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1.
Cancers (Basel) ; 16(5)2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38473339

ABSTRACT

The current study aimed to elucidate the regulatory mechanisms of the circRNA hsa_circ_0139697 (circSTAG2(16-25)) in BCa and to consider the opportunity of using circSTAG2(16-25) isolated from BCa patient urine as a marker for disease development prediction. The selection of this circRNA was determined by the special role of its parental gene STAG2 in BCa biology. The circRNA hsa_circ_0139697 was chosen from 25 STAG2 circRNAs due to its differential expression in the urine of BCa patients and healthy volunteers. Higher levels of circSTAG2(16-25) were detected in urine samples obtained from patients with recurrent tumors. A higher expression of circSTAG2(16-25) was also detected in more tumorigenic BCa cell lines. The overexpression of circSTAG2(16-25) in BCa cells induced the elevation of proliferation, motility, and invasion. To study the mechanisms of circSTAG2(16-25) activity, we confirmed that circSTAG2(16-25) can bind miR-145-5p in vitro as was predicted by bioinformatic search. miR-145-5p was shown to suppress some genes that promoted BCa progression. One of these genes, TAGLN2, encodes the protein Transgelin 2, which plays a role in BCa cell motility and invasion. Therefore, the possible mechanism of action of circSTAG2(16-25) could be sponging the tumor suppressor miR-145-5p, which results in activation of TAGLN2. In addition, circSTAG2(16-25) might be considered as a potential biomarker for recurrence prediction.

3.
World J Urol ; 38(4): 965-970, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31190154

ABSTRACT

PURPOSE: To assess the impact of implementing the recommendations included in the 2014 American Urological Association (AUA) white paper on complications of transrectal prostate needle biopsy (PNB). METHODS: In the outpatient setting of a single tertiary-care institution, prophylactic antibiotic use and rate of infectious complications were compared before and after implementation by nursing of a standardized algorithm to select antibiotic prophylaxis (derived from the recommendations of the AUA white paper). The 584 patients in cohort A (January 2011-January 2012) received antimicrobial prophylaxis at the discretion of the treating physician; 654 patients in cohort B (January 2014-January 2015) received standardized risk-adapted antibiotic prophylaxis. Data on antibiotics administered and infectious complications were analyzed. RESULTS: Fluoroquinolone was the most common prophylactic regimen in both cohorts. In cohort A, 73% of men received a single-drug regimen, although 19 different regimens were utilized with duration of 72 h. In cohort B, 97% received 1 of 4 standardized single-drug antibiotic regimens for duration of 24 h. Infectious complications occurred in 19 men (3.3%) in cohort A, and in 18 men (2.8%) in cohort B (difference - 0.5%; one-sided 95% CI 1.1%). No clinically relevant increase in infectious complication rates was found after implementing this quality improvement initiative. CONCLUSIONS: Use of a standardized risk-adapted approach to select antibiotic prophylaxis for PNB by nursing staff reduced the duration of antimicrobial prophylaxis and number of antibiotic regimens used, without increasing the rate of infectious complications. Our findings validate the current AUA recommendations for antibiotic prophylaxis.


Subject(s)
Antibiotic Prophylaxis/standards , Antimicrobial Stewardship/standards , Bacterial Infections/prevention & control , Postoperative Complications/microbiology , Postoperative Complications/prevention & control , Prostate/pathology , Quality Improvement , Aged , Biopsy, Needle/adverse effects , Biopsy, Needle/methods , Cohort Studies , Diagnostic Self Evaluation , Guideline Adherence , Humans , Male , Middle Aged , Rectum
4.
Eur Urol Focus ; 5(6): 977-979, 2019 11.
Article in English | MEDLINE | ID: mdl-31029560

ABSTRACT

Our recently reported phase III trial demonstrated that patients undergoing nephron-sparing surgery (NSS) with an estimated glomerular filtration rate (eGFR) of ≥45 ml/min/1.73 m2 who received mannitol had no improvement in renal function at 6 mo compared with those who received placebo. Some authors have suggested that benefit is restricted to subgroups, such as those with comorbidities. We assessed whether preoperative eGFR, or other patient and surgical factors modified the effect of mannitol on postoperative outcomes at 6 mo and with extended follow-up. We also assessed whether mannitol was associated with differences in long-term GFR years after surgery. No significant difference between the mannitol or placebo groups (mean eGFR difference: 1.4; 95% confidence interval: -2.6, 5.3; p = 0.5) was found in the 134 patients with known eGFR at 3 yr after NSS. At both 6 mo and 3 yr, the effect of mannitol was not significantly modified by patient or surgical factors including preoperative eGFR. In summary, we validated our original trial conclusions by finding that intraoperative use of mannitol does not improve either short- or long-term renal function in patients undergoing NSS. Specifically, there is no evidence that comorbidities, including lower preoperative eGFR, modify the effect of mannitol. PATIENT SUMMARY: Use of mannitol at the time of partial nephrectomy does not improve either short- or long-term renal function even in patients with comorbidities, including lower preoperative renal function. The routine use of intraoperative mannitol should be discontinued.


Subject(s)
Diuretics, Osmotic/administration & dosage , Kidney Neoplasms/surgery , Mannitol/administration & dosage , Nephrons/physiopathology , Organ Sparing Treatments/methods , Comorbidity , Diuretics, Osmotic/pharmacology , Glomerular Filtration Rate/drug effects , Humans , Intraoperative Care/statistics & numerical data , Mannitol/pharmacology , Nephrectomy/methods , Nephrons/drug effects , Nephrons/surgery , Outcome Assessment, Health Care , Placebos/administration & dosage , Postoperative Period , Preoperative Period
5.
ACS Nano ; 13(2): 1354-1364, 2019 02 26.
Article in English | MEDLINE | ID: mdl-30624916

ABSTRACT

Cancers of the gastrointestinal (GI) tract are among the most frequent and most lethal cancers worldwide. An important reason for this high mortality is that early disease is typically asymptomatic, and patients often present with advanced, incurable disease. Even in high-risk patients who routinely undergo endoscopic screening, lesions can be missed due to their small size or subtle appearance. Thus, current imaging approaches lack the sensitivity and specificity to accurately detect incipient GI tract cancers. Here we report our finding that a single dose of a high-sensitivity surface-enhanced resonance Raman scattering nanoparticle (SERRS-NP) enables reliable detection of precancerous GI lesions in animal models that closely mimic disease development in humans. Some of these animal models have not been used previously to evaluate imaging probes for early cancer detection. The studies were performed using a commercial Raman imaging system, a newly developed mouse Raman endoscope, and finally a clinically applicable Raman endoscope for larger animal studies. We show that this SERRS-NP-based approach enables robust detection of small, premalignant lesions in animal models that faithfully recapitulate human esophageal, gastric, and colorectal tumorigenesis. This method holds promise for much earlier detection of GI cancers than currently possible and could lead therefore to marked reduction of morbidity and mortality of these tumor types.


Subject(s)
Endoscopy/methods , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Tract/metabolism , Nanoparticles/chemistry , Spectrum Analysis, Raman/methods , Animals , Disease Models, Animal , Male , Mice , Mice, Inbred C57BL , Mice, Knockout
6.
Urology ; 119: 55-61, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29935265

ABSTRACT

OBJECTIVE: To report a case of pelvic angiosarcoma in a 27-year-old man with Li-Fraumeni Syndrome (LFS) and evaluate the presentation and timeline of genitourinary (GU) tract involvement in LFS patients. METHODS: We retrospectively identified 39 LFS patients treated at our institution between 2000 and 2014; 7 (18%) had experienced a GU malignancy or an LFS-related malignancy involving the GU tract. Clinical characteristics, including dates of onset of first GU tract malignancies; pathologic findings; multimodal management; and familial history of LFS were reviewed. RESULTS: Median age at first malignancy was 14.0 years (interquartile range [IQR] 5.5-24.0). There was a slight male predominance (4 of 7). Median time between first malignancy and the malignancy involving the GU tract was 10.1 years (IQR 8.0-19.5). Six of the 7 patients (86%) had a form of sarcoma involving the GU tract; 1 developed adrenocortical carcinoma. The cancer pedigree of all patients showed LFS-associated malignancies in family members. Multimodal management included surgical resection in 6 patients with adjuvant chemotherapy or radiotherapy in 1 patient each. One patient received chemotherapy only. Following diagnosis of malignancy involving the GU tract, 5 of the 7 patients developed additional primary malignancies. At a median follow-up of 4.7 years (IQR 3.0-12.1), 2 patients are alive, 3 died of disease, and 1 died of unknown cause. One patient was lost at follow-up. CONCLUSION: Continued follow-up of LFS cancer patients aimed at the determination of optimal screening, management, and surveillance protocols is recommended and may result in longer survival expectations.


Subject(s)
Li-Fraumeni Syndrome , Urogenital Neoplasms , Adult , Fatal Outcome , Humans , Li-Fraumeni Syndrome/diagnosis , Li-Fraumeni Syndrome/therapy , Male , Retrospective Studies , Urogenital Neoplasms/diagnosis , Urogenital Neoplasms/therapy
7.
J Surg Oncol ; 117(7): 1464-1468, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29473967

ABSTRACT

BACKGROUND AND OBJECTIVES: We evaluated the effect of re-resection with wide margins (undertaken because initial resection performed elsewhere was incomplete) on survival in patients with spermatic cord sarcoma (SCS). METHODS: After excluding those with metastatic disease and those not undergoing surgical intervention, the records of 72 consecutive patients treated for SCS between 1981 and 2011 at Memorial Sloan Kettering Cancer Center were reviewed. Recurrence-free survival (RFS) and cancer-specific survival were calculated using the Kaplan-Meier method for comparing between the 48 patients who underwent wide re-resection (WRR) within 5 months of diagnosis and the 24 who did not. The relationship of age, tumor size, tumor histology, adjuvant radiation, and wide re-resection with recurrence and death was assessed by univariate Cox regression. RESULTS: WRR significantly improved RFS (hazard ratio [HR] 0.16, 95%CI 0.07-0.37; P < 0.0001), despite the fact that patients receiving WRR had higher-grade disease. Tumor-positive margins upon WRR were strongly associated with both disease recurrence (HR 5.56; 95%CI 1.14-27.11, P = 0.034) and death from cancer (HR 6.16, 95%CI 1.25-30.29; P = 0.025). CONCLUSIONS: A WRR with negative margins is effective in the management of patients with SCS and leads to improved RFS.


Subject(s)
Neoplasm Recurrence, Local/mortality , Sarcoma/mortality , Spermatic Cord/surgery , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Margins of Excision , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Prognosis , Retrospective Studies , Sarcoma/pathology , Sarcoma/surgery , Spermatic Cord/pathology , Survival Rate
8.
Eur Urol ; 73(1): 53-59, 2018 01.
Article in English | MEDLINE | ID: mdl-28822586

ABSTRACT

BACKGROUND: Mannitol is currently used as a renal protective agent to mitigate the effects of renal ischemia during nephron-sparing surgery (NSS). This routine practice lacks rigorous methodological study. OBJECTIVE: To assess the effect on renal function outcomes after surgery of mannitol infusion prior to renal ischemia during NSS. DESIGN, SETTING, PARTICIPANTS: This prospective, randomized, placebo-controlled, double-blind trial included 199 patients with a preoperative estimated glomerular filtration rate (eGFR) >45ml/min/1.73m2 scheduled for NSS; the trial was conducted between July 2012 and July 2015. INTERVENTION: Patients undergoing NSS were randomized to receive mannitol (12.5g) or placebo intravenously within 30min prior to renal vascular clamping. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the difference in eGFR (renal function) between the two groups at 6 mo following surgery assessed with an analysis of covariance model using preoperative eGFR, treatment group, and surgical approach as covariates. RESULTS AND LIMITATIONS: At baseline, the median age of the patients was 58 yr, and the median eGFR was 88ml/min/1.73m2. Comparing placebo with mannitol infusion, the adjusted difference of 0.2 eGFR units at 6 mo was not significant (p=0.9), with the upper bound of the 95% confidence interval (-3.1 to 3.5) excluding a clinically relevant effect of mannitol. Limitations include evaluation of a single mannitol dose and patients all had excellent preoperative renal function. CONCLUSIONS: Intraoperative 12.5g mannitol infusion during NSS has no demonstrable clinical benefit when compared with standardized fluid hydration in patients with normal preoperative renal function, and its use in this setting is not warranted. PATIENT SUMMARY: In this randomized trial, patients with normal kidney function who received mannitol during surgery to remove part of their kidney had no better kidney function 6 mo after surgery than those who did not receive mannitol. We conclude that this routine practice should be discontinued.


Subject(s)
Carcinoma, Renal Cell/surgery , Diuretics/administration & dosage , Glomerular Filtration Rate/drug effects , Kidney Neoplasms/surgery , Kidney/drug effects , Kidney/surgery , Mannitol/administration & dosage , Nephrectomy/methods , Postoperative Complications/prevention & control , Aged , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/physiopathology , Diuretics/adverse effects , Double-Blind Method , Female , Humans , Infusions, Intravenous , Kidney/pathology , Kidney/physiopathology , Kidney Neoplasms/pathology , Kidney Neoplasms/physiopathology , Male , Mannitol/adverse effects , Middle Aged , Nephrectomy/adverse effects , Organ Sparing Treatments , Postoperative Complications/pathology , Postoperative Complications/physiopathology , Prospective Studies , Time Factors , Treatment Outcome
9.
Int. braz. j. urol ; 43(6): 1075-1083, Nov.-Dec. 2017. tab
Article in English | LILACS | ID: biblio-892933

ABSTRACT

ABSTRACT Objectives: Based on imaging features, nephrometry scoring systems have been conceived to create a standardized and reproducible way to characterize renal tumor anatomy. However, less is known about which of these individual measures are important with regard to clinically relevant perioperative outcomes such as ischemia time (IT), estimated blood loss (EBL), length of hospital stay (LOS), and change in estimated glomerular filtration rate (eGFR) after robotic partial nephrectomy (PN). We aimed to assess the utility of the RENAL and PADUA scores, their subscales, and C-index for predicting these outcomes. Materials and Methods: We analyzed imaging studies from 283 patients who underwent robotic PN between 2008 and 2014 to assign nephrometry scores (NS): PADUA, RENAL and C-index. Univariate linear regression was used to assess whether the NS or any of their subscales were associated with EBL or IT. Multivariable linear regression and linear regression models were created to assess LOS and eGFR. Results: The three NS were significantly associated with EBL, IT, LOS, and eGFR at 12 months after surgery. All subscales with the exception of anterior/posterior were significantly associated with EBL and IT. Collecting system, renal rim location, renal sinus, exophytic/endophytic, and nearness to collecting system were significant predictors for LOS. Only renal rim location, renal sinus invasion and polar location were significantly associated with eGFR at 12 months. Conclusions: Tumor size and depth are important characteristics for predicting robotic PN outcomes and thus could be used individually as a simplified way to report tumors features for research and patient counseling purposes.


Subject(s)
Humans , Male , Female , Robotic Surgical Procedures , Glomerular Filtration Rate/physiology , Kidney Neoplasms/surgery , Nephrectomy/methods , Retrospective Studies , Blood Loss, Surgical , Treatment Outcome , Tumor Burden , Ischemia/etiology , Ischemia/physiopathology , Kidney Neoplasms/physiopathology , Middle Aged , Neoplasm Staging
10.
Int Braz J Urol ; 43(6): 1075-1083, 2017.
Article in English | MEDLINE | ID: mdl-28727381

ABSTRACT

OBJECTIVES: Based on imaging features, nephrometry scoring systems have been conceived to create a standardized and reproducible way to characterize renal tumor anatomy. However, less is known about which of these individual measures are important with regard to clinically relevant perioperative outcomes such as ischemia time (IT), estimated blood loss (EBL), length of hospital stay (LOS), and change in estimated glomerular filtration rate (eGFR) after robotic partial nephrectomy (PN). We aimed to assess the utility of the RENAL and PADUA scores, their subscales, and C-index for predicting these outcomes. MATERIALS AND METHODS: We analyzed imaging studies from 283 patients who underwent robotic PN between 2008 and 2014 to assign nephrometry scores (NS): PADUA, RENAL and C-index. Univariate linear regression was used to assess whether the NS or any of their subscales were associated with EBL or IT. Multivariable linear regression and linear regression models were created to assess LOS and eGFR. RESULTS: The three NS were significantly associated with EBL, IT, LOS, and eGFR at 12 months after surgery. All subscales with the exception of anterior/posterior were significantly associated with EBL and IT. Collecting system, renal rim location, renal sinus, exophytic/endophytic, and nearness to collecting system were significant predictors for LOS. Only renal rim location, renal sinus invasion and polar location were significantly associated with eGFR at 12 months. CONCLUSIONS: Tumor size and depth are important characteristics for predicting robotic PN outcomes and thus could be used individually as a simplified way to report tumors features for research and patient counseling purposes.


Subject(s)
Glomerular Filtration Rate/physiology , Kidney Neoplasms/surgery , Nephrectomy/methods , Robotic Surgical Procedures , Blood Loss, Surgical , Female , Humans , Ischemia/etiology , Ischemia/physiopathology , Kidney Neoplasms/physiopathology , Male , Middle Aged , Neoplasm Staging , Retrospective Studies , Treatment Outcome , Tumor Burden
11.
World J Urol ; 34(12): 1667-1672, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27106493

ABSTRACT

PURPOSE: To examine the incidence of secondary primary malignancies in patients with renal cortical neoplasms. METHODS: Between January 1989 and July 2010, 3647 patients underwent surgery at our institution for a renal cortical neoplasm and were followed through 2012. Occurrence of other malignancies was classified as antecedent, synchronous, or subsequent. All patients with antecedent malignancies (n = 498) and a randomly selected half of those with synchronous malignancies (n = 83) were excluded. The expected number of second primaries was calculated by multiplying Surveillance, Epidemiology, and End Results Program incidence rates of renal cortical neoplasms by person-years at risk within categories of age, sex, and year of diagnosis. The standardized incidence ratio (SIR) was calculated as observed cancers divided by expected incidence of the cancer, with approximation to the exact Poisson test used to obtain confidence intervals (CI) and p values. RESULTS: Of 3066 patients with renal cortical neoplasms, 267 had a second primary cancer; the five most common in men were prostate, colorectal, bladder, lung, and non-Hodgkin's lymphoma; the five most common in women were breast, colorectal, lung, endometrium, and thyroid. Men demonstrated higher than expected thyroid cancer rate (SIR 5.0; 95 % CI 1.83-10.88, p = 0.002), and women had higher than expected rates of stomach cancer (SIR 5.0; 95 % CI 1.61-11.67, p = 0.004) and thyroid cancer (SIR 4.62; 95 % CI 1.69-10.05, p = 0.003). CONCLUSIONS: The incidence of certain types of second malignancies may be higher in patients after diagnosis of renal cortical neoplasms compared to the general population. These observations can inform clinical follow-up in kidney cancer survivorship and future research studies.


Subject(s)
Carcinoma, Renal Cell/diagnosis , Kidney Cortex/pathology , Kidney Neoplasms/diagnosis , Lymphoma, Non-Hodgkin/epidemiology , Neoplasms, Second Primary/epidemiology , Aged , Female , Humans , Incidence , Lymphoma, Non-Hodgkin/diagnosis , Male , Middle Aged , Retrospective Studies , Risk Factors , United States/epidemiology
12.
Mol Imaging Biol ; 18(5): 677-85, 2016 10.
Article in English | MEDLINE | ID: mdl-26943129

ABSTRACT

PURPOSE: The accurate detection of lymph node metastases in prostate cancer patients is important to direct treatment decisions. Our goal was to develop an intraoperative imaging approach to distinguish normal from metastasized lymph nodes. We aimed at developing and testing gold-silica surface-enhanced resonance Raman spectroscopy (SERRS) nanoparticles that demonstrate high uptake within normal lymphatic tissue and negligible uptake in areas of metastatic replacement. PROCEDURES: We evaluated the ability of SERRS nanoparticles to delineate lymph node metastases in an orthotopic prostate cancer mouse model using PC-3 cells transduced with mCherry fluorescent protein. Tumor-bearing mice (n = 6) and non-tumor-bearing control animals (n = 4) were injected intravenously with 30 fmol/g SERRS nanoparticles. After 16-18 h, the retroperitoneal lymph nodes were scanned in situ and ex vivo with a Raman imaging system and a handheld Raman scanner and data corroborated with fluorescence imaging for mCherry protein expression and histology. RESULTS: The SERRS nanoparticles demonstrated avid homing to normal lymph nodes, but not to metastasized lymph nodes. In cases where lymph nodes were partially infiltrated by tumor cells, the SERRS signal correctly identified, with sub-millimeter precision, healthy from metastasized components. CONCLUSIONS: This study serves as a first proof-of-principle that SERRS nanoparticles enable high precision and rapid intraoperative discrimination between normal and metastasized lymph nodes.


Subject(s)
Lymphatic Metastasis/diagnosis , Lymphatic Metastasis/pathology , Nanoparticles/chemistry , Spectrum Analysis, Raman/methods , Animals , Cell Line, Tumor , Disease Models, Animal , Fluorescence , Humans , Male , Prostatic Neoplasms/pathology , Signal Processing, Computer-Assisted
13.
Eur Urol ; 69(1): 72-9, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26298208

ABSTRACT

BACKGROUND: Tumor characteristics affect surgical complexity and outcomes of partial nephrectomy (PN). OBJECTIVE: To develop an Arterial Based Complexity (ABC) scoring system to predict morbidity of PN. DESIGN, SETTING, AND PARTICIPANTS: Four readers independently scored contrast-enhanced computed tomography images of 179 patients who underwent PN. INTERVENTION: Renal cortical masses were categorized by the order of vessels needed to be transected/dissected during PN. Scores of 1, 2, 3S, or 3H were assigned to tumors requiring transection of interlobular and arcuate arteries, interlobar arteries, segmental arteries, or in close proximity of the renal hilum, respectively during PN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Interobserver variability was assessed with kappa values and percentage of exact matches between each pairwise combination of readers. Linear regression was used to evaluate the association between reference scores and ischemia time, estimated blood loss, and estimated glomerular filtration rates at 6 wk and 6 mo after surgery adjusted for baseline estimated glomerular filtration rate. Fisher's exact test was used to test for differences in risk of urinary fistula formation by reference category assignment. RESULTS AND LIMITATIONS: Pairwise comparisons of readers' score assignments were significantly correlated (all p<0.0001); average kappa = 0.545 across all reader pairs. The average proportion of exact matches was 69%. Linear regression between the complexity score system and surgical outcomes showed significant associations between reference category assignments and ischemia time (p<0.0001) and estimated blood loss (p=0.049). Fisher's exact test showed a significant difference in risk of urinary fistula formation with higher reference category assignments (p=0.028). Limitations include use of a single institutional cohort to evaluate our system. CONCLUSIONS: The ABC scoring system for PN is intuitive, easy to use, and demonstrated good correlation with perioperative morbidity. PATIENT SUMMARY: The ABC scoring system is a novel anatomy-reproducible tool developed to help patients and doctors understand the complexity of renal masses and predict the outcomes of kidney surgery.


Subject(s)
Arteries/surgery , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/surgery , Kidney/blood supply , Nephrectomy/adverse effects , Urinary Fistula/etiology , Aged , Blood Loss, Surgical , Contrast Media , Female , Glomerular Filtration Rate , Humans , Kidney Neoplasms/pathology , Male , Middle Aged , Nephrectomy/methods , Observer Variation , Predictive Value of Tests , Retrospective Studies , Tomography, X-Ray Computed , Warm Ischemia
14.
Sci Transl Med ; 7(271): 271ra7, 2015 Jan 21.
Article in English | MEDLINE | ID: mdl-25609167

ABSTRACT

The inability to visualize the true extent of cancers represents a significant challenge in many areas of oncology. The margins of most cancer types are not well demarcated because the cancer diffusely infiltrates the surrounding tissues. Furthermore, cancers may be multifocal and characterized by the presence of microscopic satellite lesions. Such microscopic foci represent a major reason for persistence of cancer, local recurrences, and metastatic spread, and are usually impossible to visualize with currently available imaging technologies. An imaging method to reveal the true extent of tumors is desired clinically and surgically. We show the precise visualization of tumor margins, microscopic tumor invasion, and multifocal locoregional tumor spread using a new generation of surface-enhanced resonance Raman scattering (SERRS) nanoparticles, which are termed SERRS nanostars. The SERRS nanostars feature a star-shaped gold core, a Raman reporter resonant in the near-infrared spectrum, and a primer-free silication method. In genetically engineered mouse models of pancreatic cancer, breast cancer, prostate cancer, and sarcoma, and in one human sarcoma xenograft model, SERRS nanostars enabled accurate detection of macroscopic malignant lesions, as well as microscopic disease, without the need for a targeting moiety. Moreover, the sensitivity (1.5 fM limit of detection) of SERRS nanostars allowed imaging of premalignant lesions of pancreatic and prostatic neoplasias. High sensitivity and broad applicability, in conjunction with their inert gold-silica composition, render SERRS nanostars a promising imaging agent for more precise cancer imaging and resection.


Subject(s)
Diagnostic Imaging/methods , Nanoparticles , Neoplasms/diagnosis , Spectrum Analysis, Raman/methods , Animals , Cell Line, Tumor , Disease Models, Animal , Female , Humans , Neoplasm Metastasis , Pinocytosis , Precancerous Conditions/pathology , Tissue Distribution
15.
World J Urol ; 33(6): 853-8, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25149471

ABSTRACT

PURPOSE: To assess interobserver variability of R.E.N.A.L., preoperative aspects and dimensions used for an anatomical classification system (PADUA), and centrality index (C-Index) systems among observers with varying degrees of clinical experience and each system's subscale correlation with surgical outcome metrics. METHODS: Computed tomography images of 90 patients who underwent open, laparoscopic, or robot-assisted laparoscopic partial nephrectomy were scored by one radiology fellow, two urology fellows, one radiology resident, and one secondary school student. Agreement among readers was determined calculating intraclass correlation coefficients. Associations between radiology fellow scores (reference standard as reader with greatest clinical experience), ischemia time, and percent change in postoperative estimated glomerular filtration rate (eGFR) were evaluated using Spearman's correlation. RESULTS: Agreement using C-Index method (ICC = 0.773) was higher than with PADUA (ICC = 0.677) or R.E.N.A.L (ICC = 0.660). Agreement between reference and secondary school student was lower than with other physicians, although the differences were not statistically significant. The reference's scores were significantly (p < 0.05) associated with ischemia time on all three scoring systems and with percent change in eGFR at 6 weeks using C-Index (p = 0.016). Tumor size, nearness to sinus, and location relative to polar lines (R.E.N.A.L.) and tumor size, renal sinus involvement, and collecting system involvement (PADUA) correlated with ischemia time (all p ≤ 0.001). No R.E.N.A.L. or PADUA subscales significantly correlated with percent change in postoperative eGFR. CONCLUSIONS: Clinical experience reduces interobserver variability of existing nephrometry systems though not significantly and less so when using directly measureable anatomic variables. Consistently, only measures of tumor size and distance to intrarenal structures were useful in predicting clinically relevant outcomes.


Subject(s)
Carcinoma, Renal Cell/diagnostic imaging , Fellowships and Scholarships , Internship and Residency , Kidney Neoplasms/diagnostic imaging , Kidney/diagnostic imaging , Observer Variation , Radiology/education , Urology/education , Aged , Anthropometry , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/surgery , Cohort Studies , Female , Humans , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Laparoscopy , Male , Middle Aged , Nephrectomy , Outcome Assessment, Health Care , Retrospective Studies , Robotic Surgical Procedures , Schools , Students , Tomography, X-Ray Computed , Tumor Burden
16.
Urol Pract ; 2(3): 131, 2015 May.
Article in English | MEDLINE | ID: mdl-37559334
17.
Urology ; 84(6): 1355-60, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25288573

ABSTRACT

OBJECTIVE: To evaluate and compare perioperative outcomes of transperitoneal and retroperitoneal (RP) laparoscopic and robotic partial nephrectomies (LPNs) while adjusting for tumor complexity. MATERIALS AND METHODS: Retrospective review was conducted of 191 patients who underwent transperitoneal (n = 116) or RP (n = 75) LPN. To adjust for tumor complexity, individual components of the radius, exophytic or endophytic properties, nearness to the collecting system or sinus, anterior or posterior location, and location in reference to polar lines (R.E.N.A.L.) nephrometry score were used in multivariate linear and logistic regression models to compare perioperative outcomes between the 2 groups. A propensity approach was also used to adjust for multiple covariates. Investigated outcomes included estimated blood loss (EBL), ischemia and operative times, length of hospital stay, margin status, opioid use, postoperative estimated glomerular filtration rate, complications within 30 days, and readmission rates. RESULTS: Tumors resected by RPLPN were more likely to have lower complexity score by nephrometry (P = .04). Four of the 5 components of the R.E.N.A.L. nephrometry score were significantly different between the groups. After adjustment for these factors, a lower EBL was noted in the RP group (ß, -97; 95% confidence interval, -156 to -39; P = .001). Risk of readmission for the RP group was significantly lower (odds ratio, 0.15; P = .024) using propensity analysis. CONCLUSION: Using adjustment for tumor complexity, RPLPN was associated with lower EBL and readmission rates supporting the potential clinical advantage for this approach when feasible.


Subject(s)
Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Laparoscopy/methods , Nephrectomy/methods , Robotics/methods , Aged , Blood Loss, Surgical/physiopathology , Cohort Studies , Female , Follow-Up Studies , Humans , Kidney Neoplasms/mortality , Length of Stay , Linear Models , Logistic Models , Male , Middle Aged , Minimally Invasive Surgical Procedures/methods , Multivariate Analysis , Neoplasm Invasiveness/pathology , Neoplasm Staging , Operative Time , Perioperative Period/methods , Peritoneum/surgery , Retroperitoneal Space/surgery , Retrospective Studies , Risk Assessment , Survival Rate , Treatment Outcome
18.
J Urol ; 192(3): 702-7, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24603101

ABSTRACT

PURPOSE: We report cancer specific outcomes of micropapillary nonmuscle invasive bladder cancer. MATERIALS AND METHODS: We retrospectively reviewed the records of 36 cases restaged within 3 months of the initial diagnosis of micropapillary nonmuscle invasive bladder cancer. Early radical cystectomy within a 3-month landmark after restaging transurethral bladder tumor resection or conservative treatment with intravesical bacillus Calmette-Guérin, surveillance or deferred radical cystectomy was offered according to surgeon and patient preference. The cumulative incidence of cancer specific mortality and metastasis was estimated using the Kaplan-Meier method. Differences in the cumulative incidence of cancer specific mortality and metastasis between the groups were tested using the log rank test. RESULTS: Median patient age was 68 years (IQR 63-77). The male-to-female ratio was 3:1. At restaging all patients had cT1 disease or less. Early radical cystectomy was performed in 15 patients (42%) while 21 (58%) underwent conservative treatment. Median followup after landmark in cancer specific survivors was 3.1 years (IQR 1.1-5.9). The 5-year cumulative incidence of cancer specific mortality was 17% in the early radical cystectomy group and 25% in the conservative management group for an absolute difference of 7% (95% CI -26-41, p = 0.8). The 5-year cumulative incidence of metastasis was 21% and 34%, respectively, with an absolute difference of 13% (95% CI -23-49, p = 0.9). The extent of the micropapillary component was not significantly associated with cancer specific mortality (p = 0.4) or metastasis (p = 0.9). CONCLUSIONS: Using proper selection criteria, including patient and pathological factors, certain patients in whom cT1 micropapillary urothelial carcinoma was managed conservatively did not have significantly worse outcomes than patients treated with early radical cystectomy.


Subject(s)
Adjuvants, Immunologic/therapeutic use , BCG Vaccine/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/surgery , Cystectomy , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/surgery , Aged , Female , Humans , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Retrospective Studies , Treatment Outcome , Urinary Bladder Neoplasms/pathology
19.
J Urol ; 191(3): 660-4, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24018237

ABSTRACT

PURPOSE: Prostate biopsy related infectious complications are associated with significant morbidity. The risk of infectious complications in patients with prostate cancer on active surveillance remains under studied. MATERIALS AND METHODS: A total of 591 consecutive men who underwent prostate biopsy were prospectively enrolled in a study evaluating prostate biopsy related complications between January 2011 and January 2012. Of these men 403 were previously diagnosed with prostate cancer and were included in this study. They underwent a 14-core transrectal ultrasound guided prostate biopsy as part of an active surveillance regimen. A nurse contacted all men within 14 days of biopsy, and information was collected on potential complications, antibiotics received and bacterial culture results. RESULTS: Fourteen patients (3.5%) had infectious complications including 13 requiring hospitalization. Five patients had positive urine cultures, and fluoroquinolone resistant isolates were identified in 4 patients, including 2 with extended spectrum beta-lactamase producing isolates. We evaluated the impact of risk factors including diabetes, benign prostatic hyperplasia and antibiotic regimen. However, only the number of previous prostate biopsies was significantly associated with an increased risk of infectious complications (p = 0.041). For every previous biopsy the odds of an infection increased 1.3 times (OR 1.33, 95% CI 1.01-1.74). CONCLUSIONS: In men with prostate cancer on active surveillance the number of previous prostate biopsies is associated with a significant risk of infectious complications and every previous biopsy increases the risk of infectious complication. Fluoroquinolone resistant and extended spectrum beta-lactamase producing isolates represent the most commonly identified organisms. Men with prostate cancer on active surveillance should be informed of the risks associated with serial repeat prostate biopsies.


Subject(s)
Biopsy , Postoperative Complications/epidemiology , Prostatic Neoplasms/pathology , Surgical Wound Infection/epidemiology , Aged , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Bacterial , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Postoperative Complications/drug therapy , Prospective Studies , Retreatment , Risk Factors , Surgical Wound Infection/drug therapy , Treatment Outcome , Ultrasonography, Interventional
20.
Lasers Med Sci ; 28(2): 473-8, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22460737

ABSTRACT

We evaluate the efficacy and safety of GreenLight HPS™ laser photoselective vaporization prostatectomy (PVP) for the treatment of benign prostatic hyperplasia (BPH) with different prostate configuration. Patients were stratified into two groups: bilobe (group I) and trilobe (group II) BPH. Transurethral PVP was performed using a 120 W GreenLight HPS™ side-firing laser system. American Urological Association Symptom Score (AUASS), Quality of Life (QoL) score, maximum flow rate (Q max), and postvoid residual (PVR) were measured preoperatively and at 1 and 4 weeks and 3, 6, 12, 18, 24 and 36 months postoperatively. A number of 160 consecutive patients were identified (I: 86, II: 74). Among the preoperative parameters, there were significant differences (p < 0.05) in prostate volume (I: 46.0 ± 19.8; II: 87.5 ± 39.6 ml), Q max (I: 9.9 ± 3.9; II: 8.7 ± 3.5 ml/sec), PVR (I: 59.2 ± 124.6; II: 97.7 ± 119.1 ml) and PSA (I: 1.4 ± 1.4; II: 3.6 ± 2.6 ng/ml), while AUASS and QoL were similar (p > 0.05). Significant differences (p < 0.05) in laser utilization (I: 9.5 ± 6.6; II: 19.5 ± 11.6 min) and energy usage (I: 63.1 ± 43.9; II: 132.5 ± 81.1 kJ) were noted. Clinical outcomes (AUASS, QoL, Q max, and PVR) showed immediate and stable improvement from baseline (p < 0.05) within each group, but no significant differences between the two groups were observed during the follow-up period (p > 0.05). The incidences of adverse events were low and similar in both groups. Our experience suggests that BPH configuration has little effect on the efficacy and safety of GreenLight HPS™ laser PVP.


Subject(s)
Laser Therapy/methods , Prostate/anatomy & histology , Prostate/surgery , Prostatectomy/methods , Prostatic Hyperplasia/surgery , Adult , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , Humans , Laser Therapy/adverse effects , Male , Middle Aged , Postoperative Complications/etiology , Prostatectomy/adverse effects , Quality of Life , Transurethral Resection of Prostate/adverse effects , Transurethral Resection of Prostate/methods , Treatment Outcome , Volatilization
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