Discordance Between Clinical and Pathological Staging and Grading in Upper Tract Urothelial Carcinoma

IntroductionThis study aimed to evaluate the concordance in tumor stage and grade between ureteroscopic (URS) biopsy and radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC).Patients and MethodsRecords of 1,214 UTUC patients who had undergone URS biopsy followed by RNU were included. Univariable and multivariable logistic regression analyses were performed to identify factors contributing to the pathological upstaging.ResultsThe concordance between URS biopsy-based clinical and RNU pathological staging was 34.5%. Clinical understaging occurred in 59.5% patients. Upstaging to muscle-invasive disease occurred in 240 (41.7%) of 575 patients diagnosed with ≤cT1 disease. Of those diagnosed with muscle-invasive disease on final pathology, 89.6% had been clinically diagnosed with ≤cT1 disease. In the univariable analyses, computed tomography urography (CTU)–based invasion, ureter location, hydronephrosis, high-grade cytology, high-grade biopsy, sessile architecture, age, and women sex were significantly associated with pathological upstaging (P < .05). In the multivariable analyses, CTU-based invasion and hydronephrosis remained associated with pathological upstaging (P < .05). URS biopsy-based clinical and pathological gradings were concordant in 634 (54.2%) patients. Clinical undergrading occurred in 496 (42.4%) patients.ConclusionsClinical understaging/undergrading and upstaging to muscle-invasive disease occurred in a high proportion of UTUC patients undergoing RNU. Despite the inherent selection bias, these data underline the challenges of accurate UTUC staging and grading. In daily clinical practice, URS biopsy and CTU offer the most accurate preoperative information albeit with limited predictive value when used alone. These findings should be considered when utilizing preoperative, risk-adapted strategies.     

Feasibility and Clinical Utility of a Workflow Interfacing Radiation Oncology Lung Stereotactic Body Radiation Therapy Treatment Planning and Diagnostic Radiology

Stereotactic body radiation therapy (SBRT) is commonly used to treat early-stage non-small cell lung cancer. Beam arrangements for SBRT include multiple entry and exit pathways resulting in irregular low-dose distributions within normal lung parenchyma. An improved understanding of posttreatment radiographic changes may improve the ability to predict clinical complications including radiation pneumonitis as well as assist in early detection of local failures. Radiation treatment planning is conducted using software systems separate from diagnostic radiology, often not accessible to the diagnostic radiologist. We developed a workflow for interfacing radiation dose information from lung SBRT treatments with a diagnostic radiology picture archiving and communication system (PACS). In an anonymized PACS study folder, SBRT dose maps depicting high-dose, low-dose, and nonirradiated lung volumes were viewable side by side with pretreatment and follow-up diagnostic computed tomography scans. Clinical utility was evaluated by 2 thoracic diagnostic radiologists reviewing posttreatment diagnostic follow-up scans in the PACS both with and without radiation dose maps available. The addition of the biologically effective dose map did not significantly change identification rates of radiation induced lung injury) (92% vs 95%; P = .32) but did significantly decrease radiologic suspicion for local recurrence (22% vs 8%; P = .003). The addition of biologically effective dose maps significantly increased confidence in identifying radiation induced lung injury (7.75 vs 8.82; P = .004) and local recurrence (5.5 vs 6.6; P = .005). The recommendation for additional workup was not significantly different (10% vs 7%; P = .41). We demonstrated the feasibility and clinical utility of a workflow generating simplified radiation dose maps that are viewable within a PACS for diagnostic radiology review.     

RESIRT: A Phase 1 Study of Selective Internal Radiation Therapy Using Yttrium-90 Resin Microspheres in Patients With Primary Renal Cell Carcinoma

IntroductionSelective internal radiation therapy (SIRT) is a potential treatment of primary renal cell carcinoma (RCC) deemed unsuitable for conventional therapy. RESIRT is the first-in-human study to evaluate safety and feasibility of SIRT for primary RCC.Patients and MethodsPatients with RCC, unsuitable for, or who declined conventional therapy, were eligible. A single transfemoral micro-catheter administration of yttrium-90 (Y-90) resin microspheres (SIR-Spheres) was delivered super selectively via the renal artery to the tumour at intended radiation doses of 75, 100, 150, 200, 300 Gy and a final cohort with a procedural endpoint of “imminent stasis,” in a dose-escalation design. Post-SIRT follow-up was 12 months. Study endpoints included safety and toxicity 30-days and 12-months post-SIRT and tumour response (RECIST v1.1).ResultsIn total, 21 patients were enrolled, mean (SD) age was 75 (9.3) years, WHO performance status was 0 in 81%, 12 (57%) had stage 3 chronic kidney disease, and 7 (33%) had prior contralateral nephrectomy. Overall, 71% of patients completed 12 months of follow-up. Intended doses were delivered without any dose-limiting toxicity. Seventeen out of 21 (81%) patients experienced an adverse event (AE) from any cause within 30 days post-SIRT; all SIRT-related AEs were grade 1 to 2. Best overall tumour responses were partial response 1/21 (4.8%), stable disease 19/21 (90.5%) and progressive disease 1/21 (4.8%).ConclusionThis study demonstrated good tolerability of SIRT at all dose levels including “imminent stasis” in treating primary tumours in RCC patients otherwise unsuitable for conventional therapy. SIRT with Y-90 resin microspheres may be a feasible treatment option for RCC.     

Coming Soon: Ability to Orgasm After Gender Affirming Vaginoplasty

BackgroundMany patients have goals related to sexual health when seeking gender-affirming vaginoplasty, and previous investigations have only studied the ability to orgasm at cross-sectional timepoints.AimOur aim is to quantify the time to orgasm postoperative gender-affirming vaginoplasty and describe potential correlative factors, including preoperative orgasm, to improve preoperative counseling.MethodsA retrospective chart review was utilized to extract factors thought to influence pre and postoperative orgasm in patients undergoing robotic peritoneal flap vaginoplasty. Mean days to orgasm plus one standard deviation above that mean was used to define the time at which patients would be considered anorgasmic.OutcomesOrgasm was documented as a categorical variable on the basis of surgeon interviews during pre and postoperative appointments while time to orgasm was measured as days from surgery to first date documented as orgasmic in the medical record.ResultsA total of 199 patients underwent surgery from September 2017 to August 2020. The median time to orgasm was 180 days. 178 patients had completed 1 year or greater of follow-up, and of these patients, 153 (86%) were orgasmic and 25 patients (14%) were not. Difficulty in preoperative orgasm was correlated only with older age (median age 45.9 years vs 31.7, P = .03). Postoperative orgasm was not significantly correlated with preoperative orgasm. The only factor related to postoperative orgasm was smoking history: 12 of 55 patients (21.8%) who had a positive smoking history and sufficient follow-up reported anorgasmia (P-value .046). Interventions for anorgasmic patients include testosterone replacement, pelvic floor physical therapy, and psychotherapy.Clinical ImplicationsPreoperative difficulty with orgasm improves with gender-affirming robotic peritoneal flap vaginoplasty, while smoking had a negative impact on postoperative orgasm recovery despite negative cotinine test prior to surgery.Strengths & LimitationsThis investigation is the first effort to determine a timeline for the return of orgasmic function after gender-affirming vaginoplasty. It is limited by retrospective review methodology and lack of long-term follow-up. The association of smoking with postoperative orgasm despite universal nicotine cessation prior to surgery may indicate prolonged smoking cessation improves orgasmic outcomes or that underlying, unmeasured exposures correlated with smoking may be the factor inhibiting recovery of orgasm.ConclusionThe majority of patients were orgasmic at their 6-month follow-up appointments, however, patients continued to become newly orgasmic in appreciable numbers more than 1 year after surgery.Blasdel G, Kloer C, Parker A, et al. Coming Soon: Ability to Orgasm After Gender Affirming Vaginoplasty. J Sex Med 2022;19:781–788.     

Biological Disease-Modifying Antirheumatic Drugs and Osteoporotic Fracture Risk in Patients with Rheumatoid Arthritis: A Danish Cohort Study

ObjectivesClinical trials have shown a beneficial effect from biological disease-modifying antirheumatic drugs (bDMARDs) on hand or axial bone loss in patients with rheumatoid arthritis; however, it is unclear if this translates to a reduced fracture risk. We investigated the effect of bDMARDs on osteoporotic fracture risk compared to no biological treatment in rheumatoid arthritis.MethodsA cohort of patients with rheumatoid arthritis aged 18+ from DANBIO was linked to population-based health registries in Denmark (2006-2016). Adopting a prevalent new-user design, we matched bDMARD users to bDMARD-naïve patients using time-conditional propensity scores. The risk of incident osteoporotic fractures (including hip, vertebrae, humerus, and forearm) was estimated among the matched patients by Cox proportional hazards models.ResultsOut of 24,678 patients with rheumatoid arthritis, 4265 bDMARD users were matched to the same number of bDMARD-naïve patients (mean age 56.2 years, 74% female). During follow-up, 229 osteoporotic fractures occurred among bDMARD users and 205 fractures among bDMARD-naïve patients (incidence rates 12.1 and 13.0 per 1000 person-years, respectively). The use of bDMARDs was not associated with a reduced risk of osteoporotic fractures among patients with rheumatoid arthritis (hazard ratio 0.97, 95% confidence interval 0.78-1.20), compared with no biological treatment. The risk estimates were similar for all osteoporotic fracture sites.ConclusionWe found no independent beneficial effect from using bDMARDs on reducing the risk of osteoporotic fractures in patients with rheumatoid arthritis.     

Future Perspectives on Prehabilitation Interventions in Cancer Surgery

ObjectiveThis article provides a map of key knowledge gaps regarding the evidence supporting prehabilitation and its integration with enhanced recovery after surgery (ERAS) programs. Filling this lack of knowledge with future research will further establish the effectiveness of prehabilitation.Data SourcesThese are electronic databases including PubMed and CINAHL.ConclusionFuture efforts must embrace the elderly frail or cognitively impaired patient with specific needs to further promote restoration of postoperative function throughout the surgical pathway. Prehabilitation should be coupled and integrated within the existent concept of the ERAS framework, to facilitate the continuous evolution of screening, assessment, and optimization of high-risk surgical patients who are at risk of not being restored to physical and psychological function after surgery, including independence.Implications for Nursing PracticeIn the future, the ERAS nurse will be an essential figure of the prehabilitation program, proactively coordinating the assessment, optimization, and adjustment of perioperative comorbidity and guiding the rehabilitation process to improve patients’ outcomes. These skills and characteristics will be required to provide optimal nursing care in the context of an integrated prehabilitation ERAS pathway.