Plasma-Derived Cell-Free DNA as a Biomarker for Early Detection, Prognostication, and Personalized Treatment of Urothelial Carcinoma.

Bladder cancer (BC) is one of the most common malignancies in the United States, with over 80,000 new cases and 16,000 deaths each year. Urothelial carcinoma (UC) is the most common histology and accounts for 90% of cases. BC management is complicated by recurrence rates of over 50% in both muscle-invasive and non-muscle-invasive bladder cancer. As such, the American Urological Association (AUA) recommends that patients undergo close surveillance during and after treatment. This surveillance is in the form of cystoscopy or imaging tests, which can be invasive and costly tests. Considering this, there have been recent pushes to find complements to bladder cancer surveillance. Cell-free DNA (CfDNA), or DNA released from dying cells, and circulating tumor DNA (ctDNA), or mutated DNA released from tumor cells, can be analyzed to detect and characterize the molecular characteristics of tumors. Research has shown promising results for ctDNA use in the BC care realm. A PubMed literature review was performed finding studies discussing cfDNA and ctDNA in BC detection, prognostication, and monitoring for recurrence. Keywords used included bladder cancer, cell-free DNA, circulating tumor DNA, urothelial carcinoma, and liquid biopsy. Studies show that ctDNA can serve as prognostic indicators of both early- and late-stage BC, aid in risk stratification prior to major surgery, assist in detection of disease progression and metastatic relapse, and can assess patients who may respond to immunotherapy. The benefit of ctDNA is not confined to BC, as studies have also suggested its promise as a biomarker for neoadjuvant chemotherapy in upper-tract UC. However, there are some limitations to ctDNA that require improvements in ctDNA-specific detection methods and BC-specific mutations before widespread utilization can be achieved. Further prospective, randomized trials are needed to elucidate the true potential ctDNA has in advancements in BC care.

The Association Between Duration of Antibiotics and Infectious Complications Following Radical Cystectomy: Analysis of the 2019-2021 NSQIP Database.

OBJECTIVES: To identify the impact of the duration of peri-operative antibiotics on infectious complications following radical cystectomy. METHODS: The National Surgical Quality Improvement Project (NSQIP) targeted database was queried for patients undergoing radical cystectomy from 2019-2021. Baseline patient characteristics were collected. Antibiotic duration was classified as <24 hours (short), 24-72 hours (intermediate) or >72 hours (long). Infectious complication data was collected including surgical site infection (SSI), urinary tract infection (UTI), organ space infection, pneumonia, sepsis, and clostridium difficile infection up to 30 days after surgery. Univariate and multivariable analyses were performed to compare duration of antibiotic therapy to infectious outcomes. RESULTS: Of the 4,363 patients who underwent radical cystectomy, 3,250(74%), 827(19%) and 286(6.6%) received short, intermediate, and long duration of peri-operative antibiotics respectively. Infectious complication occurred in 954(22%) patients, including 227(5.2%) SSI, 280(6.4%) UTI, 268(6.1%) organ space infection, 87(2%) pneumonia, and 378(8.7%) sepsis. Clostridium difficile infection occurred in 89(2%) patients. On multivariable analysis, there was no significant difference in overall infectious complication rates with long duration antibiotics. However, intermediate duration of antibiotics in open surgery was associated with a decreased risk of SSI (OR 0.58; 95%CI 0.37-0.91) compared to those treated with short term antibiotics. CONCLUSIONS: Despite guideline recommendations, 26% of patients in this database received >24 hours of peri-operative antibiotics without decreased risk of overall infectious complication. An intermediate course of antibiotics decreased risk of SSI in open surgery compared to the guideline recommend <24-hour course. Greater education regarding antibiotic stewardship and further studies investigating infectious complications are warranted.

Pelvic lymphadenectomy: Evaluating nodal stage migration and will rogers effect in bladder cancer.

INTRODUCTION: Pelvic lymphadenectomy (PLND) alongside radical cystectomy (RC), provides crucial diagnostic and therapeutic value in patients with bladder cancer. With the advent of neoadjuvant chemotherapy and prospective data supporting standard PLND, controversy remains regarding the optimal PLND extent and patient selection. Nearly 40% of patients may not receive adequate PLND, even though 25% of patients have positive lymph nodes (LN) at time of RC. We hypothesized that PLND still remains an important facet of bladder cancer treatment. To clarify the prognostic importance of nodal yield, we performed a retrospective investigation of a heterogenous population (pTanyNx/0M0) of patients undergoing RC. METHODS: From the Surveillance, Epidemiology, and End Results (SEER) program, we identified pTanyNx/0M0 bladder cancer patients undergoing RC from 2004 to 2015. Kaplan Meier curves and Cox proportional hazards models assessed cancer-specific survival. Patients were analyzed with PLND performed as the primary covariate. Survival analysis then stratified patients undergoing PLND by LN yield, both as a continuous and categorial variable (≤10, 11-20, 21-30, and >30), and T stage. RESULTS: The final cohort included pTanyNx/0M0 patients with urothelial bladder cancer (n = 12,096); median follow up was 39 (IQR: 17-77) months. PLND was performed in 81.45% of patients with a median LN yield of 14 (IQR: 7-23). Most commonly, patients had T2 disease (44.68%). After controlling for age and T stage, patients receiving PLND had improved CSS (HR = 0.56, [95% CI: 0.51-0.62]) compared to those that did not receive PLND. When grouping patients by LN yield, survival improved in a "dose dependent" manner (>30 LN: HR = 0.76, [95% CI: 0.66-0.87]). We noted similar results when stratifying patients into non-muscle-invasive (NMIBC) and muscle-invasive bladder cancer (MIBC). CONCLUSIONS: In a large contemporary series of pTanyNx/0M0 bladder cancer patients, we found a significant oncologic benefit to PLND. Higher LN yield correlated to improved CSS in non-muscle-invasive and muscle-invasive disease. Our data support the possibility of occult micrometastasis even in non-muscle-invasive disease. Additionally, in light of recent advances in adjuvant immunotherapy, our results emphasize the importance of adequate nodal yield for accurate staging and optimal treatment.

Prevalence of Low Testosterone in Men With Cystic Fibrosis and Congenital Bilateral Absence of the Vas Deferens: A Cross-sectional Study Using a Large, Multi-institutional Database.

OBJECTIVE: To investigate the prevalence and treatment rates of low testosterone (T) in men with cystic fibrosis (CF). CF is a genetic disease with highly variable presentation that results from a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Phenotypic manifestations of CF include alterations in function of the lungs, liver, pancreas, and reproductive system. Despite the well-described association between CF and infertility secondary to congenital bilateral absence of the vas deferens (CBAVD), men with CF report further sexual and reproductive health concerns, many of which are often associated with low testosterone. METHODS: We queried the TrinetX database for men over 18years old with CF or CBAVD to assess what percentage of men had a T level measured, and if hypogonadal (below 300 ng/dL), what percentage received T therapy (TT). We hypothesized that low T would be under-evaluated in the CF population. RESULTS: Serum T levels were measured in 10.1% of men with CF and 8.9% of men with CBAVD. Within each group, 464 men with CF (32.7%) and 132 with CBAVD (43.0%) demonstrated low T. The majority of men with T < 300 ng/dL went on to appropriately receive TT: 59.3% of men with CF and 78% with CBAVD. CONCLUSION: Our data suggests that hypogonadism is highly prevalent in men with CF and CBAVD. Investigation and appropriate treatment of testosterone deficiency may significantly improve quality of life.

Modern Management of Localized Renal Cell Carcinoma- Is Ablation Part of the Equation?

While the gold-standard for management of localized renal cell carcinoma (RCC) is partial nephrectomy, recent ablative strategies are emerging as alternatives with comparable rates of complications and oncologic outcomes. Thermal ablation, in the form of radiofrequency ablation and cryoablation, is being increasingly accepted by professional societies, and is particularly recommended in patients with a significant comorbidity burden, renal impairment, old age, or in those unwilling to undergo surgery. Maturation of long-term oncologic outcomes has further allowed increased confidence in these management strategies. New and exciting ablation technologies such as microwave ablation, stereotactic body radiotherapy, and irreversible electroporation are emerging. In this article, we review the existing management options for localized RCC, with specific focus on the oncologic outcomes associated with the various ablation modalities.

Combined intra- and extra-peritoneal bladder perforation following rectal impalement injury.

A 62-year-old male presented with abdominal pain and hematuria following impalement of the rectum with a wooden foreign object. CT imaging showed air and fluid in the peritoneum prompting the patient to undergo abdominal exploration. An anterior rectal perforation was discovered along with dual bladder lacerations of the posterior wall and dome. The patient underwent a diverting colostomy and primary bladder repair. Post-operative course was uncomplicated and bladder repair was followed via cystograms with catheter removal 2 months post-operatively. Four months after the injury the patient underwent colostomy closure and remains with normal bladder and bowel function at 21-month follow-up.

Ten-Year Comparison Study of Type 1 and 2 Endometrial Cancers: Risk Factors and Outcomes.

AIMS: To compare baseline risk factors for type 1 vs. 2 endometrial cancers and analyze these risk factors for association with overall survival and time to recurrence. METHODS: Retrospective review of 816 consecutive endometrial cancer cases was conducted with diagnosis from January 2005 to December 2010 and clinical course until 2016. Risk factors, treatment, recurrence, and death were compared using 2 sample t tests, χ2 test and Cox Regression models. RESULTS: There were 550 cases of type 1 and 266 cases of type 2 cancer. Patients with type 2 disease were older (p < 0.001), less obese (p = 0.03), non-white (p < 0.001), and menopausal (p = 0.02). There was no difference in use of oral contraceptives, hormone replacement therapy (HRT), smoking, or major cardiovascular disease. Cox Regression models showed that type 2 disease (p < 0.001) and advanced stage (p = 0.001) were associated with recurrence. CONCLUSIONS: Consistent with previous literature, our analysis found that type 2 cancer is more common in non-white, older, and less obese patients and associated with higher mortality and recurrence. However, inconsistent with previous literature, we found no association between type 2 cancer and diabetes mellitus or use of HRT. These factors should be considered when approaching patients with endometrial cancer.

Adjuvant Hormonal Therapy for Low-Grade Endometrial Stromal Sarcoma.

OBJECTIVE: To compare aromatase inhibitors (AIs) with progestins as adjuvant hormonal therapy(AHT) for low-grade endometrial stromal sarcomas (LGESSs). METHODS: We reviewed cases with LGESS at our institution from 1984 to 2017. Disease recurrence and recurrence-free survival (RFS) were assessed among patients who received AI, progestins, or no AHT. RESULTS: Among 39 patients with LGESS, 18 received progestins, 13 received AI, and 8 received no AHT. Thirty patients had stage I disease, and 9 had stage II to IV disease. All underwent hysterectomies. Disease recurred in 70% (7/10) of stage I patients who received no AHT, compared to 14.3% (1/7) receiving AI, and 7.7% (1/13) receiving progestins ( P = .003). Among stage I patients taking AI, mean RFS was 153.1 months (95% confidence interval [CI]: 110-195.6) versus 306.2 months (95% CI: 259.7-352.6) for progestin patients and 90.8 months (95% CI: 56.8-124.9) for those who received no AHT. In stage II to IV patients, mean RFS was 148.5 months (95% CI: 148.5-148.5) and 120.8 months (95% CI: 55.8-185.9) for the AI and progestin groups, respectively. All stage II to IV patients received AHT. Among stage I patients, median follow-up time for RFS was 159.1 months for progestin patients, 52.6 months for AI, and 53.1 months for those who received no AHT. Of this, 69% of stage I patients taking progestins reduced/stopped treatment prematurely due to side effects. None of the patients taking AI discontinued treatment early. CONCLUSION: Aromatase inhibitor is associated with longer RFS in patients with advanced LGESS, is better tolerated than progestins, and can be primary AHT for LGESS.

Associated characteristics and impact on recurrence and survival of free-floating tumor fragments in the lumen of fallopian tubes in Type I and Type II endometrial cancer.

OBJECTIVE: This study sought to evaluate characteristics of cases of free-floating tumor fragments within the lumen of fallopian tubes ('floaters') on final pathology for Type I and Type II endometrial adenocarcinoma, including relationships with disease recurrence and mortality. METHODS: A single institution experience of 1022 consecutive cases of uterine cancer presenting between 2005 and 2010 was retrospectively reviewed, with data extraction from electronic medical records. Associations of floaters with baseline characteristics were studied with logistic regression, and relationships with disease recurrence and survival were assessed with Cox proportional hazards models. RESULTS: Among 816 included cases of Type I or Type II endometrial adenocarcinoma, floaters were identified on final pathology for 20 patients (2.5%). Patient characteristics of cases with floaters mirrored the overall sample. With adjustment, presence of floaters trended towards association with laparoscopic/robotic approach (OR = 3.84; 95%CI 0.98-15.1), and was significantly associated with lymphovascular invasion (OR = 9.65; 95%CI 2.35-39.6) and higher stage disease. Although floaters were associated with increased risk of recurrence in unadjusted analysis (HR = 3.22; 95%CI 1.41-7.37), after adjustment for disease type, stage, and patient comorbidities, no evidence for impact on disease recurrence or overall survival was found. CONCLUSIONS: The presence of floaters is rare. Floaters were generally associated with more extensive disease, but no evidence was found to show any independent prognostic impact on risk of recurrence or death. In agreement with prior research, this study found a trend towards association of floaters with laparoscopic/robotic approach, indicating the possibility of floaters sometimes being the result of trauma from uterine manipulator insertion.