An in-depth analysis on the effects of body composition in patients receiving neoadjuvant chemotherapy for urothelial cell carcinoma.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is the standard of care for patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC); however, NAC can be associated with significant side effects and morbidity in some patients. NAC may contribute to sarcopenia, obesity, and the combination of the two. Our study examined the effects of NAC on body composition and the association between body composition and adverse events. METHODS: We created a retrospective database of patients with non-metastatic MIBC receiving NAC prior to RC. The change in skeletal muscle index (SMI) and fat mass index (FMI) was calculated using computed tomography (CT) scans done within three months prior to NAC and after the first two cycles. The association between body composition (sarcopenia, obesity, and sarcopenic obesity) and preoperative adverse events was investigated using a multivariable logistic regression. Changes in body composition were calculated using a paired Student's t-test. RESULTS: A total of 70 patients were included in our study. There was a mean decrease in SMI of 2.2±3.2 cm2/m2. Adiposity and FMI were unchanged by NAC. Sarcopenic obesity was found to be associated with adverse events among patients receiving NAC in the multivariable analysis. There was a total of 637 preoperative complications with grades 1-2 and 33 complications with grades 3-5. CONCLUSIONS: Based on our retrospective cohort study, NAC did not affect obesity and FMI, but there was a significant decrease in SMI. Sarcopenic obesity was associated with increased severity of NAC adverse events. As such, the presence of this factor may help predict tolerance of NAC.

Examining the impact of postoperative opioid use on length of hospital stay following radical cystectomy.

INTRODUCTION: Radical cystectomy (RC) is associated with high rates of morbidity, prolonged hospital stay, and increased opioid use for postoperative pain management; however, the relationship between postoperative opioid use and length of stay (LOS ) remains uncharacterized. This study serves to investigate the association between postoperative opioid use and length of hospital stay after RC. The relationship between patient and surgical factors on LOS was also characterized. METHODS: We retrospectively reviewed all patients between 2009 and 2019 who underwent RC at our institution. Patient and perioperative variables were analyzed to determine the relationship between postoperative opioid use and LOS using multivariable linear regression analysis. RESULTS: We identified 240 patients for study inclusion with a median age of 70.0 years. Median LOS was 10.0 days, with median daily mg morphine equivalent use of 57.5 for patients. Daily mg morphine equivalent use was significantly associated with an increased LOS, as were previous pelvic radiation, postoperative ileus, and higher Clavien-Dindo grade complication during admission (all p<0.05). Median LOS increased by one day for each increase of 13.2 daily mg morphine equivalents received. CONCLUSIONS: Increased daily opioid use was associated with increased length of hospital stay after RC. Non-opioid-based pain management approaches may be effective in reducing LOS after RC.

Clinical utility of routine postoperative serial hemoglobin measurements in patients undergoing radical cystectomy for urothelial carcinoma.

INTRODUCTION: Routine measurements of serum hemoglobin (sHgb) are common after abdominal surgery; however, prolonged measurements may be associated with patient anxiety, increased costs, and longer hospitalization without clinical benefit. The objective of this study was to determine the utility of routine sHgb measurements after radical cystectomy (RC) and factors associated with transfusion of packed red blood cell (pRB C) beyond postoperative day (POD ) 2. METHODS: We retrospectively reviewed patients who underwent RC between 2009 and 2019 at a single academic tertiary care center. The number of sHgb measurements for each patient was examined and pRB C transfusion rates were calculated. Multivariable logistic regression was used to determine factors associated with transfusion beyond POD 2. RESULTS: The median number of sHgb measurements per patient during admission was nine (interquartile range [IQR] 7, 25). Overall, 69/240 (28.7%) patients received a postoperative transfusion, including 46/240 (19.2%) patients receiving a transfusion beyond POD 2. Among patients with a sHgb ≥100 g/L on POD 2, 7/85 (8.2%) went on to receive a transfusion beyond this day compared with 39/155 (25.2%) patients with sHgb <100 g/L. On multivariable analysis, risk factors associated with pRB C transfusion beyond POD 2 included older age, lower sHgb on POD 2, and longer length of stay in hospital. CONCLUSIONS: Transfusion of pRB Cs beyond POD 2 was found to be common; however, patients with sHgb ≥100 g/L on POD 2 were at low risk of requiring subsequent transfusion. Discontinuing further routine sHgb checks in these patients may serve to decrease patient anxiety, healthcare costs, and delays in hospital discharge.

Utility of Postoperative Serial Renal Function Monitoring in Patients Undergoing Radical Cystectomy for Urothelial Carcinoma.

PURPOSE: The aim of this study is to examine the rates of clinical actions (CAs) as a result of serial creatinine (SCr) values and to examine postoperative SCr trends to assess the utility of SCr measurements in radical cystectomy (RC) patients. METHODS: We performed a retrospective chart review using our institution's database on all patients who underwent radical cystectomy for urothelial carcinoma (UC) from 2009 to 2019. Preoperative and all postoperative inpatient creatinine values were recorded. Minor CAs included fluid boluses, fluid rate changes, and medication changes. Major CAs included OR take-backs for stent repositioning, nephrostomy tube placement, nephrology consultation, and hemodialysis. RESULTS: A total of 238 RCs were performed with a resultant 2952 SCr measurements. The median number of SCr measurements per patient was 9 (interquartile range, IQR 7) with median length of hospital stay of 10 days (IQR 9 days). There were 92 minor and 12 major CAs as a result of 3% and 0.44% of SCr measurements, respectively. All major CAs were seen in patients experiencing complicated postoperative course. The median postoperative day with the highest creatinine was day 2. Predictors of postoperative CAs included preoperative renal dysfunction and obesity. CONCLUSION: SCr measurements remain a clinically valuable tool in postoperative management. Nonetheless, this present study suggests that prolonged SCr monitoring is of limited clinical utility. As such, discontinuing SCr checks after postoperative day 3 in patients experiencing uncomplicated postoperative course is safe and may lead to both cost savings and decreased patient discomfort.

Inhibition of urothelial carcinoma through targeted type I interferon-mediated immune activation.

Type I interferon (IFN-I) has potent anti-tumor effects against urothelial carcinoma (UC) and may be an alternative treatment option for patients who do not respond to Bacillus Calmette-Guerin. However, the mechanisms that mediate the IFN-I-stimulated immune responses against UC have yet to be elucidated. Herein, we evaluated the anti-tumor mechanisms of IFN-I in UC in human patients and in mice. Patient tumors from a Phase I clinical trial with adenoviral interferon-α (Ad-IFNα/Syn3) showed increased expression of T cell and checkpoint markers following treatment with Ad-IFNα/Syn3 by RNAseq and immunohistochemistry analysis in 25% of patients. In mice, peritumoral injections of poly(I:C) into MB49 UC tumors was used to incite an IFN-driven inflammatory response that significantly inhibited tumor growth. IFN-I engaged both innate and adaptive cells, seen in increased intratumoral CD8 T cells, NK cells, and CD11b+Ly6G+ cells, but tumor inhibition was not reliant on any one immune cell type. Nonetheless, poly(I:C)-mediated tumor regression and change in the myeloid cell landscape was dependent on IL-6. Mice were also treated with poly(I:C) in combination with anti-PD-1 monoclonal antibody (mAb) to assess for additional benefit to tumor growth and animal survival. When used in combination with anti-PD-1 mAb, IFN-I stimulation prolonged survival, coinciding with inhibition of angiogenesis and enriched gene signatures of metabolism, extracellular matrix organization, and MAPK/AKT signaling. Altogether, these findings suggest IFN-I's immune-driven antitumor response in UC is mediated by IL-6 and a collaboration of immune cells, and its use in combination with checkpoint blockade therapy can increase clinical benefit.

Urological Follow-up in Adult Spina Bifida Patients: Is There an Ideal Interval?

OBJECTIVE: To establish the time to development of urological issues over time in adult spina bifida (SB) patients. MATERIALS AND METHODS: This is a retrospective study of adult patients attending a multidisciplinary adult SB clinic from 2000 to 2013. Patient age, sex, number of clinic visits, and length of follow-up were recorded. For each unique visit, presence of symptoms, type of urological issue (if any), and time lapsed since last appointment were obtained. The interval between the development of urological issues was assessed using a time-to-event analysis. RESULTS: One hundred twenty-three patients (46% male, 54% female, median age 26.8years) were followed for a median of 48 months, contributing to 586 unique clinic visits. Urological issues were identified in 109 patients (88.5%) during 267 visits (46%), and of those 21% were asymptomatic. In symptomatic patients, the median time to present with a urological issue was 12 months. Among the asymptomatic cases, 12%, 23%, and 34% had developed a urological issue at 12, 24, and 36 months of follow-up, respectively. Eighty-one percent of the urological issues seen in the clinic required some form of treatment or intervention. The treatment or intervention in 56% of asymptomatic urological issues was surgery. CONCLUSION: Most adult SB patients with urological issues are symptomatic by 2 years of follow-up; however, over time the proportion of asymptomatic patients with urological issues rises steadily, reaching a worrisome 34% at 3 years. Closer follow-up seems warranted.

Compliance with semen analysis.

PURPOSE: We calculated the compliance rate and determined which population of men would be more or less likely to be compliant with semen analysis followup based on demographic information and complication rates. MATERIALS AND METHODS: We retrospectively reviewed the records of 946 consecutive patients who underwent vasectomy at an ambulatory clinic, as performed by 1 urologist. Standard followup consisted of a telephone call or prebooked appointment 2 months after vasectomy and 2 semen analyses 4 months after vasectomy. RESULTS: Average ± SD patient age was 33.6 ± 5.4 years. Of the 946 study patients 47.9% did not submit a negative semen sample, 15.7% submitted 1 and 36.4% submitted the required 2 negative samples to confirm successful vasectomy according to the sampling protocol. Mean time to semen analysis was 4.53 ± 2.14 months. Complications included infection in 1.9% of cases, hematoma in 1% and sperm granuloma in 0.5%. Men 34 years or younger, men with 3 or more children and men without complications were more likely to be noncompliant with semen analysis. CONCLUSIONS: The number of men who provided samples for semen analysis in this study was low, although they were given written and verbal reminders. This poor patient compliance is similar to that in previous studies. We identified a subset of patients with poor compliance, which may allow urologists to target preprocedure counseling more appropriately.

Tissue eosinophilia in a mouse model of colitis is highly dependent on TLR2 and independent of mast cells.

The mechanisms initiating eosinophil influx into sites of inflammation have been well studied in allergic disease but are poorly understood in other settings. This study examined the roles of TLR2 and mast cells in eosinophil accumulation during a nonallergic model of eosinophilia-associated colitis. TLR2-deficient mice (TLR2(-/-)) developed a more severe colitis than wild-type mice in the dextran sodium sulfate (DSS) model. However, they had significantly fewer eosinophils in the submucosa of the cecum (P < 0.01) and mid-colon (P < 0.01) than did wild-type mice after DSS treatment. Decreased eosinophilia in TLR2(-/-) mice was associated with lower levels of cecal CCL11 (P < 0.01). Peritoneal eosinophils did not express TLR2 protein, but TLR2 ligand injection into the peritoneal cavity induced local eosinophil recruitment, indicating that TLR2 activation of other cell types can mediate eosinophil recruitment. After DSS treatment, mast cell-deficient (Kit(W-sh/W-sh)) mice had similar levels of intestinal tissue eosinophilia were observed as those in wild-type mice. However, mast cell-deficient mice were partially protected from DSS-induced weight loss, an effect that was reversed by mast cell reconstitution. Overall, this study indicates a critical role for indirect TLR2-dependent pathways, but not mast cells, in the generation of eosinophilia in the large intestine during experimental colitis and has important implications for the regulation of eosinophils at mucosal inflammatory sites.