Pathologic Outcomes In Patients Research Articles

Pathologic Outcomes of Short-Course and Long-Course Radiotherapy for Locally Advanced Rectal Cancers Treated With Total Neoadjuvant Therapy.

Total neoadjuvant therapy (TNT) for patients with locally advanced rectal cancer (LARC) is now the standard of care. Randomized trials suggest the use of short-course radiotherapy (SCRT) and long-course radiotherapy (LCRT) are oncologically equivalent. To describe pathologic outcomes after surgical resections of patients receiving SCRT versus LCRT as part of TNT for LARC. All patients with LARC treated at a single tertiary hospital who underwent proctectomy after completing TNT were included. Patients were excluded if adequate details of TNT were not available in the electronic medical record. A total of 53 patients with LARC were included. Thirty-nine patients (73.5%) received LCRT and 14 (26.4%) received SCRT. Forty-nine patients (92.5%) were clinical stage III (cN1-2) prior to treatment. The average lymph node yield after proctectomy was 20.9 for SCRT and 17.0 for LCRT (P = .075). Of the 49 patients with clinically positive nodes before treatment, 76.9% of those who received SCRT and 72.2% of those who received LCRT achieved pN0 disease after TNT. Additionally, there were no significant differences in rates of pathologic complete response between patients who received SCRT and LCRT, 7.1% and 12.8%, respectively (P = .565). Pathologic outcomes of patients with LARC treated with SCRT or LCRT, as part of TNT, may be similar. Further prospective trials are needed to assess long-term clinical outcomes and to determine best treatment protocols.

Pathologic and survival outcomes following radical cystectomy for “progressive” and “de novo” muscle-invasive bladder cancer: A meta-analysis stratified by neoadjuvant chemotherapy status

ObjectiveTo compare survival and pathologic outcomes in patients with progressive muscle-invasive bladder cancer (pgMIBC) and de novo muscle-invasive bladder cancer (dnMIBC) after radical cystectomy (RC), with a focus on the role of neoadjuvant chemotherapy (NAC). MethodsA comprehensive literature search was conducted on PubMed and EMBASE databases to identify studies comparing pgMIBC to dnMIBC. Survival outcomes, including cancer-specific survival (CSS), overall survival (OS), and recurrence-free survival (RFS), and pathologic outcomes (rates of ≤pT1, pT0, pT3/T4, and pN+ disease) were compared between pgMIBC and dnMIBC. ResultsThe analysis included 19 cohorts from 16 studies, categorized into 3 groups based on NAC use: 1. patients who underwent RC and were all treated with NAC (RC + NAC only group); 2. patients who underwent RC, with or without NAC (RC +/- NAC group); 3. patients who only underwent RC without NAC (RC only group). Compared to dnMIBC, pgMIBC demonstrated worse outcomes for CSS, OS, and RFS. In the RC + NAC only group (3 cohorts), the hazard ratio (HR) for CSS was 1.52 (95% confidence interval [CI] = 1.05–2.2), while the HR for OS was 1.46 (95%CI = 1.05–2.02). Similarly, in the RC +/- NAC group (6 cohorts for CSS and 3 cohorts for OS), the HR for CSS was 1.27 (95%CI = 1.05–1.55), and the HR for OS was 1.27 (95%CI = 1.08–1.51). There were no significant differences observed in pathologic outcomes, including rates of ≤pT1, pT0, and pT3/T4 disease, across all subgroups. However, pgMIBC was associated with a higher risk of nodal metastatic (pN+) disease in the RC + NAC only group (4 cohorts, relative risk [RR] = 1.43, 95%CI = 1.12–1.84). ConclusionsThe findings highlight the potentially worse prognosis in patients with pgMIBC compared to dnMIBC, even with the modern use of NAC. The study emphasizes the importance of careful patient counseling, further classification of patients for treatment selection, and the consideration of additional or innovative systemic therapies for pgMIBC.

Exploring treatment outcomes in Stage II-III rectal cancer patients undergoing neoadjuvant therapy at a tertiary care center in Pakistan: a comprehensive analysis of pathological outcomes.

Rectal cancer treatment has transformed in recent years, with neoadjuvant treatment (NT) and total neoadjuvant treatment (TNT) aiming to enhance pathological responses. This pioneering study in our country delves into rectal cancer management, offering crucial insights by examining pathological outcomes in patients treated with the NT and TNT approach, shaping the evolving landscape. In this retrospective-cohort study spanning January 2017 to December 2022 at a tertiary care hospital in Pakistan, ethical approval was obtained to examine outcomes of two treatments. Patients were divided into TNT (chemoradiation and pre-surgery 5 FU-based chemotherapy) and NT (chemoradiation, surgery, and subsequent 5 FU-based chemotherapy). The primary end-point was response rates-no response, pathological complete response (pCR), near complete response (near CR), and partial response (PR). The Chi-Square Test for Independence assessed the association between treatment response and type (TNT or NT). Data analysis used STATA MP 64; significance was set at p < 0.05 for all two-tailed tests. We analyzed 77 patients, 60 underwent standard neoadjuvant chemoradiation, and 17 followed the total neoadjuvant approach. Predominantly male, most were > 65 with ECOG 0-1. The TNT group showed higher response rates (76% vs 62%, p = 0.039), with 40.38% achieving pCR. In the overall population, pCR and near-CR were similar (27.2% vs 26%), while PR were 14%. Treatment characteristics correlated significantly with chemotherapy type, concurrent chemoradiation, LVI, PNI, and T, N, M staging (p < 0.05). Median overall survival was not reached, and mean survival was 89.1months (CI: 95.0 to 83.3). Side effects varied, with notable differences in neuropathy, diarrhea, oral mucositis, and thrombocytopenia between NT and TNT groups. Our study adds to evidence favoring neoadjuvant approaches in managing rectal cancer in pakistan. Demonstrating a favorable pcr rate, ongoing research with extended follow-up is essential, given the dynamic landscape of rectal cancer treatment for improved patient outcomes.

Association of radiographic and pathologic outcomes in patients (pts) with advanced renal cell carcinoma (RCC) with and without thrombus receiving preoperative immune checkpoint inhibitor (ICI) regimens and circulating biomarkers.

415 Background: Primary RCC tumors and associated IVC thrombus have similar histology, however response to ICI is not always concordant. RCC with IVC thrombus is often difficult to manage, and perioperative ICI treatment responses remain largely unstudied. Methods: We conducted a retrospective analysis of pts with advanced RCC receiving preoperative ICI-based regimens at UTSW stratified by the presence of tumor thrombus. The primary objectives were pathologic change in both groups and radiographical response by RECIST 1.1 criteria for tumor and thrombus level change. The secondary objective was to evaluate biomarkers associated with thrombus. Comparisons were performed using a two-sample t-test or aChi-square test. Results: 65 pts were included (median age 64 years), 31 (48%) with baseline thrombus (9 (29%) renal vein thrombus; 6 (19%) level 1 IVC thrombus; 10 (32%) level 2; 2 (7%) level 3; and 4 (13%) level 4). 28 pts (43%) received ICI+ICI, while 20 pts (31%) received ICI+TKI and the rest received ICI monotherapy. 18/31 pts (58%) with thrombus and 20/34 without thrombus (59%) had metastasis at baseline. Pathological Tumor (pT) downstaging occurred in 13 pts with and 11 pts without thrombus; of these, 12 pts had received ICI+TKI and 12 pts ICI+ICI. Radiographic tumor (cT) downstaging occurred in 8/31 pts with thrombus and 7/34 pts without. 12/31 pts experienced thrombus downstaging. 5 pts with thrombus vs 2 pts without had complete tumor necrosis/pCR in the primary and radiographic PR, of whom 4/7 received ICI+TKI. In pts with IVC thrombus, preoperative ICI based regimens reduced median tumor size from 9.1 to 7.7 cm. Among responders in pts with IVC thrombus, ICI+TKI had a trend toward higher tumor shrinkage median (-3.3 vs -1.9 cm, p=0.3) and thrombus downstaging median ( -2 vs -1 levels , p=0.27) than ICI+ICI. Baseline anemia (Hemoglobin (Hgb), 11.1 vs 13.1 g/dL, p=0.002), lower Absolute Lymphocyte Count (ALC) (1.35x10^3 vs 1.55 x10^3 cells/uL, p=0.03), and higher Neutrophil-to-Lymphocyte ratio (NLR) (3.6 vs 3.2, p=0.03) were observed in pts with IVC thrombus. Conclusions: ICI+TKI regimens tend to have tumor downstaging, complete tumor necrosis/pCR in primary tumors, and some IVC thrombus control compared to ICI+ICI regimens. IVC thrombus is associated with lower Hgb and ALC and higher NLR levels. Prospective trials are ongoing to investigate perioperative treatment in pts with IVC thrombus. [Table: see text]

The influence of prostate volume on pathological outcomes after radical prostatectomy: A single-center retrospective study.

Currently, the association between prostate volume (PV) or prostate weight with pathological outcomes in patients with prostate cancer (PCa) is not well understood. This study aimed to explore whether PV can predict the adverse pathological outcomes of PCa patients after radical prostatectomy (RP). A total of 1063 men with confirmed localized PCa who underwent RP at the First Affiliated Hospital of Zhejiang University from January 2014 to April 2019 were retrospectively analyzed. Patients were assigned into small, medium and large groups based on the PV. The analysis of variance, χ2 test or Student t test was performed to compare differences among groups. Univariate and multivariate analyses were performed to identify significant predictors of pathological outcomes upgrading. Among the 1063 cases, approximately 35.0% had an upgrade of postoperative pathology. Compared with the small prostate group, more patients in the large prostate group achieved a Gleason score (GS) 6 and International Society of Urological Pathology (ISUP) grade 1 of postoperative pathological findings, clinical cT1c and cT2a stages and pathological pT2a and pT2b stages; the incidence of positive surgical margins and extraprostatic extension was relatively low (all P < .001). In multiple logistic regression, PV served as a significant predictor of any Gleason score upgrading (GSU) (odds ratio [OR] 0.988, 95% confidence interval [CI] 0.978-0.998), major GSU (OR 0.980, 95% CI 0.965-0.995) and any ISUP grade group upgrading (GGU) (OR 0.989, 95% CI 0.979-0.999). This study shows that PV can predict adverse pathological outcomes in PCa patients after radical prostatectomy. Pca patients with smaller prostate volume tend to have the high-grade disease at postoperative pathology as well as pathological outcome upgrading.

Effect of preoperative PI-RADS assessment on pathological outcomes in patients who underwent radical prostatectomy

ObjectiveTo assess the effect of preoperative MRI with standardized Prostate Imaging–Reporting and Data System (PI-RADS) assessment on pathological outcomes in prostate cancer (PCa) patients who underwent radical prostatectomy (RP).Patients and methodsThis retrospective cohort study included patients who had undergone prostate MRI and subsequent RP for PCa between January 2017 and December 2022. The patients were divided into the PI-RADS group and the non-PI-RADS group according to evaluation scheme of presurgery MRI. The preoperative characteristics and postoperative outcomes were retrieved and analyzed. The pathological outcomes included pathological T stage (pT2 vs. pT3–4) and positive surgical margins (PSMs). Patients were further stratified according to statistically significant preoperative variables to assess the difference in pathological outcomes. A propensity score matching based on the above preoperative characteristics was additionally performed.ResultsA total of 380 patients were included in this study, with 201 patients in the PI-RADS group and 179 in the non-PI-RADS group. The two groups had similar preoperative characteristics, except for clinical T stage (cT). As for pathological outcomes, the PI-RADS group showed a significantly lower percentage of pT3–4 (21.4% vs. 48.0%, p < 0.001), a lower percentage of PSMs (31.3% vs. 40.9%, p = 0.055), and a higher concordance between the cT and pT (79.1% vs. 64.8%, p = 0.003). The PI-RADS group also showed a lower proportion of pT3–4 (p < 0.001) in the cT1–2 subgroup and the cohort after propensity score matching. The PSM rate of cT3 patients was reduced by 39.2% in the PI-RADS group but without statistical significance (p = 0.089).ConclusionsPreoperative MRI with standardized PI-RADS assessment could benefit the decision-making of patients by reducing the rate of pathologically confirmed non-organ-confined PCa after RP and slightly reducing the PSM rate compared with non-PI-RADS assessment.

Abstract 17464: Peripheral Immune Cell Inflammatory Activation and Metabolic Dysregulation in Single Ventricle Congenital Heart Disease

Introduction: While heart failure (HF) is a leading cause of death and indication for transplant in single ventricle (SV) patients, the molecular mechanisms underlying HF progression are poorly understood. Chronic inflammation can initiate and accelerate pathological outcomes in patients with virtually every form of cardiovascular disease, yet our understanding of the impacts of immunologic alterations in SV are inadequate. Here, we test the hypothesis that peripheral immune cells (PBMCs) from SV patients display a pro-inflammatory and metabolically dysfunctional phenotype that contributes to progressive cardiac dysfunction. Methods: Pediatric SV patients were categorized based on ventricular function, including those with reduced systolic function (SVHF, n=32), Fontan failure (Fontan Failure, n=7), or healthy control (healthy control, n=18). PBMCs were isolated from whole blood by density gradient centrifugation. To assess the impact of the PBMC extracellular milieu, we treated isolated cardiomyocytes with human plasma. Mitochondrial bioenergetics were assessed using the Seahorse Bioanalyzer (Agilent). Statistical analysis was performed using a Kruskal-Wallis and post-hoc Dunn’s multiple comparisons test. Total RNA sequencing was performed to identify dysregulated pathways. Results: PBMCs from SVHF patients display decreased metabolic function (OCR, A) and increased glycolysis (ECAR, B). PBMCs from SVHF patients also display significant alterations in immune, inflammatory, and metabolic pathways (C). Moreover, plasma from SVHF patients decreases cardiomyocyte energetics. Conclusions: These data suggest that immune cells from SV patients display a pro-inflammatory and metabolically dysfunctional phenotype, with an increased dependence on glycolysis. Therefore, our data highlight a role for SV PBMCs to potentiate progressive cardiac dysfunction in this population and provide a novel avenue for therapeutic intervention.

Impact of trans-anal versus laparoscopic total mesorectal excision on the surgical and pathologic outcomes of patients with rectal cancer: meta-analysis of randomized controlled trials.

Despite its profound impact on the oncologic outcomes of rectal cancer, the most optimal surgical approach to total mesorectal excision (TME) has not been identified yet. All previous meta-analyses on this subject have been based on observational studies. This meta-analysis was conducted to assess the surgical and oncologic outcomes of laparoscopic TME (LaTME) compared to trans-anal TME (TaTME), utilizing only randomized controlled trials. Systematic review and meta-analysis of randomized controlled trials. We searched electronic databases (MEDLINE, Cochrane CENTRAL, Clinicaltials.gov) from 2010 onwards, for all published clinical trials comparing TaTME to LaTME. Results are presented as risk ratios, with 95% CI, and pooled using the random effects model. A total of 1691 patients, from 6 eligible randomized controlled trials, were included for analysis. Analyzed data showed no significant difference in morbidity (RR: 0.85, p = 0.15), mortality (RR: 0.50, p = 0.44), conversion to open (RR: 0.40, p = 0.07), or anastomotic leakage (RR: 0.73, p = 0.10) between TaTME and LaTME. There was also no difference in the rate of positive distal resection margin (DRM) (RR: 0.55, p = 0.10) or positive circumferential resection margin (CRM) (RR: 0.67, p = 0.30). Patients undergoing TaTME were more likely to have a complete TME (RR: 1.06, p = 0.002) and shorter hospital stays (RR: - 0.97, p < 0.00001). Patients undergoing TaTME for rectal cancer were more likely to have a complete TME when compared to LaTME, though this did not translate into improved distal or circumferential resection margin. Additionally, TaTME and LaTME had similar surgical outcomes except for shorter length of stay with TaTME.

Machine Learning for the Prediction of Adverse Pathological Outcomes in Patients Treated with Radical Prostatectomy.

Extracapsular extension (ECE) and seminal vesicle invasion (SVI) are associated with negative oncologic outcomes in patients with prostate cancer. We have developed and validated a machine learning model to more accurately identify patients at risk of these adverse surgical outcomes prior to radical prostatectomy (RP). This study included a cohort of patients diagnosed with prostate cancer and treated with RP and lymph node dissection at a tertiary care medical center from 2010 to 2020. An ensemble model using a base gradient-boosted trees-based machine learning model and isotonic calibrators was trained on 80% of the cohort, with 20% held out for validation. The model uses age at surgery, prostate specific antigen level (PSA) at diagnosis, biopsy Gleason grade group, numbers of positive and negative cores on biopsy, and clinical T-stage (cT) as input variables. Model performance was assessed on the hold-out set using the area under the receiver operating curve (AUC). The full dataset included 18,729 eligible patients. Median PSA at diagnosis was 7.3 ng/mL. Most patients had clinically organ confined disease (cT1 - cT2) with only 136 (0.7%) having cT3. The most common biopsy Gleason grade group was 2 (7,118 or 38% of patients), with Gleason grade 4 in 1,796 (9.6%), and 5 in 1,064 (5.7%) patients. After RP, 11,931 (64%) of patients had organ confined disease, 4,298 (23%) had ECE, and 2,500 (13%) had SVI. When validated on the hold-out set (n = 3,746), the model had AUCs of 0.79 (95%-CI 0.77 - 0.80), 0.67 (0.65 - 0.69), and 0.83 (0.81 - 0.85) for the prediction of organ confined disease, ECE, and SVI, respectively. In conclusion, we have developed a machine learning model that predicts individual patient risk of pathologic T-stage. The model can be used to provide more accurate risk assessments and improve surgical treatment planning. We are currently working on externally validating our results on patients from different institutions.

Pathological Outcomes of Patients With Advanced Renal Cell Carcinoma Who Receive Nephrectomy Following Immunotherapy.

Even though cytoreductive nephrectomy (CN) was once the standard of care for patients with advanced renal cell carcinoma (RCC), its role in treatment has not been well analyzed or defined in the era of immunotherapy (IO). This study analyzed pathological outcomes in patients with advanced or metastatic RCC who received IO prior to CN. This was a multi-institutional, retrospective study of patients with advanced or metastatic RCC. Patients were required to receive IO monotherapy or combination therapy prior to radical or partial CN. The primary endpoint assessed surgical pathologic outcomes, including American Joint Committee on Cancer (AJCC) staging and frequency of downstaging, at the time of surgery. Pathologic outcomes were correlated to clinical variables using a Wald-chi squared test from Cox regression in a multi-variable analysis. Secondary outcomes included objective response rate (ORR) defined by response evaluation criteria in solid tumors (RECIST) version 1.1 and progression-free survival (PFS), which were estimated using the Kaplan-Meier method with reported 95% CIs. Fifty-two patients from 9 sites were included. Most patients were male (65%), 81% had clear cell histology, 11% had sarcomatoid differentiation. Overall, 44% of patients experienced pathologic downstaging, and 13% had a complete pathologic response. The ORR immediately prior to nephrectomy was stable disease in 29% of patients, partial response in 63%, progressive disease in 4%, and 4% unknown. Median follow-up for the entire cohort was 25.3 months and median PFS was 3.5 years (95% CI, 2.1-4.9). IO-based interventions prior to CN in patients with advanced or metastatic RCC demonstrates efficacy, with a small fraction of patients showing a complete response. Additional prospective studies are warranted to investigate the role of CN in the modern IO-era.

Identification and prediction of m7G-related Alzheimer's disease subtypes: insights from immune infiltration and machine learning models.

Alzheimer's disease (AD) is a complex and progressive neurodegenerative disorder that primarily affects older individuals. N7-methylguanosine (m7G) is a common RNA chemical modification that impacts the development of numerous diseases. Thus, our work investigated m7G-related AD subtypes and established a predictive model. The datasets for AD patients, including GSE33000 and GSE44770, were obtained from the Gene Expression Omnibus (GEO) database, which were derived from the prefrontal cortex of the brain. We performed differential analysis of m7G regulators and examined the immune signatures differences between AD and matched-normal samples. Consensus clustering was employed to identify AD subtypes based on m7G-related differentially expressed genes (DEGs), and immune signatures were explored among different clusters. Furthermore, we developed four machine learning models based on the expression profiles of m7G-related DEGs and identified five important genes from the optimal model. We evaluated the predictive power of the 5-gene-based model using an external AD dataset (GSE44770). A total of 15 genes related to m7G were found to be dysregulated in patients with AD compared to non-AD patients. This finding suggests that there are differences in immune characteristics between these two groups. Based on the differentially expressed m7G regulators, we categorized AD patients into two clusters and calculated the ESTIMATE score for each cluster. Cluster 2 exhibited a higher ImmuneScore than Cluster 1. We performed the receiver operating characteristic (ROC) analysis to compare the performance of four models, and we found that the Random Forest (RF) model had the highest AUC value of 1.000. Furthermore, we tested the predictive efficacy of a 5-gene-based RF model on an external AD dataset and obtained an AUC value of 0.968. The nomogram, calibration curve, and decision curve analysis (DCA) confirmed the accuracy of our model in predicting AD subtypes. The present study systematically examines the biological significance of m7G methylation modification in AD and investigates its association with immune infiltration characteristics. Furthermore, the study develops potential predictive models to assess the risk of m7G subtypes and the pathological outcomes of patients with AD, which can facilitate risk classification and clinical management of AD patients.

OGC P17 Surgical and Pathological Outcomes in Patients with a CDH-1 Mutation undergoing Total Gastrectomy: A Systematic Review

Abstract Background Patients with CDH1 (E-cadherin) gene mutations have a 60–80% increased lifetime risk of hereditary diffuse gastric cancer (HDGC). Although prophylactic total gastrectomy may reduce long-term risk of gastric cancers, the associated morbidity and mortality remains unclear. This systematic review aims to characterise postoperative surgical outcomes in patients choosing to undergo a prophylactic total gastrectomy. Methods A systematic literature search was conducted for studies reporting endoscopic surveillance, surgical outcomes and quality of life (QoL) for patients with a CDH1 mutation undergoing a total gastrectomy. Results A total of 991 patients were looked at across 33 studies, with 96% harbouring a CDH1 mutation (n=948). Seven hundred and seventy six patients had endoscopy results reported across 27 studies, with 72% presenting without evidence of cancer foci (n=555). Of these patients, 60% proceeded to have a total gastrectomy (n=333) and histological analysis revealed cancer foci in 83% of the gastrectomy specimens (n=276). Six hundred and forty nine patients were reported to have a total gastrectomy across 33 studies. Pathology outcomes were reported for 528 patients across 26 studies, of which 87% had pT1aN0M0 disease (n=458). Surgical complications were reported for 406 patients across 20 studies. Only 3 studies reported 0 complications. A total of 188 complications were reported across 17 studies, with the most common presentations being anastomotic strictures (23%), pulmonary complications (13%), wound infections (12%) and anastomotic leaks (11%). A total of 5 mortalities were reported in 23 studies over the follow-up period. Conclusions Prophylactic total gastrectomy is recommended for patients with a CDH1 mutation. Currently, reliable endoscopic surveillance is lacking and total gastrectomy remains the definitive method for preventing advanced diffuse gastric cancer. Patients choosing to undergo surgery should be provided with adequate counselling, with careful consideration of the associated morbidity.

Molecular biomarkers to help select neoadjuvant systemic therapy for urothelial carcinoma of the bladder.

In this review, we aimed to summarize the available evidence on pretreatment molecular biomarkers that may help to predict oncologic and pathologic outcomes in patients treated with neoadjuvant systemic therapy (NAST) for urothelial carcinoma of the bladder (UCB). Several readily available and easily measurable blood-based biomarkers (e.g., neutrophil to lymphocyte or platelet-lymphocyte ratios) seems to help improve the selection of UCB patients who are most likely to benefit from NAST. Recent evidence suggests liquid biopsy including circulating tumor DNA (ctDNA) to be a promising tool to guide the administration of NAST in UCB patients. Pretreatment molecular and genetic characterization of transurethral resection of the bladder tumor samples may also help understand the tumor biology as luminal and basal tumor subtypes seems to be more responsive to NAST, while claudin-low and luminal-infiltrated tumor subtypes are less. In the context of neoadjuvant immunotherapy, programmed death-ligand 1 (PD-L1) status and ctDNA remain the only biomarker with possible value as the clinical utility of tumor mutational burden remains controversial/poor. Biomarker approach is a necessary step to usher the age of precision/personalized medicine for muscle-invasive UCB with the overarching good to prevent both over- and under-therapy. The present review may offer a robust framework to compare and assess current and future molecular biomarkers for the selection of NAST in muscle-invasive UCB.

What is the clinical impact of occult HBV infections and anti-HBc positivity in patients with chronic hepatitis C?

Occult hepatitis B infection (OBI) is defined by the persistence of the hepatitis B virus (HBV) genome in the liver of individuals testing negative for hepatitis B surface antigen (HBsAg). Hepatitis B core antibody (anti-HBc) is the serological marker that indicates HBV exposure. The impact of anti-HBc and OBI on patients with chronic hepatitis C remains unclear. The aim of the present study was to determine the prevalence of anti-HBc and OBI and to evaluate their impact on the clinical and pathological outcomes of patients with chronic hepatitis C. The study included 59 HBsAg-negative chronic hepatitis C patients who underwent a liver parenchymal biopsy. The presence of HBV DNA was investigated using an in-house nested PCR method. OBI was detected in 16 (27.1%) of the 59 cases and also in 10 (62.5%) of 22 (37.3%) anti-HBc-positive patients. None of the patients had positive serum HBV DNA. OBI was associated with the presence of anti-HBV antibodies (P < 0.05). There was also an association between anti-HBc positivity and the activity grades and fibrosis stages of the liver and also a prevalence of liver steatosis (P < 0.05). Positive anti-HBc results may predict OBI and may also be associated with the progression of liver injury in HBsAg-negative patients with chronic hepatitis C. Therefore, it is suggested that patients with chronic hepatitis C should be screened for anti-HBc positivity, and anti-HBc-positive patients should be carefully evaluated for disease progression.

MP15-06 RISK OF ADVERSE RADICAL PROSTATECTOMY OUTCOMES IN PATIENTS DIAGNOSED WITH IUSP ≤2 PROSTATE CANCER ON MRI/TRUS FUSION BIOPSY

You have accessJournal of UrologyCME1 May 2022MP15-06 RISK OF ADVERSE RADICAL PROSTATECTOMY OUTCOMES IN PATIENTS DIAGNOSED WITH IUSP ≤2 PROSTATE CANCER ON MRI/TRUS FUSION BIOPSY Claudia Kesch, Vlad Pantea, Timo Soeterik, Alessandro Marquis, Giulia La Bombarda, Allesandro Morlacco, Francesco Barletta, Felix Preisser, Fabio Zattoni, Giancarlo Marra, Roderik C.N. van den Bergh, Jan Philipp Radtke, Boris Hadaschik, and Giorgio Gandaglia Claudia KeschClaudia Kesch More articles by this author , Vlad PanteaVlad Pantea More articles by this author , Timo SoeterikTimo Soeterik More articles by this author , Alessandro MarquisAlessandro Marquis More articles by this author , Giulia La BombardaGiulia La Bombarda More articles by this author , Allesandro MorlaccoAllesandro Morlacco More articles by this author , Francesco BarlettaFrancesco Barletta More articles by this author , Felix PreisserFelix Preisser More articles by this author , Fabio ZattoniFabio Zattoni More articles by this author , Giancarlo MarraGiancarlo Marra More articles by this author , Roderik C.N. van den BerghRoderik C.N. van den Bergh More articles by this author , Jan Philipp RadtkeJan Philipp Radtke More articles by this author , Boris HadaschikBoris Hadaschik More articles by this author , and Giorgio GandagliaGiorgio Gandaglia More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002544.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To avoid overtreatment, active surveillance (AS) is recommended for prostate cancer (PC) patients with low- to favorable intermediate-risk features. However, previous studies based on 12-core transrectal ultrasound (TRUS) biopsy have demonstrated high upgrading rates (up to 70%) at radical prostatectomy (RP) in men potentially suitable for AS. We aim at exploring rate and risk factors for adverse pathologic outcomes in patients with multiparmetric magnetic resonance imaging (mpMRI)/TRUS fusion biopsy confirmed ISUP ≤2 PC. METHODS: Multicentre, retrospective analysis of 477 consecutive patients with ISUP ≤2 PC on mpMRI/TRUS fusion biopsy treated with RP. Adverse outcomes (AO) were defined as any ISUP upgrading, upgrading to ISUP ≥3, ≥pT3 at RP, any AO (=ISUP upgrading to ≥ 3 and/or ≥pT3 and/or N1) or biochemical recurrence (BCR) in men with available follow-up (n=327). Rates of AO were calculated for the overall cohort, biopsy ISUP 1 (n=149) and biopsy ISUP 2 (n=328) PC. Groups were compared using Qui-square test. Logistic regression was used to determine predictive factors. RESULTS: The overall rates of ISUP upgrading, ISUP upgrading to ≥ 3, ≥pT3 on RP and any AO were 39%, 21%, 32% and 43%, respectively. Compared to biopsy ISUP 2, men with biopsy ISUP 1 PC experienced more frequently ISUP upgrading (27% vs. 67%, p<0.001), but less ISUP upgrading to ≥ 3 (27% vs. 10%, p<0.001) and any AO (48% vs. 32%, p=0.001). No differences were recorded for ≥pT3 on RP (34% vs. 26%, p=0.052). PSA density, PIRADS score on mpMRI, number of positive targeted biopsy (TB) cores, ISUP of TB cores, overall number of biopsy cores and positive biopsy cores were all predictive factors for ISUP upgrading to ≥3, ≥pT3 at RP as well as for any AO. Neither PSA nor positive digital rectal examination significantly predicted AOs. Median time of follow-up was 12 months. The 1-year BCR-free survival was 94%. No significant differences in BCR rates were observed comparing men with biopsy ISUP 1 and biopsy ISUP 2 (5% vs. 7%, p=0.518). Positive TB cores, ISUP at RP, ISUP upgrading, ISUP upgrading to ≥3, ≥pT3 on RP and any AO were all predictive for BCR. CONCLUSIONS: In men with mpMRI/TRUS fusion biopsy confirmed ISUP ≤ 2 PC adverse outcomes at RP are still frequent. When counseling patients regarding AS, especially PSA density, ISUP, mpMRI findings and number of positive biopsy cores should be taken into account to identify the men at higher risk of AO. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e243 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Claudia Kesch More articles by this author Vlad Pantea More articles by this author Timo Soeterik More articles by this author Alessandro Marquis More articles by this author Giulia La Bombarda More articles by this author Allesandro Morlacco More articles by this author Francesco Barletta More articles by this author Felix Preisser More articles by this author Fabio Zattoni More articles by this author Giancarlo Marra More articles by this author Roderik C.N. van den Bergh More articles by this author Jan Philipp Radtke More articles by this author Boris Hadaschik More articles by this author Giorgio Gandaglia More articles by this author Expand All Advertisement PDF DownloadLoading ...

Adverse pathological outcomes of patients with de novo muscle invasive bladder cancer in Northern Ontario.

This study aimed to investigate the clinical and pathological characteristics of patients with de novo muscle-invasive bladder cancer (MIBC) who underwent radical cystectomy in Northern Ontario. This is a retrospective cross-sectional study of patients with de novo T2 MIBC who underwent radical cystectomy over a 2-year-period in Thunder Bay Regional Health Sciences Centre. Clinical and pathological characteristics of Trans Urethral Resection of Bladder Tumors and cystectomy specimens were analyzed. Of the 59 patients aged 67 ± 8.8 years, predominated by males (80%), 27.1% were younger than age 60. After surgery, upstaging was noted in 59.3% (T3 in 27.1% and T4 in 32.2%) while node positive was noted in 36% of patients. Prostate adenocarcinoma was incidentally discovered in 20 (34%) of patients with 50% considered significant (Gleason score ≥ 7). Downstaging was found in those who had neoadjuvant chemotherapy (p = 0.001). The high prevalence of younger ages (less than 60), a high rate of upstaging, the presence of high-grade incidental prostate cancer, and lymph node positives in T2 de novo MIBC in Northern Ontario, warrants further investigation of potential causes and risk factors at individual, public, and population health levels in the region.

An Artificial Intelligence Ultrasound Platform for Screening and Staging of Thyroid Cancer

<h3>Purpose/Objective(s)</h3> Thyroid cancer is one of the most rapidly increasing cancer in the US, largely due to increased detection. BRAF mutation (V600E) is common in papillary thyroid carcinoma (PTC) and is associated with poor prognosis. The purpose of this study was to establish a multimodal artificial intelligence (AI) ultrasound platform that consists of radiomics, topological data analysis (TDA), TI-RADS features, and deep learning (DL) to predict malignancy and pathological outcome in patients with papillary thyroid cancer. <h3>Materials/Methods</h3> Between 2010 and 2021, 464 patients (511 nodules) underwent fine needle biopsy at our institution. The median age was 49 years. The dataset was divided into an internal training (103 malignant, 259 benign nodules), an internal validation (51 malignant and 98 benign nodules), and an external validation (270 malignant and 50 benign nodules) datasets. High-resolution ultrasonography (sagittal and transverse views) was performed preoperatively for all patients. We employed multimodal machine learning (ML) methods: radiomics (a high-throughput quantitative analysis of image features), TDA (a rapidly growing ML pipeline that analyzes geometric relationships between data points in images), and deep learning (where algorithms run data through layers of neural network to achieve prediction). One hundred and four quantitative radiomics features, 476 topological algebraic-geometric features), and TI-RADS features were obtained for all patients. Linear discriminant analysis (LDA) along with the Pearson correlation coefficient (0.85 threshold) were employed for feature extraction. Support vector machine (SVM) was chosen as the machine learning classifier. <h3>Results</h3> For malignancy prediction, radiomics, TDA, TI-RADS, and deep learning model achieves an accuracy of 88.7% (0.87 AUC), 81.5% (0.81 AUC), 80% (0.76 AUC), and 87.4% (0.92 AUC), respectively. Our multimodal AI platform which utilizes radiomics, TDA, TI-RADS, and deep learning achieves a 98.7% accuracy (0.99 AUC), which is significantly improved when compared to individual model (radiomics, TDA, TI-RADS: p<0.001, deep learning: p=0.002). On the external validation dataset, our model achieves a 91.4% accuracy (0.94 AUC) for malignancy prediction. Using multimodal that consists of radiomics, TDA, and TI-RADS, an accuracy of 93% accuracy (0.93 AUC), 89% accuracy (0.88 AUC), and 98% (0.96 AUC) is achieved for T, N, and extrathyroidal extension, respectively. Employing a 5-fold cross validation, we achieve an accuracy of 96% (0.97 AUC) for predicting BRAF mutation. <h3>Conclusion</h3> We established a robust AI platform for predicting thyroid malignancy, pathological stage, and BRAF mutation using routine ultrasonography. This low-cost reproducible approach would allow developing of personalized treatment planning, especially in countries where resources are limited.

Pathologic and radiographic outcomes following prostate cancer diagnosis aided by IsoPSA testing.

276 Background: IsoPSA is a structure-based assay previously demonstrated to outperform prostate specific antigen (PSA) and free-to-total PSA ratio in detecting clinically significant prostate cancer at the time of biopsy (Stovsky, Klein 2019). Herein we report pathologic outcomes in patients treated via radical prostatectomy (RP) whom had undergone IsoPSA testing prior to their diagnostic biopsy. We also explore IsoPSA status in the context of MRI dependent findings, including PIRADS scores and PSA density. Methods: We conducted a retrospective review of patients whom had undergone IsoPSA testing prior to biopsy and RP at our institution between 2019-2021. We also identified subsets of patients with pre-operative prostate MRI’s. Exploratory analyses were performed to determine associations between IsoPSA and adverse histologic (cribiform, intraductal status (CB/ID), grade group status) pathologic (extraprostatic extension, seminal vesicle involvement, surgical margins) and radiographic (PSA density, PIRADS, location) features. We examined these data points in a randomly selected control group of RP patients whom had not had IsoPSA testing. Student’s T-test, Mann Whitney U, Kruskal Wallis, were used where appropriate. Results: A total of 83 patients underwent RP following IsoPSA testing, with 72.2% (60/83) also undergoing pre-operative prostate MRI. The mean total PSA was 10.3 ng/dL, IsoPSA index was 10.2 and prostate size 46.8 cc. IsoPSA was significantly associated with PSA density (median IsoPSA of 9.9 vs 7.8 for PSA density &gt; 0.15, &lt;0.15 respectively, p &lt; 0.001). The median IsoPSA index was higher when the dominant tumor was found in the transitional zone versus peripheral zone (12.7 vs 8.8 p = 0.011). IsoPSA trended towards but was not associated with PIRADS-v2 score (1-2 vs 3 vs 4-5) (p = 0.1). IsoPSA was not selectively associated with adverse pathological or histological features. Conclusions: IsoPSA has been shown to predict clinically significant disease on biopsy, and as such may improve the selection of men for such intervention. In our initial cohort, IsoPSA reliably identified patients with clinically significant disease without selecting for unique adverse pathologic/histologic features when compared to a control group. Radiographically, IsoPSA was significantly associated with elevated PSA density ( &gt; 0.15), tumor location (TZ vs PZ), and trended towards significance with PIRADS v.2 score (p = 0.1. Further work is encouraged to explore its adjunctive benefit in correlation to MRI features.

Impact of somatic mutations on clinical and pathologic outcomes in borderline resectable and locally advanced pancreatic cancer treated with neoadjuvant chemotherapy and stereotactic body radiotherapy followed by surgical resection.

PurposeThe purpose of this study was to determine if somatic mutations are associated with clinical and pathologic outcomes in patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) who were treated with neoadjuvant chemotherapy and stereotactic body radiotherapy (SBRT). Materials and MethodsPatients treated with neoadjuvant chemotherapy and SBRT followed by surgical resection from August 2016 to January 2019 and who underwent next generation sequencing of their primary tumor were included in the study. Next-generation sequencing was performed either in-house with a Solid Tumor Panel or with FoundationOne CDx. Univariate (UVA) and multivariable analyses (MVA) were performed to determine associations between somatic mutations and pathologic and clinical outcomes. ResultsThirty-five patients were included in the study. Chemotherapy consisted of modified FOLFIRINOX, gemcitabine and nab-paclitaxel, or gemcitabine and capecitabine. Patients were treated with SBRT in 33 Gy in 5 fractions. On UVA and MVA, tumors with KRAS G12V mutation demonstrated better pathologic tumor regression grade (TRG) to neoadjuvant therapy when compared to tumors with other KRAS mutations (odds ratio = 0.087; 95% confidence interval [CI], 0.009–0.860; p = 0.036). On UVA and MVA, mutations in NOTCH1/2 were associated with worse overall survival (hazard ratio [HR] = 4.15; 95% CI, 1.57–10.95; p = 0.004) and progression-free survival (HR = 3.61; 95% CI, 1.41–9.28; p = 0.008). On UVA, only mutations in NOTCH1/2 were associated with inferior distant metastasis-free survival (HR = 3.38; 95% CI, 1.25–9.16; p = 0.017). Conclusion In BRPC and LAPC, the KRAS G12V mutation was associated with better TRG following chemotherapy and SBRT. Additionally, NOTCH1/2 mutations were associated with worse overall survival, distant metastasis-free survival, and progression-free survival.

SC230 - Role of inflammatory markers as predictors of adverse pathological outcomes in patients with testicular cancer: a multicenter analysis

SC230 - Role of inflammatory markers as predictors of adverse pathological outcomes in patients with testicular cancer: a multicenter analysis