Focal Application of Neurotrophic Factors Augments Outcomes of Nerve-Muscle-Endplate Grafting Technique for Limb Muscle Reinnervation.

BACKGROUND: We have developed a novel muscle reinnervation technique called "nerve-muscle-endplate grafting (NMEG) in the native motor zone (NMZ)." This study aimed to augment the outcomes of the NMEG-NMZ (NN) by focal application of exogenous neurotrophic factors (ENFs) for limb reinnervation. METHODS: Adult rats were used to conduct NN plus ENF (NN/ENF) and autologous nerve grafting (ANG, technique control). The nerve innervating the left tibialis anterior (TA) muscle was resected and the denervated TA was immediately treated with NN/ENF or ANG. For NN procedure, an NMEG pedicle was taken from the lateral gastrocnemius muscle and transferred to the NMZ of the denervated TA. For ANG, the nerve gap was bridged with sural nerve. Three months after treatment, the extent of functional and neuromuscular recovery was assessed by measuring static toe spread, maximal muscle force, wet muscle weight, regenerated axons, and innervated motor endplates (MEPs). RESULTS: NN/ENF resulted in 90% muscle force recovery of the treated TA, which is far superior to ANG (46%) and NN alone (79%) as reported elsewhere. Toe spread recovered up to 89 and 49% of the control for the NN/ENF and ANG groups, respectively. The average wet muscle weight was 87 and 52% of the control for muscles treated with NN/ENF and ANG, respectively. The mean number of the regenerated axons was 88% of the control for the muscles treated with NN/ENF, which was significantly larger than that for the ANG-repaired muscles (39%). The average percentage of the innervated MEPs in the NN/ENF-treated TA (89%) was higher compared with that in the ANG-repaired TA (48%). CONCLUSION: ENF enhances nerve regeneration and MEP reinnervation that further augment outcomes of NN. The NN technique could be an alternative option to treat denervated or paralyzed limb muscles caused by traumatic nerve injuries or lesions.

Reinnervation of Paralyzed Limb Muscle by Nerve-Muscle-Endplate Grafting Technique.

BACKGROUND: We have developed a novel reinnervation technique called nerve-muscle-endplate grafting in the native motor zone (NMEG-NMZ). However, it remains unknown whether the NMEG-NMZ is effective for limb reinnervation. OBJECTIVE: To evaluate the efficacy of the NMEG-NMZ in limb muscle reinnervation. METHODS: Forty-five adult rats were divided into 3 groups: NMEG, end-to-end anastomosis (EEA, technique control), and denervation control (DC). The left tibialis anterior muscle was denervated by resecting its nerve. For NMEG-NMZ, the denervated tibialis anterior was reinnervated by transferring a NMEG pedicle from the lateral gastrocnemius muscle. Three months after surgery, static toe spread analysis was performed for all rats and muscle force was measured for the rats treated with NMEG and EEA. Muscle weight, myofiber morphology, regenerated axons, and reinnervated motor endplates in the treated muscles were also quantified and compared with those in the DC group. RESULTS: NMEG-NMZ technique resulted in better muscle force recovery (79% of the control) compared with EEA (51% of the control, P = .048). Toe spread analysis in NMEG-NMZ reinnervated muscles showed static sciatic index = -16.8, whereas -41.4 in EEA, P < .0001). The average weight of the NMEG-NMZ reinnervated muscles (86%) was greater than those of the EEA treated (71%) and DC (26%) muscles (all P < .0001). The mean count of the regenerated axons in the muscles with NMEG-NMZ was 76% of the control, which was larger than that in the muscles with EEA (46%), P < .0001. CONCLUSION: NMEG-NMZ technique has unique advantages and is superior to EEA for muscle reinnervation and functional recovery.

The Mount Sinai Prebiopsy Risk Calculator for Predicting any Prostate Cancer and Clinically Significant Prostate Cancer: Development of a Risk Predictive Tool and Validation with Advanced Neural Networking, Prostate Magnetic Resonance Imaging Outcome Database, and European Randomized Study of Screening for Prostate Cancer Risk Calculator.

Background: The European Association of Urology guidelines recommend the use of imaging, biomarkers, and risk calculators in men at risk of prostate cancer. Risk predictive calculators that combine multiparametric magnetic resonance imaging with prebiopsy variables aid as an individualized decision-making tool for patients at risk of prostate cancer, and advanced neural networking increases reliability of these tools. Objective: To develop a comprehensive risk predictive online web-based tool using magnetic resonance imaging (MRI) and clinical data, to predict the risk of any prostate cancer (PCa) and clinically significant PCa (csPCa) applicable to biopsy-naïve men, men with a prior negative biopsy, men with prior positive low-grade cancer, and men with negative MRI. Design setting and participants: Institutional review board-approved prospective data of 1902 men undergoing biopsy from October 2013 to September 2021 at Mount Sinai were collected. Outcome measurements and statistical analysis: Univariable and multivariable analyses were used to evaluate clinical variables such as age, race, digital rectal examination, family history, prostate-specific antigen (PSA), biopsy status, Prostate Imaging Reporting and Data System score, and prostate volume, which emerged as predictors for any PCa and csPCa. Binary logistic regression was performed to study the probability. Validation was performed with advanced neural networking (ANN), multi-institutional European cohort (Prostate MRI Outcome Database [PROMOD]), and European Randomized Study of Screening for Prostate Cancer Risk Calculator (ERSPC RC) 3/4. Results and limitations: Overall, 2363 biopsies had complete clinical information, with 57.98% any cancer and 31.40% csPCa. The prediction model was significantly associated with both any PCa and csPCa having an area under the curve (AUC) of 81.9% including clinical data. The AUC for external validation was calculated in PROMOD, ERSPC RC, and ANN for any PCa (0.82 vs 0.70 vs 0.90) and csPCa (0.82 vs 0.78 vs 0.92), respectively. This study is limited by its retrospective design and overestimation of csPCa in the PROMOD cohort. Conclusions: The Mount Sinai Prebiopsy Risk Calculator combines PSA, imaging and clinical data to predict the risk of any PCa and csPCa for all patient settings. With accurate validation results in a large European cohort, ERSPC RC, and ANN, it exhibits its efficiency and applicability in a more generalized population. This calculator is available online in the form of a free web-based tool that can aid clinicians in better patients counseling and treatment decision-making. Patient summary: We developed the Mount Sinai Prebiopsy Risk Calculator (MSP-RC) to assess the likelihood of any prostate cancer and clinically significant disease based on a combination of clinical and imaging characteristics. MSP-RC is applicable to all patient settings and accessible online.

Association between Incidental Pelvic Inflammation and Aggressive Prostate Cancer.

The impact of pelvic inflammation on prostate cancer (PCa) biology and aggressive phenotype has never been studied. Our study objective was to evaluate the role of pelvic inflammation on PCa aggressiveness and its association with clinical outcomes in patients following radical prostatectomy (RP). This study has been conducted on a retrospective single-institutional consecutive cohort of 2278 patients who underwent robot-assisted laparoscopic prostatectomy (RALP) between 01/2013 and 10/2019. Data from 2085 patients were analyzed to study the association between pelvic inflammation and adverse pathology (AP), defined as Gleason Grade Group (GGG) > 2 and ≥ pT3 stage, at resection. In a subset of 1997 patients, the association between pelvic inflammation and biochemical recurrence (BCR) was studied. Alteration in tumor transcriptome and inflammatory markers in patients with and without pelvic inflammation were studied using microarray analysis, immunohistochemistry, and culture supernatants derived from inflamed sites used in functional assays. Changes in blood inflammatory markers in the study cohort were analyzed by O-link. In univariate analyses, pelvic inflammation emerged as a significant predictor of AP. Multivariate cox proportional-hazards regression analyses showed that high pelvic inflammation with pT3 stage and positive surgical margins significantly affected the time to BCR (p ≤ 0.05). PCa patients with high inflammation had elevated levels of pro-inflammatory cytokines in their tissues and in blood. Genes involved in epithelial-to-mesenchymal transition (EMT) and DNA damage response were upregulated in patients with pelvic inflammation. Attenuation of STAT and IL-6 signaling decreased tumor driving properties of conditioned medium from inflamed sites. Pelvic inflammation exacerbates the progression of prostate cancer and drives an aggressive phenotype.

Prostate MRI percentage tumor involvement or "PI-RADS percent" as a predictor of adverse surgical pathology.

BACKGROUND: This study assesses magnetic resonance imaging (MRI) prostate % tumor involvement or "PI-RADs percent" as a predictor of adverse pathology (AP) after surgery for localized prostate cancer (PCa). Two separate variables, "All PI-RADS percent" (APP) and "Highest PI-RADS percent" (HPP), are defined as the volume of All PI-RADS 3-5 score lesions on MRI and the volume of the Highest PI-RADS 3-5 score lesion each divided by TPV, respectively. METHOD: An analysis was done of an IRB approved prospective cohort of 557 patients with localized PCa who had targeted biopsy of MRI PIRADs 3-5 lesions followed by RARP from April 2015 to May 2020 performed by a single surgeon at a single center. AP was defined as ISUP GGG ≥3, pT stage ≥T3 and/or LNI. Univariate and multivariable analyses were used to evaluate APP and HPP at predicting AP with other clinical variables such as Age, PSA at surgery, Race, Biopsy GGG, mpMRI ECE and mpMRI SVI. Internal and External Validation demonstrated predicted probabilities versus observed probabilities. RESULTS: AP was reported in 44.5% (n = 248) of patients. Multivariable regression showed both APP (odds ratio [OR]: 1.10, 95% confidence interval [CI]: 1.04-1.14, p = 0.0007) and HPP (OR: 1.10; 95% CI: 1.04-1.16; p = 0.0007) were significantly associated with AP with individual area under the operating curves (AUCs) of 0.6142 and 0.6229, respectively, and AUCs of 0.8129 and 0.8124 when incorporated in models including preoperative PSA and highest biopsy GGG. CONCLUSIONS: Increasing PI-RADS Percent was associated with a higher risk of AP, and both APP and HPP may have clinical utility as predictors of AP in GGG 1 and 2 patients being considered for AS. PATIENT SUMMARY: Using PIRADs percent to predict AP for presurgical patients may help risk stratification, and for low and low volume intermediate risk patients, may influence treatment decisions.

Development and External Validation of a Prediction Model to Identify Candidates for Prostate Biopsy.

PURPOSE: Prostate biopsies are associated with infectious complications and approximately 80% are either benign or clinically insignificant prostate cancer. Our aim is to develop and independently validate prediction model to avoid unnecessary prostate biopsies by predicting clinically significant prostate cancer (csPCa) Materials and Methods: Retrospective analysis of single-center cohort (Mount Sinai Hospital, NY) of 1632 men who underwent systematic or combined systematic and Magnetic Resonance Imaging (MRI)/ultrasound fusion targeted prostate biopsy between 2014-2020. External cohort (University of Miami) included 622 men that underwent biopsy. Outcome for predicting csPCa was defined as International Society of Urologic Pathology (ISUP) Gleason grade ≥ 2 on biopsy. Multivariable logistic regression analysis was performed to build nomogram using coefficients of logit function. Nomogram validation was performed in external cohort by plotting receiver operating characteristics (ROC). We also plotted decision curve analysis (DCA) and compared nomogram-predicted probabilities with actual rates of csPCa probabilities in external cohort. RESULTS: Of 1632 men, 43% showed csPCa on biopsy. PSA density, prior negative biopsy, and Prostate Imaging and Reporting Data System (PI-RADS) scores 3, 4, and 5 were significant predictors for csPCa. ROC for prediction of csPCa was 0.88 in external cohort. There was agreement between predicted and actual rate of csPCa in external cohort. DCA demonstrated net benefit using the model. Using the prediction model at threshold of 30, 35% of biopsies and 46% of diagnosed indolent PCa could be avoided, while missing 5% of csPCa. CONCLUSION: Using our prediction model can help reduce unnecessary prostate biopsies with minimal impact on csPCa detection rates.

Morphometric and Immunohistochemical Characteristics of the Adult Human Soft Palate Muscles.

The soft palate is the only structure that reversibly separates the respiratory and gastrointestinal systems. Most species can eat and breathe at the same time. Humans cannot do this and malfunction of the soft palate may allow food to enter the lungs and cause fatal aspiration pneumonia. Speech is the most defining characteristic of humans and the soft palate, along with the larynx and tongue, plays the key roles. In addition, palatal muscles are involved in snoring and obstructive sleep apnea. Considering the significance of the soft palate, its function is insufficiently understood. The objectives of this study were to document morphometric and immunohistochemical characteristics of adult human soft palate muscles, including fiber size, the fiber type, and myosin heavy chain (MyHC) composition for better understanding muscle functions. In this study, 15 soft palates were obtained from human autopsies. The palatal muscles were separated, cryosectioned, and stained using histological and immunohistochemical techniques. The results showed that there was a fast type II predominance in the musculus uvulae and palatopharyngeus and a slow type I predominance in the levator veli palatine. Approximately equal proportions of type I and type II fibers existed in both the palatoglossus and tensor veli palatine. Soft palate muscles also contained hybrid fibers and some specialized myofibers expressing slow-tonic and embryonic MyHC isoforms. These findings would help better understand muscle functions.

Unified model involving genomics, magnetic resonance imaging and prostate-specific antigen density outperforms individual co-variables at predicting biopsy upgrading in patients on active surveillance for low risk prostate cancer.

BACKGROUND: Active surveillance (AS) is the reference standard treatment for the management of low risk prostate cancer (PCa). Accurate assessment of tumor aggressiveness guides recruitment to AS programs to avoid conservative treatment of intermediate and higher risk patients. Nevertheless, underestimating the disease risk may occur in some patients recruited, with biopsy upgrading and the concomitant potential for delayed treatment. AIM: To evaluate the accuracy of mpMRI and GPS for the prediction of biopsy upgrading during active surveillance (AS) management of prostate cancer (PCa). METHOD: A retrospective analysis was performed on 144 patients recruited to AS from October 2013 to December 2020. Median follow was 4.8 (IQR 3.6, 6.3) years. Upgrading was defined as upgrading to biopsy grade group ≥2 on follow up biopsies. Cox proportional hazard regression was used to investigate the effect of PSA density (PSAD), baseline Prostate Imaging-Reporting and Data System (PI-RADS) v2.1 score and GPS on upgrading. Time-to-event outcome, defined as upgrading, was estimated using the Kaplan-Meier method with log-rank test. RESULTS: Overall rate of upgrading was 31.9% (n = 46). PSAD was higher in the patients who were upgraded (0.12 vs. 0.08 ng/ml2 , p = .005), while no significant difference was present for median GPS in the overall cohort (overall median GPS 21; 22 upgrading vs. 20 no upgrading, p = .2044). On univariable cox proportional hazard regression analysis, the factors associated with increased risk of biopsy upgrading were PSA (HR = 1.30, CI 1.16-1.47, p = <.0001), PSAD (HR = 1.08, CI 1.05-1.12, p = <.0001) and higher PI-RADS score (HR = 3.51, CI 1.56-7.91, p = .0024). On multivariable cox proportional hazard regression analysis, only PSAD (HR = 1.10, CI 1.06-1.14, p = <.001) and high PI-RADS score (HR = 4.11, CI 1.79-9.44, p = .0009) were associated with upgrading. A cox regression model combining these three clinical features (PSAD ≥0.15 ng/ml2 at baseline, PI-RADS Score and GPS) yielded a concordance index of 0.71 for the prediction of upgrading. CONCLUSION: In this study PSAD has higher accuracy over baseline PI-RADS score and GPS score for the prediction of PCa upgrading during AS. However, combined use of PSAD, GPS and PI-RADS Score yielded the highest predictive ability with a concordance index of 0.71.

Limb Muscle Reinnervation with the Nerve-Muscle-Endplate Grafting Technique: An Anatomical Feasibility Study.

BACKGROUND: Peroneal nerve injuries results in tibialis anterior (TA) muscle paralysis. TA paralysis could cause "foot drop," a disabling condition that can make walking difficult. As current treatment methods result in poor functional recovery, novel treatment approaches need to be studied. The aim of this study was to explore anatomical feasibility of limb reinnervation with our recently developed nerve-muscle-endplate grafting (NMEG) in the native motor zone (NMZ). METHODS: As the NMEG-NMZ technique involves in nerves and motor endplates (MEPs), the nerve supply patterns and locations of the MEP bands within the gastrocnemius (GM) and TA muscles of rats were investigated using Sihler's stain and whole-mount acetylcholinesterase (AChE) staining, respectively. Five adult rats underwent TA nerve transaction. The denervated TA was reinnervated by transferring an NMEG pedicle from the ipsilateral lateral GM. At the end of a 3-month recovery period, maximal muscle force was measured to document functional recovery. RESULTS: The results showed that the TA was innervated by the deep peroneal nerve. A single MEP band was located obliquely in the middle of the TA. The GM was composed of two neuromuscular compartments, lateral (GM-l) and medial (GM-m), each of which was innervated by a separate nerve branch derived from the tibial nerve and had a vertically positioned MEP band. The locations of MEP bands in the GM and TA muscles and nerve supply patterns demonstrated that an NMEG pedicle can be harvested from the GM-l and implanted into the NMZ within the TA muscle. The NMEG-NMZ pilot study showed that this technique resulted in optimal muscle force recovery. CONCLUSION: NMEG-NMZ surgery is feasible for limb reinnervation. Specifically, the denervated TA caused by peroneal nerve injuries can be reinnervated with a NMEG from the GM-l.

Multiphoton Microscopy for Identifying Collagen Signatures Associated with Biochemical Recurrence in Prostate Cancer Patients.

Prostate cancer is a heterogeneous disease that remains dormant for long periods or acts aggressively with poor clinical outcomes. Identifying aggressive prostate tumor behavior using current glandular-focused histopathological criteria is challenging. Recent evidence has implicated the stroma in modulating prostate tumor behavior and in predicting post-surgical outcomes. However, the emergence of stromal signatures has been limited, due in part to the lack of adoption of imaging modalities for stromal-specific profiling. Herein, label-free multiphoton microscopy (MPM), with its ability to image tissue with stromal-specific contrast, is used to identify prostate stromal features associated with aggressive tumor behavior and clinical outcome. MPM was performed on unstained prostatectomy specimens from 59 patients and on biopsy specimens from 17 patients with known post-surgery recurrence status. MPM-identified collagen content, organization, and morphological tumor signatures were extracted for each patient and screened for association with recurrent disease. Compared to tumors from patients whose disease did not recur, tumors from patients with recurrent disease exhibited higher MPM-identified collagen amount and collagen fiber intensity signal and width. Our study shows an association between MPM-identified stromal collagen features of prostate tumors and post-surgical disease recurrence, suggesting their potential for prostate cancer risk assessment.

Clinical Utility of Negative Multiparametric Magnetic Resonance Imaging in the Diagnosis of Prostate Cancer and Clinically Significant Prostate Cancer.

BACKGROUND: Multiparametric magnetic resonance imaging (MRI) is increasingly used to diagnose prostate cancer (PCa). It is not yet established whether all men with negative MRI (Prostate Imaging-Reporting and Data System version 2 score <3) should undergo prostate biopsy or not. OBJECTIVE: To develop and validate a prediction model that uses clinical parameters to reduce unnecessary prostate biopsies by predicting PCa and clinically significant PCa (csPCa) for men with negative MRI findings who are at risk of harboring PCa. DESIGN SETTING AND PARTICIPANTS: This was a retrospective analysis of 200 men with negative MRI at risk of PCa who underwent prostate biopsy (2014-2020) with prostate-specific antigen (PSA) >4 ng/ml, 4Kscore of >7%, PSA density ≥0.15 ng/ml/cm3, and/or suspicious digital rectal examination. The validation cohort included 182 men from another centre (University of Miami) with negative MRI who underwent systematic prostate biopsy with the same criteria. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: csPCa was defined as Gleason grade group ≥2 on biopsy. Multivariable logistic regression analysis was performed using coefficients of logit function for predicting PCa and csPCa. Nomogram validation was performed by calculating the area under receiver operating characteristic curves (AUC) and comparing nomogram-predicted probabilities with actual rates of PCa and csPCa. RESULTS AND LIMITATIONS: Of 200 men in the development cohort, 18% showed PCa and 8% showed csPCa on biopsy. Of 182 men in the validation cohort, 21% showed PCa and 6% showed csPCa on biopsy. PSA density, 4Kscore, and family history of PCa were significant predictors for PCa and csPCa. The AUC was 0.80 and 0.87 for prediction of PCa and csPCa, respectively. There was agreement between predicted and actual rates of PCa in the validation cohort. Using the prediction model at threshold of 40, 47% of benign biopsies and 15% of indolent PCa cases diagnosed could be avoided, while missing 10% of csPCa cases. The small sample size and number of events are limitations of the study. CONCLUSIONS: Our prediction model can reduce the number of prostate biopsies among men with negative MRI without compromising the detection of csPCa. PATIENT SUMMARY: We developed a tool for selection of men with negative MRI (magnetic resonance imaging) findings for prostate cancer who should undergo prostate biopsy. This risk prediction tool safely reduces the number of men who need to undergo the procedure.

Clinical characteristics and oncological outcomes in negative multiparametric MRI patients undergoing robot-assisted radical prostatectomy.

BACKGROUND: Efforts are ongoing to try and find ways to reduce the number of unnecessary prostate biopsies without missing clinically significant prostate cancers (csPCa). The utility of multiparametric magnetic resonance imaging (mpMRI) in detecting prostate cancer (PCa) shows promise to be used as triage test for systematic prostate biopsy. Our aim is to Study clinical parameters and oncological outcomes in men with negative mpMRI (nMRI; PI-RADS v2 scores of ≤ 2) who underwent robot-assisted radical prostatectomy (RARP) to evaluate nMRI's practicality as a biopsy triage test. METHODS: Retrospective analysis of 331 men with nMRI who underwent RARP between 2014 and 2020 compared with men with positive mpMRI (pMRI; PI-RADS v2 scores ≥ 3, N = 1770). csPCa was defined as Gleason score ≥ 3 + 4 and biochemical recurrence (BCR) was defined as PSA > 0.2 ng/ml on two occasions. Biopsies were graded with the International Society of Urologic Pathology [ISUP] grade. Descriptive statistics for nMRI and pMRI were performed. Mann-Whitney U test was used for continuous variables and χ 2 for categorical variables. Univariable and multivariable regression analyses were performed. RESULTS: Univariable analysis shows statistically significant difference (p < .05) between median age (nMRI-61 years vs. pMRI 63 years), race (higher incidence of nMRI in African American men), use of 5-alpha reductase inhibitors (higher rate in nMRI). While incidence rates of family history of PCa, suspicious digital rectal examination (DRE) findings, median PSA levels and 4Kscore, were lower in nMRI versus pMRI. Rates of positive surgical margins and BCR were comparable in nMRI versus pMRI. Biopsy ISUP Grades I and II upgraded by 51% and 12%, respectively in final pathology. African American race and no history of the prior negative biopsy were significant predictors for upgrading. CONCLUSION: Men with nMRI pose diagnostic challenges as they tend to be younger patients with lower rates of suspicious DRE findings and lower 4K scores, yet comparable oncological outcomes in csPCa rates, positive surgical margins, and BCR rates.

Increased Hospitalization and Mortality from COVID-19 in Prostate Cancer Patients.

BACKGROUND: Cancer patients with COVID-19 have a poor disease course. Among tumor types, prostate cancer and COVID-19 share several risk factors, and the interaction of prostate cancer and COVID-19 is purported to have an adverse outcome. METHODS: This was a single-institution retrospective study on 286,609 patients who underwent the COVID-19 test at Mount Sinai Hospital system from March 2020 to December 2020. Chi-square/Fisher's exact tests were used to summarize baseline characteristics of categorical data, and Mann-Whitney U test was used for continuous variables. Univariable logistic regression analysis to compare the hospitalization and mortality rates and the strength of association was obtained by the odds ratio and confidence interval. RESULTS: This study aimed to compare hospitalization and mortality rates between men with COVID-19 and prostate cancer and those who were COVID-19-positive with non-prostate genitourinary malignancy or any solid cancer, and with breast cancer patients. We also compared our studies to others that reported the incidence and severity of COVID-19 in prostate cancer patients. Our studies highlight that patients with prostate cancer had higher susceptibility to COVID-19-related pathogenesis, resulting in higher mortality and hospitalization rates. Hospitalization and mortality rates were higher in prostate cancer patients with COVID-19 when compared with COVID-19 patients with non-prostate genitourinary (GU) malignancies.

De-Escalated Adjuvant Therapy After Transoral Robotic Surgery for Human Papillomavirus-Related Oropharyngeal Carcinoma: The Sinai Robotic Surgery (SIRS) Trial.

BACKGROUND: Treatment of human papillomavirus-related oropharyngeal squamous cell carcinoma (HPVOPC) results in unprecedented high survival rates but possibly unnecessary toxicity. We hypothesized that upfront surgery and neck dissection followed by reduced-dose adjuvant therapy for early and intermediate HPVOPC would ultimately result in equivalent progression-free survival (PFS) and overall survival while reducing toxicity. METHODS: This study was a nonrandomized phase II trial for early-stage HPVOPC treated with transoral robotic surgery (TORS) followed by reduced-dose radiotherapy. Patients with previously untreated p16-positive HPVOPC and <20 pack years' smoking history were enrolled. After robotic surgery, patients were assigned to group 1 (no poor risk features; surveillance), group 2 (intermediate pathologic risk factors [perineural invasion, lymphovascular invasion]; 50-Gy radiotherapy), or group 3 (poor prognostic pathologic factors [extranodal extension [ENE], more than three positive lymph nodes and positive margin]; concurrent 56-Gy chemoradiotherapy with weekly cisplatin). RESULTS: Fifty-four patients were evaluable; there were 25 in group 1, 15 in group 2, and 14 in group 3. Median follow-up was 43.9 months (9.6-75.8). Disease-specific survival was 98.1%, and PFS was 90.7%. PFS probability via Kaplan-Meier was 91.3% for group 1, 86.7% for group 2, and 93.3% for group 3. There were five locoregional failures (LRFs), including one distant metastasis and one contralateral second primary. Average time to LRF was 18.9 months (9.6-59.0); four LRFs were successfully salvaged, and the patients remain disease free (11.0-42.7 months); one subject remains alive with disease. CONCLUSION: The results indicate that upfront surgery with neck dissection with reduced-dose radiation for T1-2, N1 stage (by the eighth edition American Joint Committee on Cancer staging manual) HPVOPC results in favorable survival with excellent function in this population. These results support radiation dose reduction after TORS as a de-escalation strategy in HPVOPC. IMPLICATIONS FOR PRACTICE: Transoral robotic surgery can provide a safe platform for de-escalation in carefully selected patients with early-stage human papillomavirus-related oropharyngeal cancer. In this clinical trial, disease-specific survival was 100%, over 90% of the cohort had a reduction of therapy from standard of care with excellent functional results, and the five patients with observed locoregional failures were successfully salvaged.

A 4K score/MRI-based nomogram for predicting prostate cancer, clinically significant prostate cancer, and unfavorable prostate cancer.

BACKGROUND: The detection of prostate cancer requires histological confirmation in biopsy core. Currently, number of unnecessary prostate biopsies are being performed in the United States. This is due to the absence of appropriate biopsy decision-making protocol. AIM: To develop and validate a 4K score/multiparametric magnetic resonance imaging (mpMRI)-based nomogram to predict prostate cancer (PCa), clinically significant prostate cancer (csPCa), and unfavorable prostate cancer (uPCa). METHODS AND RESULTS: Retrospective, single-center study evaluating a cohort of 574 men with 4K score test >7% or suspicious digital rectal examination (DRE) or Prostate Imaging Reporting and Data System (PI-RADS) scores 3, 4, or 5 on mpMRI that underwent systematic and/or mpMRI/ultrasound fusion-targeted prostate biopsy between 2016 and 2020. External cohort included 622 men. csPCa and uPCa were defined as Gleason score ≥3 + 4 and ≥4 + 3 on biopsy, respectively. Multivariable logistic regression analysis was performed to build nomogram for predicting PCa, csPCa, and uPCa. Validation was performed by plotting the area under the curve (AUC) and comparing nomogram-predicted probabilities with actual rates of PCa, csPCa, and uPCa probabilities in the external cohort. 4K score, a PI-RADS ≥4, prostate volume and prior negative biopsy were significant predictors of PCa, csPCa, and uPCa. AUCs were 0.84, 0.88, and 0.86 for the prediction of PCa, csPCa, and uPCa, respectively. The predicted and actual rates of PCa, csPCa, and uPCa showed agreement across all percentage probability ranges in the validation cohort. Using the prediction model at threshold of 30, 30% of overall biopsies, 41% of benign biopsies, and 19% of diagnosed indolent PCa could be avoided, while missing 9% of csPCa. CONCLUSION: This novel nomogram would reduce unnecessary prostate biopsies and decrease detection of clinically insignificant PCa.

Innervation of human soft palate muscles.

Our objective was to determine the branching and distribution of the motor nerves supplying the human soft palate muscles. Six adult specimens of the soft palate in continuity with the pharynx, larynx, and tongue were processed with Sihler's stain, a technique that can render large specimens transparent while counterstaining their nerves. The cranial nerves were identified and dissection followed their branches as they divided into smaller divisions toward their terminations in individual muscles. The results showed that both the glossopharyngeal (IX) and vagus (X) nerves have three distinct branches, superior, middle, and inferior. Only the middle branches of each nerve contributed to the pharyngeal plexus to which the facial nerve also contributed. The pharyngeal plexus was divided into two parts, a superior innervating the palatal and neighboring muscles and an inferior innervating pharyngeal constrictors. The superior branches of the IX and X nerves contributed innervation to the palatoglossus, whereas their middle branches innervated the palatopharyngeus. The palatoglossus and palatopharyngeus muscles appeared to be composed of at least two neuromuscular compartments. The lesser palatine nerve not only supplied the palatal mucosa and palatine glandular tissue but also innervated the musculus uvulae, palatopharyngeus, and levator veli palatine. The latter muscle also received its innervation from the superior branch of X nerve. The findings would be useful for better understanding the neural control of the soft palate and for developing novel neuromodulation therapies to treat certain upper airway disorders such as obstructive sleep apnea.

Hood Technique for Robotic Radical Prostatectomy-Preserving Periurethral Anatomical Structures in the Space of Retzius and Sparing the Pouch of Douglas, Enabling Early Return of Continence Without Compromising Surgical Margin Rates.

BACKGROUND: A common side effect following radical prostatectomy is urinary incontinence. Here, we describe a novel surgical technique to reduce postoperative urinary incontinence and facilitate early return of continence. OBJECTIVE: To describe the novel "hood technique" for robotic-assisted radical prostatectomy (RARP). DESIGN, SETTING, AND PARTICIPANTS: This is an institutional review board-approved prospective study of 300 patients (median age 64 yr) with localized prostate cancer treated with the RARP hood technique at a major urban hospital between April 2018 and March 2019. The exclusion criteria were as follows: patients with anterior tumor location based on biopsy or multiparametric magnetic resonance imaging. All but one patient participated in follow-up over 12 mo after the procedure. SURGICAL PROCEDURE: The RARP "hood technique" was performed to preserve the detrusor apron, puboprostatic ligament complex, arcus tendineus, endopelvic fascia, and pouch of Douglas. MEASUREMENTS: Clinical data collected included pre- and intraoperative variables, and postoperative functional and oncological outcomes and complications. Descriptive statistical analysis was performed. RESULTS AND LIMITATIONS: Continence rates at 1, 2, 4, 6 12, 24, and 48 wk after catheter removal were 21%, 36%, 83%, 88%, 91%, 94%, and 95%, respectively. Positive surgical margin rate was 6%. Thirty patients (9.7%) experienced complications after RARP: 17 (5.7%), 11 (3.6%), and one (0.4%) had Clavien-Dindo grade I, II, and III complications, respectively. This study was conducted within a single health system and may not be generalizable. The study lacked randomization and a comparative arm. CONCLUSIONS: Results indicate that the hood technique spares musculofascial structures anterior to the urethral sphincter complex with early return of continence after surgery, without compromising positive surgical margin rates. Exclusion of anterior tumor location contributed to a reduction in positive surgical margins. PATIENT SUMMARY: By better preservation of anatomical structures around the urethra, we were able to achieve early return of urinary continence without a negative impact on complications and cancer outcomes.

Oral squamous carcinoma: Aggressive tumor pattern of invasion predicts direct mandible invasion.

BACKGROUND: Aggressive histologic worst pattern of invasion (WPOI) in surrounding soft tissue has been shown to be predictive of higher local recurrence and poorer survival in oral cavity squamous cell carcinoma (OCSCC) patients. This study investigates whether aggressive WPOI can predict the mandibular invasion phenotype. METHODS: Patients consecutively diagnosed with OCSCC undergoing a mandibulectomy (marginal or segmental) between 2013 and 2018 were reviewed. Senior physicians re-reviewed radiologic scans and pathologic slides of 44 cases. RESULTS: Aggressive WPOI (WPOI-4, 5) is significantly associated with infiltrative bone invasion. Non-aggressive WPOI (WPOI-1, 2, 3) is significantly associated with the absence of bone invasion. CONCLUSIONS: WPOI has become a useful tool that further characterizes the biologic behavior of OCSCC. Potentially, planned surgery may escalate from a marginal to segmental mandibulectomy based on aggressive WPOI for patients with radiographically uncertain cortical status. Further studies are needed to validate the relationship between OCSCC WPOI and mandible status.

Staging Accuracy of Multiparametric Magnetic Resonance Imaging in Caucasian and African American Men Undergoing Radical Prostatectomy.

PURPOSE: We compared the performance of multiparametric magnetic resonance imaging for the prediction of extraprostatic extension in African American and Caucasian American men and evaluated racial disparities in pathological outcomes after radical prostatectomy. MATERIALS AND METHODS: We identified 975 patients who underwent radical prostatectomy with preoperative multiparametric magnetic resonance imaging between January 2013 and April 2019 at our institution. Multivariable logistic regression analysis was performed predicting pathological extraprostatic extension, high grade prostate cancer (final pathology GGG [Gleason Grade Group] 3 or greater) in the overall population and pathological upgrading (final pathology GGG 3 or greater) in patients with a diagnosis of GGG 1-2 prostate cancer. Adverse pathology was defined as pT3 and/or GGG 3 or greater. RESULTS: A total of 221 (23%) patients were African American. Preoperatively 594 (60.9%) were GGG 1-2 (low risk group) and 381 (39.1%) GGG 3 or greater (high risk group). In the low risk group rates of pathological extraprostatic extension (18% vs 12.8%, p=0.14), adverse pathology (18% vs 13.4%, p=0.2) or upgrading (9.4% vs 12.1%, p=0.4) were similar between races. Similarly, in the high risk group there was no difference in rates of pathological extraprostatic extension. On multivariable analysis multiparametric magnetic resonance imaging predicted the presence of extraprostatic extension (OR 1.80, 95% CI 1.29-2.50) and high grade prostate cancer (OR 1.82, 95% CI 1.25-2.67) on final pathology. Conversely, race did not predict the outcomes of interest (all values p >0.05). Multiparametric magnetic resonance imaging showed comparable sensitivity (22.22% vs 27.84%), specificity (89.2% vs 79.2%), positive predictive value (89.2% vs 83.4%) and negative predictive value (89.2% vs 83.4%) between African American and Caucasian America men, respectively. CONCLUSIONS: The accuracy of multiparametric magnetic resonance imaging in staging prostate cancer was similar in African American and Caucasian American patients and no difference was found between races in pathological outcomes after radical prostatectomy. These findings suggest that access to and use of advanced diagnostic tests may help mitigate prostate cancer racial disparities.

Impact of COVID-19 on Prostate Cancer Management: Guidelines for Urologists.

CONTEXT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in a global health emergency, the like of which has never been seen before. Prostate cancer (PCa) services across the globe have been on hold due to changing medical and surgical priorities. There is also epidemiological evidence that PCa patients have increased incidence and mortality from SARS-CoV-2 infection due to gender differences, age, and higher propensity for risk factors (eg, respiratory disease, obesity, hypertension, and smoking status). OBJECTIVE: To contribute to the emerging body of knowledge on the risks of SARS-CoV-2 infection to PCa patients and, in the face of PCa treatment delays, provide evidence-based recommendations for ongoing management of specific PCa patient groups. EVIDENCE ACQUISITION: A literature search was performed using all sources (MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science) as well as the media to harness emerging data on the SARS-CoV-2 pandemic and its influence on PCa. Eligibility criteria were originality of data and relevance to PCa management. The authors note that during these unprecedented times, retrospective data are constantly being updated from multiple sources globally. EVIDENCE SYNTHESIS: A total of 72 articles and data sources were found initially. Owing to repetition, lack of originality, or nonrelevance, six articles were rejected, leaving 23 retrospective studies, seven basic science research articles, 15 societal and journal guidelines, and 21 epidemiological data sources, from countries at different stages of SARS-CoV-2 pandemic. These were analyzed qualitatively to produce evidence-based guidelines for the management of PCa patients at different stages of the patient journey, with strategies to reduce the risk of viral spread. CONCLUSIONS: PCa patients may have an increased risk of SARS-CoV-2 infection as well as morbidity and mortality if infected. Once appropriately triaged, and to reduce viral spread, PCa patients can have surveillance by telemedicine, and institute lifestyle changes and social quarantining measures. If risk stratification suggests that treatment should be planned, androgen deprivation therapy can be started, or potentially surgery or radiation therapy is possible on a case-by-case basis. PATIENT SUMMARY: Prostate cancer patients can be followed up remotely until the severe acute respiratory syndrome coronavirus 2 pandemic resolves, but higher-risk cases may have treatment expedited to limit any negative impact on prostate cancer outcomes.