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Abstract Objectives Functional problems, including nasal flow problems, are associated with specific skeletal and dental features. Further, maxillary expansion has been associated with nasal airway resistance alterations. This study aimed to investigate whether there is a correlation between skeletal features and nasal airflow‐ and olfaction‐related problems. Materials and methods This prospective study included 68 patients (30 boys, 38 girls; mean age 9 ± 2 years) examined at the Ohu University Hospital. We classified patients into three skeletal Classes (Class I, II, and III) based on the ANB angle. Olfactory disorder history was collected from the guardians. Maxillofacial measurements, nasal airflow assessments, and olfactory tests were performed using cephalometric analysis, rhinomanometry, and T&T olfactometer, respectively. Results Malocclusion, resulting from skeletal mandibular protrusion and smaller maxilla, was associated with reduced olfaction in children. The detection and recognition thresholds of skeletal Class III were significantly higher than those of Classes I (p = .01) and II (p = .01). Significant correlations were observed between SNA and the detection threshold (r = −.50) as well as between nasion perpendicular‐point A and the recognition threshold (r = −.53). The detection and recognition thresholds were significantly higher in Class III than in Classes I (r = .3) and II (r = −.1). Conclusions Maxillary growth and development may be associated with olfaction in children. Changing the maxillofacial morphology may improve olfactory function. In the future, we will investigate how malocclusion treatment affects olfactory function.

Endodontic–periodontal lesions (EPLs) are chronic inflammatory lesions in the mouth caused by multiple factors. Both periapical and marginal periodontitis are characterized by infection and inflammation around the affected teeth, suggesting that the theory of complex systems might describe the progression of EPL. The diagnosis and treatment of EPLs are complicated by variations of this condition and difficulties distinguishing EPLs from other diseases. Technological advances in diagnostic and treatment methods, including cone beam computed tomography, microscopy, mineral trioxide aggregates, and periodontal regenerative treatment, have improved outcomes, even in untreatable teeth. However, treating EPLs with iatrogenic problems and/or severe periodontitis remains challenging. Assessing the risk of each EPL based on the possible pathogenesis of each EPL is essential for determining individualized treatment and optimizing personalized medicine for individual patients.

The aim of this study is to evaluate the factors of implant failure in patients with periodontitis and their impact on the prognosis of having a peri-implant disease and/or implant failure. Data regarding 325 implants among 84 patients with periodontitis were retrospectively examined. Patients were classified by Stage (I, II, III, IV) and Grade (A, B, C), implant failures for peri-implant disease and lack of osseointegration. Clinical data, including implant- and patient-related variables were evaluated by principal components analysis (PCA) and two-step cluster analysis (CA). Survival and success rates were 96.3% and 87.1%, respectively. Prevalence of peri-implant disease was significantly higher in Stage IV patients (p < 0.05), and incidence of lost implant due to peri-implantitis was significantly higher in patients with bone augmentation (BA) (p < 0.05). PCA and CA revealed five of eleven variables and four clusters at patient level, and six of fourteen variables and three clusters at implant level. Stage and Grade are useful indicators for the development of peri-implant diseases in which BA and the number of implants are involved.

With the spread of oral implant therapy, serious medical complications related to implant surgery are becoming a social problem. Although the number of complications after implant surgery in the edentulous jaw is decreasing in Japan, maxillary-sinus-related complications (MSRCs) have reached the highest number since 2012. It is essential to identify and eliminate possible predisposing risk factors for MSRCs at an early stage to prevent MSRCs. In this review article, we highlight the causal factors of postoperative complications with or without sinus augmentation for the maxillary molar region to achieve optimal treatment outcomes and reduce complications. In particular, we focus on anatomical variations that can cause the impairment of maxillary sinus drainage. Furthermore, we emphasize that the paradigm for personalized medicine for patients with a maxillary edentulous jaw by ENT specialist and dentist cooperation is shifting from the traditional assessment of maxillary sinus pathologies alone to the new assessment of anatomic variations that can cause the impairment of maxillary sinus drainage in addition to maxillary sinus pathologies.

Maxillary sinus floor elevation (sinus lift) is a widely recognized dental-surgical approach for dental implant placement. However, for an otorhinolaryngological high-risk patient with severe anatomic-structural impairments of the maxillary sinus drainage pathway, surgical intervention is recommended before sinus lift to avoid postsinus lift maxillary sinusitis. Here, we show a case that postsinus lift maxillary sinusitis in such a high-risk patient was noninvasively prevented by the collaboration of otorhinolaryngologist and dentist. A 48-year-old Japanese male intended to undergo a sinus lift for dental implant placement by periodontist. Otorhinolaryngologist found septal deviation, concha bullosa, the presence of Haller cell, and nasal mucosal swelling by the nasal allergy, while no sinusitis and diagnosed him as a “high-risk case” for postsinus lift maxillary sinusitis. The patient was administered preoperative topical steroid and leukotriene receptor antagonist in addition to perioperative antibiotic prophylaxis so that his complication was noninvasively prevented. Thus, this case suggested that consultation from dentist to otorhinolaryngologist provides benefit to the patients who have been diagnosed as “high-risk case” for postsinus lift maxillary sinusitis.

Summary: Initial studies of cancer metabolism in the early 1920s found that cancer cells were phenotypically characterized by aerobic glycolysis, in that these cells favor glucose uptake and lactate production, even in the presence of oxygen. This property, called the Warburg effect, is considered a hallmark of cancer. The mechanism by which these cells acquire aerobic glycolysis has been uncovered. Acidic extracellular fluid, secreted by cancer cells, induces a malignant phenotype, including invasion and metastasis. Cancer cells survival depends on a critical balance of redox status, which is regulated by amino acid metabolism. Glutamine is extremely important for oxidative phosphorylation and redox regulation. Cells highly dependent on glutamine and that cannot survive with glutamine are called glutamine-addicted cells. Metabolic reprogramming has been observed in cancer stem cells, which have the property of self-renewal and are resistant to chemotherapy and radiotherapy. These findings suggest that studies of cancer metabolism can reveal methods of preventing cancer recurrence and metastasis. Keywords: Glycolysis, Warburg effect, Glutamine metabolism, Acidic extracellular pH

Mineral trioxide aggregate (MTA) has been recommended for various uses in endodontics. To understand the effects of MTA on alveolar bone, we examined whether MTA induces osteoblastic differentiation using MC3T3-E1 cells. MTA enhanced mineralization concomitant with alkaline phosphatase activity in a dose- and time-dependent manner. MTA increased production of collagens (Type I and Type III) and matrix metalloproteinases (MMP-9 and MMP-13), suggesting that MTA affects bone matrix remodeling. MTA also induced Bglap (osteocalcin) but not Bmp2 (bone morphogenetic protein-2) mRNA expression. We observed induction of Atf6 (activating transcription factor 6, an endoplasmic reticulum (ER) stress response transcription factor) mRNA expression and activation of Atf6 by MTA treatment. Forced expression of p50Atf6 (active form of Atf6) markedly enhanced Bglap mRNA expression. Chromatin immunoprecipitation assay was performed to investigate the increase in p50Atf6 binding to the Bglap promoter region by MTA treatment. Furthermore, knockdown of Atf6 gene expression by introduction of Tet-on Atf6 shRNA expression vector abrogated MTA-induced mineralization. These results suggest that MTA induces in vitro osteoblastogenesis through the Atf6–osteocalcin axis as ER stress signaling. Therefore, MTA in endodontic treatment may affect alveolar bone healing in the resorbed region caused by pulpal infection.

Head and neck squamous cell carcinoma (HNSCC) is known to be intrinsically resistant to inhibitors for epidermal growth factor receptor (EGFR). Until now, clinical outcomes for HNSCC using EGFR inhibitors as single agents have yielded disappointing results. Here, we aimed to study whether combinatorial treatment using AG1478 (EGFR tyrosine kinase inhibitor) and deguelin, which is a rotenoid isolated from the African plant Mundulea sericea, could enhance the anti-tumor effects of AG1478 in HNSCC. For Ca9-22 cells with EGFR, KRAS, and PIK3CA wild types, AG1478 alone suppressed both phosphorylated levels of ERK and AKT and induced apoptosis. On the contrary, for HSC-4 cells with EGFR and KRAS wild types, and a PIK3CA mutant, AG1478 alone did not suppress the phosphorylated level of AKT nor induce apoptosis, while it suppressed ERK phosphorylation. Forced expression of constitutively active PIK3CA (G1633A mutation) significantly reduced the apoptotic effect of AG1478 on the PIK3CA wild-type Ca9-22 cells. When HSC-4 cells with the PIK3CA G1633A mutation were treated with a combination of AG1478 and deguelin, combination effects on apoptosis induction were observed through the inhibition of the AKT pathway. These results suggest that the combination of EGFR tyrosine kinase inhibitor with deguelin is a potential therapeutic approach to treat PIK3CA-mutated HNSCC.

Laryngeal carcinoma and laryngeal papilloma are the most commonly encountered tumorous lesions in the larynx. Herein, we report a case of the mass arising from the left vocal cord in a 49-year-old Japanese man. Endoscopic examination suggested that the mass is a tumor such as carcinoma and papilloma. Pathological examination showed that the specimen demonstrated actinomycosis in the left vocal cord. Although vocal cord actinomycosis is extremely rare, the otolaryngologist should recognize this condition during the inspection of the larynx.

Exostosis, osteoma, and adenoma are the most commonly encountered benign lesions in the external auditory canal. Herein, we report a case of the mass arising from the external auditory canal in a 24-year-old Japanese man. CT revealed the soft tissue mass without bony erosion, and MRI revealed that the mass showed a homogenous, iso signal intensity on a both T1- and T2-weighted image, suggesting that the mass is a benign tumor such as adenoma. Pathological examination showed that the specimen demonstrated xanthogranuloma in the external auditory canal. Although xanthogranuloma of the external auditory canal is extremely rare, otolaryngologists should recognize this condition during the inspection of the external auditory canal.

Purpose: Preoperative prediction of postoperative complications (PCs) in inpatients with cancer is challenging. We developed an explainable machine learning (ML) model to predict PCs in a heterogenous population of inpatients with cancer undergoing same-hospitalization major operations., Methods: Consecutive inpatients who underwent same-hospitalization operations from December 2017 to June 2021 at a single institution were retrospectively reviewed. The ML model was developed and tested using electronic health record (EHR) data to predict 30-day PCs for patients with Clavien-Dindo grade 3 or higher (CD 3+) per the CD classification system. Model performance was assessed using area under the receiver operating characteristic curve (AUROC), area under the precision recall curve (AUPRC), and calibration plots. Model explanation was performed using the Shapley additive explanations (SHAP) method at cohort and individual operation levels., Results: A total of 988 operations in 827 inpatients were included. The ML model was trained using 788 operations and tested using a holdout set of 200 operations. The CD 3+ complication rates were 28.6% and 27.5% in the training and holdout test sets, respectively. Training and holdout test sets' model performance in predicting CD 3+ complications yielded an AUROC of 0.77 and 0.73 and an AUPRC of 0.56 and 0.52, respectively. Calibration plots demonstrated good reliability. The SHAP method identified features and the contributions of the features to the risk of PCs., Conclusion: We trained and tested an explainable ML model to predict the risk of developing PCs in patients with cancer. Using patient-specific EHR data, the ML model accurately discriminated the risk of developing CD 3+ complications and displayed top features at the individual operation and cohort level.

The Warburg effect-related metabolic dysfunction of the tricarboxylic acid (TCA) cycle has emerged as a hallmark of various solid tumors, particularly renal cell carcinoma (RCC). RCC is characterized by high immune infiltration and thus recommended for immunotherapeutic interventions at an advanced stage in clinical guidelines. Nevertheless, limited benefits of immunotherapy have prompted investigations into underlying mechanisms, leading to the proposal of metabolic dysregulation-induced immunoevasion as a crucial contributor. In this study, a significant decrease is found in the abundance of alpha-ketoglutarate (αKG), a crucial intermediate metabolite in the TCA cycle, which is correlated with higher grades and a worse prognosis in clinical RCC samples. Elevated levels of αKG promote major histocompatibility complex-I (MHC-I) antigen processing and presentation, as well as the expression of β2-microglobulin (B2M). While αKG modulates broad-spectrum demethylation activities of histone, the transcriptional upregulation of B2M is dependent on the demethylation of H3K4me1 in its promoter region. Furthermore, the combination of αKG supplementation and PD-1 blockade leads to improved therapeutic efficacy and prolongs survival in murine models when compared to monotherapy. Overall, the findings elucidate the mechanisms of immune evasion in anti-tumor immunotherapies and suggest a potential combinatorial treatment strategy in RCC., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for individuals with a prostate who opt to participate in an early detection program after receiving the appropriate counseling on the pros and cons. These NCCN Guidelines Insights provide a summary of recent updates to the NCCN Guidelines with regard to the testing protocol, use of multiparametric MRI, and management of negative biopsy results to optimize the detection of clinically significant prostate cancer and minimize the detection of indolent disease.

Background: The feasibility of remote perioperative telemonitoring of patient-generated physiologic health data and patient-reported outcomes in a high risk complex general and urologic oncology surgery population is evaluated., Methods: Complex general surgical/urologic oncology patients wore a pedometer, completed ePROs (electronic patient-reported outcome surveys) and record their vitals (weight, pulse, pulse oximetry, blood pressure, and temperature) via a telehealth app platform. Feasibility (% adherence) was assessed as the primary outcome measure., Results: Twenty-one patients with a median age 58 (32-82) years were included. The readmission rate was 33% and the incidence of ≥Grade 3a morbidity was 24%. Adherence to vital sign and ePRO measurements was 95% before surgery, 91% at discharge, and 82%, 68%, and 64% at postdischarge d2, 7, 14, and 30, respectively. There was significant worsening of mobility, self-care and usual daily activity at postdischarge d2 compared to preoperative baseline (p < 0.05). Median daily preoperative steps taken by patients with

Background: Men with grade group 2 or 3 prostate cancer are often considered ineligible for active surveillance; some patients with grade group 2 prostate cancer who are managed with active surveillance will have early disease progression requiring radical therapy. This study aimed to investigate whether MRI-guided focused ultrasound focal therapy can safely reduce treatment burden for patients with localised grade group 2 or 3 intermediate-risk prostate cancer., Methods: In this single-arm, multicentre, phase 2b study conducted at eight health-care centres in the USA, we recruited men aged 50 years and older with unilateral, MRI-visible, primary, intermediate-risk, previously untreated prostate adenocarcinoma (prostate-specific antigen ≤20 ng/mL, grade group 2 or 3; tumour classification ≤T2) confirmed on combined biopsy (combining MRI-targeted and systematic biopsies). MRI-guided focused ultrasound energy, sequentially titrated to temperatures sufficient for tissue ablation (about 60-70°C), was delivered to the index lesion and a planned margin of 5 mm or more of normal tissue, using real-time magnetic resonance thermometry for intraoperative monitoring. Co-primary outcomes were oncological outcomes (absence of grade group 2 and higher cancer in the treated area at 6-month and 24-month combined biopsy; when 24-month biopsy data were not available and grade group 2 or higher cancer had occurred in the treated area at 6 months, the 6-month biopsy results were included in the final analysis) and safety (adverse events up to 24 months) in all patients enrolled in the study. This study is registered with ClinicalTrials.gov, NCT01657942, and is no longer recruiting., Findings: Between May 4, 2017, and Dec 21, 2018, we assessed 194 patients for eligibility and treated 101 patients with MRI-guided focused ultrasound. Median age was 63 years (IQR 58-67) and median concentration of prostate-specific antigen was 5·7 ng/mL (IQR 4·2-7·5). Most cancers were grade group 2 (79 [78%] of 101). At 24 months, 78 (88% [95% CI 79-94]) of 89 men had no evidence of grade group 2 or higher prostate cancer in the treated area. No grade 4 or grade 5 treatment-related adverse events were reported, and only one grade 3 adverse event (urinary tract infection) was reported. There were no treatment-related deaths., Interpretation: 24-month biopsy outcomes show that MRI-guided focused ultrasound focal therapy is safe and effectively treats grade group 2 or 3 prostate cancer. These results support focal therapy for select patients and its use in comparative trials to determine if a tissue-preserving approach is effective in delaying or eliminating the need for radical whole-gland treatment in the long term., Funding: Insightec and the National Cancer Institute., Competing Interests: Declaration of interests BE attends the medical advisory board of Insightec as an unpaid consultant, and has previously received consulting funds from Myriad Genetics. CMT reports consulting funds from Profound. DDS reports consulting funds from OPKO Health and Steba. ASK is on the medical advisory board of Insightec, Profound, and Janssen, and has received consulting funds from Advantagene DSMC, Bristol Myers Squibb, Merck, Bayer, and General Electric. Q-DT reports consulting funds from Astellas, Bayer, Intuitive Surgical, and Janssen. JCD is the Chief Clinical Officer for Ajax Health and Cordis Accelco and has equity interests in Cordis; is on the advisory board and has ownership or equity interests in Serpex Health and Adient Medical; and serves as the past chair of the Society of Interventional Radiology Foundation. OA has ownership or equity interests in Ezra AI. AJV is named on a patent for a statistical method to detect prostate cancer that has been commercialised by OPKO Health (from which he receives royalties and stock options) and has received consulting funds from Insightec and Steba. PTS is named on a patent for a statistical method to detect prostate cancer that has been commercialised by OPKO Health (from which he receives royalties and stock options) and chairs the medical advisory board of Insightec as an unpaid consultant. DS is the medical director and founder of Sperling Prostate Center, a private facility for prostate cancer treatment in Delray Beach, FL, USA. LAM has collaborative and research agreements with Philips Healthcare and Biobot Surgical. GAS is on the medical advisory board of miR Scientific. PG is on the medical advisory boards of Insightec and SonALASense and has ownership or equity interests in SonALASense. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Approximately 7% of patients with newly diagnosed prostate cancer (PCa) in the US will have have metastatic disease. The dogma that there is no role for surgery in this population has been questioned recently. Here we report long-term outcomes of a phase 1 clinical trial on cytoreductive radical prostatectomy., Materials and Methods: This is a multicenter phase 1 trial. The major inclusion criterion was biopsy proven N1M0 or NxM1a/b PCa. Primary end point was the Clavien-Dindo-based major complication rate. Secondary outcomes were biochemical progression and overall survival. RNA-seq correlative study was conducted in nine select cases as a pilot study., Results: Final accrual was 32 patients of which 25 and 7 were cNxM1 and cN1M0, respectively. With the median follow-up of 46 months (interquartile range 31.7 - 52.7 months), 25 out of the 32 patients (75%) were alive at the time of last contact. There were three disparate groups based on the oncologic outcome: favorable, intermediate, and poor. In seven men with favorable response, androgen deprivation therapy was switched to intermittent approach and five remain free of any evidence of disease after more than two years off all systemic therapy with the normalization of serum testosterone. Of these five patients, three had M1 disease. Long-term use of one pad or less per day was 80%. RNA-seq analysis revealed an enriched downregulation of tumor necrosis factor (TNF)-α signature in the favorable group., Conclusion: Overall long-term oncologic outcome of cytoreductive radical prostatectomy was significantly higher than historical results. Importantly, the combination of surgery with systemic therapy may result in a long durable response in a minority of men who present with metastatic PCa., Competing Interests: All authors have no significant conflict of interest., (© 2022 Asian Pacific Prostate Society. Publishing services by Elsevier B.V.)

Background: Prostate cancer is the most commonly diagnosed cancer in American men, with striking differences between ethnic groups. Given the potential for lifestyle or genetic variations between subsets of Asian-American men to impact prostate cancer behavior, we sought to define the outcomes after radical prostatectomy among various Asian groups treated at an NCI-designated comprehensive cancer center., Methods: The City of Hope IRB-approved prostatectomy database was searched from 2003 to 2015 to identify Asian-American men. Clinical and pathologic features were collected and analyzed for association with biochemical recurrence-free survival and overall survival (OS). Categorical data were evaluated using χ 2 and Fisher's exact tests. Survival curves were compared between groups using log-rank testing., Results: Three hundred and eighty-three Asian-American men were included in the dataset. While Asian men as a group had lower BMI than African-American and white men in the database, there was a wide range between ethnic sub-groups. Chinese men more commonly presented with D'Amico low risk disease features (P= .04) compared to other Asian men. Pacific Islander men had the lowest rate of ≥T3 stage and the highest biochemical recurrence-free survival. OS for Chinese men was better than for all Asian patients combined (P= .046). After controlling for D'Amico risk and in multivariate analysis, Chinese men still had improved OS than other Asian men after prostatectomy (P= .03)., Conclusions: Asian-American men have differing prostate cancer characteristics. Future efforts to delineate and impact upon prostate cancer outcomes should categorize Asian men by subgroup in order to better elucidate biology, lifestyle factors and/or treatment preferences that may contribute to observed differences., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Evaluation of safety is of paramount importance with adoption of novel surgical technology. Although robotic surgery has become widely used in oncologic surgery, analysis of safety is lacking in comparison to traditional techniques. Standardized assessment of robotic surgical outcomes and adverse events following oncologic surgery is necessary for quality improvement with innovative technology. Between 2003 and 2016, 10,013 unique robotic operations were performed in 9,858 patients. Our prospectively maintained database was retrospectively reviewed for hospital readmissions and Clavien-Dindo grade ≥ 2 complications within 30 days. Multivariable logistic regression was used to identify predictors of surgical complications and hospital readmissions. Cases were stratified by discipline: genitourinary (n = 8240), gynecologic (n = 857), thoracic (n = 457), gastrointestinal (n = 322), hepatobiliary (n = 60), ear/nose/throat (n = 44) and general (n = 33). Intraoperative complications occurred in 42 surgeries (0.4%). Postoperative complications occurred in 946 patients [9.4%, highest grade 2 (n = 574), 3 (n = 288), 4 (n = 72), 5 (n = 10)]. Most frequent complications were ileus (154, 16.3%), anemia (91, 9.6%), cardiac arrhythmia (62, 6.6%), deep vein thrombosis/pulmonary embolus (47, 5.0%), wound infection (45, 4.8%) and urinary leak (43, 4.5%). 405 patients (4.0%) required readmission. Most common causes for hospital readmission were ileus (44, 10.9%), urinary leak (23, 5.7%), urinary tract infection (23, 5.7%), intra-abdominal abscess/fluid collection (23, 5.7%), and small bowel obstruction (19, 4.7%). On multivariable analysis, longer operative time and older age predicted complications and readmissions (p ≤ 0.02). Robotic-assisted surgery appears a safe for oncologic surgery with acceptable hospital readmission and complication rates. Older age and longer operative time were associated with complications and readmission.

As the US transitions from volume- to value-based cancer care, many cancer centers and community groups have joined to share resources to deliver measurable, high-quality cancer care and clinical research with the associated high patient satisfaction, provider satisfaction, and practice health at optimal costs that are the hallmarks of value-based care. Multidisciplinary oncology care pathways are essential components of value-based care and their payment metrics. Oncology pathways are evidence-based, standardized but personalizable care plans to guide cancer care. Pathways have been developed and studied for the major medical, surgical, radiation, and supportive oncology disciplines to support decision-making, streamline care, and optimize outcomes. Implementing multidisciplinary oncology pathways can facilitate comprehensive care plans for each cancer patient throughout their cancer journey and across large multisite delivery systems. Outcomes from the delivered pathway-based care can then be evaluated against individual and population benchmarks. The complexity of adoption, implementation, and assessment of multidisciplinary oncology pathways, however, presents many challenges. We review the development and components of value-based cancer care and detail City of Hope's (COH) academic and community-team-based approaches for implementing multidisciplinary pathways. We also describe supportive components with available results towards enterprise-wide value-based care delivery.

Objective: To compare the perioperative outcomes of intracorporeal (ICUD) vs extracorporeal urinary diversion (ECUD) after robot-assisted radical cystectomy (RARC)., Patients and Methods: We retrospectively reviewed the prospectively maintained International Robotic Cystectomy Consortium (IRCC) database. A total of 972 patients from 28 institutions who underwent RARC were included. Propensity score matching was used to match patients based on age, gender, body mass index (BMI), American Society of Anesthesiologists Score (ASA) score, Charlson Comorbidity Index (CCI) score, prior radiation and abdominal surgery, receipt of neoadjuvant chemotherapy, and clinical staging. Matched cohorts were compared. Multivariate stepwise logistic and linear regression models were fit to evaluate variables associated with receiving ICUD, operating time, 90-day high-grade complications (Clavien-Dindo Classification Grade ≥III), and 90-day readmissions after RARC., Results: Utilisation of ICUD increased from 0% in 2005 to 95% in 2018. The ICUD patients had more overall complications (66% vs 58%, P = 0.01) and readmissions (27% vs 17%, P = 0.01), but not high-grade complications (21% vs 24%, P = 0.22). A more recent RC era and ileal conduit diversion were associated with receiving an ICUD. Higher BMI, ASA score ≥3, and receiving a neobladder were associated with longer operating times. Shorter operating time was associated with male gender, older age, ICUD, and centres with a larger annual average RC volume. Longer intensive care unit stay was associated with 90-day high-grade complications. Higher CCI score, prior radiation therapy, neoadjuvant chemotherapy, and ICUD were associated with a higher risk of 90-day readmissions., Conclusions: Utilisation of ICUD has increased over the past decade. ICUD was associated with more overall complications and readmissions compared to ECUD, but not high-grade complications., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)

Purpose: Shapley additive explanation (SHAP) values represent a unified approach to interpreting predictions made by complex machine learning (ML) models, with superior consistency and accuracy compared with prior methods. We describe a novel application of SHAP values to the prediction of mortality risk in prostate cancer., Methods: Patients with nonmetastatic, node-negative prostate cancer, diagnosed between 2004 and 2015, were identified using the National Cancer Database. Model features were specified a priori: age, prostate-specific antigen (PSA), Gleason score, percent positive cores (PPC), comorbidity score, and clinical T stage. We trained a gradient-boosted tree model and applied SHAP values to model predictions. Open-source libraries in Python 3.7 were used for all analyses., Results: We identified 372,808 patients meeting the inclusion criteria. When analyzing the interaction between PSA and Gleason score, we demonstrated consistency with the literature using the example of low-PSA, high-Gleason prostate cancer, recently identified as a unique entity with a poor prognosis. When analyzing the PPC-Gleason score interaction, we identified a novel finding of stronger interaction effects in patients with Gleason ≥ 8 disease compared with Gleason 6-7 disease, particularly with PPC ≥ 50%. Subsequent confirmatory linear analyses supported this finding: 5-year overall survival in Gleason ≥ 8 patients was 87.7% with PPC < 50% versus 77.2% with PPC ≥ 50% ( P < .001), compared with 89.1% versus 86.0% in Gleason 7 patients ( P < .001), with a significant interaction term between PPC ≥ 50% and Gleason ≥ 8 ( P < .001)., Conclusion: We describe a novel application of SHAP values for modeling and visualizing nonlinear interaction effects in prostate cancer. This ML-based approach is a promising technique with the potential to meaningfully improve risk stratification and staging systems.

Purpose: The primary objectives of this study were to evaluate toxicity of escalating doses of prostate bed stereotactic body radiation therapy and to provide dose recommendations for a phase 2 study., Methods and Materials: Patients with organ-confined, node-negative prostate cancer who had biochemical failure (prostate-specific antigen [PSA] less than 2.0) after prostatectomy were eligible for this phase 1 dose-escalation trial. Doses delivered were 35 Gy, 40 Gy, and 45 Gy in 5 fractions, given every other day. Dose-limiting toxicity (DLT) was defined as Common Terminology Criteria for Adverse Events (version 4.0) grade 3 or higher gastrointestinal or genitourinary (GU) toxicity within 90 days of treatment. Maximum tolerated dose was the highest dose to be tested where fewer than 2 of the patients experienced DLT. Patients completed quality-of-life questionnaires at regular time intervals., Results: Twenty-six patients completed treatment between October 2013 and December 2017. Three patients received 35 Gy, 8 patients received 40 Gy, and 15 patients received 45 Gy. The median follow-up was 60 months for 35 Gy, 48 months for 40 Gy, and 33 months for 45 Gy. No acute DLT events were observed. Late grade ≥2 and ≥3 gastrointestinal toxicity occurred in 11% and 0%, respectively, and late grade ≥2 and ≥3 GU toxicity occurred in 38% and 15%, respectively. No difference was observed in late GU toxicity between 40 Gy and 45 Gy. Sexual function scores were significantly lower in the patients receiving androgen deprivation therapy (P < .01). In all patients, the crude rate of PSA control (<0.2 ng/mL) was 11 out of 26 (42%)., Conclusions: Dose escalation to 45 Gy did not result in acute DLT events, had similar rates of late grade 3 toxicity, and did not demonstrate higher rates of PSA control, compared with 40 Gy. While allowing for higher plan heterogeneity, the recommended dose for phase 2 study will be 40 Gy in 5 fractions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: We sought to determine the trend of neoadjuvant chemotherapy use for nonmetastatic muscle invasive urothelial bladder cancer and whether it is associated with adverse perioperative morbidity after robot-assisted radical cystectomy., Materials and Methods: We retrospectively reviewed the IRCC (International Robotic Cystectomy Consortium) database between 2006 and 2017. After excluding patients with nonmuscle invasive bladder cancer the patients were divided into 2 groups, including those who did vs did not receive neoadjuvant chemotherapy. Data were reviewed for demographics, preoperative, operative and 90-day perioperative outcomes. We used the Cochran-Armitage trend test to assess trends of neoadjuvant chemotherapy associations with high grade and overall complications with time. Multivariate stepwise regression analyses were done to determine whether neoadjuvant chemotherapy was associated with prolonged operative time, 90-day postoperative complications, readmissions, reoperations and mortality after robot-assisted radical cystectomy., Results: A total of 298 patients (26%) received neoadjuvant chemotherapy. These patients were younger (age 67 vs 69 years, p=0.01) and more frequently had an ASA™ (American Society of Anesthesiologists™) score of 3 or greater (62% vs 55%, p=0.02) and pathological T3 stage or greater disease (28% vs 22%, p=0.04). The use of neoadjuvant chemotherapy increased significantly from 10% in 2006 to 2007 to 42% in 2016 to 2017 (p <0.01). On multivariate analysis neoadjuvant chemotherapy was not significantly associated with prolonged operative time, hospital stay, 90-day postoperative complications, reoperation or mortality. Neoadjuvant chemotherapy was associated with 90-day readmissions after robot-assisted radical cystectomy (OR 5.90, 95% CI 3.30-10.90, p <0.01)., Conclusions: Neoadjuvant chemotherapy utilization has significantly increased in the last decade. It was not associated with perioperative surgical morbidity after robot-assisted radical cystectomy.

Optimal management of node-positive prostate cancer patients after prostatectomy remains a challenge. We evaluated clinically localized patients who demonstrated node positivity and identified predictors for secondary treatment. From 2010 to 2015, clinically localized prostate cancer patients who underwent robot prostatectomy with extended lymphadenectomy and node-positive disease on pathologic analysis were identified. Clinical N1, M1 or salvage cases were excluded. Patients were stratified based on secondary treatments. Kaplan-Meier method was used to determine the time to biochemical and metastatic recurrence. Multivariate logistic regression was used to identify predictors for additional treatment. 145 patients (45 no additional therapy, 47 adjuvant, 53 salvage) had a median follow-up of 31.2 months. Salvage patients had higher median pre-operative prostate-specific antigen (10.8 vs. 9.7 vs. 8.2, p = 0.1), higher percentage of pathologic Gleason ≥8 (50.9 vs. 38.3% and 22.2%, p < 0.01), and higher median-positive nodes (3 vs. 1 and 1, p < 0.0001) compared to adjuvant and no treatment groups, respectively. Pathologic Gleason ≥8 (OR = 3.5, p = 0.007) and positive nodes ≥2 (OR = 3.3, p = 0.006) were associated with additional therapy. In the no treatment group, two-year estimated BCRFS was 74.3%. Two-year metastatic recurrence-free rates for no treatment, adjuvant and salvage groups were 100, 87.5, and 80.9%, respectively (p = 0.01). Observation is a viable alternative for low metastatic burden patients. In the largest series of node-positive patients from robotic prostatectomy and extended lymphadenectomy, those with pathologic Gleason ≥8 and positive lymph nodes ≥2 were more likely to receive additional treatment.

Background and Objectives: Cytoreductive surgery with complete macroscopic resection in patients with ovarian cancer is associated with improved survival. Institutional reports of combined upper and lower abdominal cytoreductive surgery for more advanced disease have described multidisciplinary approaches. We sought to investigate outcomes in patients undergoing cytoreductive surgery in patients with upper and lower abdominal disease at our institution., Methods: Patients who underwent cytoreductive surgery for ovarian malignancies from 2008 to 2015 were retrospectively identified from an institutional database. Upper abdominal cytoreduction was defined anatomically as debulking of disease proximal to the ligament of Treitz. Perioperative outcomes were analyzed., Results: A total of 258 operations were performed, the majority for serous ovarian carcinoma (70%). The gynecologic oncologist was the primary surgeon and often assisted by either a surgical oncology fellow and/or attending. In operations with combined upper and lower abdominal cytoreduction, patients were more likely to have an American society of anesthesiologists physical status classification system (ASA) of 3, peritoneal implants, and liver/spleen metastases. Preoperative chemotherapy and optimal cytoreduction were similar between groups. Perioperative morbidity and mortality were not significantly different between groups., Conclusions: A collaborative surgical approach to combined upper and lower abdominal cytoreductive surgery in patients with ovarian cancer should be performed, if needed, to achieve an optimal cytoreduction., (© 2018 Wiley Periodicals, Inc.)