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The aim of this study was to construct the sixth in a series of guidelines on the treatment of urolithiasis by the International Alliance of Urolithiasis (IAU) that by providing a clinical framework for the management of pediatric patients with urolithiasis based on the best available published literature. All recommendations were summarized following a systematic review and assessment of literature in the PubMed database from January 1952 to December 2023. Each generated recommendation was graded using a modified GRADE methodology. Recommendations are agreed upon by Panel Members following review and discussion of the evidence. Guideline recommendations were developed that addressed the following topics: etiology, risk factors, clinical presentation and symptoms, diagnosis, conservative management, surgical interventions, prevention, and follow-up. Similarities in the treatment of primary stone episodes between children and adults, incorporating conservative management and advancements in technology for less invasive stone removal, are evident. Additionally, preventive strategies aiming to reduce recurrence rates, such as ensuring sufficient fluid intake, establishing well-planned dietary adjustments, and selective use pharmacologic therapies will also result in highly successful outcomes in pediatric stone patients. Depending on the severity of metabolic disorders and also anatomical abnormalities, a careful and close follow-up program should inevitably be planned in each pediatric patient to limit the risk of future recurrence rates., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

While there is intense interest in the production of allogeneic CAR-T cells from umbilical cord units, little is known about the reactivity and persistence of CAR-T cells of umbilical origin. We report the case of a patient at our hematological center with multiple relapsing Ph+ B-ALL, notably a Blinatunomab non-responder, who underwent therapy with Brexucabtagene Autoleucel following relapse on Ponatinib post-allogeneic hematopoietic stem cell transplantation. The patient achieved a rapid CAR-T expansion and durable remission presenting in good clinical conditions 6 months post-CAR-T infusion, without manifestations of graft-versus-host disease. The case report provides insight into the reactivity and persistence of CAR-T cells of umbilical origin, confirming the potential promise of allogeneic umbilical cord-derived CAR-T cells., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Renal hypertension causes left ventricular (LV) hypertrophy leading to cardiomyopathy. Nephrectomy has been utilized to improve blood pressure and prepare for kidney transplantation in the pediatric population. We sought to investigate antihypertensive medication (AHM) requirement and LV mass in patients undergoing nephrectomy with renal hypertension., Methods: We performed a single institution retrospective review from 2009 to 2021 of children who have undergone nephrectomy for hypertension. Primary outcome was decrease in number of AHM. Secondary outcomes included change in LV mass and elimination of AHM. LV mass was measured using echocardiogram area-length and linear measurements. Non-parametric analyses were utilized to assess significance., Results: Thirty-one patients underwent nephrectomy. Median age was 12.5 years (0.8-19 years). Median of 3 AHM (range 1-5 medications) were used pre-operatively and patients had been managed for median 2.5 years. Twenty-nine had preoperative echocardiogram. Forty-eight percent of patients had LVH at nephrectomy. Median AHM after surgery was 1 (range 0-4 medications) at 30 days and 12 months, (p < 0.001). By 12 months after nephrectomy, 79.2% of patients had decreased the number of AHM. Eight (26%) patients were on no AHM 30 days after surgery, and 13 (43%) at 12 months. Systemic vascular disease and multicystic dysplastic kidney were the only factors associated with lack of improvement in AHM (p = 0.040). Fourteen patients had pre- and post-operative echocardiogram and 11 (79%) had improvement in LV mass (p = 0.016, 0.035)., Conclusions: Nephrectomy is effective in improving LV mass and reducing AHM for children with renal hypertension. Improvement is less likely in patients with systemic vascular disease and multicystic dysplastic kidneys. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Nearly 13,000 pediatric renal transplantations have been performed since 1987 with improving overall mortality and morbidity; however, graft infection remains a significant post-transplant concern. Recurrent urinary tract infections in pediatric patients with vesicoureteral reflux into their renal transplant can result in graft dysfunction, increased hospital cost, and impaired social and cognitive development due to time spent hospitalized., Objective: To evaluate the effect of revision ureteroneocystostomy on pediatric renal transplant patients with symptomatic vesicoureteral reflux in reducing hospitalizations and recurrent urinary tract infections., Methods: We retrospectively reviewed pediatric patients from 2002 through 2021 who underwent renal transplantation and required revision ureteroneocystostomy due to symptomatic vesicoureteral reflux. We analyzed the differences in days hospitalized, days hospitalized due to urinary tract infection, and treated urinary tract infections prior to and after revision ureteroneocystostomy., Results: Ten patients requiring revision ureteroneocystostomy secondary to symptomatic vesicoureteral reflux were identified. There was no difference in the observation time between transplant to revision, and revision to last follow up (2.3 years (IQR 1.3-6.5) vs 1.7 years (IQR 1-6.7), p = 0.4446). Overall, there was a significant decrease in the total number of hospitalization days (21.5 days (IQR 3-43) vs 5.5 days (IQR 0-9), p = 0.006), total number of hospitalization days related to urinary tract infection (14.5 days (IQR 3-28) vs 0 days (IQR 0-3), p = 0.008) and treated urinary tract infections (3.5 (IQR 3-6) vs 1 (IQR 0-2), p = 0.019) following revision ureteroneocystostomy. The rate of hospitalization days for urinary tract infection was also significantly decreased following revision ureteroneocystostomy (7.15 per/year (IQR 0.4-11.75) vs 0 per/year (IQR 0-0.8), p = 0.008)., Discussion: Symptomatic vesicoureteral reflux in pediatric transplant patients is difficult to manage and some patients will ultimately require surgery. There have been previous studies on the success of revision ureteroneocystostomy in treating reflux but no data on the reduction in hospitalizations associated with recurrent infections following the procedure. Limitations of this study are the small cohort size, retrospective nature, multi-surgeon study, and inherent selection bias due to evaluation of only surgical patients., Conclusion: Revision ureteroneocystostomy can limit the negative consequences of recurrent graft infections with reduction in hospitalization days and improved hospitalization rates due to urinary tract infections. The reduction in hospitalizations can greatly improve the cost of care along with quality of life for transplant patients and should be strongly considered in children with symptomatic vesicoureteral reflux who have failed conservative therapy., (Published by Elsevier Ltd.)

Background: Indwelling ureteral stents are commonly placed in urologic surgeries where optimal urinary drainage is necessary. In the pediatric population, removing a stent without retrieval string (SWOS) requires a secondary operation and additional anesthetic exposure. Although these burdens can be mitigated through the placement of a stent with retrieval string (SWS), fears of complications may prevent widespread adoption of this practice by pediatric urologists., Objective: The authors sought to assess the differential cost of removing SWS and SWOS. It was hypothesized that costs associated with removing SWS are significantly lower than those associated with removing SWOS, without increasing complications., Study Design: A retrospective chart review was performed on pediatric patients undergoing common urologic surgeries with concurrent stent placement at a single tertiary referral center. Charges and healthcare costs surrounding the removal of ureteral stents were evaluated using the institution-specific ratio of cost to charges, by estimating lost wages, and by exploring differences in poststent healthcare-related events that incur additional cost., Results: A total of 109 patients with a median age of 5 years (range: 6 months-20 years) were reviewed. A total of 29 patients had SWS, and 80 had SWOS. The theoretical cost of SWS removal in clinic was $400.48 compared with $2290.86 ± $119.30 for operative removal of SWOS, with mean difference of $1890.38 (P < 0.01). The mean stent duration of SWOS was 34.0 ± 13.2 days vs. 10.1 ± 4.9 days for SWS (P < 0.01). Subgroup analysis of the ureteral reconstruction group showed no difference in any complications (35% vs 27%, respectively), early dislodgment (7% vs 7%, respectively) or costly healthcare utilization (23% vs 20%, respectively) among patients with SWOS compared with those with SWS. In SWS group with early dislodgment, neither required a secondary procedure., Discussion: With rising healthcare expenditures, physicians must be able to provide cost-effective treatment while not compromising safety or outcomes. Unlike prior analyses of cost related to the type of the stent used, the present study specifically reviewed costs of removing SWS versus SWOS and evaluated rates of costly complications. The study findings provide a preliminary basis for advocating the more economical use of SWS when indicated. Lack of power and heterogeneity of the groups need to be addressed in future analyses with larger, matched cohorts., Conclusion: Removal of SWS is more cost-effective than that of SWOS while maintaining similar safety outcomes and should be considered in certain pediatric urology cases to decrease healthcare cost. SWS should be preferred for uncomplicated ureteroscopy, but benefits are less certain in ureteral reconstruction; further studies are needed., (Copyright © 2019 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Purpose: The vesicostomy button has been shown to be a safe and effective bladder management strategy for short- or medium-term use when CIC cannot be instituted. This study reports our use with the vesicostomy button, highlighting the pros and cons of its use and complications. We then compared the quality or life in patients with vesicostomy button to those performing clean intermittent catheterization., Materials and Methods: Retrospective chart review was conducted on children who had a vesicostomy button placed between 2011 and 2015. Placement was through existing vesicostomy, open or endoscopically. We then evaluated placement procedure and complications. A validated quality of life questionnaire was given to patients with vesicostomy button and to a matched cohort of patients performing clean intermittent catheterization., Results: Thirteen children have had a vesicostomy button placed at our institution in the 4 year period, ages 7 months to 18 years. Indications for placement included neurogenic bladder (5), non-neurogenic neurogenic bladder (3), and valve bladders (5). Five out of 7 placed via existing vesicostomy had leakage around button. None of the endoscopically placed buttons had leakage. Complications were minor including UTI (3), wound infection (1), and button malfunction/leakage (3). QOL was equal and preserved in patients living with vesicostomy buttons when compared to CIC., Conclusion: The vesicostomy button is an acceptable alternative to traditional vesicostomy and CIC. The morbidity of the button is quite low. Endoscopic insertion is the optimal technique. QOL is equivalent in patients with vesicostomy button and those who perform CIC., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Purpose: We assessed the impact of a 2-phase Plan-Do-Study-Act cycle to decrease opioid prescriptions following pediatric urological surgery., Materials and Methods: Parents of children undergoing outpatient urological procedures were given questionnaires to assess opioid dosing and pain scores using the Parents' Postoperative Pain Measure scale. Age, procedure and opioid prescription data were recorded, as well as volume of medication administered. During the first phase of data collection children received an opioid prescription for 10 doses. In the second phase opioid prescriptions were reduced by 50%. Nonparametric tests and Fisher exact test were used for analysis., Results: Of 250 eligible children 98 (39%) with a median age of 3.0 years (IQR 7.0) participated. In the 81 patients prescribed opioids a median of 2 doses (IQR 3.6) were used in the preintervention and postintervention groups (p = 0.68). Using nonparametric statistical testing, no significant differences were found between pain scores in the 5-dose group (31 patients) and the 10-dose group (24 patients; p = 0.05 for day 1, p = 0.07 for day 2, p = 0.06 for day 3). There was no association between age and percent opioid used (p = 0.83). There were no significant differences in median pain scores or median doses among procedure types., Conclusions: In outpatient pediatric surgical practice opioid prescriptions can be decreased without increasing pain scores. Physician prescribing practices may contribute more to opioid consumption than actual pain patterns.

We performed a retrospective analysis of 88 adult patients with B-ALL diagnosed in our center by a flow-cytometric assessment. Immunophenotypic expression of leukemic cells was explored by simultaneous evaluation of positivity, percentage of expressing cells and median fluorescence intensity (MFI). BCR/ABL1 fusion transcripts were assessed by RT-PCR analysis and were identified in 36 patients (40.9%). CD10 and CD34 were positive in the totality of BCR/ABL1-positive cases. Patients with gene rearrangement had a greater frequency of CD66c, CD13 and CD33 positivity compared with BCR/ABL1-negative cases. Moreover, BCR/ABL1-positive cases exhibited a greater median percentage and MFI values of CD13, CD33, CD66c, CD10, CD34 and CD25 expressions, but a lower median percentage and MFI values of CD38 and CD22 expressions than patients without gene rearrangement. Multivariate logistic regression analysis showed that CD10, CD38 and CD13 expressions were independent predictors for the presence of BCR/ABL1 rearrangement. Predictive probabilities of molecular occurrence based on these markers are proposed. © 2017 International Clinical Cytometry Society., (© 2017 International Clinical Cytometry Society.)

To describe a multicenter experience with management of ureteral obstruction after injection of Dx/HA for VUR in pediatric renal transplant patients. The records of all pediatric renal transplant patients who underwent Dx/HA injection for VUR and had subsequent obstruction were identified, and the management and outcomes were reviewed. Follow-up ranged from 1 to 10 years. There were four patients identified, all of whom had a history of rising creatinine, recurrent UTI, and increasing hydronephrosis which led to the diagnosis of high-grade VUR. Obstruction was diagnosed within 24-72 hours after injection in three patients. One patient was asymptomatic, and rising creatinine and hydronephrosis were noted 1 month after injection. One patient was managed expectantly, while three patients underwent ureteral stent placement. After the stent was removed, one patient went on to open reimplant due to delayed obstruction, the second patient with voiding dysfunction is currently managed with an indwelling ureteral stent and may require further definitive surgery, the third patient recovered, and the fourth is being observed. Our cases illustrate that despite initial successful management of the obstruction in some, delayed obstruction is possible and may necessitate open reimplant. It is imperative that these patients have close follow-up after Dx/HA., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: To describe our experience utilizing Laparoendoscopic single site (LESS) surgery in pediatric urology., Materials and Methods: Retrospective chart review was performed on LESS urologic procedures from November 2009 through March 2013. A total of 44 patients underwent 54 procedures including: nephrectomy (23), orchiopexy (14), varicocelectomy (9), orchiectomy (2), urachal cyst excision (3), and antegrade continence enema (3) (ACE)., Results: Median patient age was 6.9 years old. Estimated blood loss (EBL), ranged from less than 5cc to 47cc for a bilateral nephrectomy. Operative time varied from 56 mins for varicocelectomy to a median of 360 minutes for a bilateral nephroureterectomy. Incision length ranged between 2 and 2.5cm. In our initial experience we used a commercial port. However, as we progressed, we were able to perform the majority of our procedures via adjacent fascial punctures for instrumentation at the single incision site. One patient did require conversion to an open procedure as a result of bleeding. Three complications were noted (6.8%), with two Clavien Grade 3b complications. Two patients required additional procedures at 1-year follow-up., Conclusions: The use of LESS applies to many pediatric urologic procedures, ideally for ablative procedures or simple reconstructive efforts. The use of adjacent fascial puncture sites for instrumentation can obviate the need for a commercial port or multiple trocars.

Approximately 800 pediatric renal transplants are performed annually in the United States. VUR or obstruction may cause graft failure requiring redo ureteroneocystostomy. We examined possible risk factors and cost using the PHIS national database. We examined the PHIS for 8.5 yr to determine the association between redo ureteroneocystostomy following pediatric renal transplant to demographics, comorbidities, GU conditions, insurance status, and hospital characteristics, and looked at relative costs using descriptive and comparative statistics. A total of 2390 pediatric renal transplants were identified, of which 69 (2.3%) underwent redo ureteroneocystostomy (median 11.6 months post-transplant). Risk factors for redo ureteroneocystostomy are younger age (p = 0.048), PUVs (p < 0.001), female gender (p = 0.005), race (p = 0.014), insurance type (p < 0.027), region (p = 0.045), and transplant surgery volume (p = 0.048). Redo ureteroneocystostomy after transplant does not significantly increase the overall cost of transplant (p = 0.175). We confirmed previous findings that younger age and PUVs increase the risk of post-transplant redo ureteroneocystostomy, with a five-yr plateau. We found an association with gender, race, insurance status, and hospital characteristics. Redo ureteroneocystostomy, which increases costs, does not statistically significantly increase overall cost of individual treatment in this database, although costs may be underreported., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Studies have demonstrated that variables other than duration of symptoms can affect outcomes in children with acute testicular torsion. We examined demographic and logistical factors, including inter-hospital transfer, which may affect outcomes at a tertiary pediatric referral center., Methods: We reviewed charts of all pediatric patients with acute testicular torsion during a five-year period. Data were collected regarding age, insurance type, socioeconomic status, duration of symptoms prior to presentation, transfer status, time of day, time to surgical exploration, and testicular salvage., Results: Our study included 114 patients. Testicular salvage was possible in 55.3% of patients. Thirty-one percent of patients included in the study were transferred from another facility. Inter-hospital transfer did not affect testicular salvage rate. Time to surgery and duration of pain were higher among patients who underwent orchiectomy versus orchidopexy. Patients older than eight years of age were more likely to undergo orchidopexy than those younger than eight (61.5% vs. 30.4%, p=0.01). Ethnicity, insurance type, or time of day did not affect the testicular salvage rates. On multivariate analysis, only duration of symptoms less than six hours predicted testicular salvage (OR 22.5, p<0.001)., Conclusion: Even though inter-hospital transfer delays definitive surgical management, it may not affect testicular salvage rates. Time to presentation is the most important factor in predicting outcomes in children with acute testicular torsion.

Background: Bladder reconstruction in the pediatric population is challenging for many reasons, including perioperative complications and readmissions., Objectives: On a national scale, determine readmission rates at 30, 60 and 90 days after bladder reconstruction in a pediatric population over a 7-year period, evaluating the influence of hospital and patient-specific variables., Patients and Methods: Using the Pediatric Health Information System database, we identified patients 0-17 years of age, from 2004-2010, undergoing bladder reconstruction using ICD-9 procedure codes. Descriptive statistics characterized demographics, prevalence of surgeries, and readmission rates. Surgery prevalence over time was examined using linear regression. Readmission rates were compared using the Chi2 test. Regression was used to evaluate the influence of variables on readmission risk., Results: We identified 1,985 patients for inclusion, of which 52.7% were female. Median age was 9 years. There has been no change in the prevalence of bladder reconstruction surgeries (P = 0.327). There was no change in 30-day (P = 0.272), 60-day (P = 0.788) or 90-day readmission rates (P = 0.924). Despite surgical volume adjustment, 90-day readmission rates did not significantly vary among the majority of hospitals. Initial LOS > 7 days (P < 0.001) and complex chronic condition males (P < 0.001) were significantly associated with 90-day readmission., Conclusions: No improvement in readmission rates after pediatric bladder reconstruction was observed during the study period. Nearly all centers have a similar readmission rate despite volume adjustment.

Minimal incision laparoscopy-assisted open pyeloplasty (MILAP) incorporates elements of open pyeloplasty (OP) and single incision laparoscopy to improve technical ease and cosmetic outcomes. Six MILAP procedures were performed using a single transumbilical incision through which the ureteropelvic junction (UPJ) is mobilized with standard laparoscopic instrumentation. The UPJ is brought extracorporeally through a 1-cm flank incision, and a traditional Anderson-Hynes open pyeloplasty is performed. Compared with OP, perioperative outcomes were similar. Follow-up renal scans all showed improvement of obstruction. A 1-cm flank incision is the only obvious scar., (Copyright © 2013 Journal of Pediatric Urology Company. All rights reserved.)

Objectives: (1) Determine the number of urologic conditions diagnosed by computed tomography (CT) in children in the emergency department setting. (2) Identify which diagnoses were incidental. (3) Determine how often there was urologic follow-up by a local pediatric urologist., Patients and Methods: We reviewed the charts and radiologist interpretations of all CT scans of the abdomen and pelvis performed within 2 days of admission via our emergency department from July 2007 to June 2009. Patients were included if the diagnosis was new. If a urologic finding was noted on final read, the CT was re-examined by one of our urologists to verify the finding., Results: Among 2991 CT scans (one CT scan per patient), there were 213 (7%) new urologic findings: 124 were incidental; 144 patients (68% of patients with urologic findings) did not receive follow-up. Renal abnormalities were present in 127. The most common finding was renal cyst (69 patients). Ureteral abnormalities were present in 47. The most common ureteral finding was hydroureteronephrosis (40). Other anomalies identified included bladder (7) and scrotal (14) abnormalities, stones (13), and adrenal lesions (5)., Conclusion: Many urologic diagnoses are revealed during CT scans of the abdomen and pelvis. The majority are cysts, hydroureteronephrosis, and pyelonephritis. Many incidental findings have also been revealed in the emergency department setting., (Copyright © 2012 Journal of Pediatric Urology Company. All rights reserved.)

Objective: To determine which clinical (health status) and nonclinical (demographic) factors may affect perceptions of quality of life in children with spina bifida and their parents., Design: A prospective study by using a validated questionnaire., Setting: A multidisciplinary spina bifida clinic at a pediatric tertiary referral center., Patients: Thirty-three children with spina bifida aged 5-18 years and 41 parents of children with spina bifida aged 2-18 years completed questionnaires after informed consent was obtained., Methods: The Peds QL 4.0 Short Form 15 questionnaire was administered to children with spina bifida and their parents. Additional data were collected, including socioeconomic status, self-reported ethnicity, insurance status, ambulatory status, presence of shunted hydrocephalus, and continence. All completed questionnaires were included in the final analysis., Results: Self-reported physical and psychosocial health scores for patients in our study were lower than previously published scores from healthy children. Patients with a shunted hydrocephalus had significantly lower self-reported physical health scores compared with those without shunted hydrocephalus (61.4 versus 39.3; P = .015). Self-reported physical health score in those with shunted hydrocephalus improved with age (Spearman ρ = 0.42; P = .017). Shunted hydrocephalus remained significant on multivariate analysis. Ethnicity, insurance, socioeconomic status, ambulatory status, and urinary and fecal continence were not associated with self-reported physical or psychosocial scores. Parent-reported scores were not associated with any of the variables of interest. There was excellent correlation between parent-reported and self-reported psychosocial health scores (Spearman ρ = 0.636; P < .001) but not physical health scores (Spearman ρ = 0.023; P = .905)., Conclusions: Shunted hydrocephalus has a negative impact on the perception of quality of life, an effect that may be attenuated by age. Further study and more-specific measurement tools are needed to better understand health-related quality of life in children with spina bifida., (Copyright © 2013 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

Genitourinary rhabdomyosarcoma of the newborn is extremely rare. We present a case report of a newborn delivered with a palpable abdominal mass revealing rhabdomyosarcoma on biopsy. Prenatal care was normal. The child was treated with multimodal therapy including extensive chemotherapy, surgical excision, and radiation therapy. Surgical excision included cystoprostatectomy, ureterostomy, abdominoperineal resection and colostomy placement. He continued to progress and eventually succumbed to his disease., (Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

The current standard first line therapy for fit patients with B-CLL/SLL is based on combination of fludarabine-cyclophosphamide and rituximab. However, elderly patients or patients with comorbidities poorly tolerate purine analogue-based chemotherapy and they are often treated with Chlorambucil (Chl) only. However, complete response (CR) and overall response (OR) rates with Chl are relatively low. We now investigated whether the addition of Rituximab to Chl will improve the efficacy without impairing the tolerability in elderly and unfit patients. We included in our study 27 elderly or unfit patients that had not received prior therapy. All patients were treated with Chl (1mg/Kg per 28-day cycle for 8 cycles) plus Rituximab (375 mg/m(2) for the first course and 500 mg/m(2) for subsequent cycles until the 6(th) cycle). We obtained an OR rate of 74%. The most frequent adverse effect was grade 3-4 neutropenia, which occurred in 18.5% of the patients. Infections or grade 3-4 extra-hematological side effects were not recorded. None of the patients required reduction of dose, delay of therapy or hospitalization. Overall, these data suggest that Chl-R is an effective and well tolerated regimen in elderly/unfit patients with CLL.

End-stage renal failure management in children may require bilateral kidney removal prior to transplantation secondary to recurrent urinary tract infections, renin-dependent hypertension, vesicoureteral reflux, proteinuria, risk of malignancy (Denys-Drash), or high output renal failure. Conventional laparoscopy or open nephrectomy has been employed to date. However, we present our method of bilateral nephrectomy in four patients via the SILS Covidien © system. Patient age ranged from 18 months to 18 years. Operative time ranged from 308 to 370 minutes. Estimated blood loss was minimal, all cases were completed via the single incision and no cases were converted to open. Laparoendoscopic single-site bilateral nephrectomy is safe and feasible in children and well-suited for the pre-transplant population., (© 2011 John Wiley & Sons A/S.)

The fludarabine plus cyclophosphamide (FC) regimen was reported to be superior to chlorambucil or fludarabine alone in terms of complete response (CR), overall response (OR) and progression-free survival (PFS) in previously untreated patients with chronic lymphocytic leukaemia (CLL). In the present study, we compared the efficacy and toxicity of FC administered through oral and intravenous route in 65 untreated patients affected by advanced CLL. No statistical differences were noticed between the two routes of administration in terms of OR, PFS, time to re-treatment (TTR) and overall survival (OS) of analysed patients. We also assessed the influence on the clinical outcome of the mutation status of the immunoglobulin variable region heavy chain (IgVH) gene, of the cytogenetic abnormalities and of the expression of ZAP70 and CD38 in patients' primary samples. Among the 58 evaluable patients, 31 (53%) achieved a CR and 18 (31%) a partial response. The median PFS was 35 months, median TTR was 42 months and median OS was not reached after 45 months (range, 1-161). A significantly lower OR rate was noticed in patients with high-risk cytogenetic abnormalities (del 17p, del 11q). In this study, high-risk cytogenetic abnormalities and unmutated IgVH genes were independent predictors of TTR. These results underline the importance of biological stratifications in front-line treatment of CLL patients. We confirm that FC is an effective regimen with mild toxicities; it could be recommended for patients with low-risk biological parameters who represent, in our experience, about 30% of the total.

Xanthogranulomatous pyelonephritis is a chronic, inflammatory disease of the kidney rarely found in the pediatric population. We report the case of a 16-year-old boy with fever, microscopic hematuria, and an enlarging cystic renal mass on ultrasonography. The patient had no evidence of renal stones and no known risk factors, other than a recent tattoo performed with unsterile equipment. Because the differential diagnoses included Wilms tumor, he underwent open exploration and nephrectomy. The histopathologic findings were consistent with xanthogranulomatous pyelonephritis, and cultures grew methicillin-resistant Staphylococcus aureus. The etiology was believed to be bacterial seeding from the unsterile tattoo., (Copyright © 2010 Elsevier Inc. All rights reserved.)

We recently reported that leukemic cells from IgVH-unmutated/progressive CLL more frequently proliferate in response to CpG-ODN stimulation than their corresponding counterparts. Here we evaluated the prognostic impact of this proliferative response in 91 CLL patients. The proliferative response was highly predictive of PFS, TTT and OS in the whole series and refined prognosis in patients with M-CLL. BCR stimulation modulated the response to CpG-ODN, suggesting that the proliferative capacity of the leukemic cells is related to antigen-encounter history. These data support the hypothesis that the capacity of the leukemic cells to respond to external stimuli influences disease progression in CLL., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Background and Purpose: To present our initial experience with single-incision laparoscopy in the pediatric urologic population., Patients and Methods: Four patients underwent eight single-incision laparoscopic procedures. One patient underwent bilateral nephrectomies, a hernia repair, and an orchiectomy. The remaining three patients underwent unilateral nephrectomies. All procedures were performed in children using the Covidien SILS port system via an umbilical incision., Results: Procedures in three of four patients, representing seven of eight cases, were successfully performed via a single incision. Operative times ranged from 114 minutes to 360 minutes. There were no conversions to traditional laparoscopy. One nephrectomy was converted to an open procedure secondary to bleeding. There were no complications postoperatively, and at follow-up, all wounds were well healed., Conclusions: Single-incision laparoscopic urologic surgery is safe and feasible in the pediatric population. The umbilical (trans or peri) approach confers improved cosmesis over traditional laparoscopy, and the scar is essentially concealed.

Genetic polymorphisms affecting methylentetrahydrofolate reductase (MTHFR) activity may influence hematological and neurological dysfunction in cobalamin-deficient patients. We studied the prevalence of C677T and A1298C polymorphisms by analyzing genomic DNA in 30 cobalamin-deficient patients. No significant difference was found in 677 and 1298 genotype distribution with respect to hematological parameters, B12 and folate levels, and neurological symptoms. The two MTHFR polymorphisms were not protective against anemia or neurological dysfunction in patients with cobalamin deficiency; however, we found evidence of a significant increase in atrophic gastritis in the 677TT group (P = 0.009) but not for the 1298CC genotype. Based on observations that inadequate cobalamin intake and reduced MTHFR activity might be significant risk factors for gastric cancer, and the increased risk of gastric cancer shown in patients affected by atrophic gastritis, we speculate that concomitant atrophic gastritis and impaired MTHFR function could have a role in the development of gastric cancer.

Background and Objectives: The protein tyrosine kinase ZAP-70 has recently emerged as a major prognostic indicator in chronic lymphocytic leukemia (CLL). ZAP-70 is structurally and functionally homologous to Syk, a key mediator of B-cell receptor signaling. We therefore evaluated ZAP-70 expression in CLL B cells using Syk as an intracellular standard., Design and Methods: The relative amounts of ZAP-70 and Syk were determined in purified B cells from 92 CLL patients using a novel reverse transcriptase/polymerase chain reaction (RT-PCR) procedure that co-amplifies both transcripts with equal efficiency. The ZAP-70/Syk mRNA ratio was correlated with VH gene mutation status, median treatment-free survival and FACS analysis of ZAP-70 expression., Results: ZAP-70 was expressed in the majority of cases with unmutated VH genes (88%), but also at lower levels in a substantial fraction of cases with mutated VH genes (44%). High levels of ZAP-70, defined as ZAP-70/Syk mRNA ratios above 0.25, were observed mainly in cases with unmutated VH genes and correlated with short treatment-free survival. In contrast, no difference was observed in the median treatment-free survival between patients with low ZAP-70/Syk ratios (0.05-0.25) and patients with no or negligible ZAP-70 expression (ZAP-70/Syk<0.05). In 73 cases ZAP-70 expression was investigated by RT/PCR and FACS analysis; concordance with VH gene mutation status was 86% and 71%, respectively., Interpretation and Conclusions: ZAP-70 is frequently expressed in CLL B cells, but only high levels correlate with unmutated VH gene status and progressive disease. Expression of ZAP-70 can be accurately assessed by analysis of the ZAP-70/Syk mRNA ratio, thus providing an alternative to FACS analysis.

The clinical course of chronic lymphocytic leukemia (CLL) differs significantly between patients with mutated (M-CLL) and unmutated (U-CLL) immunoglobulin (Ig) variable heavy-chain (V(H)) genes, implying a role for B-cell receptor (BCR) signaling in the pathogenesis of this disease. We have now investigated activation of downstream BCR signaling pathways in U-CLL and M-CLL B cells using soluble anti-IgM (sol-IgM) and immobilized anti-IgM (imm-IgM) antibodies as models for antigenic stimulation. Ligation of the BCR with sol-IgM induced incomplete responses in both CLL subsets, resembling the pattern described for tolerant B cells. This response was characterized by transient phosphorylation of extracellular signal-related kinase (ERK) and Akt (protein kinase B [PKB]), lack of activation of c-JUN NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), and variable activation of phospholipase Cgamma2 (PLCgamma2) and nuclear factor-kappaB (NF-kappaB). Stimulation with imm-IgM elicited a more complete BCR signal and significantly prolonged phosphorylation of ERK and Akt, indicating persistent or repetitive BCR signaling. Moreover, this type of stimulation increased the levels of the antiapoptotic protein myeloid cell leukemia-1 (Mcl-1) and protected from chemotherapy-induced apoptosis, whereas induction of apoptosis and down-regulation of Mcl-1 was observed following stimulation with sol-IgM. These data demonstrate that only sustained BCR signaling can promote survival of CLL B cells and indicate that the main difference between CLL with mutated and unmutated V(H) genes may reside in the availability of such stimulation.

Objective: Three protease-activated receptor (PAR1, 3, and 4) isoforms have been shown to be responsible for the cellular effects of thrombin; another PAR isoform (PAR2) is responsible for the cellular effects of trypsin. The present studies sought to test the hypothesis that one (or more) of these PAR isoforms is expressed in myometrial tissue, thereby accounting for the uterotonic effects of these novel agonists., Methods: The rat PAR3 and 4 isoforms were cloned from a rat spleen cDNA library. PAR isoform mRNA expression was determined by using reverse-transcriptase polymerase chain reactions (PCR) in Sprague-Dawley rats. Confirmation of the identity of the amplified mRNA was done by sequence analysis. Relative quantification of the PAR1 and PAR2 isoforms was performed using a real-time quantitative reverse transcriptase PCR (RT-PCR) technique. PAR protein expression was confirmed by Western blots using polyclonal antibodies., Results: The rat PAR3 and 4 homologues showed significant sequence homology to the mouse and human amino acid and nucleotide sequences. The RT-PCR studies confirmed PAR1-4 expression in myometrium from rats in estrus. PAR3 was expressed in uterus, spleen, kidney, liver, lung, brain, and heart. PAR4 was expressed in uterus, spleen, and lung. Messenger RNA for the PAR1 and 2 isoforms was expressed during the second half of gestation in myometrium from timed-pregnant rats. In contrast, mRNA for the PAR3 and 4 isoforms was not detected in gestational myometrium. PAR protein expression appeared to match tissue mRNA expression patterns., Conclusion: These RT-PCR studies confirmed ubiquitous expression of the PAR1 and PAR2 isoforms in myometrium and other rat tissues; in contrast, the PAR3 and PAR4 isoforms are expressed in a tissue-specific and gestationally related pattern.