First name
Thomas
Middle name
F
Last name
Kolon

Title

Kidney Outcomes and Hypertension in Survivors of Wilms Tumor: A Prospective Cohort Study.

Year of Publication

2020

Date Published

2020 Dec 05

ISSN Number

1097-6833

Abstract

<p>Supported by a Pilot Grant from the Children's Hospital of Philadelphia Center for Pediatric Clinical Effectiveness (to D.C.). D.C. is also supported by the NIH/NIDDK (K23 DK125670). G.T. was supported by the NIH/NIDDK (K23 DK106428). Ja.G. was supported by NIH/NIDDK (K08 DK110536). M.D. was supported by the NIH/NIDDK (K23 DK093556). The NIH and NIDDK had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The views expressed in this article are those of the authors and do not necessarily represent the official view of the NIDDK nor NIH. G.T. serves on the scientific advisory boards for Allena Pharmaceuticals, Novome Biotechnology, and Dicerna Pharmaceuticals and serves as a consultant for Alnylam Pharmaceuticals, all of which are unrelated to this work. M.D. receives research funding from Mallinckrodt unrelated to this work. The other authors declare no conflicts of interest. Portions of this study were presented at the Pediatric Academic Society annual meeting, May 5-8, 2020, Toronto, Canada.</p>

<p><strong>OBJECTIVE: </strong>To assess the prevalence of therapy-related kidney outcomes in survivors of Wilms tumor (WT).</p>

<p><strong>STUDY DESIGN: </strong>This prospective cohort study included survivors of WT who were ≥5 years old and ≥1 year from completing therapy, excluding those with pre-existing hypertension, prior dialysis or kidney transplant. Participants completed 24-hour ambulatory blood pressure monitoring (ABPM). Abnormal blood pressure (BP) was defined as ≥90 percentile. Masked hypertension was defined as having normal office BP and abnormal ABPM findings. Urine was analyzed for KIM-1, IL-18, EGF, albumin, and creatinine. Estimated glomerular filtration rate (eGFR) was calculated using the bedside CKiD equation. Recent kidney ultrasounds and echocardiograms were reviewed for contralateral kidney size and left ventricular hypertrophy (LVH), respectively. Clinical follow-up data was collected for approximately 2 years following study enrollment.</p>

<p><strong>RESULTS: </strong>Thirty-two participants (median age 13.6 [IQR: 10.5-16.3] years; 75% ≥Stage 3 WT) were evaluated at a median of 8.7 years (IQR: 6.5-10.8) post-therapy; 29 participants underwent unilateral radical nephrectomy, two bilateral partial nephrectomy, and one radical and contralateral partial nephrectomy. 72% received kidney radiotherapy and 75% received doxorubicin. Recent median eGFR was 95.6 ml/min/1.73m (IQR: 84.6-114.0; 11 (34%) had an eGFR &lt;90). Abnormal ABPM results were found in 22/29 participants (76%), masked hypertension in 10/29 (34%), and microalbuminuria in 2/32 (6%). 22/32 (69%) participants had abnormal EGF; few had abnormal KIM-1 or IL-18. Seven participants with previous unilateral nephrectomy lacked compensatory contralateral kidney hypertrophy. None had LVH.</p>

<p><strong>CONCLUSION: </strong>In survivors of WT, adverse kidney outcomes were common and should be closely monitored.</p>

DOI

10.1016/j.jpeds.2020.12.005

Alternate Title

J Pediatr

PMID

33290810

Title

Case report: Ampicillin-induced stone formation causing bilateral ureteral obstruction during pelvic surgery.

Year of Publication

2019

Number of Pages

100851

Date Published

2019 May

ISSN Number

2214-4420

Abstract

<p>Numerous medications can predispose patients to stone formation. Some induce metabolic changes that alter urine chemistries, such as topiramate, which can cause a mixed renal tubular acidosis. Others or their breakdown products form stones composed of the drugs themselves, like those that are renally excreted and become supersaturated in the urine in a favorable environment. Like all stones, they can cause obstruction and infection.</p>

<p>Here we present a case of ampicillin stone formation in an 11-year-old girl during a pelvic reconstructive procedure, which required ureteral stenting to prevent obstruction from an institutional guideline's perioperative antimicrobial dosing. While there are many reports of amoxicillin and ampicillin crystalluria, there is only one account in the literature of an adult with resultant ureteral obstruction requiring intervention. Our case is the first report, to our knowledge, in a child, and highlights the potential for significant crystal formation and if unrecognized, complete urinary obstruction. Since ampicillin is a commonly administered perioperatively, awareness of ampicillin stone formation during surgery is important.</p>

DOI

10.1016/j.eucr.2019.100851

Alternate Title

Urol Case Rep

PMID

31211062

Title

The natural history of semen parameters in untreated asymptomatic adolescent varicocele patients: A retrospective cohort study.

Year of Publication

2016

Date Published

2016 Oct 24

ISSN Number

1873-4898

Abstract

<p><strong>INTRODUCTION: </strong>Adolescent males with varicoceles present a dilemma for surveillance and treatment. Testicular volumetrics have not been shown to predict SA outcomes. Serial SAs are thus recommended in asymptomatic adolescent males with varicoceles and normal testicular development, but the natural history of semen parameters is unknown.</p>

<p><strong>OBJECTIVE: </strong>To explore the natural history of semen parameters in adolescent boys with a left varicocele under active surveillance.</p>

<p><strong>STUDY DESIGN: </strong>Adolescents with an asymptomatic unilateral left varicocele, Tanner V development, normal testicular volumes, and an initial SA were retrospectively reviewed in a single-institution prospectively followed cohort. Total motile count (TMC) was calculated. A cutoff of TMC Z 20 million was used to dichotomize SA results into "normal" or "poor." Those with poor SA were offered repeat SA. Cumulative probabilities of normal TMC over successive rounds of SA were calculated. Bivariate models were used to explore associations of a second consecutive poor TMC with age and varicocele grade.</p>

<p><strong>RESULTS: </strong>A total of 216 patients provided an initial SA between 1992 and 2015. We excluded 17 for a history of cryptorchidism or incomplete SA data for a final cohort of 199 patients with median follow-up of 3.3 years (interquartile range 1.5-5.6 years). The mean age at initial SA was 17.9 years (range 14.8-21.8 years). One hundred and nine out of 199 had an initial normal TMC. Of the 90 out of 199 with an initially poor TMC, 51 had repeat SA and 24 of the 51 patients improved to normal TMC. Of the 27 patients with two consecutive poor TMCs, 15 had a third SA and five out of 15 improved to normal TMC. Thus, cumulatively, 55%, 67%, and 69% of all patients had a normal TMC after an initial, second, and third SA, respectively. However, fewer patients in each round of SA normalized their TMC (Figure). Neither age nor varicocele grade was associated with a second consecutive poor TMC.</p>

<p><strong>DISCUSSION: </strong>Two-thirds of Tanner V boys with an uncorrected varicocele and normal testicular volumes achieve a normal TMC regardless of varicocele grade or age. Despite Tanner V development, 47% with an initial "poor" SA will improve to normal status without surgery. However, a small subgroup of patients will have persistently poor TMC and thus should be targeted in future research for timely intervention.</p>

<p><strong>CONCLUSION: </strong>Semen parameters improve over time. SA should be followed and repeated at least once in symptomatic Tanner V boys with varicoceles.</p>

DOI

10.1016/j.jpurol.2016.09.008

Alternate Title

J Pediatr Urol

PMID

27815047

Title

Does varicocelectomy improve semen analysis outcomes in adolescents without testicular asymmetry?

Year of Publication

2016

Date Published

2016 Oct 26

ISSN Number

1873-4898

Abstract

<p><strong>PURPOSE: </strong>The main indications for adolescent varicocelectomy are testicular hypotrophy or pain. However, we have previously shown that both serial total testicular volume and volume differential are weakly associated with semen quality. The ultimate patient goal is paternity, but semen analysis is critical to appropriate management of varicocele. We hypothesize that varicocelectomy improves total motile count (TMC) among patients who only have abnormal semen analysis (SA) parameters, but not among those with potential hormonal dysfunction such as Klinefelter syndrome or cryptorchidism.</p>

<p><strong>METHODS: </strong>We retrospectively reviewed our registry of adolescent males followed with a clinical left varicocele. For this study, subjects without sustained testicular asymmetry, who were Tanner V, and gave at least one preoperative SA were included. Subjects were excluded if they had embolization for their varicocele or no postoperative SA. Primary outcome was change in TMC before and after surgery, compared using the Wilcoxon signed rank test after stratifying by surgical indication. Secondary outcomes included rates of improved TMC and normalized TMC (&gt;20 million) after surgery, compared across covariates using the Fisher exact test.</p>

<p><strong>RESULTS: </strong>Seventeen patients met the eligibility criteria, 11 of whom underwent repair for only abnormal preoperative TMC. Overall, median age (interquartile range [IQR]) at first preoperative SA was 17.6 (15.9-17.9) years. The median preoperative TMC across all SA was 2.8 (0.7-7.4) million. The median age at surgery was 18.2 (16.8-18.9) years. Postoperatively, the median TMC across all SA increased to 18.2 (3.6-18.2) million (Wilcoxon signed rank test, p&nbsp;&lt;&nbsp;0.01; see Figure). The improvement in TMC occurred primarily in the group who only had abnormal preoperative TMC (82% improved, 55% normalized); lack of improvement was seen in patients who had a history of Klinefelter or orchiopexy for cryptorchidism.</p>

<p><strong>CONCLUSIONS: </strong>Adolescent varicocele patients should undergo SA after development of Tanner V. Varicocelectomy has a high success rate for improving TMC in adolescent or young adult males who only have abnormal TMC and no history of cryptorchidism.</p>

DOI

10.1016/j.jpurol.2016.09.010

Alternate Title

J Pediatr Urol

PMID

27818033

Title

Evaluation and treatment of cryptorchidism: AUA guideline.

Year of Publication

2014

Number of Pages

337-45

Date Published

2014 Aug

ISSN Number

1527-3792

Abstract

<p><strong>PURPOSE: </strong>Cryptorchidism is one of the most common pediatric disorders of the male endocrine glands and the most common genital disorder identified at birth. This guideline is intended to provide physicians and non-physician providers (primary care and specialists) with a consensus of principles and treatment plans for the management of cryptorchidism (typically isolated non-syndromic).</p>

<p><strong>MATERIALS AND METHODS: </strong>A systematic review and meta-analysis of the published literature was conducted using controlled vocabulary supplemented with key words relating to the relevant concepts of cryptorchidism. The search strategy was developed and executed by reference librarians and methodologists to create an evidence report limited to English-language, published peer-reviewed literature. This review yielded 704 articles published from 1980 through 2013 that were used to form a majority of the guideline statements. Clinical Principles and Expert Opinions were used for guideline statements lacking sufficient evidence-based data.</p>

<p><strong>RESULTS: </strong>Guideline statements were created to inform clinicians on the proper methods of history-taking, physical exam, and evaluation of the boy with cryptorchidism, as well as the various hormonal and surgical treatment options.</p>

<p><strong>CONCLUSIONS: </strong>Imaging for cryptorchidism is not recommended prior to referral, which should occur by 6 months of age. Orchidopexy (orchiopexy is the preferred term) is the most successful therapy to relocate the testis into the scrotum, while hormonal therapy is not recommended. Successful scrotal repositioning of the testis may reduce but does not prevent the potential long-term issues of infertility and testis cancer. Appropriate counseling and follow-up of the patient is&nbsp;essential.</p>

DOI

10.1016/j.juro.2014.05.005

Alternate Title

J. Urol.

PMID

24857650

Title

Histology of Testicular Biopsies Obtained for Experimental Fertility Preservation Protocol in Boys with Cancer.

Year of Publication

2015

Number of Pages

1420-4

Date Published

2015 Nov

ISSN Number

1527-3792

Abstract

<p><strong>PURPOSE: </strong>Cryopreservation of testicular tissue with subsequent reimplantation after therapy has the potential to preserve fertility for prepubertal boys with cancer. We present the histology and feasibility of testicular tissue procurement for this novel approach.</p>

<p><strong>MATERIALS AND METHODS: </strong>We performed a prospective cohort study of boys at significant risk for treatment associated gonadotoxicity who were eligible for an experimental research protocol between 2008 and 2011. Open testicular biopsy was performed while the patients were anesthetized for another treatment related procedure. Half of the specimen was reserved for cryopreservation, while the other half was used for research purposes. Semithin sections of the biopsy specimens were evaluated for histological features and compared to age adjusted reference values.</p>

<p><strong>RESULTS: </strong>A total of 34 boys underwent biopsy between March 2008 and October 2011. Of the patients 29 had solid tumors and 5 underwent hematopoietic stem cell transplantation for benign disease. A total of 27 patients had adequate tissue for histological analysis. Median patient age was 8.7 years (IQR 2.2 to 11.5). All children had either normal (81.5% of patients) or increased (18.5%) numbers of germ cells per tubule for their age. However, 5 of 26 patients (19%) older than 6&nbsp;months had no evidence of adult dark spermatogonia and 9 of 16 (56%) older than 6 years had no evidence of primary spermatocytes on biopsy, which would be expected based on age norms. These findings are suggestive of abnormal germ cell maturation.</p>

<p><strong>CONCLUSIONS: </strong>The preliminary histological findings of abnormal spermatogenesis maturation in the testes of prepubertal boys with cancer warrants further investigation.</p>

DOI

10.1016/j.juro.2015.04.117

Alternate Title

J. Urol.

PMID

26032139

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