Distant metastasis without regional progression in non-muscle invasive bladder cancer: case report and pooled analysis of literature.

BACKGROUND: Non-muscle invasive bladder cancer (NMIBC) represents the majority of bladder neoplasms. It is unusual for NMIBC metastasizing distantly without regional progression, namely metastatic NMIBC (mNMIBC), which is still poorly understood and easily omitted based on current management policies. So far, description of mNMIBC is limited to a few case reports. METHODS: We reported a 70-year-old man with NMIBC who suffered from cervical metastasis without pelvic recurrence at 41 months after initial diagnosis. Then we performed a collective analysis of this case together with published mNMIBC cases searched from PubMed, Embase, and Web of Science, aiming to illustrate baseline clinicopathologic parameters, metastatic patterns, and treatment outcomes of these patients and analyze associated influencing factors. RESULTS: After scrupulous review, 45 cases previous reported and the one from our center were incorporated into the aggregated cohort of mNMIBC, including 34 males and 12 females. Primary tumors from 46.7% of patients were high-grade (HG) or grade 3 (G3) and 65.1% had T1 lesions. Aberrant biomarker expression was found in tumors of some cases. Most (40/46) metastases of mNMIBC occurred at a single site, mainly in lung, bone and lymph nodes. Apart from three cases of de novo mNMIBC, the mean metastasis-free survival (MFS) interval of metachronous mNMIBC was 42.5 months, which was obviously longer than conventional metastatic bladder cancer. Shortened MFS interval was associated with old age, T1 or HG/G3 primary tumors, and non-lung metastases. Systemic chemotherapy and metastasectomy or radiotherapy for oligometastatic lesion were main therapeutic approaches of mNMIBC, and immunotherapy was adopted for the case from our center. Lung and bone metastases correlated with relatively favorable and unfavorable survival outcomes, respectively. Compared with monotherapy, chemotherapy, or immunotherapy combined with local cytoreduction got more favorable outcomes. CONCLUSION: Although rare, mNMIBC occurs more in tumors with high-risk features. Usually, mNMIBC metastasizes later than conventional metastatic bladder cancer and manifests as solitary lesion. Outcomes of mNMIBC would be influenced by metastatic site and post-metastatic treatment. Systemic treatment combined with local cytoreduction may render survival benefit in selected patients.

Dl-3n-butylphthalide improves traumatic brain injury recovery via inhibiting autophagy-induced blood-brain barrier disruption and cell apoptosis.

Blood-brain barrier (BBB) disruption and neuronal apoptosis are important pathophysiological processes after traumatic brain injury (TBI). In clinical stroke, Dl-3n-butylphthalide (Dl-NBP) has a neuroprotective effect with anti-inflammatory, anti-oxidative, anti-apoptotic and mitochondrion-protective functions. However, the effect and molecular mechanism of Dl-NBP for TBI need to be further investigated. Here, we had used an animal model of TBI and SH-SY5Y/human brain microvascular endothelial cells to explore it. We found that Dl-NBP administration exerts a neuroprotective effect in TBI/OGD and BBB disorder, which up-regulates the expression of tight junction proteins and promotes neuronal survival via inhibiting mitochondrial apoptosis. The expressions of autophagy-related proteins, including ATG7, Beclin1 and LC3II, were significantly increased after TBI/OGD, and which were reversed by Dl-NBP treatment both in vivo and in vitro. Moreover, rapamycin treatment had abolished the effect of Dl-NBP for TBI recovery. Collectively, our current studies indicate that Dl-NBP treatment improved locomotor functional recovery after TBI by inhibiting the activation of autophagy and consequently blocking the junction protein loss and neuronal apoptosis. Dl-NBP, as an anti-inflammatory and anti-oxidative drug, may act as an effective strategy for TBI recovery.

Associations between Hospital Volume and Outcomes of Robot-Assisted Radical Prostatectomy.

PURPOSE: Robot-assisted radical prostatectomy has become the predominant surgical modality to manage localized prostate cancer in the U.S. However, there are few studies focusing on the associations between hospital volume and outcomes of robot-assisted radical prostatectomy. MATERIALS AND METHODS: We identified robot-assisted radical prostatectomies for clinically localized (cT1-2N0M0) prostate cancer diagnosed between 2010 and 2014 in the National Cancer Database. We categorized annual average hospital robot-assisted radical prostatectomy volume into very low, low, medium, high and very high by most closely sorting the final included patients into 5 equal-sized groups (quintiles). Outcomes included 30-day mortality, 90-day mortality, conversion (to open), prolonged length of stay (more than 2 days), 30-day (unplanned) readmission, positive surgical margin and lymph node dissection rates. RESULTS: A total of 114,957 patients were included in the study, and hospital volume was categorized into very low (3 to 45 cases per year), low (46 to 72), medium (73 to 113), high (114 to 218) and very high (219 or more). Overall 30-day mortality (0.12%), 90-day mortality (0.16%) and conversion rates (0.65%) were low. Multivariable logistic regressions showed that compared with the very low volume group, higher hospital volume was associated with lower odds of conversion to open surgery (OR 0.23, p <0.001 for very high), prolonged length of stay (OR 0.25, p <0.001 for very high), 30-day readmission (OR 0.53, p <0.001 for very high) and positive surgical margins (OR 0.61, p <0.001 for very high). Higher hospital volume was also associated with higher odds of lymph node dissection in the intermediate/high risk cohort (OR 3.23, p <0.001 for very high). CONCLUSIONS: Patients undergoing robot-assisted radical prostatectomy at higher volume hospitals are likely to have improved perioperative and superior oncologic outcomes compared to lower volume hospitals.

Prolonged Length of Stay After Robotic Prostatectomy: Causes and Risk Factors.

BACKGROUND: Robot-assisted radical prostatectomy (RARP) can generally be performed with 1-2 nights of postoperative monitoring before discharge from the hospital. Little is known about what causes individual patients to remain in hospital beyond the second postoperative day. METHODS: Data for RARPs performed between 2013 and 2015 were extracted from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database. The fraction of cases with prolonged length of stay (PLOS) that can be reasonably attributed to complications was examined. Logistic regression was performed to identify risk factors for PLOS in the overall population and separately in the population of patients with PLOS without any perioperative complications. RESULTS: Of 11,440 patients, 10,342 (90.4%) were discharged on postoperative days 0-2; 80.6% (887/1101) of patients with PLOS did not experience any perioperative complications. The most common complication was bleeding requiring transfusion, but this was present in only 5.6% (62/1101) of patients with PLOS. Logistic regression identified predictors of PLOS as age, race, wound class, American Society of Anesthesiologists class, smoking, diabetes, dyspnea, dependent functional health status, congestive heart failure, operative time, and pelvic lymph node dissection. Results of this regression were insensitive to the exclusion of patients who experienced no perioperative complications. CONCLUSIONS: This study utilizes logistic regression on NSQIP data to identify risk factors for PLOS after RARP and, in particular, to evaluate the role of postoperative complications in PLOS. The analysis shows that postoperative complications account for a small minority of cases of PLOS after RARP.

Suprapubic Versus Urethral Catheter for Urinary Drainage After Robot-Assisted Radical Prostatectomy.

PURPOSE OF REVIEW: To review the evidence regarding the usage of suprapubic tube (SPT) versus indwelling urethral catheter (IUC) after robot-assisted radical prostatectomy (RARP). RECENT FINDINGS: Available data on the use of SPT for urinary drainage after RARP is somewhat limited mostly because of the variations of study designs and non-standardized outcomes. Although it may provide some mild benefit in terms of catheter-related pain and discomfort, the benefit seems not to be clinically significant. The evidence in the literature so far does not support routine usage of SPT as the primary urinary drainage method after RARP. Further higher-quality studies that can show clinically significant advantages over IUC are still needed to justify its usage.

A clinical trial of intraoperative near-infrared imaging to assess tumor extent and identify residual disease during anterior mediastinal tumor resection.

BACKGROUND: The management of most solid tumors of the anterior mediastinum involves complete resection. Because of their location near mediastinal structures, wide resection is not possible; therefore, surgeons must use subjective visual and tactile cues to determine disease extent. This clinical trial explored intraoperative near-infrared (NIR) imaging as an approach to improving tumor delineation during mediastinal tumor resection. METHODS: Twenty-five subjects with anterior mediastinal lesions suspicious for malignancy were enrolled in an open-label feasibility trial. Subjects were administered indocyanine green (ICG) at a dose of 5 mg/kg, 24 hours before resection (via a technique called TumorGlow). The NIR imaging systems included Artemis (Quest, Middenmeer, the Netherlands) and Iridium (VisionSense Corp, Philadelphia, Pennsylvania). Intratumoral ICG uptake was evaluated. The clinical value was determined via an assessment of the ability of NIR imaging to detect phrenic nerve involvement or incomplete resection. Clinical and histopathologic variables were analyzed to determine predictors of tumor fluorescence. RESULTS: No drug-related toxicity was observed. Optical imaging added a mean of 10 minutes to case duration. Among the subjects with solid tumors, 19 of 20 accumulated ICG. Fluorescent tumors included thymomas (n = 13), thymic carcinomas (n = 4), and liposarcomas (n = 2). NIR feedback improved phrenic nerve dissection (n = 4) and identified residual disease (n = 2). There were no false-positives or false-negatives. ICG preferentially accumulated in solid tumors; this was independent of clinical and pathologic variables. CONCLUSIONS: NIR imaging for anterior mediastinal neoplasms is safe and feasible. This technology may provide a real-time tool capable of determining tumor extent and specifically identify phrenic nerve involvement and residual disease.

National Variation in Opioid Prescription Fills and Long-Term Use in Opioid Naïve Patients after Urological Surgery.

PURPOSE: Prescription opioid use is increasing, leading to increased addiction and mortality. Postoperative care is often the first exposure to opioids of a patient but little data exist on national prescription patterns in urology. We examined post-discharge opioid fills after urological procedures and the association with long-term use. MATERIALS AND METHODS: We identified patients in a private national insurance database who underwent 1 of 15 urological procedures between October 1, 2010 and September 30, 2014. Patients with an opioid fill in the preceding 6 months were excluded from study. Claims for opioids from 30 days before the operation until 7 days after discharge characterized an initial prescription. Factors associated with persistent opioid use (an opioid claim 91 to 180 days after the operation) and chronic opioid use (10 or more refills of a 120-day or greater supply in the year after the operation) were analyzed using multivariable logistic regression. RESULTS: Overall 96,580 patients were included in study, of whom 49,391 (51%) filled an initial opioid prescription. Variation in the initial prescribed amount existed within procedures. Persistent use occurred in 6.2% of patients while chronic use occurred in 0.8%. Increased prescription in patients treated with transurethral prostate resection, vasectomy, female sling surgery, cystoscopy and stent insertion were associated with an increased risk of persistent as well as chronic use. CONCLUSIONS: National variation in opioid prescribing practice exists after urological operations. Patients who fill larger amounts of opioids after certain major and minor urological procedures are at increased risk for long-term opioid use. This provides evidence for procedure specific prescribing guidelines to minimize risk and promote standardization.

Next-day discharge after minimally invasive partial nephrectomy: an analysis of the US National Surgical Quality Improvement Program.

PURPOSE: Clinical care pathways and new technologies have decreased the length of stay after many surgeries. However, doubt exists about the safety of shorter hospital stays. We sought to evaluate the feasibility of next-day discharge after minimally invasive partial nephrectomy in a national cohort of US patients and surgeons. METHODS: Using the National Surgical Quality Improvement Program database, we analyzed patients who underwent minimally invasive partial nephrectomy from 2012 to 2016. Patients were grouped into discharge on post-operative day 1, or discharge on days 2 and 3. Propensity score matching was used to balance patient characteristics and univariable analysis was used to determine the effect of next-day discharge on readmission, post-discharge complications, and major post-discharge complications. RESULTS: A total of 8153 patients were included in the analysis and 4430 were matched. The matched cohort was balanced on all patient and peri-operative characteristics. On univariable analysis, no increase in odds were observed in the next-day discharge group for readmission (odds ratio 0.8; 95% confidence interval 0.6-1.4; p = 0.2), post-discharge complications (odds ratio 1.0; 95% confidence interval 0.7-1.4; p = 0.9), or post-discharge major complications (odds ratio 0.9; 95% confidence interval 0.5-1.4; p = 0.6). CONCLUSIONS: Next-day discharge in select patients after minimally invasive partial nephrectomy is effectively being utilized by a large, nationwide cohort of surgeons. This approach is feasible in certain patient populations though further research must determine selection criteria for safe next-day discharge.

Surgical Management of Early-Stage Esophageal Adenocarcinoma Based on Lymph Node Metastasis Risk.

BACKGROUND: In early-stage esophageal adenocarcinoma (EAC), esophagectomy improves staging but also increases mortality compared with endoscopic resection. Our objective was to quantify esophagectomy mortality and lymph node metastasis (LNM) risk in early-stage EAC to improve surgical treatment allocation. METHODS: We identified National Cancer Database (2004-2014) patients with nonmetastatic, Tis, T1a, or T1b EAC who had primary surgical resection and microscopic examination of at least 15 lymph nodes. Univariate and multivariable logistic regression identified predictors of LNM. Cox regression identified predictors of death. The Kaplan-Meier method predicted overall survival (OS). RESULTS: In 782 patients, LNM rates were: all patients 13.8%, Tis 0%, T1a 3.6%, T1b 23.4%. Independent predictors of LNM were submucosal invasion, lymphovascular invasion (LVI), decreasing differentiation, and tumor size ≥ 2 cm (P < 0.05). For T1a tumors with poor differentiation or size ≥ 2 cm, LNM rates were 10.2 and 6.7%, respectively; 90-day mortality was 3.1%. The LNM rate in well differentiated T1b tumors < 2 cm was 4.2%; 90-day mortality was 6.0%. Estimated 5-year OS was 80.2% versus 64.4% (T1a vs. T1b). LNM increased risk of death for T1a (hazard ratio [HR] 8.52, 95% confidence interval [CI] 3.13-23.22, P < 0.001) and T1b tumors (HR 2.52, 95% CI 1.59-4.00, P < 0.001). CONCLUSIONS: In T1a EAC with poor differentiation or size ≥ 2 cm, esophagectomy should be considered, whereas in T1b EAC with low-risk features (well-differentiated T1b EAC < 2 cm without LVI), endoscopic resection may be sufficient. Treatment guidelines for early-stage EAC should include all high-risk tumor features for LNM and stage-specific esophagectomy mortality.

Early discharge and post-discharge outcomes in patients undergoing radical cystectomy for bladder cancer.

OBJECTIVE: To assess whether discharging patients early after radical cystectomy (RC) is associated with an increased risk of readmission and post-discharge complications. MATERIALS AND METHODS: The National Surgical Quality Improvement Program database was queried to identify patients who underwent an elective RC from 2012 to 2015. Patients were stratified into two groups: those with a length of hospital stay (LOS) of 4-5 days (early-discharge group) and those with an LOS of 6-9 days (routine-discharge group). We used multivariable logistic regression analyses to assess the impact of early discharge on 30-day readmission and post-discharge complication rates. Sensitivity analyses and subgroup analyses were performed to validate the robustness of our primary analyses. RESULTS: A total of 3 311 patients were included. Unadjusted outcomes comparison showed no difference in readmission rate (21.6% vs 23.0%) or post-discharge complication rate (17.7% vs 19.6%) between the early-discharge and the routine-discharge group. Multivariable logistic regression also showed that early discharge was not associated with increased odds of readmission (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.82-1.22; P = 1.000) or post-discharge complications (OR 0.95, 95% CI 0.77-1.17; P = 0.616). Two-step sensitivity analyses (excluding patients with LOS of 8-9 days, followed by patients with any pre-discharge adverse event) validated the robustness of our primary analyses. Subgroup analyses also yielded similar results in all subgroups except for the subgroup of patients aged ≥85 years. CONCLUSIONS: Early discharge after RC was not associated with increased readmissions or post-discharge complications. Future prospective studies, with defined peri-operative care pathways, are needed to identify potential components that may enable hospitals to discharge patients early without compromising post-discharge outcomes.

Hospital volume and outcomes of robot-assisted partial nephrectomy.

OBJECTIVE: To evaluate the impact of hospital volume on outcomes of robot-assisted partial nephrectomy (RAPN). MATERIALS AND METHODS: Patients with renal cell carcinoma who underwent RAPN between 2010 and 2013 were identified in the National Cancer Database. Hospital yearly RAPN volume was categorized into groups by sorting patients as closely as possible into five groups of equal size (quintiles): very low; low; medium; high; and very high volume. Outcomes included 30-day mortality, 90-day mortality, open conversion, prolonged length of hospital stay (PLOS; defined as >3 days), 30-day readmission rate, and positive surgical margin (PSM) rate. Unadjusted analyses and multivariable logistic regressions were used to compare outcomes. Sensitivity analyses with hospital volume considered as a continuous variable were also performed. RESULTS: A total of 18 724 RAPN cases were included. Hospital volume quintiles were: very low volume, 1-7 cases (n = 3 693); low volume, 8-14 cases (n = 3 719); medium volume, 15-23 cases (n = 3 833); high volume, 24-43 cases (n = 3 649); and very high volume, ≥44 cases (n = 3 830). There was no significant difference in 30-day or 90-day mortality among the five groups. Multivariable logistic regression analysis (reference: very low volume) showed that higher hospital volume was associated with lower odds of conversion (low [odds ratio {OR}: 0.88; P = 0.377]; medium [OR: 0.60; P = 0.001]; high [OR: 0.57; P < 0.001]; very high [OR: 0.47; P < 0.001]), lower odds of PLOS (low [OR: 0.93; P = 0.197], medium [OR: 0.75; P < 0.001]; high [OR: 0.62; P < 0.001]; very high [OR: 0.45; P < 0.001]), and lower odds of PSMs (low [OR: 0.76; P < 0.001]; medium [OR: 0.76, P < 0.001]; high [OR: 0.59; P < 0.001]; very high [OR: 0.34; P < 0.001]). Sensitivity analyses confirmed increasing hospital volume (per 1-case increase) was associated with lower odds of conversion (OR: 0.986; P < 0.001), PLOS (OR: 0.989; P < 0.001) and PSMs (OR: 0.984; P < 0.001). A difference in 30-day readmission rate was found in unadjusted analysis but not in adjusted analyses. CONCLUSION: Undergoing RAPN at higher-volume hospitals may have better peri-operative outcomes (conversion to open and LOS) and lower PSM rates. Future studies are needed to explore the detailed components that lead to the superior outcomes in higher-volume hospitals.

Hospital volume and short-term outcomes after cytoreductive nephrectomy.

PURPOSE: To investigate the impact of hospital volume on short-term outcomes after cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC). METHODS: We identified mRCC patients who underwent CN from 2006 to 2013 in the National Cancer Database. Annual hospital CN volume was categorized as high (top 20th percentile) and low. Multivariable logistic regressions were used to compare 30-day mortality, 90-day mortality, prolonged length of stay (PLOS, ≥7 days), and 30-day readmission rates. Sensitivity analyses were performed with hospital volume considered as a continuous variable. RESULTS: A total of 9789 patients were included with high-volume (n = 1916) defined as ≥8 cases and low-volume (n = 7873) as 1-7 cases annually. Multivariable logistic regression showed that high-volume was associated with lower odds of 30-day mortality (OR = 0.69, P = 0.013), 90-day mortality (OR = 0.65, P < 0.001), PLOS (OR = 0.82, P = 0.002), and 30-day readmission (OR = 0.78, P = 0.028). Sensitivity analyses showed that increasing hospital volume (per case) was associated with lower odds of 30-day mortality (OR = 0.965, P = 0.008), 90-day mortality (OR = 0.966, P < 0.001), PLOS (OR = 0.982, P = 0.001), and 30-day readmission (OR = 0.975, P = 0.012). CONCLUSION: Higher hospital volume was associated with better short-term outcomes after CN. Future studies are needed to validate our findings and explore the potential components leading to better outcomes in the higher volume hospitals.

Intraoperative Molecular Imaging Combined With Positron Emission Tomography Improves Surgical Management of Peripheral Malignant Pulmonary Nodules.

OBJECTIVE: To determine if intraoperative molecular imaging (IMI) can improve detection of malignant pulmonary nodules. BACKGROUND: 18-Fluorodeoxyglucose positron emission tomography (PET) is commonly utilized in preoperative assessment of patients with solid malignancies; however, false negatives and false positives remain major limitations. Using patients with pulmonary nodules as a study model, we hypothesized that IMI with a folate receptor targeted near-infrared contrast agent (OTL38) can improve malignant pulmonary nodule identification when combined with PET. METHODS: Fifty patients with pulmonary nodules with imaging features suspicious for malignancy underwent preoperative PET. Patients then received OTL38 before pulmonary resection. During resection, IMI was utilized to evaluate known pulmonary nodules and identify synchronous lesions. Tumor size, PET standardized uptake value, and IMI tumor-to-background ratios were compared for known and synchronous nodules via paired and unpaired t tests, when appropriate. Test characteristics of PET and IMI with OTL38 were compared. RESULTS: IMI identified 56 of 59 (94.9%) malignant pulmonary nodules identified by preoperative imaging. IMI located an additional 9 malignant lesions not identified preoperatively. Nodules only detected by IMI were smaller than nodules detected preoperatively (0.5 vs 2.4 cm; P < 0.01), but displayed similar fluorescence (tumor-to-background ratio 3.3 and 3.1; P = 0.50). Sensitivity of IMI and PET were 95.6% and 73.5% (P = 0.001), respectively; and positive predictive values were 94.2% and 89.3%, respectively (P > 0.05). Additionally, utilization of IMI clinically upstaged 6 (12%) subjects and improved management of 15 (30%) subjects. CONCLUSIONS: These data suggest that combining IMI with PET may provide superior oncologic outcomes for patients with resectable lung cancer.

Update on the Management of Low-stage Seminoma.

The contemporary paradigm of testicular cancer management is achieving high and durable cure rates while minimizing the burden of treatment given the potential long-term toxicities associated with radiation therapy and systemic therapies. The management of low-stage seminoma has seen significant changes in recent years. Nuances of surveillance strategies for stage I seminoma exist and continue to evolve. Emerging data show retroperitoneal lymph node dissection is a viable treatment option for selected patients with clinical stage IIA and IIB seminoma.

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

OBJECTIVE: To 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). METHODS: A 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. RESULTS: The 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). CONCLUSIONS: The 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.

Oncologic control and predictors of urologic reconstruction after Mohs micrographic surgery for low-risk penile malignancy.

PURPOSE: Mohs micrographic surgery (MMS) is a low-risk penile cancer management option. However, contemporary patients' short-term oncologic control and preoperative characteristics predicting reconstruction needs are undefined. This study assesses MMS's oncologic efficacy for low-risk penile cancer and identifies baseline predictors of post-resection reconstruction referral. METHODS: We retrospectively reviewed 73 adult males with 78 penile cutaneous malignancies treated with MMS from 2005 to 2019. Patients underwent MMS with or without surgical reconstruction. Demographic information, MMS operative details, lesion pathology, and short-term outcomes were recorded. Descriptive statistics for all variables were calculated, and logistic regression identified predictive factors for urologic referral for complex reconstruction. RESULTS: Seventy-three men with 78 lesions, all staged ≤ cT1a prior to MMS, were identified. Twenty-one men were found to have invasive SCC. Median follow-up was 2.0 years (IQR 0.8-5.2 years). MMS was able to clear the disease in 90.4% of cases. One patient had disease related death following progression. Dermatology closed primarily in 68% of patients. Twenty percent of patients had a complication, most commonly poor wound healing. On univariate and multivariate linear regression analysis, lesion size > 3 cm and involvement of the glans independently predicted the need for referral to a reconstructive surgeon. CONCLUSIONS: MMS for penile cancer appears to provide sound oncologic control in the properly selected patient. Involvement of a reconstructive surgeon may be needed for glandular and large lesions, necessitating early referral to a comprehensive multidisciplinary care team.

Diminished Short-Term Efficacy of Reduced-Dose Induction BCG in the Treatment of Non-Muscle Invasive Bladder Cancer.

The ongoing Bacillus Calmette-Guérin (BCG) shortage has created challenges for the treatment of non-muscle invasive bladder cancer (NMIBCa). Our objective was to evaluate the efficacy of reduced-dose induction BCG (RD-iBCG) compared to full-dose induction BCG (FD-iBCG) regarding recurrence rates. We hypothesized that patients receiving RD-iBCG may recur at a higher rate compared to those who received FD-iBCG therapy. A retrospective review of all patients with NMIBCa treated with intravesical therapy at our institution between 2015-2020 was conducted. Inclusion criteria consisted of having a diagnosis of AUA intermediate or high-risk NMIBCa with an indication for a six-week induction course of FD or RD-BCG with at least 1 year of documented follow up. The data were censored at one year. Propensity score matching for age, sex, tumor pathology, and initial vs. recurrent disease was performed. The primary endpoint was bladder cancer recurrence, reported as recurrence-free survival. A total of 254 patients were reviewed for this study. Our final cohort was 139 patients after exclusion. Thirty-nine percent of patients had HGT1 disease. 38.6% of patients receiving RD-BCG developed a recurrence of bladder cancer within a one-year follow-up as compared to 33.7% of patients receiving FD therapy. After propensity matching, this value remained statistically significant (p = 0.03). In conclusion, RD-iBCG for NMIBCa is associated with a significantly greater risk of recurrence than full-dose induction therapy, suggesting that RD-iBCG may not be equivalent or non-inferior to full-dose administration in the short term.

Platelet derived growth factor promotes the recovery of traumatic brain injury by inhibiting endoplasmic reticulum stress and autophagy-mediated pyroptosis.

Autophagy and endoplasmic reticulum stress (ER stress) are important in numerous pathological processes in traumatic brain injury (TBI). Growing evidence has indicated that pyroptosis-associated inflammasome is involved in the pathogenesis of TBI. Platelet derived growth factor (PDGF) has been reported to be as a potential therapeutic drug for neurological diseases. However, the roles of PDGF, autophagy and ER stress in pyroptosis have not been elucidated in the TBI. This study investigated the roles of ER stress and autophagy after TBI at different time points. We found that the ER stress and autophagy after TBI were inhibited, and the expressions of pyroptosis-related proteins induced by TBI, including NLRP3, Pro-Caspase1, Caspase1, GSDMD, GSDMD P30, and IL-18, were decreased upon PDGF treatment. Moreover, the rapamycin (RAPA, an autophagy activator) and tunicamycin (TM, an ER stress activator) eliminated the PDGF effect on the pyroptosis after TBI. Interestingly, the sodium 4-phenylbutyrate (4-PBA, an ER stress inhibitor) suppressed autophagy but 3-methyladenine (3-MA, an autophagy inhibitor) not for ER stress. The results revealed that PDGF improved the functional recovery after TBI, and the effects were markedly reversed by TM and RAPA. Taken together, this study provides a new insight that PDGF is a potential therapeutic strategy for enhancing the recovery of TBI.