TPS253 Background: Oxaliplatin (Ox) remains a cornerstone of CRC therapy, but its utility is limited by CIPN—a debilitating, dose-limiting toxicity that compromises quality of life and treatment adherence. Despite its prevalence, no effective preventive strategies exist. The endocannabinoid system, central to pain modulation, inflammation, and neuronal excitability, offers a novel therapeutic target. CBD, a non-psychoactive phytocannabinoid, exerts anti-inflammatory, neuroprotective, and analgesic effects in preclinical neuropathy models and has shown early promise in retrospective studies. However, no prospective trials have rigorously tested CBD for Ox-induced CIPN in CRC, making this study a first-of-its-kind effort to address a critical unmet need. Methods: GI-249/IRB 25-1032 is a National Institutes of Health–funded (1R21CA292276-01A1), single-institution, randomized pilot study evaluating feasibility and acceptability of hemp-based CBD supplementation during Ox-based Ctx. Thirty patients with advanced CRC, initiating Ox-based Ctx with preserved liver function and no major psychiatric illness, will be randomized 2:1 to receive oral CBD (150 mg twice daily) starting one day before each Ox cycle and continuing for seven days post-infusion versus Ctx alone. The primary endpoint is feasibility (binary outcome: ≥70% of patients missing ≤3 doses per cycle in ≥75% of Ox treatments) and acceptability (assessed via the FIM Acceptability Survey). With 10 participants in the control arm, the study has 80% power to test a discouraging response rate of 40% versus an encouraging rate of 76% (1-sided α=0.055, binomial exact test). Secondary endpoints include comparing rates of acute and chronic CIPN and other adverse events between the two groups (CTCAE v5, FACT GOG NTX-13, Brief Pain Inventory). Correlative analyses will evaluate miRNAs and pro-inflammatory cytokines associated with neuropathy and compare between the groups, aiming to elucidate CBD’s neuroprotective mechanisms and identify predictive biomarkers. This pilot study will inform the design of future trials and advance the understanding of CBD as a novel approach in reducing CIPN in CRC patients. Clinical trial information: pending .
Purpose Altmetric Attention Score (AAS) is a measure of the quantity of attention that a scholarly work receives, and evidence about gender gaps in AAS in oncology is lacking. Our objective was to analyze potential disparities in the AAS within oncology by comparing research publications authored by women first and last authors with those authored by men. Secondarily, we aimed to quantify the extent of over-/undercitation by gender. Materials and Methods The initial data set was compiled from the Altmetric database through Application Programming Interface (API) using oncology-related search terms. Author gender categories were assigned on the basis of the Gender Guesser API. For example, those with first and last authors labeled woman were categorized as woman first author/woman last author (WW). Over-/undercitation was calculated using observed citations and expected citations. Analyses were completed both for the oncology literature as a whole and for prominent subspecialty peer-reviewed journals. Results Our search yielded 652,834 articles published between January 1, 2009, and January 31, 2024. For AAS, women in the first author position had a 15.2% lower score compared with men counterparts and women in the last author position had an 8.3% lower score than men (P < .01 for both). Although the proportion of WW authors in oncology publications increased over time, the man first author/man last author combination was overcited (mean citation percentage difference [MCD] = +16.2%), whereas WW was undercited (MCD = -7.7%). There was variation in both proportion of WW papers and over-/undercitation among oncologic subspecialties. Conclusion Significant gender disparities in citation rates and AAS exist across various fields within oncology. This highlights a systemic issue where woman-authored research is undercited and receives less attention compared with man-authored work, with the potential to affect career advancement, funding opportunities, and academic recognition.
To compare the outcomes of Neoadjuvant Chemotherapy (NAC) versus Adjuvant chemotherapy (AC) in upper tract urothelial carcinoma (UTUC) with Clinical Nodal Disease (CN+). Multicenter retrospective analysis of patients with CN + who underwent RNU from the ROBUUST (ROBotic surgery for Upper Tract Urothelial cancer STudy) database. Patients were divided into those who received NAC versus AC. Primary outcome was all-cause mortality (ACM). Secondary outcomes were cancer-specific mortality (CSM) and recurrence. Cox-regression multivariable analysis (MVA) was used to elucidate predictive factors for ACM, CSM, and recurrence. Kaplan-Meier Analysis (KMA) was performed to analyze 5-year overall survival (OS), cancer-specific survival (CSS), and recurrence free survival (RFS). 102 patients were analyzed (53 neoadjuvant/49 adjuvant; median follow-up 17.0 months). Groups did not differ with respect to median age at diagnosis (p = 0.692), BMI (p = 0.551), clinical tumor size (p = 0.514), or ECOG performance status (p = 0.44). MVA revealed receipt of NAC to be associated with improved ACM (HR 0.36, p = 0.023), CSM (HR 0.38, p = 0.046), and recurrence (HR 0.51, p = 0.048). KMA comparing NAC and AC revealed significantly greater 5-year OS (65
Objectives: To report the outcomes of minimally invasive (MIS) nephrectomy following immune checkpoint inhibitor (ICI) therapy. Materials and Methods: This multicenter retrospective cohort study included consecutive patients who underwent nephrectomy following ICI therapy at five high-volume US academic centers between 2015 and 2023. Baseline clinical features and perioperative findings were recorded. After propensity-score matching (PSM), outcomes were compared between MIS and open nephrectomies. The primary outcome was 90-day complications, and secondary outcomes included length of hospital stay (LOS) and 90-day readmission. Results: A total of 158 patients were included, of whom 76 and 82 underwent MIS and open nephrectomies, respectively. The MIS procedures included robotic (n = 56) and laparoscopic (n = 20). A total of six (8%) patients converted to open. On multivariable analysis, patients with nonmetastatic vs metastatic renal-cell carcinoma (RCC) (hazard ratio [HR] 3.1, p = 0.01), those with smaller tumor size (HR 1.2 for each cm, p = 0.001), and no clinical evidence of inferior vena cava thrombus (HR 29, p = 0.002) were more likely to undergo the MIS approach compared with open approach. After PSM, including 56 MIS and 36 open nephrectomies, the MIS group compared with the open group had lower estimated blood loss (100 vs 460 mL, p < 0.001) and shorter LOS (2 vs 4 days, p < 0.001). Nevertheless, 90-day complications and readmissions were similar between the two groups. There were no 90-day mortality rates in either group. Conclusion: The MIS approach appears safe and offers more favorable perioperative outcomes compared with open surgery in properly selected patients with advanced RCC who are candidates for nephrectomy following ICI therapy.
PURPOSE:To evaluate survival outcomes and recurrence patterns by pathologic nodal status in upper tract urothelial carcinoma (UTUC) patients receiving neoadjuvant chemotherapy (NAC) prior to radical nephroureterectomy (RNU) and lymph node dissection (LND). MATERIALS AND METHODS:Using the international ROBUUST 2.0 database, a retrospective analysis of UTUC patients who underwent robotic/laparoscopic RNU+LND±NAC was performed. Patients were stratified by NAC and pathologic nodal status into pN0, ypN0, pN+, and ypN+ subgroups. Overall (OS), metastasis-free (MFS), and urothelial recurrence-free survivals (RFS) were compared using Kaplan-Meier curves and multivariable Cox regression modeling. RESULTS:The cohort included 883 patients (15% received NAC). 212 (24%) patients had (y)pN+ disease. Median follow-up was 19 months. Compared to pN+ patients, ypN+ patients had significantly worse 1- (64% vs. 72%), 3- (40% vs. 54%), and 5-year (20% vs. 31%) OS rates. Node-negative patients had similar OS, irrespective of NAC treatment (1-year: 94%; 3-year: 77%-82%). At 1 year, all ypN+ patients had metastases, while 13% of pN+ patients remained metastasis-free. Among ypN+ patients, 89% experienced nodal/regional or distant metastases as the site of initial recurrence, compared to 39% of pN+ patients. Initial nodal/regional or distant metastases occurred in 42% and 18% of ypN0 and pN0 patients, respectively. CONCLUSION:ypN+ patients have worse survival compared to pN+ patients. Recurrence patterns differ by nodal and NAC status, with ypN+ patients having a significantly higher incidence of nodal/regional or distant metastases as the initial site of recurrence. These survival outcomes and recurrence patterns differences may have important surveillance and treatment implications.
Inflammatory myofibroblastic tumors (IMT) are exceedingly rare, particularly when originating in the bladder. Complete surgical resection is the gold standard treatment for IMTs. We describe a case of IMT of the urinary bladder that achieved complete radiographic and endoscopic resolution after systemic treatment with ipilimumab and nivolumab directed towards metastatic melanoma. This case is noteworthy due to the tumor's serendipitous and remarkable response to immunotherapy.
BACKGROUND:The ability to predict muscle invasion in the final pathology of upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU) potentially influences the selection of the most appropriate treatment modality. The present study aims to develop a model predicting muscle-invasive status in high-risk UTUC. METHODS:The ROBUUST (RObotic surgery for Upper tract Urothelial cancer - UTUC - STudy) 2.0 dataset is an international, multicenter registry of patients undergoing curative surgery for UTUC between 2015 and 2022. Data about high-risk patients, classified according to EAU and NCCN prognostic stratification criteria, who underwent RNU were retrieved. The primary outcome was the identification of muscle-invasiveness. Two multivariable models, differing in the inclusion of biopsy-related data, were fitted with pT stage results at final pathology. Their predictive ability was calculated using the area under the receiver operating characteristic curve and decision curve analysis (DCA). A nomogram was developed using the model demonstrating the highest area under the curve (AUC) and clinical net benefit. RESULTS:In the overall cohort, 1558 patients met the inclusion criteria, with 934 patients having ≥pT2 disease. Patients in the ≥pT2 cohort had significantly worse oncological outcomes in terms of metastases, all-cause, and cancer-specific deaths (all P<0.001). The biopsy-related model had the highest AUC (74%) and the highest net benefit in DCA. The DCA showed an improvement in the clinical risk prediction of muscle-invasiveness, and a reduction in the number of upfront or unnecessary RNU, at every ≥pT2 probability threshold. CONCLUSIONS:The proposed prognostic model is a valuable tool for estimating the risk of muscle-invasiveness in high-risk UTUC patients, owing to its optimal predictive ability and user-friendly design.
OBJECTIVE:To investigate the prevalence, predictors and impact of surgically induced chronic kidney disease (CKD-S) on survival outcomes in patients with upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU). METHODS:Utilising the ROBUUST 2.0 registry, a multicentre retrospective analysis was conducted in patients with UTUC undergoing RNU between 2006 and 2022 who did not have baseline chronic kidney disease (CKD) stages 3-5. We calculated the prevalence of postoperative CKD-S3a (estimated glomerular filtration rate [eGFR] 59-45 mL/min/1.73 m2) and CKD-S3b (eGFR <45 mL/min/1.73 m2) as measured by the Chronic Kidney Disease Epidemiology Collaboration 2021 equation. The analytical cohort was stratified by postoperative CKD stage [no CKD-S [eGFR ≥60 mL/min/1.73 m2]; CKD-S3a [eGFR 59-45 mL/min/1.73 m2] and CKD-S3b [eGFR <45 mL/min/1.73 m2]). The primary outcome was all-cause mortality (ACM). Predictors for development of CKD-S3a/3b and ACM/cancer-specific mortality (CSM) were analysed using logistic and Cox regression, respectively. Kaplan-Meier analysis was used to analyse overall survival (OS) and cancer-specific survival (CSS) among postoperative CKD groups. RESULTS:We analysed 1862 patients; 34.7% (646) and 39.6% (738), respectively, developed CKD-S3a and CKD-S3b. Predictors of CKD-S3b included increasing age (odds ratio [OR] 1.03, P = 0.029), decreasing preoperative eGFR (OR 1.06, P < 0.001) and receipt of neoadjuvant (OR 2.07, P = 0.006) and adjuvant chemotherapy (OR 1.41, P = 0.012). Worsened ACM was associated with CKD-S3b (hazard ratio 1.42, P = 0.032), but not CKD-S3a (P = 0.766). Development of CKD-S3a (P = 0.812) and CKD-S3b (P = 0.316) were not associated with CSM. The 5-year OS rate was significantly worse in CKD-S3b (no-CKD 71%, CKD-S3a 70%, CKD-S3b 59%; P = 0.017). No differences between CKD-S groups were noted for 5-year CSS (no-CKD 78%, CKD-S3a 77%, CKD-S3b 82%; P = 0.44). CONCLUSIONS:A significant proportion of UTUC patients undergoing RNU developed CKD-S. Development of CKD-S3b was associated with worse ACM. Increasing age, preoperative eGFR, and chemotherapy were associated with developing CKD-S3b. Our findings call for further exploration and refinement of nephron-preserving surgical strategies and non-nephrotoxic systemic therapy to improve survival outcomes in UTUC.
To assess the impact of neoadjuvant and adjuvant chemotherapy on survival outcomes, within a large multicenter cohort of Upper tract urothelial carcinoma patients treated with Nephroureterectomy. A multicenter retrospective analysis utilizing the Robotic surgery for Upper Tract Urothelial Cancer Study registry was performed. Baseline, preoperative, perioperative, and pathologic variables of three groups of patients receiving surgery only, neoadjuvant or adjuvant chemotherapy were compared. Categorical and continuous variables among the three subgroups were compared with Chi square and ANOVA tests. The impact of perioperative chemotherapy on survival outcomes was assessed with the Kaplan Meier method. Univariable and multivariable Cox regression analyses were performed to identify predictors of survival. Overall, 1,994 patients were included. Overall and Clavien grade ≥3 complications rates were comparable among the three subgroups (p = 0.65 and p = 0.92). At Kaplan Meier analysis, neoadjuvant chemotherapy significantly improved cancer-specific survival (p = 0.03) and overall survival (p = 0.03) probabilities of patients with cT ≥ 3 tumors and of those with positive cN (p = 0.03 and p = 0.02). On multivariable analysis, neoadjuvant chemotherapy was independently associated with an improvement of cancer-specific survival in cT ≥ 3 patients (HR 0.44; p = 0.04), and of both cancer-specific survival (HR 0.50; p = 0.03) and overall survival (HR 0.53; p = 0.02) probabilities in positive cN patients. This large multicenter retrospective analysis suggests significant survival benefit in Upper tract urothelial carcinoma patients with either locally advanced or clinically positive nodes disease receiving neoadjuvant chemotherapy. These findings can be regarded as “hypothesis generating”, stimulating future trials focusing on such advanced stages.
Background: Renal cell carcinoma (RCC) accounts for approximately 90% of kidney cancers, with a significant percentage of patients presenting with metastatic disease. Recent evidence suggests a notable role of the human microbiome in the onset, progression, and therapeutic outcomes of RCC. Objective: This systematic review aims to synthesise current knowledge on the association between the microbiome and RCC, focusing on pathogenesis, progression, and response to therapy. Methods: Complying with PRISMA guidelines, databases including PubMed, Embase, and Web of Science were searched for relevant studies up to December 7, 2023. The inclusion criterion was English-language articles that discussed RCC in relation to the microbiome of any body region. Screening was performed in a two-phase manner by three authors. Results: From 570 articles, 65 met the inclusion criteria. The gut microbiome (GM) emerged as a potential RCC pathogenesis driver, with certain bacteria associated with increased or decreased risk. Studies have also demonstrated that antibiotics and other medications can influence RCC therapeutic outcomes, reducing the effectiveness of immune-modulating therapies. Conclusions: While multiple bacterial species and antibiotics have been implicated in influencing RCC, further research is necessary to elucidate these relationships and investigate the efficacy of microbiome modulation on therapy effectiveness. Findings underscore the significant impact of the microbiome on RCC, suggesting the potential for microbiota-targeted therapeutics.
You have accessJournal of UrologyBladder Cancer: Upper Tract Transitional Cell Carcinoma II (MP38)1 May 2024MP38-03 PREDICTORS AND OUTCOME OF LYMPH NODE INVOLVEMENT FOLLOWING NEOADJUVANT CHEMOTHERAPY AND RADICAL NEPHROURETERECTOMY FOR PRIMARY UPPER TRACT UROTHELIAL CARCINOMA (ROBUUST COLLABORATIVE GROUP) Farshad Sheybaee Moghaddam, Alireza Ghoreifi, Erika Wood, Antonio Franco, Zhenjie Wu, Linhui Wang, Alessandro Antonelli, Francesco Ditonno, Firas Abdollah, Marco Finati, Giuseppe Simone, Gabriele Tuderti, Emma Helstrom, Andreas Correa, Ottavio De Cobelli, Matteo Ferro, Francesco Porpiglia, Daniele Amparore, Antonio Tufano, Sisto Perdonà, Stephan Broenimann, Nirmish Sigla, Margaret F. Meagher, Ithaar H. Derweesh, Dinno F. Mendiola, Mark L. Gonzalgo, Benjamine M. Eilender, Reza Mehrazin, Sol C. Moon, Soroush Rais-Bahrami, Courtney Yong, Chandru P. Sundaram, Raj Bhanvadia, Vitaly Margulis, Riccardo Autorino, and Hooman Djaladat Farshad Sheybaee MoghaddamFarshad Sheybaee Moghaddam , Alireza GhoreifiAlireza Ghoreifi , Erika WoodErika Wood , Antonio FrancoAntonio Franco , Zhenjie WuZhenjie Wu , Linhui WangLinhui Wang , Alessandro AntonelliAlessandro Antonelli , Francesco DitonnoFrancesco Ditonno , Firas AbdollahFiras Abdollah , Marco FinatiMarco Finati , Giuseppe SimoneGiuseppe Simone , Gabriele TudertiGabriele Tuderti , Emma HelstromEmma Helstrom , Andreas CorreaAndreas Correa , Ottavio De CobelliOttavio De Cobelli , Matteo FerroMatteo Ferro , Francesco PorpigliaFrancesco Porpiglia , Daniele AmparoreDaniele Amparore , Antonio TufanoAntonio Tufano , Sisto PerdonàSisto Perdonà , Stephan BroenimannStephan Broenimann , Nirmish SiglaNirmish Sigla , Margaret F. MeagherMargaret F. Meagher , Ithaar H. DerweeshIthaar H. Derweesh , Dinno F. MendiolaDinno F. Mendiola , Mark L. GonzalgoMark L. Gonzalgo , Benjamine M. EilenderBenjamine M. Eilender , Reza MehrazinReza Mehrazin , Sol C. MoonSol C. Moon , Soroush Rais-BahramiSoroush Rais-Bahrami , Courtney YongCourtney Yong , Chandru P. SundaramChandru P. Sundaram , Raj BhanvadiaRaj Bhanvadia , Vitaly MargulisVitaly Margulis , Riccardo AutorinoRiccardo Autorino , and Hooman DjaladatHooman Djaladat View All Author Informationhttps://doi.org/10.1097/01.JU.0001008700.92603.b1.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Lymph node dissection (LND) is recommended for optimal staging and therapy in high-risk upper tract urothelial carcinoma (UTUC). Neoadjuvant chemotherapy (NAC) has been shown to improve oncological outcomes in this group of patients. We aimed to identify the clinical and pathological predictors of positive lymph nodes in UTUC patients who had extirpative surgery following NAC. METHODS: In this multicenter retrospective study, we utilized the ROBUUST 2.0 (ROBotic surgery for Upper tract Urothelial Cancer STudy) database. Patients without LND or missing data in pathologic lymph node status were excluded. Multivariable logistic regression was performed to evaluate the factors associated with pathological node involvement by NAC status. RESULTS: Of 2,433 UTUCs, 883 patients were included, of whom 131 had NAC. Table 1 shows baseline and clinical features. Multivariable analysis revealed high grade histology (OR 2, CI 95% 1.1–3.8, p<0.03), pT stage >2 (OR 1.7, CI 95% 1.1–2.6, p<0.02) and lymphovascular invasion (OR 6.8, CI 95% 4.4–10.6, p<0.001) as independent predictors of LN positivity in non-NAch group, while lymphovascular invasion (OR 34.3, CI 95% 6.8–171.9, p<0.001) was the only predictors in NAch group. Distant metastasis was higher in ypN+ compared to pN+ patients (33% vs. 13%, p=0.02) (Figure 1). Median (IQR) time to distant metastasis in ypN+ and pN+ groups were 4 (IQR 1-9) and 3 (IQR 1–6) months, respectively. With a median (IQR) follow-up of 20 (6–41) months, the rate of being alive with no recurrence was higher in the pN+ compared to ypN+ group (55% vs 33%, p<0.001). CONCLUSIONS: Lymphovascular invasion is the only predictor of lymph node involvement in patients with UTUC who had extirpative surgery following NAC. Positive lymph node status following NAC is associated with a higher rate of distant metastasis and earlier disease-specific mortaility. Effective adjuvant systemic treatment is desperately warranted in this very high-risk group. Download PPT Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e641 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Farshad Sheybaee Moghaddam More articles by this author Alireza Ghoreifi More articles by this author Erika Wood More articles by this author Antonio Franco More articles by this author Zhenjie Wu More articles by this author Linhui Wang More articles by this author Alessandro Antonelli More articles by this author Francesco Ditonno More articles by this author Firas Abdollah More articles by this author Marco Finati More articles by this author Giuseppe Simone More articles by this author Gabriele Tuderti More articles by this author Emma Helstrom More articles by this author Andreas Correa More articles by this author Ottavio De Cobelli More articles by this author Matteo Ferro More articles by this author Francesco Porpiglia More articles by this author Daniele Amparore More articles by this author Antonio Tufano More articles by this author Sisto Perdonà More articles by this author Stephan Broenimann More articles by this author Nirmish Sigla More articles by this author Margaret F. Meagher More articles by this author Ithaar H. Derweesh More articles by this author Dinno F. Mendiola More articles by this author Mark L. Gonzalgo More articles by this author Benjamine M. Eilender More articles by this author Reza Mehrazin More articles by this author Sol C. Moon More articles by this author Soroush Rais-Bahrami More articles by this author Courtney Yong More articles by this author Chandru P. Sundaram More articles by this author Raj Bhanvadia More articles by this author Vitaly Margulis More articles by this author Riccardo Autorino More articles by this author Hooman Djaladat More articles by this author Expand All Advertisement PDF downloadLoading ...
Introduction The current standard of care for high-risk non-muscle invasive bladder cancer (HR-NMIBC) is Bacillus Calmette Guerin (BCG), however, it carries a non-responder rate of 30-50% with high risk of progression and side effect profile. Sequential intravesical gemcitabine and docetaxel (Gem/Doce) is an increasingly utilized treatment for HR-NMIBC, although prospective validation is pending. Our previous analyses have demonstrated an increased abundance of Lactobacillus rhamnoses GG (LGG) within the tumor stroma of responders, thus, we aimed to assess the role of intravesical LGG instillation as potential therapy in tumor-bearing mice. Methods We used the BBN model to recapitulate the histological and genetic characteristics of human bladder cancer in C57BL/6 mice. Upon ultrasound confirmation of tumor, mice were treated with live LGG (106 CFU) given via intravesical instillation for six weeks. Tumor burden was measured weekly with US. Additional comparative therapy included saline, BCG (106 CFU), and Gem/Doce. (Figure 1A) Cytokine urine analysis utilizing CodePlex Secretome Adaptive Panel* was collected at week 4. Immunohistochemistry was performed with bladder tissue and T-lymphocyte and total CD8 T-lymphocytes per high-power field were calculated. Following monocyte purification and stimulation, we assessed differentiation into macrophage and dendritic cells in both BCG and LGG group using FACS Aria, and processed results through Cell Quest. Additional supernatant cytokine production of monocytes, T-cells, and monocytes and T-cells to LGG and BCG was evaluated using Human CodePlex Adaptive Panel**. Results Complete response was seen in LGG (4/10), NS (0/10), BCG (2/10), and Gem/Doce (4/10) with tumor volume in LGG and Gem/Doce (5.1 cm3, 5.6 cm3). (Figure 1B). Week 4 urine cytokine demonstrated increased expression of KC (CXCL-1, 538.95 pg/ml), IP-10(CXCL10, 355.17 pg/ml), IL-6(477.05 pg/ml), IL-4(89.35 pg/ml), IL-1B (240.21 pg/ml) and MIP-1a (210.67 pg/ml) in LGG group (p<0.001).(Figure 1E) IHC of LGG demonstrated an increased Tumor/Stroma T-cell Infiltration;(0.93;±0.70).(Figure 1C, D) In vitro stimulation of human monocytes (CD14+/CD16+) and T-cells (CD3+/CD8+/CD4+) with LGG resulted in increased of IL-6 (1.82±;0.82pg/ml), IL-7 (0.68±0.14 pg/ml), and Granzyme B (0.64;±;1.91 pg/ml),;(Figure 1F) with increasing differentiation to immature dendritic cells (CD1+/CD11C-) (88.41 vs 54.33%) Conclusions Analysis of a murine intravesical therapy model revealed superior tumor response in both LGG and Gemcitabine/Docetaxel groups compared to control NS and standard of care BCG in the treatment of BBN induced tumor. Analysis of urinary LGG cytokine profile demonstrates enhanced immune activation through dendritic cell differentiation and Th2 pathway with direct antitumor effects through enhanced apoptosis.**(GM-CSF, Granzyme B, IFN-γ, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-13, IL-15, IL-17A, IP-10, MCP-1, MIP-1α, MIP-1β, Perforin, sCD137, TNF-α, TNF-β).*(GM-CSF, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-17A, IP-10, KC, MCP-1, MIP-1α, RANTES, TNF-α)
You have accessJournal of UrologyKidney Cancer: Advanced (Including Drug Therapy) II (PD18)1 May 2024PD18-12 OUTCOMES OF MINIMALLY INVASIVE NEPHRECTOMY FOLLOWING IMMUNE-CHECKPOINT INHIBITOR THERAPY: DATA FROM A MULTICENTER STUDY Alireza Ghoreifi, Farshad Sheybaee Moghaddam, Stephan Bronimann, Thomas Gerald, Emma K. Helstrom, Ekam S. Deol, Sina Sobhani, Inderbir Gill, R. Houston Thompson, Robert Uzzo, Abhinav Khanna, Randall Lee, Vitaly Margulis, Nirmish Singla, and Hooman Djaladat Alireza GhoreifiAlireza Ghoreifi , Farshad Sheybaee MoghaddamFarshad Sheybaee Moghaddam , Stephan BronimannStephan Bronimann , Thomas GeraldThomas Gerald , Emma K. HelstromEmma K. Helstrom , Ekam S. DeolEkam S. Deol , Sina SobhaniSina Sobhani , Inderbir GillInderbir Gill , R. Houston ThompsonR. Houston Thompson , Robert UzzoRobert Uzzo , Abhinav KhannaAbhinav Khanna , Randall LeeRandall Lee , Vitaly MargulisVitaly Margulis , Nirmish SinglaNirmish Singla , and Hooman DjaladatHooman Djaladat View All Author Informationhttps://doi.org/10.1097/01.JU.0001008596.32809.c5.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: There is high-level evidence supporting the use of immune checkpoint inhibitors (ICIs) in advanced renal cell carcinoma (RCC); however, limited data is available regarding nephrectomy, especially through a minimally invasive (MIS) approach, in this setting. The aim of this study is to report the outcomes of MIS nephrectomy following ICI therapy. METHODS: Using our IRB-approved multicenter data registry, we included patients with advanced RCC who underwent nephrectomy following ICI therapy at five high-volume US academic centers between 2015 and 2023. Clinical features and perioperative outcomes of those who underwent MIS approach were reviewed. Multivariable logistic regression was performed to evaluate the factors influencing the choice between MIS and open approach. RESULTS: A total of 158 patients were included, of whom 76 and 82 underwent MIS and open nephrectomies, respectively. Baseline clinical features of patients are shown in Table 1. The MIS procedures included robotic (n=56) and laparoscopic (n=20). A total of 6 (8%) patients converted to open (4 robotic and 2 lap) due to pancreatic injury (n=1), vascular injury (n=1), and failure to progress (n=4). On multivariable analysis, patients with non-metastatic vs. metastatic RCC (HR 3.1, 95%CI 1.3–7.3, p=0.01), those with smaller tumor size (HR 1.2 for each cm, 95%CI 1.1–1.3, p=0.001) and no clinical evidence of inferior vena cava thrombus (HR 29, 95% CI 3.5–237.4, p=0.002) were more likely to undergo MIS compared to open approach. Perioperative outcomes of MIS nephrectomies are shown in Figure 1. The 90-day complication and readmission rates were 22% (Clavien≥3: 8%) and 9%, respectively. No 90-day mortality was reported. CONCLUSIONS: Minimally invasive approach appears safe in properly selected patients with advanced renal cell carcinoma who are candidates for nephrectomy following ICI therapy. Download PPT Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e437 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Alireza Ghoreifi More articles by this author Farshad Sheybaee Moghaddam More articles by this author Stephan Bronimann More articles by this author Thomas Gerald More articles by this author Emma K. Helstrom More articles by this author Ekam S. Deol More articles by this author Sina Sobhani More articles by this author Inderbir Gill More articles by this author R. Houston Thompson More articles by this author Robert Uzzo More articles by this author Abhinav Khanna More articles by this author Randall Lee More articles by this author Vitaly Margulis More articles by this author Nirmish Singla More articles by this author Hooman Djaladat More articles by this author Expand All Advertisement PDF downloadLoading ...