Background
Given the low incidence of urachal carcinoma of the bladder (UCB), there is limited published data from contemporary population‐based cohorts. This study aimed to describe demographic, ...clinicopathological features, and survival outcomes of patients diagnosed with UCB.
Methods
The National Cancer Database (2004–2016) was queried for UCB patients. Descriptive analyses characterized demographics and clinicopathologic features. We assessed 5‐year overall survival (OS) rates of the entire cohort and subgroups of localized/locally advanced and metastatic disease. We utilized Cox proportional hazards models to assess the association between covariates of interest and all‐cause mortality and to examine the impact of surgical technique and chemotherapy.
Results
We identified 841 patients with UCB. The most common histologic subtype was non‐mucinous adenocarcinoma (39.6%). Approximately 50% had ≥cT2 disease, and 14.3% were metastatic at diagnosis. Altogether, partial cystectomy (60%) was most performed, and lymph node dissection was performed in 377 patients (44.8%), with specific temporal increase in utilization over the study period (p < 0.001). Overall, median OS was 59 months, and 5‐year OS was 49%. In patients with localized/locally advanced disease, we found no association between partial and radical cystectomy (Hazards ratio HR 1.75; 95% CI 0.72–4.3) as well as receipt of perioperative chemotherapy (HR 1.97, 95% CI 0.79–4.90) and outcomes. Lastly, receipt of systemic therapy was not associated with survival benefit (HR 0.785, 95% CI 0.37–1.65) in metastatic disease cohort.
Conclusion
This large population‐based cohort provides insight into the surgical management and systemic therapy, without clear evidence on the association of chemotherapy and survival in the perioperative and metastatic setting.
This large population‐based cohort of urachal carcinoma of the bladder (UCB) provides insight into the surgical management and systemic therapy, without clear evidence on the association of chemotherapy and survival in the peri‐operative and metastatic setting. Prospective, multi‐intuitional studies are needed to identify multi‐modal approaches to improve outcomes for patients with UCB.
To systematically review and meta-analyze the current literature in a methodologically rigorous and transparent manner for quantitative evidence on survival outcomes among patients diagnosed with ...muscle-invasive bladder cancer that were treated by either trimodal therapy or radical cystectomy.
MEDLINE, EMBASE, CENTRAL were systematically searched for comparative observational studies reporting disease-specific survival and/or overall survival on adult patients diagnosed with localized muscle-invasive bladder cancer that were exposed to either trimodal therapy or radical cystectomy. Studies qualified for meta-analysis (random effects model) if they were not at critical risk of bias (RoB).
The literature search identified 12 eligible studies. Three (all rated as "moderate RoB") out of 6 studies reporting on disease-specific survival qualified for quantitative analysis and yielded a pooled hazard ratio (trimodal therapy versus radical cystectomy) of 1.39 (95% confidence interval: 1.03-1.88). Four (mainly rated as "serious RoB") out of 12 studies were included in the meta-analysis of overall survival and estimated a hazard ratio of 1.39 (1.20-1.59).
Pooled results were significant in favor of radical cystectomy. The conclusion is mainly driven by large population-based studies that are at high RoB. Hence, the certainty of these treatment estimates can be considered very low and further research will likely have an important impact on these estimates. At present, the ultimate decision between trimodal therapy and radical cystectomy should be left to the patient based on individual preferences and on the recommendation of a multidisciplinary provider team experienced with both approaches.
Osteoarthritis is a common complication in the elderly and is often associated with osteophyte growth on vertebral bodies. The clinical presentation of vertebral osteophytes is related to anatomical ...structures adjacent to the spinal column. For instance, cervical osteophytes potentially involve the pharynx and esophagus, leading to dysphagic symptoms that may be accompanied by food aspiration, vocal fold paralysis and obstructive sleep apnea. In addition to anterior cervical osteophytes, posterior and uncinate process osteophytes may form, compressing the spinal cord and vertebral artery blood supply, respectively. Cervical osteophytes have also been shown to form an accessory median atlanto-occipital joint when the relationship between the atlas, dens and basiocciput is involved. In the thorax, the esophagus is often affected by osteophytes and may result in dysphagia. Traumatic and non-traumatic thoracic aorta pseudoaneurysm formation has been attributed to sharp osteophytes lacerating the aorta, a direct complication of the relationship between the aorta anterior vertebral column. Additionally, aspiration pneumonia was reported in patients with compression of a main stem bronchus, due to mechanical compression by thoracic osteophytes. In the lumbar spinal region, the two major structures in close proximity to the spine are the inferior vena cava and abdominal aorta, both of which have been reported to be affected by osteophytes. Treatment of osteophytes is initially conservative with anti-inflammatory medications, followed by surgical removal. Increasing obesity and geriatric populations will continue to result in an array of osteoarthritic degenerative changes such as osteophyte formation.
The mechanism by which newly synthesized sterols are transported from their site of synthesis, the endoplasmic reticulum (ER), to the sterol-enriched plasma membrane (PM) is not fully understood. ...Studies in mammalian cells suggest that newly synthesized cholesterol is transported to the PM in Golgi-bypassing vesicles and/or via a nonvesicular process. Using the yeast Saccharomyces cerevisiae as a model system, we now rule out an essential role for known vesicular transport pathways in transporting the major yeast sterol, ergosterol, from its site of synthesis to the PM. We use a cyclodextrin-based sterol capture assay to show that transport of newly synthesized ergosterol to the PM is unaltered in cells defective in Sec18p, a protein required for almost all intracellular vesicular trafficking events; we also show that transport is not blocked in cells that are defective in formation of transport vesicles at the ER or in vesicle fusion with the PM. Our data suggest instead that transport occurs by equilibration (t 1/2 ∼ 10−15 min) of ER and PM ergosterol pools via a bidirectional, nonvesicular process that is saturated in wild-type exponentially growing yeast. To reconcile an equilibration process with the high ergosterol concentration of the PM relative to ER, we note that a large fraction of PM ergosterol is found condensed with sphingolipids in membrane rafts that coexist with free sterol. We propose that the concentration of free sterol is similar in the PM and ER and that only free (nonraft) sterol molecules have access to a nonvesicular transport pathway that connects the two organelles. This is the first description of biosynthetic sterol transport in yeast.
To characterize the contribution of the extirpative and reconstructive portions of radical cystectomy (RC) to complications rates, and assess differences between urinary diversion (UD) types.
We ...conducted a retrospective cohort study comparing patients undergoing UD alone or RC+UD for bladder cancer from 2006 to 2017 using ACS National Surgical Quality Improvement Program database. The primary outcome was major complications, while secondary outcomes included minor complications and prolonged length of stay. Propensity score matching (PSM) was utilized to assess the association between surgical procedure (UD alone or RC+UD) and outcomes, stratified by diversion type. Lastly, we examined differences in complication rates between ileal conduit (IC) vs. continent UD (CUD).
When comparing RC + IC and IC alone, PSM yielded 424 pairs. IC alone had a lower risk of any complication (HR 0.63, 95% CI 0.52-0.75), venous thromboembolism (HR 0.45, 95% CI 0.22-0.91) and bleeding needing transfusion (HR 0.41, 95% CI 0.32-0.52). This trend was also noted when comparing RC + CUD to CUD alone. CUD had higher risk of complications than IC, both with (56.6% vs 52.3%, p = 0.031) and without RC (47.8% vs 35.1%, p=0.062), and a higher risk of infectious complications, both with (30.5% vs 22.7%, p< 0.001) and without RC (34.0% vs 22.0%, p=0.032).
RC+UD, as compared to UD alone, is associated with an increased risk of major complications, including bleeding needing transfusion and venous thromboembolism. Additionally, CUD had a higher risk of post-operative complication than IC.
Objectives
To evaluate the association between obesity and positive surgical margins in patients undergoing retropubic radical prostatectomy versus robotic‐assisted laparoscopic prostatectomy.
...Methods
We retrospectively reviewed the data of 3141 men undergoing retropubic radical prostatectomy and 1625 undergoing robotic‐assisted laparoscopic prostatectomy between 1988 and 2017 at eight Veterans Health Administration hospitals. The positive surgical margin location (peripheral, apical, bladder neck, overall) was determined from pathology reports. We adjusted for age, race, prostate‐specific antigen, surgery year, prostate weight, pathological grade group, extracapsular extension, seminal vesicle invasion, hospital surgical volume and surgical method (in analyses not stratified by surgical method). Interactions between body mass index and surgical approach were tested.
Results
Among all patients, higher body mass index was associated with increased odds of overall, peripheral and apical positive surgical margins (OR 1.02–1.03, P ≤ 0.02). Although not statistically significant, there was a trend between higher body mass index and increased odds of bladder neck positive surgical margins (OR 1.03, P = 0.09). Interactions between body mass index and surgical method were significant for peripheral positive surgical margins only (P = 0.024). Specifically, there was an association between body mass index and peripheral positive surgical margins among men undergoing retropubic radical prostatectomy (OR 1.04, P < 0.001), but not robotic‐assisted laparoscopic prostatectomy (OR 1.00, P = 0.98). Limitations include lacking individual surgeon data and lacking central pathology review.
Conclusions
In this multicenter cohort, higher body mass index was associated with increased odds of positive surgical margins at all locations except the bladder neck. Furthermore, there was a significant association between obesity and peripheral positive surgical margins in men undergoing retropubic radical prostatectomy, but not robotic‐assisted laparoscopic prostatectomy. Long‐term clinical significance requires further study.
While studies have demonstrated an association between preoperative hypoalbuminemia and adverse clinical outcomes, the optimal serum albumin threshold for risk-stratification in the broader surgical ...population remains poorly defined. We sought define the optimal threshold of preoperative serum albumin concentration for risk-stratification of adverse post-operative outcomes. Using the American College of Surgeons National Surgical Quality Improvement Program Database, we identified 842,672 patients that had undergone a common surgical procedure in one of eight surgical specialties. An optimal serum albumin concentration threshold for risk-stratification was determined using receiver-operating characteristic analysis. Multivariable logistic regression analysis was used to evaluate the odds of adverse surgical events; a priori defined subgroup analyses were performed. A serum albumin threshold of 3.4 g/dL optimally predicted adverse surgical outcomes in the broader cohort. After multivariable analysis, patients with hypoalbuminemia had increased odds of death within 30 days of surgery (odds ratio OR 2.01, 95% confidence interval CI 1.94–2.08). Hypoalbuminemia was associated with greater odds of primary adverse events among patients with disseminated cancer (OR 2.03, 95% CI 1.88–2.20) compared to patients without disseminated cancer (OR 1.47, 95% CI 1.44–1.51). The standard clinical threshold for hypoalbuminemia is the optimal threshold for preoperative risk assessment.
Purpose
Limited data exist to help surgeons decide between active surveillance (AS) versus treatment for men with favorable intermediate risk (FIR) prostate cancer. To estimate the theoretical excess ...risk of prostate cancer‐specific mortality (PCSM) with AS versus radical prostatectomy (RP), we determined the risk of PCSM in FIR men undergoing RP and modeled the PCSM risk for AS using a range of increased PSCM scenarios ranging from 1.25x to 2x higher relative to RP.
Materials and Methods
We retrospectively reviewed data from men undergoing RP from 1988 to 2017 at 8 Veterans Affairs hospitals within the SEARCH cohort. Men with FIR PC were identified using the NCCN risk criteria. Risk of PCSM at 5, 10, and 15 years after RP was estimated. Using these estimates, PCSM was then modeled for AS using a range of increased risk of PCSM relative to RP ranging from 1.25x to 2x higher.
Results
For the 920 FIR men identified, 5‐, 10‐, and 15‐year survival estimates for PCSM after RP were 99.9%, 99.0%, and 97.8%, respectively. If the risk of PCSM on AS were 1.25–2x greater than RP, there would be 0.54%–2.17% excess risk of PCSM at 15 years.
Conclusions
The risk of death for FIR after RP is very low. Assuming even modestly increased PCSM with AS versus RP, the excess risk of death for AS in FIR is low even up to 15 years. These data support the consideration of AS as a relatively safe alternative to RP in FIR men, though prospective randomized trials are needed to validate these findings.
The risk of death for patients with favorable intermediate risk prostate cancer after undergoing radical prostatectomy is very low. Even if we assume that active surveillance confers double the risk of prostate cancer‐specific mortality compared to surgery for this patient population, the excess risk of death for active surveillance is low. These data support the consideration of active surveillance as a relatively safe alternative to radical prostatectomy in men with favorable intermediate risk prostate cancer.