Publications by authors named "John L Phillips"

26 Publications

  • Page 1 of 1

Contemporary Trends in Percutaneous Nephrolithomy Across New York State: A Review of the Statewide Planning and Research Cooperative System.

J Endourol 2019 09 23;33(9):699-703. Epub 2019 Jul 23.

Department of Urology, New York Medical College, Valhalla, New York.

Percutaneous nephrolithotomy (PCNL) is a complex multistep surgery that has shown a steady increase in use for the past decade in the United States. We sought to evaluate the trends and factors associated with PCNL usage across New York State (NYS). Our goal was to characterize patient demographics and socioeconomic factors across high-, medium-, and low-volume institutions. We searched the NYS, Statewide Planning and Research Cooperative System (SPARCS) database from 2006 to 2014 using ICD-9 Procedure Codes 55.04 (percutaneous nephrostomy with fragmentation) for all hospital discharges. Patient demographics including age, gender, race, insurance status, and length of hospital stay were obtained. We characterized each hospital as a low-, medium-, or high-volume center by year. Patient and hospital demographics were compared and reported using chi-square analysis and Student's -test for categorical and continuous variables, respectively, with statistical significance as a -value of <0.05. We identified a total of 4576 procedures performed from 2006 to 2014 at a total of 77 hospitals in NYS (Table 1). Total PCNL volume performed across all NYS hospitals increased in the past decade, with the greatest number of procedures performed in 2012 to 2013. Low-volume institutions were more likely to provide care to minority populations (21.4% 17.3%,  < 0.001) and those with Medicaid (25.5% 21.5%,  < 0.001). High-volume institutions provided care to patients with private insurance (42.1% 34.0%,  < 0.001) and had a shorter length of stay (3.3 days 4.1 days,  < 0.001). Our data provide insight into the patient demographics of those treated at high-, medium-, and low-volume hospitals for PCNL across NYS. Significant differences in race, insurance status, and length of stay were noted between low- and high-volume institutions, indicating that racial and socioeconomic factors play a role in access to care at high-volume centers.
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http://dx.doi.org/10.1089/end.2019.0115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918525PMC
September 2019

The Two-Point Technique for Fluoroscopic-Guided Endoscopic Procedures in Urology: A Validation Study.

J Endourol 2019 09 28;33(9):691-695. Epub 2019 Jun 28.

Department of Urology, New York Medical College, Valhalla, New York.

The widespread use of diagnostic and therapeutic ionizing radiation raises concerns regarding excessive occupational and patient exposure. In this study, we test a novel fluoroscopic technique that has the potential to minimize radiation dose during urologic procedures. A prospective evaluation of all patients undergoing endoscopic urologic procedures in our institution was conducted. A "two-point technique (TPT)" is described in which the fluoroscope image intensifier (c-arm) is shifted between caudal and cephalad set points of the operative field. We wished to determine whether patient radiation exposure was lower with TPT than with a non-structured conventional technique, referred to as the cognitive fluoroscopic technique (CFT), in which the manipulation of the c-arm was at the discretion of the user. We obtained all clinical, radiographic, and fluoroscopic data of patients in the study period and used unpaired nonparametric statistical analysis of univariates entered stepwise into a logistic regression model. A total of 106 endoscopic urologic procedures from January 2016 to November 2018 were reviewed. Forty-four (41.5%) cases were performed using TPT and 62 (58.5%) using CFT. The mean fluoroscopy time of TPT CFT was 71.1 (±60.8) seconds 104.5 (±91.6) seconds, respectively ( = 0.04), and the mean radiation dose on TPT CFT was 11.6 (±10.6) mGy 20.3 (±24.3) mGy, respectively ( = 0.03). TPT was an independent predictor of reduced operative room (OR) time and fluoro time ( < 0.05), while body mass index, age, and operator were not. The "TPT" helps reducing radiation dose and fluoroscopic time during endoscopic urologic procedures. The TPT is useful to lower radiation exposure to patients and OR staff.
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http://dx.doi.org/10.1089/end.2019.0077DOI Listing
September 2019

Detection of lymph node metastases in penile cancer.

Transl Androl Urol 2018 Oct;7(5):879-886

Department of Urology, New York Medical College, Valhalla, NY, USA.

Penile cancer (PC) is a relatively rare malignancy in the United States (US) but a greater concern in developing nations. Lymph node imaging remains critical to the staging and treatment of this disease as metastases develop in a predictable, anatomic fashion. Early surgical intervention remains a mainstay in treatment and imaging often aids in decision making. This review highlights the indications for imaging in both low-stage and advanced disease. Furthermore, we discuss the benefits and limitations of currently available imaging for staging of inguinal and pelvic lymph nodes in PC and novel modalities in development.
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http://dx.doi.org/10.21037/tau.2018.08.01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212620PMC
October 2018

Editorial Comment.

J Urol 2018 11 19;200(5):1003-1004. Epub 2018 Jul 19.

Department of Urology, New York Medical College, Valhalla, New York.

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http://dx.doi.org/10.1016/j.juro.2018.06.072DOI Listing
November 2018

Prostate Cancer Screening Trends After United States Preventative Services Task Force Guidelines in an Underserved Population.

Health Equity 2018 1;2(1):55-61. Epub 2018 May 1.

Department of Urology, New York Medical College, Valhalla, New York.

Prostate cancer screening is a controversial topic. We examined trends in Prostate Specific Antigen (PSA) testing in an underserved population before and after the United States Preventative Services Task Force (USPSTF) recommendation against screening. Data were collected on all PSA and cholesterol screening tests from 2008 to 2014. We examined the trend of these tests and prostate biopsies while comparing this data to lipid panel data to adjust for changes in patient population. A decrease in PSA screening was observed from 2010 through 2014, with the greatest decline in 2012. The age group most affected was patients aged 55-69 years. The amount of prostate biopsies during this period decreased as well. Decreased rates of PSA screening were observed in our urban hospital population that preceded the publication of the USPSTF guidelines. The incidence of prostate biopsies decreased in this timeframe. It now remains to be demonstrated whether decreased PSA screening rates impact the diagnosis of and ultimately the survival from prostate cancer.
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http://dx.doi.org/10.1089/heq.2018.0004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963250PMC
May 2018

Device-Related Adverse Events During Percutaneous Nephrolithotomy: Review of the Manufacturer and User Facility Device Experience Database.

J Endourol 2017 10;31(10):1007-1011

1 Department of Urology, New York Medical College , Valhalla, New York.

Introduction And Objectives: Percutaneous nephrolithotomy (PCNL) is an established technique for removal of large stones from the upper urinary tract. It is a complex multistep procedure requiring several classes of instruments that are subject to operator misuse and device malfunction. We report device-related adverse events during PCNL from the Manufacturer and User Facility Device Experience (MAUDE) database using a recently developed standardized classification system.

Materials And Methods: The MAUDE database was queried for "percutaneous nephrolithotomy" from 2006 to 2016. The circumstances and patient complications associated with classes of devices used during PCNL were identified. We then utilized a novel MAUDE classification system to categorize clinical events. Logistic regression analysis was performed to identify associations between device classes and severe adverse events.

Results: A total of 218 device-related events were reported. The most common classes included: lithotripter 53 (24.3%), wires 43 (19.7%), balloon dilators 30 (13.8%), and occlusion balloons 28 (12.8%). Reported patient complications included need for a second procedure 12 (28.6%), bleeding 8 (19.0%), retained fragments 7 (16.7%), prolonged procedure 4 (9.5%), ureteral injury 2 (4.8%), and conversion to an open procedure 3 (7.1%). Using a MAUDE classification system, 176 complications (81%) were Level I (mild/none), 26 (12%) were Level II (moderate), 15 (7%) were Level III (severe), and 1 (0.5%) was Level IV (life threatening). On univariate analysis, balloon dilators had the highest risk of Level II-IV complications compared with the other device classes [odds ratio: 4.33, confidence interval: 1.978, 9.493, p < 0.001]. The device was evaluated by the manufacturer in 93 (42.7%) cases, with 54.8% of reviewed cases listing the source of malfunction as misuse by the operator.

Conclusions: PCNL is subject to a wide range of device-related adverse events. A MAUDE classification system is useful for standardized, clinically-relevant reporting of events. Our findings highlight the importance of proper surgeon training with devices to maximize efficiency and decrease harm.
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http://dx.doi.org/10.1089/end.2017.0343DOI Listing
October 2017

Hyper IgE Syndrome and Renal Cell Carcinoma.

Case Rep Urol 2017 18;2017:7083451. Epub 2017 May 18.

Department of Urology, New York Medical College, Valhalla, NY, USA.

Hyper IgE Syndrome (HIES) is an immunodeficiency disorder characterized by increased serum levels of IgE, eczema, and recurrent cutaneous and pulmonary infections. In this report, we present, to our knowledge, the first documented case of renal cell carcinoma (RCC) found in a patient with HIES. The patient received infectious disease clearance prior to obtaining a partial nephrectomy which revealed clear cell histology. Both HIES and RCC have an immunological basis for their pathophysiology and may involve common pathways. Further studies may provide insight into any possible link and clinicians should be mindful of immunocompromised patients who present with risk factors for genitourinary malignancy.
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http://dx.doi.org/10.1155/2017/7083451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451772PMC
May 2017

Factors influencing residents' pursuit of urology fellowships.

Urology 2011 Nov;78(5):986-92

Department of Urology, New York Medical College, Valhalla, New York 10595, USA.

Objective: To assess the predictors of residents' pursuit of fellowship training by surveying current urology residents and recent graduates. Postgraduate fellowship training of urologists could be an important source of urologic physician-scientists and continued innovation in urologic care.

Methods: A Web-based survey was electronically mailed to urology residents and recent graduates of urologic residency. Variables concerning sex, marital status, debt load, research and clinical exposure, publications, and postgraduate careers were recorded.

Results: Of the 71 respondents, 46 (65%) were married and 45% had children/dependents. Of the 69% who applied for fellowship, the "most important" factors influencing the pursuit of fellowship were intellectual appeal (82%), mentors (79%), the desire for an additional point of view for surgical training (58%), and the desire to pursue a career in academics (52%). Forty of those completing a fellowship (87%) versus two of those completing residency alone (13%) would pursue a career in academics. Residents with a mentor were 20 times more likely to pursue a urology fellowship. A shorter residency (5 years), encouragement by a program director, and manuscript publication during residency were also independent predictors.

Conclusion: Mentorship, a shorter residency, and manuscript publication during residency were independent predictors of pursuing fellowship training. Debt load, age, marital status, and a desire to pursue a career in academic medicine were not significant factors.
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http://dx.doi.org/10.1016/j.urology.2011.05.068DOI Listing
November 2011

Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight.

Ophthalmology 2011 Oct 17;118(10):2058-69. Epub 2011 Aug 17.

Department of Ophthalmology, Alaska Native Medical Center, Anchorage, AK 99508, USA.

Purpose: To describe the history, clinical findings, and possible etiologies of ophthalmic findings discovered in 7 astronauts after long-duration space flight, and document vision changes in approximately 300 additional astronauts.

Design: Retrospective, observational examination of ophthalmic findings in 7 astronauts and analysis of postflight questionnaires regarding in-flight vision changes in approximately 300 additional astronauts.

Participants: Seven astronauts with ophthalmic anomalies upon return from long-duration space missions to the International Space Station and 300 additional astronauts who completed postflight questionnaires regarding in-flight vision changes.

Methods: Before and after long-duration space flight, all 7 subjects underwent complete eye examinations, including cycloplegic and/or manifest refraction and fundus photography. Six underwent postmission optical coherence tomography (OCT) and magnetic resonance imaging (MRI); 4 had lumbar punctures (LP). Approximately 300 astronauts were queried regarding visual changes during space missions.

Main Outcome Measures: Refractive change, fundus photograph examination, retina OCT, orbital MRI, LP opening pressures, and examination of visual acuity data.

Results: After 6 months of space flight, 7 astronauts had ophthalmic findings, consisting of disc edema in 5, globe flattening in 5, choroidal folds in 5, cotton wool spots (CWS) in 3, nerve fiber layer thickening by OCT in 6, and decreased near vision in 6 astronauts. Five of 7 with near vision complaints had a hyperopic shift ≥+0.50 diopters (D) between pre/postmission spherical equivalent refraction in 1 or both eyes (range, +0.50 to +1.75 D). These 5 showed globe flattening on MRI. Lumbar punctures performed in the 4 with disc edema documented opening pressures of 22, 21, 28, and 28.5 cm H(2)O performed 60, 19, 12, and 57 days postmission, respectively. The 300 postflight questionnaires documented that approximately 29% and 60% of astronauts on short and long-duration missions, respectively, experienced a degradation in distant and near visual acuity. Some of these vision changes remain unresolved years after flight.

Conclusions: We hypothesize that the optic nerve and ocular changes we describe may result from cephalad fluid shifts brought about by prolonged microgravity exposure. The findings we report may represent parts of a spectrum of ocular and cerebral responses to extended microgravity exposure.

Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.
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http://dx.doi.org/10.1016/j.ophtha.2011.06.021DOI Listing
October 2011

What is the "true" incidence of active surveillance and brachytherapy candidates in men undergoing robot-assisted radical prostatectomy?

J Endourol 2010 Oct;24(10):1671-4

Sol and Margaret Berger Department of Urology, Beth Israel Medical Center, New York, New York 10016, USA.

Purpose: To correlate clinical low-risk prostate cancers with pathologic outcomes in men who are considered for active surveillance (AS), interstitial radiation therapy, or radical prostatectomy (RP).

Patients And Methods: Clinical and pathologic data of 76 consecutive patients who underwent RP by a single surgeon between October 2001 and July 2008 were reviewed. The retrospective review identified men with clinical low-risk disease--defined as a prostate-specific antigen (PSA) level <10 ng/mL, no Gleason pattern >3, no >2 cores positive, and no core >50%--who would also have been considered for AS and/or brachytherapy based on these features. Pathologic specimens were examined for Gleason primary, secondary, and tertiary patterns, perineural invasion, capsular involvement, margins, nodal disease, and seminal vesicle involvement.

Results: Of the patients who underwent RP, 42/76 (55%) had low-risk clinical staging; 8/76 (19%) had low-risk features on final pathologic staging. Fifty-four of 76 (71%) were pT2c; 10% were pT3. Gleason 6 was seen in 41/76 (53%) of RP specimens; Gleason 7 and 8 in 41% and 4%, respectively. Favorable brachytherapy parameters were identified in 63% of those who underwent surgery, but 39 of 48 (81%) would have been inappropriately selected based on features of the pathologic specimen.

Conclusion: Clinical staging based on PSA level and biopsy findings correlates poorly with pathologic outcome when stratifying for low-risk features in men who may be candidates for brachytherapy and/or AS.
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http://dx.doi.org/10.1089/end.2009.0644DOI Listing
October 2010

Patterns, art, and context: Donald Floyd Gleason and the development of the Gleason grading system.

Urology 2009 Sep 18;74(3):497-503. Epub 2009 Apr 18.

Department of Urology, New York Medical College, Hawthorne, NY 10595, USA.

The Gleason grading system is a standard method of assessing prostate cancer. Very little is known, however, about the person behind the system, Donald Floyd Gleason, MD, PhD. Our objective was to construct a biography of Gleason and show how his work advanced prostate cancer diagnosis. We reviewed Gleason's notes, letters, and publications with the Veteran's Administration Cooperative Urology Research group (VACURG) between 1960 and 1980. Gleason described seeing five recurring histologic "pictures" in his review of 280 initial cases of prostate cancer from 1960 to 1964. By 1966, NIH statisticians combined Gleason's "pictures" with VACURG clinical data into a scoring system. By 1974, over 4,000 cases had been analyzed, and by 1978 the Gleason scale had reached widespread use. Donald F. Gleason recognized trends in histologic patterns which had eluded earlier, more sophisticated pathologic approaches and which lie as the basis for the sophisticated neural networks and nomograms in use today.
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http://dx.doi.org/10.1016/j.urology.2009.01.012DOI Listing
September 2009

Renal mass in solitary, crossed, ectopic pelvic kidney.

Urology 2009 Jun 10;73(6):1223-4. Epub 2009 Apr 10.

Berger Department of Urology, Beth Israel Medical Center, New York, New York 10003-3313, USA.

A 46-year-old healthy man presented with abdominal pain and a solitary ectopic, crossed pelvic kidney with an enhancing mass, imaged with 3-dimensional computed tomography. He underwent open partial nephrectomy, which revealed Stage T1, grade 2 conventional renal cell carcinoma with negative surgical margins. The incidence of renal cell carcinoma in the computed tomography era in a solitary crossed ectopic kidney is approximately 1 in 22 million.
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http://dx.doi.org/10.1016/j.urology.2008.07.048DOI Listing
June 2009

Limitations and use of PSA velocity in the diagnosis and characterization of prostate cancer.

Nat Clin Pract Urol 2007 Nov 25;4(11):576-7. Epub 2007 Sep 25.

Beth Israel Medical Center in New York, NY 10003, USA.

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http://dx.doi.org/10.1038/ncpuro0936DOI Listing
November 2007

Aneuploidy in bladder cancers: the utility of fluorescent in situ hybridization in clinical practice.

BJU Int 2006 Jul;98(1):33-7

Department of Urology, Beth Israel Medical Center, New York City, USA.

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http://dx.doi.org/10.1111/j.1464-410X.2006.06189.xDOI Listing
July 2006

Recurrent transitional cell carcinoma in a scrotal abscess.

Urology 2006 Apr 5;67(4):846.e1-2. Epub 2006 Apr 5.

Department of Urology, Beth Israel Medical Center, New York, New York 10010, USA.

We discuss a case of recurrent transitional cell carcinoma to the scrotum 5 years after cystectomy, along with its postoperative management and implications.
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http://dx.doi.org/10.1016/j.urology.2005.10.018DOI Listing
April 2006

Re: Urinary fistulas following external radiation or permanent brachytherapy for the treatment of prostate cancer.

Authors:
John L Phillips

J Urol 2006 Jan;175(1):390

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http://dx.doi.org/10.1016/S0022-5347(05)00023-6DOI Listing
January 2006

Digital rectal examination is barrier to population-based prostate cancer screening.

Urology 2005 Jun;65(6):1137-40

Department of Urology, Beth Israel Medical Center, Albert Einstein College of Medicine, New York, New York 10010, USA.

Objectives: To determine whether use of the digital rectal examination (DRE) results in decreased participation in prostate cancer (PCa) screening, which, in turn, would result in lower detection. Population-based PCa screening includes prostate-specific antigen (PSA) measurement with or without a DRE. PSA and DRE screening provide greater sensitivity than PSA alone; however, the increased participation rate resulting from PSA-alone screening may result in a greater detection rate.

Methods: We performed a survey of 13,580 healthy men undergoing PSA-only population-based screening. In addition to the basic demographic information, the survey asked whether the participant would still be willing to participate in the screening if it included a DRE. We modeled the willingness to participate to assess the effect of PSA screening versus PSA and DRE screening on the basis of previously published data and our results.

Results: The results of our study indicated that only 78% of men would participate in screening that included both DRE and PSA. Thus, 7800 men of a theoretical population of 10,000 would participate in a screening that included both DRE and PSA. The positive screen rate (PSA > or = 4.0 ng/mL and/or abnormal DRE) would then have been 2013, with 472 PCa cases and 1540 negative biopsies. In the PSA-alone arm, all 10,000 men would have agreed to participate, and the positive screen rate (PSA > or = 4.0 ng/mL) would have been 1480, with 499 PCa cases and 980 negative biopsies. The PSA-alone arm would thus have detected 27 more cancers and performed 560 fewer negative biopsies.

Conclusions: The results of our study have demonstrated that DRE is a significant barrier to participation in PCa screening. PSA plus DRE-based programs result in fewer cases of PCa detected, with a significant increase in negative biopsies. We, therefore, suggest that future mass screening efforts include only PSA determination and omit the DRE.
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http://dx.doi.org/10.1016/j.urology.2004.12.021DOI Listing
June 2005

Early onset hereditary papillary renal carcinoma: germline missense mutations in the tyrosine kinase domain of the met proto-oncogene.

J Urol 2004 Oct;172(4 Pt 1):1256-61

Basic Research Program, SAIC-Frederick, Inc., Frederick, Maryland, USA.

Purpose: Hereditary papillary renal carcinoma (HPRC) is characterized by a predisposition to multiple, bilateral papillary type 1 renal tumors caused by inherited activating missense mutations in the tyrosine kinase domain of the MET proto-oncogene. In the current study we evaluated the clinical phenotype and germline MET mutation of 3 new HPRC families. We describe the early onset clinical features of HPRC.

Materials And Methods: We identified new HPRC families of Italian (family 177), Spanish (family 223) and Cuban (family 268) descent. We evaluated their clinical features, performed MET mutation analysis by denaturing high performance liquid chromatography and DNA sequencing, and estimated age dependent penetrance and survival using Kaplan-Meier analysis. We characterized renal tumors by histology and fluorescence in situ hybridization.

Results: Identical germline MET c.3522G --> A mutations (V1110I) were identified in families 177 and 268 but no evidence of a founder effect was found. Affected members of family 223 carried a germline c.3906G --> C.3522G --> A MET mutation (V1238I). Age dependent penetrance but not survival was significantly earlier for the c.3522G -->A mutation than for the c.3906G --> A mutation in these HPRC families. Trisomy of chromosome 7 and papillary renal carcinoma type 1 histology were detected in papillary renal tumors.

Conclusions: HPRC can occur in an early onset form. The median age for renal tumor development in these 3 HPRC families was 46 to 63 years. HPRC associated papillary renal tumors may be aggressive and metastasize, leading to mortality. Median survival age was 60 to 70 years. Families with identical germline mutations in MET do not always share a common ancestor. HPRC is characterized by germline mutations in MET and papillary type 1 renal tumor histology.
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http://dx.doi.org/10.1097/01.ju.0000139583.63354.e0DOI Listing
October 2004

Bilateral testicular adrenal rests after bilateral adrenalectomies in a cushingoid patient with von Hippel-Lindau disease.

Urology 2004 May;63(5):981-2

Urologic Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA.

We report a case of bilateral testicular masses in a 25-year-old man with von Hippel-Lindau disease presenting with cushingoid symptoms. His medical history was significant for bilateral adrenalectomies secondary to pheochromocytomas, and he began steroid therapy at that time. After exhaustive endocrinologic, radiographic, and physical examinations, the testicular masses were postulated to be active adrenal rest tissue. Bilateral testicular venous sampling found elevated glucocorticoids that were responsive to dexamethasone suppression, which confirmed the testicular masses as testicular adrenal rests without the need for surgical intervention. Successful conservative management consisted of appropriate steroid manipulation and radiographic evaluation and resulted in the resolution of presenting symptoms, a decrease in size of the bilateral testicular masses, and testicular conservation in this young man.
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http://dx.doi.org/10.1016/j.urology.2004.01.023DOI Listing
May 2004

Solid renal tumor severity in von Hippel Lindau disease is related to germline deletion length and location.

Hum Mutat 2004 Jan;23(1):40-6

Urologic Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.

von Hippel Lindau disease (VHL) is an autosomal dominant familial cancer syndrome linked to alteration of the VHL tumor suppressor gene. Affected patients are predisposed to develop pheochromocytomas and cystic and solid tumors of the kidney, CNS, pancreas, retina, and epididymis. However, organ involvement varies considerably among families and has been shown to correlate with the underlying germline alteration. Clinically, we observed a paradoxically lower prevalence of renal cell carcinoma (RCC) in patients with complete germline deletion of VHL. To determine if a relationship existed between the type of VHL deletion and disease, we retrospectively evaluated 123 patients from 55 families with large germline VHL deletions, including 42 intragenic partial deletions and 13 complete VHL deletions, by history and radiographic imaging. Each individual and family was scored for cystic or solid involvement of CNS, pancreas, and kidney, and for pheochromocytoma. Germline deletions were mapped using a combination of fluorescent in situ hybridization (FISH) and quantitative Southern and Southern blot analysis. An age-adjusted comparison demonstrated a higher prevalence of RCC in patients with partial germline VHL deletions relative to complete deletions (48.9 vs. 22.6%, p=0.007). This striking phenotypic dichotomy was not seen for cystic renal lesions or for CNS (p=0.22), pancreas (p=0.72), or pheochromocytoma (p=0.34). Deletion mapping revealed that development of RCC had an even greater correlation with retention of HSPC300 (C3orf10), located within the 30-kb region of chromosome 3p, immediately telomeric to VHL (52.3 vs. 18.9%, p <0.001), suggesting the presence of a neighboring gene or genes critical to the development and maintenance of RCC. Careful correlation of genotypic data with objective phenotypic measures will provide further insight into the mechanisms of tumor formation.
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http://dx.doi.org/10.1002/humu.10302DOI Listing
January 2004

Prostate cancer in Klinefelter syndrome during hormonal replacement therapy.

Urology 2003 Nov;62(5):941

Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1501, USA.

Prostate cancer detection is a rare occurrence in patients with Klinefelter syndrome, in whom chronically low circulating androgen levels are common findings. Administration of exogenous testosterone has increasingly been used to treat young adolescents diagnosed with Klinefelter syndrome and documented androgen deficiency. Although testosterone replacement in adult patients has been associated with prostatic enlargement, it remains unknown whether chronic supplementation of exogenous testosterone to pubescent males with hypogonadism results in early prostate carcinogenesis. We report a first case of prostate cancer in a patient with Klinefelter syndrome who had undergone long-term testosterone replacement therapy since childhood for chronically depressed levels of testosterone.
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http://dx.doi.org/10.1016/s0090-4295(03)00693-9DOI Listing
November 2003

Signal pathway profiling of prostate cancer using reverse phase protein arrays.

Proteomics 2003 Nov;3(11):2142-6

Urologic Oncology Branch, National Cancer Institute, Bethesda, MD, USA.

Reverse phase protein arrays represent a new proteomics microarray technology with which to study the fluctuating state of the proteome in minute quantities of cells. The activation status of cell signaling pathways controls cellular fate and deregulation of these pathways underpins carcinogenesis. Changes in pathway activation that occur between early stage prostatic epithelial lesions, prostatic stroma and the extracellular matrix can be analyzed by obtaining pure populations of cell types by laser capture microdissection (LCM) and analyzing the relative states of several key phosphorylation points within the cellular circuitry. We have applied reverse phase protein array technology to analyze the status of key points in cell signaling involved in pro-survival, mitogenic, apoptotic and growth regulation pathways in the progression from normal prostate epithelium to invasive prostate cancer. Using multiplexed reverse phase protein arrays coupled with LCM, the states of signaling changes during disease progression from prostate cancer study sets were analyzed. Focused analysis of phospho-specific endpoints revealed changes in cellular signaling events through disease progression and between patients. We have used a new protein array technology to study specific molecular pathways believed to be important in cell survival and progression from normal epithelium to invasive carcinoma directly from human tissue specimens. With the advent of molecular targeted therapeutics, the identification, characterization and monitoring of the signaling events within actual human biopsies will be critical for patient-tailored therapy.
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http://dx.doi.org/10.1002/pmic.200300598DOI Listing
November 2003

The genetic basis of renal cell carcinoma.

Urol Clin North Am 2003 Aug;30(3):437-54, vii

James Buchanan Brady Urological Institute, A-345 Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue, Baltimore, MD 21224, USA.

The recognition of hereditary forms of renal cancer and the development of high-throughput genetic analysis have led to the identification of genes responsible for familial renal epithelial tumors of differing histologies and cytogenetic features. Some of these genes (VHL) are known to have an important role in sporadic renal neoplasia. This article describes the various epithelial renal tumors most commonly encountered by the urologist, the molecular and cytogenetic distinctions between them, and the hereditary syndromes that predispose to these tumors. Consideration of these syndromes is important for proper treatment when one encounters patients with multiple renal tumors, tumors at an early age of onset, or patients with a positive family history of renal cell carcinoma.
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http://dx.doi.org/10.1016/s0094-0143(03)00023-5DOI Listing
August 2003

Patterns of aneuploidy in stage IV clear cell renal cell carcinoma revealed by comparative genomic hybridization and spectral karyotyping.

Genes Chromosomes Cancer 2003 Jul;37(3):252-60

Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

We report the use of spectral karyotyping (SKY) and comparative genomic hybridization (CGH) to describe the numerous genomic imbalances characteristic of stage IV clear cell renal cell carcinoma (CCRCC). SKY and CGH were performed on 10 cell lines established from nephrectomy specimens, and CGH on uncultured material from five of the primary renal tumors. The mutational status of VHL (3p25) and MET (7q31), genes implicated in renal carcinogenesis, were determined for each case. Each case showed marked aneuploidy, with an average number of copy alterations of 14.6 (+/-2.7) in the primary tumors and 19.3 (+/-4.6) in the cell lines. Both whole-chromosome and chromosome-segment imbalances were noted by CGH: consistent losses or gains included +5q23-->ter (100%), -3p14-->ter (80%), and +7 (70%). All VHL mutations and 83% of the genomic imbalances found in the primary tumors were also found in the cell lines derived from them. SKY showed many complex structural rearrangements that were undetected by conventional banding analysis in these solid tumors. All cases with VHL inactivation had 3p loss and 5q gain related primarily to unbalanced translocations between 3p and 5q. In contrast, gains of chromosome 7 resulted primarily from whole-chromosome gains and were not associated with mutations of MET. SKY and CGH demonstrated that genomic imbalances in advanced RCC were the result of either segregation errors [i.e., whole chromosomal gains and losses (7.8/case)] or chromosomal rearrangements (10.7/case), of which the majority were unbalanced translocations.
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http://dx.doi.org/10.1002/gcc.10209DOI Listing
July 2003

Post-analysis follow-up and validation of microarray experiments.

Nat Genet 2002 Dec;32 Suppl:509-14

Pathogenetics Unit, Laboratory of Pathology and Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA.

Measurement of gene-expression profiles using microarray technology is becoming increasingly popular among the biomedical research community. Although there has been great progress in this field, investigators are still confronted with a difficult question after completing their experiments: how to validate the large data sets that are generated? This review summarizes current approaches to verifying global expression results, discusses the caveats that must be considered, and describes some methods that are being developed to address outstanding problems.
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http://dx.doi.org/10.1038/ng1034DOI Listing
December 2002

Assessment of risk for intra-abdominal adhesions at laparoscopy for urological tumors.

J Urol 2002 Dec;168(6):2391-4

Urologic Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA.

Purpose: Abdominal wall adhesions at laparoscopy may predispose patients to access related injuries and increase the complexity of the procedure. We have observed concern from referring physicians regarding the safety of laparoscopy in patients who previously underwent surgery because of the risk of abdominal adhesions. To assess the risk of adhesions at laparoscopy a retrospective cohort study was performed.

Materials And Methods: All patients who underwent a transperitoneal urological laparoscopic procedure in a 6-year period at our institution were included in this study. A chart review was performed to obtain demographic/surgical data and identify preoperative risk factors for adhesions, such as previous abdominal or pelvic surgery, radiation and/or intra-abdominal inflammatory disease. Operative videotapes were reviewed to determine the presence and location of adhesions. Standard statistical analyses were performed.

Results: During the study period 127 patients underwent transperitoneal laparoscopy and videotapes on 82 (65%) were available for review. A total of 44 patients (54%) were identified with preoperative risk factors for adhesions (group 1), while 38 (46%) had no risk factors (group 2). The relative risk of adhesions was 1.34 (95% CI 0.89 to 2.01, p = 0.18) when risk factors were identified. There were no differences in the groups in patient age, operative time, access technique, conversion to open surgery or complications. Estimated blood loss was significantly higher in group 2, likely due to the preponderance of cytoreductive laparoscopic nephrectomy in this group.

Conclusions: There was no difference in the risk of intra-abdominal adhesions in patients with and without identifiable preoperative risk factors. Preoperative risk factors for adhesions should not contraindicate the transperitoneal laparoscopic approach for urological oncology procedures.
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http://dx.doi.org/10.1097/01.ju.0000035271.15152.b1DOI Listing
December 2002