Benign splenic lesions in BAP1-tumor predisposition syndrome: a case series.

BAP1-Tumor Predisposition Syndrome (TPDS) is caused by germline variants in BAP1 and predisposes to solid tumors. After observation of a radiologically malignant-appearing splenic mass with benign pathology in a patient with BAP1-TPDS, we sought to retrospectively characterize splenic lesions in individuals with BAP1-TPDS seen at a comprehensive cancer center. A dedicated radiology review for splenic abnormalities was performed. We identified 37 individuals with BAP1-TPDS, 81% with a history of cancer. Of 33 individuals with abdominal imaging, 10 (30%) had splenic lesions, and none were shown to be malignant on follow-up. Splenectomy in an individual with suspected splenic angiosarcoma showed a benign vascular neoplasm with loss of nuclear staining for BAP1 in a subset of cells. Benign splenic lesions appear to be common and potentially BAP1-driven in individuals with BAP1-TPDS; confirmation of these findings could lead to more conservative management and avoidance of splenectomy.

Surgical Outcomes and Genomic Insights of Nonclear Cell Renal Cell Carcinoma with Synchronous and Metachronous Nodal Disease.

INTRODUCTION: Oncological outcomes in patients with nonclear cell renal cell carcinoma (non-ccRCC) treated with surgery for locoregional nodal disease (ND) remain incompletely characterized. The objective was to investigate the characteristics and outcomes of non-ccRCC patients treated with lymph node dissection (LND) and salvage-LND (S-LND). METHODS: A total of 1627 patients underwent nephrectomy for nonmetastatic non-ccRCC at Memorial Sloan Kettering Cancer Center between 2007 and 2023. Histology was grouped as papillary, chromophobe, unclassified, and rare subtypes. Retrospective evaluation identified 2.5% (n = 40) of patients with nodal disease at time of nephrectomy (synchronous-ND) and 1.1% (n = 18) with metachronous nodal disease limited to the retroperitoneum (metachronous-ND). Patients' demographics and tumor characteristics were recorded and evaluated by univariate and multivariate cox regression models. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Patients who underwent tumor DNA sequencing during their clinical course were considered for genomic analysis. RESULTS: OS trended toward longer in metachronous-ND (51 vs 105 months; P = .2), though 23% of patients with synchronous-ND were recurrence-free at 45 months median follow-up. In multivariate analysis, rare histologies were associated with decreased OS (P = .030) and metachronous-ND with improved OS (P = .036). RFS and OS after S-LND was 15 and 96 months, respectively. Late onset of metachronous-ND/recurrence was associated with improved OS (P = .008). Genetic alterations in SETD2, TP53, B2M, and FGFR3 were exclusively seen in synchronous-ND, and tumor mutation burden (TMB) was also higher in patients with synchronous-ND (P = .016). CONCLUSIONS: Patients with metachronous-ND tend to have prolonged OS compared to synchronous-ND, but a substantial portion of patients with synchronous-ND still enter a durable disease-free state following LND. S-LND can likewise provide long-term survival, particularly in patients with longer time to metachronous nodal recurrence. Synchronous-ND was associated with SETD2, TP53, and NF2 alteration as well as higher TMB.

Advances in Imaging-Based Biomarkers in Renal Cell Carcinoma: A Critical Analysis of the Current Literature.

Cross-sectional imaging is the standard diagnostic tool to determine underlying biology in renal masses, which is crucial for subsequent treatment. Currently, standard CT imaging is limited in its ability to differentiate benign from malignant disease. Therefore, various modalities have been investigated to identify imaging-based parameters to improve the noninvasive diagnosis of renal masses and renal cell carcinoma (RCC) subtypes. MRI was reported to predict grading of RCC and to identify RCC subtypes, and has been shown in a small cohort to predict the response to targeted therapy. Dynamic imaging is promising for the staging and diagnosis of RCC. PET/CT radiotracers, such as 18F-fluorodeoxyglucose (FDG), 124I-cG250, radiolabeled prostate-specific membrane antigen (PSMA), and 11C-acetate, have been reported to improve the identification of histology, grading, detection of metastasis, and assessment of response to systemic therapy, and to predict oncological outcomes. Moreover, 99Tc-sestamibi and SPECT scans have shown promising results in distinguishing low-grade RCC from benign lesions. Radiomics has been used to further characterize renal masses based on semantic and textural analyses. In preliminary studies, integrated machine learning algorithms using radiomics proved to be more accurate in distinguishing benign from malignant renal masses compared to radiologists' interpretations. Radiomics and radiogenomics are used to complement risk classification models to predict oncological outcomes. Imaging-based biomarkers hold strong potential in RCC, but require standardization and external validation before integration into clinical routines.

Current and Future Biomarkers in the Management of Renal Cell Carcinoma.

Renal cell carcinoma biomarkers include serum, urine, liquid, and tissue biomarkers. There is currently an ongoing search for predictive biomarkers in the detection, recurrence, and treatment of renal cell carcinoma. Emerging signatures in the transcriptomic and translational biomarker space seem promising, although additional work is needed to validate candidates in a larger and more generalizable patient population.

Magnetic Appendix: An Uncommon Indication for Appendectomy.

Foreign object ingestions are a common occurrence in pediatrics, often necessitating endoscopic or surgical intervention. The ingestion of multiple magnets poses an increased risk for serious complications. Our article presents a case of a five-year-old boy who swallowed two pennies and four magnets. The latter failed to pass spontaneously and were lodged in the appendiceal orifice resulting in a challenging and unsuccessful endoscopic retrieval and hence required laparoscopic exploration, appendectomy, and partial cecal resection.

Does neoadjuvant chemotherapy diminish the sex disparity in bladder cancer survival after radical cystectomy?

INTRODUCTION: Sex-specific survival disparities for bladder cancer outcomes after radical cystectomy (RC) have been demonstrated in several studies. However, these studies predate the widespread adoption of neoadjuvant chemotherapy (NAC). We evaluated the differences in sex-specific survival between patients who received NAC with those who did not, using a contemporary national outcomes database. METHODS: The National Cancer Data Base was queried from 2004 to 2015 to identify subjects who underwent RC. Kaplan-Meier method with log-rank test was performed to compare all-cause mortality between men and women at each pathologic (p) TNM stage group: T1-4N0, N+ and M+ disease. Associations for all-cause mortality were identified using an adjusted Cox regression analysis, and our findings were confirmed with a subgroup analysis. RESULTS: A total of 9,835 subjects (7,483 men and 2,532 women) were included in the analysis. Kaplan-Meier survival curves and Cox regression analysis demonstrated female sex was not associated with worse overall survival compared to males (HR 0.947, 95%CI 0.852-1.053, P = 0.947) in the overall cohort. Stratified by pT stage and node positivity, worse overall survival was seen in women with pT4 disease who did not receive NAC compared to men (5-year OS 9.6% women vs. 15.2% men, P < 0.001), but no sex-specific difference was seen across all groups in patients who received NAC. Subgroup multivariable analysis showed that female sex conferred a survival disadvantage for pT4 (HR 1.369, P = 0.026) disease only in patients who did not receive NAC. CONCLUSIONS: In a contemporary cohort of subjects who underwent RC, administration of NAC narrows the sex survival-gap in advanced stage bladder cancer. Strategies to improve NAC usage in women should be adopted to overcome potential sex-specific differences such as delayed diagnosis, anatomic differences in higher stage disease, or altered tumor biology which may contribute to differences in oncologic outcomes.

Microwave ablation of cT1a renal cell carcinoma: oncologic and functional outcomes at a single center.

PURPOSE: Percutaneous ablation is an established alternative to surgical intervention for small renal masses. Radiofrequency and cryoablation have been studied extensively in the literature. To date, series assessing the efficacy and safety of microwave ablation (MWA) are limited. We present a cohort of 110 renal tumors treated with MWA. METHODS: A review of the medical record between January 2015 and July 2019 was performed, retrospectively identifying 101 patients (110 tumors). All ablations were performed by a single board-certified urologist/interventional radiologist. Demographic information, intraoperative, postoperative, and follow-up surveillance data were recorded. RESULTS: Median (IQR) age was 69.7 years (60.8-77.0); 27 (24%) were female. Median (IQR) BMI was 27.0 (25.1-30.2) and Charleston Comorbidity Index was 5.0 (4.0-6.0). 82 tumors were biopsy-confirmed renal cell carcinoma/oncocytic neoplasms. Median (IQR) tumor size was 2.0 cm (1.5-2.6). Median (IQR) RENAL nephrometry score was 6.0 (5.0-8.0). Technical success was achieved in all patients and all but one patient were discharged on the same day. Median (IQR) eGFR at baseline and 1 year were 71.9 mL/min/1.73 m2 (56.5-82) and 63.0 mL/min/1.73 m2 (54.0-78.2); the difference was -5.3 (p = 0.12). Two Clavien-Dindo type-I complications, one type-II complication, and one type-III complication were experienced in this cohort. Median radiographic follow-up was 376.5 days with 2 tumors (2.4% of RCC/oncocytic neoplasms) having recurred to date. CONCLUSIONS: MWA is a safe and efficacious treatment option for small renal masses with minimal adverse events and low rates of recurrence in this cohort of 101 patients. Continued follow-up is needed to assess long-term outcomes.

The role of surgical experience in patient selection, surgical quality, and outcomes in robot-assisted radical cystectomy.

BACKGROUND: Robot-assisted radical cystectomy (RARC) remains one of the most complex urological procedures. Due to regionalization of bladder cancer care, there is likely an imbalance in experience among urologists performing RARC. We sought to describe changes in patient selection, surgical quality surrogates and rates of complications in relation to surgical experience. METHODS: We retrospectively reviewed 409 consecutive patients with bladder cancer who underwent RARC between 2006 and 2017 by a single surgeon. The cohort was divided into 4 quartiles (Q1-Q4) according to surgical experience, based on the chronologic order at which RARC was performed. Baseline, perioperative and pathologic characteristics of patients were compared among the 4 groups. 30-day and 90-day complications were assessed using the Clavien-Dindo system. The association between surgical experience (quartile) and complications was assessed using multivariable logistic regression analyses. RESULTS: Median age (interquartile range [IQR] from 70-73 years), body mass index (IQR from 25 to 27 kg/m2) and preoperative glomerular filtration rate (IQR from 59 to 65 ml/min) were similar among all quartiles (all P > 0.05). Patients in Q4 had higher rates of previous abdominopelvic surgery (46.1% vs. 30.4%, P = 0.031) and American Society of Anesthesiologists score of 3 to 4 (72.3% vs. 47.1%, P = 0.003) compared to patients in Q1. Patients who underwent RARC in Q4 compared to Q1, had less estimated blood loss (250 ml vs. 350 ml, P < 0.001), shorter operative time (346 vs. 360 minutes, P < 0.001), and higher lymph node yield (22 vs. 17 nodes, P < 0.001). The 30-day and 90-day complication rates were 53% and 62%, respectively. Thirty-day complication rates were similar among all 4 quartiles (P > 0.05), but higher among patients in Q4 compared to Q1 within 90 days (74% vs. 54%, P = 0.01). On multivariable analysis, patients in Q4 were more likely to experience any 90-day complication (OR 2.03, 95%Cl 1.11-3.70) compared to Q1. CONCLUSION: Our results show that with surgical experience, more complex cases can be performed while continuing to improve surgical quality. Nonetheless, there appears to be a trade-off between the increase in complexity of cases performed with experience and accepting higher rates of complications.

Survival Outcomes in Neoadjuvant Chemotherapy for High-grade Upper Tract Urothelial Carcinoma: A Nationally Representative Analysis.

OBJECTIVE: To assess the impact of neoadjuvant chemotherapy (NAC) on survival outcomes in a contemporary cohort of patients with in upper tract urothelial carcinoma (UTUC). METHODS: The National Cancer Database was queried from 2004 to 2015 to identify subjects who underwent nephroureterectomy for UTUC. Kaplan-Meier method with log-rank test was performed to compare all-cause mortality between patients who received preoperative chemotherapy to those who did not at each pathologic (p) TNM stage group: T1-4N0, N+, and M+ disease. Associations for all-cause mortality were identified using an adjusted Cox regression analysis. RESULTS: A total of 10,315 chemoeligible subjects were included in the analysis. A total of 296 (2.9%) of patients received NAC prior to NU. Kaplan-Meier survival curves of the entire cohort demonstrated an overall survival advantage associated with administration of NAC (P = .017). Stratified by clinical staging, subjects with nonorgan-confined tumors had improved overall survival outcomes with NAC administration (P = .012). On multivariate analysis there was a statistically significant improvement in overall survival between in patients who received NAC. Of patients in the preoperative chemotherapy group who had clinically nonorgan-confined disease, 27.1% had organ-confined disease at time of surgery compared to 1.4% of those who underwent surgery as initial therapy. CONCLUSION: In a contemporary cohort of subjects who underwent nephroureterectomy for UTUC, administration of NAC in patients with high-grade nonorgan-confined disease led to higher rates of pathologic downstaging and was associated with improved overall survival.

Serum miRNAs Are Pharmacodynamic Biomarkers Associated With Therapeutic Response in Pediatric Inflammatory Bowel Disease.

BACKGROUND: We sought to identify microRNAs (miRNAs) associated with response to anti-TNF-α or glucocorticoids in children with inflammatory bowel disease (IBD) to generate candidate pharmacodynamic and monitoring biomarkers. METHODS: Clinical response was assessed by Pediatric Crohn's Disease Activity Index and Pediatric Ulcerative Colitis Activity Index. Quantitative real-time polymerase chain reaction via Taqman Low-Density Array cards were used to identify miRNAs in a discovery cohort of responders (n = 11) and nonresponders (n = 8). Seven serum miRNAs associated with clinical response to treatment, along with 4 previously identified (miR-146a, miR-146b, miR-320a, miR-486), were selected for further study. Candidates were assessed in a validation cohort of serum samples from IBD patients pre- and post-treatment and from healthy controls. Expression of miRNA was also analyzed in inflamed mucosal biopsies from IBD patients and non-IBD controls. RESULTS: Discovery cohort analysis identified 7 miRNAs associated with therapeutic response: 5 that decreased (miR-126, miR-454, miR-26b, miR-26a, let-7c) and 2 that increased (miR-636, miR-193b). In the validation cohort, 7 of 11 candidate miRNAs changed in the same direction with response to anti-TNF-α therapies, glucocorticoids, or both. In mucosal biopsies, 7 out of 11 miRNAs were significantly increased in IBD vs healthy controls. CONCLUSIONS: Five candidate miRNAs associated with clinical response and mucosal inflammation in pediatric IBD patients were identified (miR-126, let-7c, miR-146a, miR-146b, and miR-320a). These miRNAs may be further developed as pharmacodynamic and response monitoring biomarkers for use in clinical care and trials.

Ejaculatory Hood-Sparing Vaporization of the Prostate and Its Impact on Erectile, Ejaculatory, and Sexual Function.

OBJECTIVE: To assess the impact of ejaculatory hood (EH)-sparing transurethral vaporization of the prostate (TUVP) on sexual function, with a specific focus on erectile and ejaculatory function. METHODS: We studied 25 patients who underwent EH-sparing Photo Selective Vaporization of the Prostate using the Greenlight Laser or Bipolar Button Plasma Vaporization of the Prostate from August 2016 to March 2018. All patients were sexually active with anterograde ejaculation prior to treatment. Patients completed the Male Sexual Health Questionnaire (MSHQ) and AUA Symptom Score pre- and postoperatively. We compared preprocedure sexual function with postprocedure sexual function at 1- and 3-month intervals. A logistic regression model was used to identify predictors of improvement in sexual function. RESULTS: Twenty-five patients underwent EH-sparing TUVP from August 2016 to March 2018. At 3-months postoperatively, patients had significant improvement in erection score (12 vs 9, P = .04) and erection bother score (5 vs 3.5, P <.01) compared to baseline. They also had improvement in ejaculation score (26 vs 23, P = .03), ejaculation bother score (5 vs 4, P = .01), and total MSHQ score (87.5 vs 73, P = .01). Anterograde ejaculation was preserved in 80.0% of patients. Logistic regression identified higher AUA score severity as an independent predictor of MSHQ score improvement (1.32, CI: 1.03-1.69, P = .03). CONCLUSION: At 3 months postoperatively, the majority of men who underwent EH-sparing TUVP had preserved anterograde ejaculation and improved overall sexual function based on MSHQ survey. This validates EH-sparing TUVP in men with BPH who wish to maintain sexual function.

Validation of risk factors for recurrence of renal cell carcinoma: Results from a large single-institution series.

PURPOSE: To validate prognostic factors and determine the impact of obesity, hypertension, smoking and diabetes mellitus (DM) on risk of recurrence after surgery in patients with localized renal cell carcinoma (RCC). MATERIALS AND METHODS: We performed a retrospective cohort study among patients that underwent partial or radical nephrectomy at Weill Cornell Medicine for RCC and collected preoperative information on RCC risk factors, as well as pathological data. Cases were reviewed for radiographic evidence of RCC recurrence. A Cox proportional-hazards model was developed to determine the contribution of RCC risk factors to recurrence risk. Disease-free survival and overall survival were analyzed using the Kaplan-Meier method and log-rank test. RESULTS: We identified 873 patients who underwent surgery for RCC between the years 2000-2015. In total 115 patients (13.2%) experienced a disease recurrence after a median follow up of 4.9 years. In multivariate analysis, increasing pathological T-stage (HR 1.429, 95% CI 1.265-1.614) and Nuclear grade (HR 2.376, 95% CI 1.734-3.255) were independently associated with RCC recurrence. In patients with T1-2 tumors, DM was identified as an additional independent risk factor for RCC recurrence (HR 2.744, 95% CI 1.343-5.605). Patients with DM had a significantly shorter median disease-free survival (1.5 years versus 2.6 years, p = 0.004), as well as median overall survival (4.1 years, versus 5.8 years, p<0.001). CONCLUSIONS: We validated high pathological T-stage and nuclear grade as independent risk factors for RCC recurrence following nephrectomy. DM is associated with an increased risk of recurrence among patients with early stage disease.

Pylephlebitis with splenic abscess following transrectal prostate biopsy: rare complications of intra-abdominal infection.

Pylephlebitis is a rare complication of intra-abdominal infection involving septic thrombosis of the portal system. If the splenic vein is compromised, this can lead to a splenic abscess, an extremely rare complication of pylephlebitis. The pathophysiology behind these clinical entities remains unclear. In both cases, symptoms are highly nonspecific and include fever, malaise and abdominal pain. Here, we discuss a case in which a patient develops both pylephlebitis and a subsequent splenic abscess following a transrectal prostate biopsy. Diagnosis was made by computerized tomography scan; the treatment included broad spectrum antibiotics and laparoscopic splenectomy, after which the patient made a full recovery.