[Show abstract][Hide abstract] ABSTRACT: Background:
Excision repair cross-complementing 1 (ERCC1) has been associated with outcomes of urothelial carcinoma of the bladder, but was not yet studied in upper tract urothelial carcinoma (UTUC). The aim of this study was to assess the prognostic role of ERCC1 expression in a large international cohort of UTUC patients.
Immunohistochemical ERCC1 expression was evaluated in 716 UTUC patients who underwent radical nephroureterectomy with curative intent. ERCC1 was considered positive when the H-score was >1.0. Associations with overall survival and cancer-specific survival were assessed using univariable and multivariable Cox models.
ERCC1 was expressed in 303 tumors (42.3 %) and linked with the presence of tumor necrosis (16.2 vs. 10.4 %, p = 0.023), but not with any other clinical or pathological variable. ERCC1 status did not predict cancer-specific survival and overall survival on both univariable (p = 0.70 and 0.32, respectively) and multivariable analyses (p = 0.48 and 0.33, respectively).
ERCC1 is expressed in a significant proportion of UTUC and is linked with tumor necrosis, but its expression appears not to be associated with prognosis following radical nephroureterectomy.
No preview · Article · Dec 2015 · World Journal of Urology
[Show abstract][Hide abstract] ABSTRACT: Introduction:
A previously-published risk-stratification algorithm based on RMB and radiographic mass size was useful in designating surveillance versus the need for immediate treatment of SRMs. Nonetheless, there were some incorrect assignments, most notably when RMB indicated low-risk malignancy but final pathology revealed high-risk malignancy. We studied other factors that might improve the accuracy of this algorithm.
For 202 clinically localized SRMs in 200 patients with RNS, preoperative RMB, and final pathology we assessed the accuracy of management assignment (surveillance versus treatment) based on the previously-published risk-stratification algorithm, confirmed by final pathology. Logistic regression was used to determine if other factors (age, gender, RNS, RNS components and nomograms based on RNS) could improve assignment.
Of the 202 SRMs, 53 (26%) were assigned to surveillance and 149 (74%) were assigned to treatment by the risk-stratification algorithm. Of the 53 assigned to surveillance, 25 (47%) had benign/favorable RMB histology and 28 (53%) had intermediate RMB histology with mass size < 2 cm. Of these 53 masses, 9 (17%) were incorrectly assigned to surveillance, in that final pathology indicated need for treatment (i.e., intermediate histology and a mass > 2 cm, or unfavorable histology). Final pathology confirmed correct assignment in all 149 masses assigned to treatment. None of the additional parameters assessed improved assignment with statistical significance.
Age, gender, RNS, RNS components and nomograms or combinations of these factors do not improve upon the predictive performance of a SRM management risk-stratification algorithm based on RMB and radiographic mass size.
No preview · Article · Nov 2015 · The Journal of urology
[Show abstract][Hide abstract] ABSTRACT: Anterior-predominant prostate cancer (APC) is an incompletely understood entity which can be difficult to sample via transrectal biopsy. Seemingly favorable biopsy results may belie the potential aggressiveness of these tumors. Here, we attempt to characterize APC by retrospectively examining the clinicopathologic features of APC at radical prostatectomy and comparing our findings with prior biopsy information. We found that 17.4 % of patients in our study had APC. APC demonstrated a significantly lower (P value < 0.05) Gleason score (GS) and pathologic stage than non-APC tumors, including the absence of seminal vesicle invasion by APC. A subset (5.6 %) of APC consisted of high-grade tumors (GS ≥ 8), and these tumors were more often detected on transperineal saturation biopsy than non-transperineal saturation (i.e., transrectal ultrasound guided) biopsy strategies. Four patients (7 %) without transperineal saturation biopsy exhibited a significantly worse GS at RP than biopsy, compared to five patients (36 %) with transperineal saturation biopsy. Our findings corroborate the difficulty in detecting APC and suggest that APC is not a uniform disease with a wholly indolent phenotype. Dedicated long-term outcome data are needed in these patients. Additionally, alternative pathologic staging parameters may be necessary.
No preview · Article · Nov 2015 · Medical Oncology
[Show abstract][Hide abstract] ABSTRACT: As a treatment for high-risk bladder cancer, radical cystectomy (RC) remains a highly morbid operation with complication rates of 40-60 % and mortality rates as high as 9 % in the first 90 days after surgery (Aziz et al., Eur Urol 66(1):156-163, 2014; Shabsigh et al., Eur Urol 55(1):164-174, 2009). Many patients suffer from a failure-to-thrive syndrome associated with anorexia, weight loss, dehydration, and immobility. In elderly patients, failure-to-thrive may result in loss of independence and a cascade of events that increases the risk of perioperative morbidity and mortality, ultimately resulting in impaired survival. Psoas muscle mass has been used to predict morbidity and mortality after major surgical procedures in vulnerable populations with substantial comorbidities. Increasingly, psoas muscle mass is also being used to predict outcomes after RC. If patients with a high risk of impaired survival are identified preoperatively, prehabilitative interventions can be integrated into their preparation for surgical treatment (Porserud et al., Clin Rehab 28(5):451-459, 2014; Friedman et al., Nutr Clin Pract: Off Publ Am Soc Parenter Enter Nutr 30(2):175-179, 2015). This chapter discusses the role of psoas muscle mass as a predictor of negative surgical outcomes after cystectomy.
No preview · Article · Sep 2015 · Current Urology Reports
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to evaluate the accuracy of our autoinitialized cascaded level set 3D segmentation system as compared with the World Health Organization (WHO) criteria and the Response Evaluation Criteria In Solid Tumors (RECIST) for estimation of treatment response of bladder cancer in CT urography.
CT urograms before and after neoadjuvant chemo-therapy treatment were collected from 18 patients with muscle-invasive localized or locally advanced bladder cancers. The disease stage as determined on pathologic samples at cystectomy after chemotherapy was considered as reference standard of treatment response. Two radiologists measured the longest diameter and its perpendicular on the pre- and posttreatment scans. Full 3D contours for all tumors were manually outlined by one radiologist. The autoinitialized cascaded level set method was used to automatically extract 3D tumor boundary. The prediction accuracy of pT0 disease (complete response) at cystectomy was estimated by the manual, autoinitialized cascaded level set, WHO, and RECIST methods on the basis of the AUC.
The AUC for prediction of pT0 disease at cystectomy was 0.78 ± 0.11 for autoinitialized cascaded level set compared with 0.82 ± 0.10 for manual segmentation. The difference did not reach statistical significance (p = 0.67). The AUCs using RECIST criteria were 0.62 ± 0.16 and 0.71 ± 0.12 for the two radiologists, both lower than those of the two 3D methods. The AUCs using WHO criteria were 0.56 ± 0.15 and 0.60 ± 0.13 and thus were lower than all other methods.
The pre- and posttreatment 3D volume change estimates obtained by the radiologist's manual outlines and the autoinitialized cascaded level set segmentation were more accurate for irregularly shaped tumors than were those based on RECIST and WHO criteria.
No preview · Article · Aug 2015 · American Journal of Roentgenology
[Show abstract][Hide abstract] ABSTRACT: Metanephric adenoma (MA) is a rare benign renal tumor comprised of a neoplastic proliferation of primitive metanephric tubular cells. A previous study identified BRAF V600E mutations in approximately 90% of MA and found that similar BRAF exon 15 mutations are exceedingly rare in other common renal tumors, including renal cell carcinoma and oncocytoma. A recent follow-up study has validated mutation-specific immunohistochemistry (IHC) for detection of BRAF V600E mutations in a small cohort of MA. Here, we extend these findings to a larger, independent cohort of MA, demonstrating an overall 88% sensitivity and 100% specificity for BRAF V600E IHC. In addition, we report 2 cases of MA with novel BRAF exon 15 mutations, including a V600D missense mutation and a compound V600D and K601L missense mutation. Finally, we evaluate BRAF V600E IHC in a large tissue microarray cohort of common renal tumors and find no significant expression in several renal cell carcinoma subtypes. These data support a role for BRAF V600E IHC in diagnostically challenging cases of MA and expand the spectrum of BRAF exon 15 mutations in this uncommon but unique renal neoplasm.
No preview · Article · Jan 2015 · American Journal of Surgical Pathology
[Show abstract][Hide abstract] ABSTRACT: Although multifocal tumors and non-invasive/invasive components are commonly encountered in surgical pathology, their genetic relationship is often poorly characterized. We used next-generation sequencing (NGS) to characterize somatic alterations in a patient with five spatially distinct, high-grade papillary urothelial carcinomas (UCs), with one tumor harboring an underlying invasive component. NGS of 409 cancer-related genes was performed on DNA isolated from formalin-fixed paraffin-embedded (FFPE) blocks representing each papillary tumor (n = 5), the invasive component of one tumor, and matched normal tissue. We identified nine unique non-synonymous somatic mutations across the six UC samples, including five present in each carcinoma sample, consistent with clonal origin and limited intertumoral heterogeneity. Copy number and loss of heterogeneity (LOH) profiles were similar in all six carcinomas; however, the invasive carcinoma component uniquely showed focal CDKN2A loss and chromosome 9 LOH and did not harbor gains of chromosomes 5p or X that were present in the other tumor samples. Phylogenetic analysis supported the invasive component arising from a shared progenitor prior to the outgrowth of cells in the non-invasive tumors. Results were extended to three additional cases of upper tract UC with paired non-invasive/invasive components, which identified driving alterations exclusive to both non-invasive and invasive components. Lastly, we performed targeted RNA sequencing (RNAseq) using a custom bladder cancer panel, which confirmed gene expression signature differences between paired non-invasive/invasive components. The results and approaches presented here may be useful in understanding the clonal relationships in multifocal cancers or paired non-invasive/invasive components from routine FFPE specimens.
Full-text · Article · Dec 2014 · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin
[Show abstract][Hide abstract] ABSTRACT: Purpose
To assess the relationship between healthcare system performance on nationally endorsed prostate cancer quality of care measures and prostate cancer treatment outcomes.
This is a retrospective cohort study including 48,050 men from Surveillance Epidemiology and End Results – Medicare linked data who were diagnosed with localized prostate cancer between 2004 and 2009 and followed through 2010. Based on a composite quality measure, we categorized the healthcare systems in which these men were treated into 1-star (bottom 20%), 2-star (middle 60%), and 3-star (top 20%) systems. We then examined the association of healthcare system-level quality of care with outcomes using multivariable logistic and Cox regression.
Patients who underwent prostatectomy in 3-star versus 1-star healthcare systems had a lower risk of perioperative complications (odds ratio 0.80, 95% confidence interval [CI] 0.64-1.00). However, these patients were more likely to undergo a procedure addressing treatment-related morbidity (e.g., 11.3% vs. 7.8% treated for sexual morbidity, p=0.043). Among patients undergoing radiotherapy, star-ranking was not associated with treatment-related morbidity. Among all patients, star-ranking was not significantly associated with all-cause mortality (Hazard Ratio [HR] 0.99, 95% CI 0.84-1.15) or secondary cancer therapy (HR 1.04, 95% CI 0.91-1.20).
We found no consistent associations between healthcare system quality and outcomes, which questions how meaningful these measures ultimately are for patients. Thus, future studies should focus on the development of more discriminative quality measures.
No preview · Article · Sep 2014 · The Journal of urology
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Prostate capsule sparing and nerve sparing cystectomies are alternative procedures for bladder cancer that may decrease morbidity while achieving cancer control. However, to our knowledge the comparative effectiveness of these approaches has not been established. We evaluated functional and oncologic outcomes in patients undergoing these procedures.
Materials and methods:
We performed a single institution trial in patients with bladder cancer in whom transurethral prostatic urethral biopsy and transrectal prostate biopsy were negative. Men were randomized to prostate capsule sparing or nerve sparing cystectomy with neobladder creation and stratified by Sexual Health Inventory for Men score (greater than 21 vs 21 or less). Our primary end point was 12-month overall urinary function as measured by Bladder Cancer Index. Secondary end points included sexual function, cancer control and complications.
A total of 40 patients were enrolled in the study with 20 patients in each arm. Urinary function at 12 months decreased by 13 and 28 points in the prostate capsule and nerve sparing groups, respectively (p = 0.10). Sexual function followed a similar pattern (p = 0.06). There was no difference in recurrence-free, metastasis-free or overall survival (each p >0.05). The rate of incidentally detected prostate cancer was similar (p = 0.15).
Our study provides a randomized comparison of prostate capsule sparing and nerve sparing cystectomy techniques. We found no difference in functional or oncologic outcomes between the 2 approaches, although our study was underpowered due to a lack of patient accrual.
No preview · Article · Jul 2014 · The Journal of Urology
[Show abstract][Hide abstract] ABSTRACT: Robot-assisted radical cystectomy (RARC) is an emerging operative alternative to open surgery for the management of invasive bladder cancer. Studies from single institutions provide limited data due to the small number of patients. In order to better understand the related outcomes, a world-wide consortium was established in 2006 of patients undergoing RARC, called the International Robotic Cystectomy Consortium (IRCC). Thus far, the IRCC has reported its findings on various areas of operative interest and continues to expand its capacity to include other operative modalities and transform it into the International Radical Cystectomy Consortium. This article summarizes the findings of the IRCC and highlights the future direction of the consortium.
No preview · Article · Jul 2014 · Indian Journal of Urology
[Show abstract][Hide abstract] ABSTRACT: Objective:
To determine the relationship between prostate gland and tumor volume in men undergoing radical prostatectomy (RP) for prostate cancer. We hypothesized that larger tumors within smaller prostate glands are associated with more aggressive disease characteristics.
Records of patients undergoing RP from 2000-2008 at a single institution were reviewed retrospectively. The dominant nodule was considered to be the largest focus of cancer within the prostate, and the dominant nodule-to-prostate volume ratio (DNVR) was calculated according to the ratio of the dominant nodule volume to the gland weight. Cox regression was performed to assess the relationship between DNVR and both pathologic outcomes (Cancer of the Prostate Risk Assessment post-Surgical score) and biochemical recurrence (BCR).
At a median follow-up of 3.7 years, 174 patients (7.2%) suffered BCR. There was no linear correlation between tumor volume and gland size (R = -0.09). DNVR above the median (≥0.033 cc/gm) was closely associated with high clinicopathologic risk as measured by Cancer of the Prostate Risk Assessment post-Surgical score (hazard ratio, 35.53; 95% confidence interval, 14.42-87.55 for high- vs low-risk groups). In the univariable analysis, both tumor diameter and DNVR were associated with increased risk of BCR. However, in the multivariable model, only tumor diameter remained a significant predictor of BCR (hazard ratio, 2.02; 95% confidence interval, 1.04-3.91).
Increased DNVR appears to be a characteristic of aggressive prostate tumors, although it did not predict BCR in the present study. However, these data support the association between tumor diameter and BCR after RP for prostate cancer independent of other key clinicopathologic features.
[Show abstract][Hide abstract] ABSTRACT: Papillary renal cell carcinoma (P-RCC) is the second most common type of malignant renal epithelial tumor, and can be subclassified into type 1, which demonstrates simple cuboidal low-grade epithelium, and type 2, which demonstrates pseudostratified high grade epithelium with abundant eosinophilic cytoplasm. Despite this clinically useful subclassification, P-RCCs exhibit considerable histomorphologic diversity, with many cases having features differing from classically described type 1 and type 2 tumors. To our knowledge, there has been no recent study which has methodically evaluated the histomorphologic features of a series of P-RCCs. To address this, we evaluated a cohort of P-RCCs diagnosed between 1997 and 2004 with long term clinical follow-up data (n = 56). Histomorphologic features previously described in the spectrum of type 1 and type 2 P-RCCs were recorded for each tumor, including nuclear grade, complete tumor capsule, and cytoplasmic eosinophilia, as well as several other features. The current TNM staging (AJCC 7th edition) was assigned to all cases. Histomorphologic features were diverse, demonstrating classic type 1 P-RCC and classic type 2 P-RCC morphology, and several tumors with non-classical features. Four patients in this cohort had distant metastasis. The primary tumor was equally divided between type 1 (2 cases) and type 2 (2 cases) morphology in the cases with metastasis. All P-RCC cases with metastases demonstrated presence of high nuclear grade and high tumor stage in the primary tumor. Cluster analysis using staging parameters and histomorphologic features divided tumors into two primary clusters. All primary tumors associated with metastasis were in the same cluster.