walking remained so he was arranged for plasmapheresis x five cycles. His weakness improved, reflexes returned, and he no longer had proprioceptive loss of his hands. A cervical MRI obtained one month after plasma exchange showed resolution of the C6-C8 enhancing lesion. He is now ambulating with a cane. This case highlights the effectiveness of plasma exchange in a case that was refractory to IVIG

The incidence and risk factors of chronic kidney disease after radical nephrectomy in patients with renal cell carcinoma

BackgroundRadical nephrectomy (RN) is the standard treatment for localized renal cell carcinoma. The decrease in nephrons from RN could lead to postoperative chronic kidney disease (CKD). In this study, we aim to investigate the incidence and risk factors for CKD in patients who have received RN.MethodsA Total of 1233 patients underwent radical nephrectomy in Zhejiang Provincial People’s Hospital from January 2010 to December 2018. Those who had an abnormal renal function before surgery or were lost to follow-up were excluded. Five hundred patients were enrolled in the end. eGFR was calculated using the abbreviated MDRD equation. CKD was defined as eGFR less than 60 ml/min/1.73m2. The incidence of postoperative CKD was estimated using the Kaplan-Meier method. The independent risk factors for CKD occurrence were determined through logistic multivariate regression analysis.ResultsPatients were followed up for a median of 40 month (3–96 months), with CKD occurring in 189 cases. The 5-year cumulative incidence of CKD was 43.4%. There was a significant difference between these189 patients and the remaining patients without post nephrectomy CKD in terms of age, sex, weight, and preoperative eGFR(P<0.05). Multivariate regression analysis showed that age (OR = 1.038, 95%CI = 1.002–1.076), preoperative eGFR of the contralateral kidney (OR = 0.934, 95%CI = 0.884–0.988) and Immediate postoperative eGFR (OR = 0.892, 95%CI = 0.854–0.931) were independent risk factors for postoperative CKD.ConclusionsThe incidence of CKD after radical nephrectomy was not uncommon. Age, preoperative eGFR of the contralateral kidney and Immediate postoperative eGFR are independent risk factors for postoperative CKD.

LBODP071 Early Detection Of Immune-mediated Hypophysitis With Use Of Checkpoint Inhibitor Immunotherapy

Abstract Hypophysitis is an inflammatory infiltration of the pituitary gland. Association with cytotoxic T-lymphocyte antigen 4 (CTLA-4) targeting was described with a recommendation of discontinuing the treatment in such conditions . Hypophysitis has become more prevalent with increased use of immune checkpoint inhibitors with late detection being associated with a high morbidity and mortality. Symptomatic presentation, along with hemodynamic and serum abnormalities warrant urgent intervention as early measures prevent progression. This case is about a 60-year-old female with metastatic renal clear cell carcinoma status post right radical nephrectomy on combined nivolumab and ipilimumab (NIVO/IPI) and history notable for persistent atrial fibrillation on warfarin presented to the hospital after a fall. Eight days after her second cycle on NIVO/IPI, the patient developed hot flashes, vomiting, weakness, and vertiginous symptoms. Her exam was notable for atrial fibrillation with rapid ventricular rate and hypotension. Serology was notable for a sodium of 119 mEq/mL, prompting admission to the hospital. Due to high clinical suspicion for hypophysitis based on serological findings, the patient was given a dose of methylprednisolone then daily hydrocortisone to reverse the pituitary inflammation. Fludrocortisone was started for adrenal insufficiency. MRI of the brain with IV contrast was notable for abnormal enhancement and thickening of the pituitary stalk concerning for hypophysitis. The patient clinically improved with resolution of her dizziness, hot flashes, and vomiting. Her serum sodium improving to 132 mEq/mL. She was discharged home with immunotherapy held. Hypophysitis is a rare inflammatory disease affecting 1 in 7 million. Typical symptoms include headache, vision changes, fatigue, and hypopituitary deficiencies. Reported immunotherapies with incidences of secondary hypophysitis include CTLA-4 and PD-1 therapeutics. Immunotherapy associated hypophysitis occurs in &amp;lt;7% of patients. Hypophysitis is diagnosed by laboratory findings and imaging which can identify this acute process via enhancement and swelling of the pituitary gland . Management modalities include surgery, anti-inflammatory therapy, and conservative therapy. Medical management is mainly directed at the correction of pituitary hormone deficiencies and reduction of pituitary inflammation using glucocorticoid therapy . Presentation: No date and time listed