Safety and feasability of ureteroscopy for pediatric stone, in children under 5 Years (SFUPA 5): A French multicentric study.

INTRODUCTION: Ureteroscopy (URS) can be proposed as first-line therapy for the management of pelvic stones from 10 to 20 mm and for lower ureteric stones in children. However, little is known about the success and the morbidity of URS in young children. Ureteroscopic treatment may present matters in young children because of the small size of the pediatric kidney and the small size of the collecting system. OBJECTIVE: To assess safety and efficacy of URS for the treatment of urinary stones in children aged of 5 years or less. STUDY DESIGN: After the institutional ethical board approval was obtained, we conducted a retrospective, analytic, multicentric study that included all URS performed between January 2016 and April 2022 in children aged of 5 years or less. In this non-comparative case series, anonymized pooled data were collected from 7 tertiary care centers of pediatric patients. Endpoints were the one-session SFR at 3 months and per and postoperatives complications. Descriptive statistics were applied to describe the cohort. RESULTS: Eighty-three patients were included. For them, 96 procedures were performed at the median age of 3.5 years (IQR: 0.8-5) and median weight of 14 Kg (6.3-23). Median stone size was 13 mm (4-45). There were 65 (67 %) renal stones treated with flexible URS, most of which were in the renal pelvis (30 %) and in the lower calix (33 %). A ureteral access sheath was used in 91 % procedures. Preoperative ureteral stent was placed in 52 (54 %) of patients. None of patients had ureteral dilatation. The single-session SFR was 67.4 % (56.3 and 89.2 % for flexible URS and semi-rigid URS respectively) and children require 1.4 procedures to achieve complete stone clearance. The overall complication rate was 18.7 %, most of them were minor (Clavien I-II). Intraoperative perirenal extravasation (Clavien IIIb) due to forniceal rupture was documented in 6.2 % of cases, related to an increased intrapelvic pressure (IPP) performed in a closed pelvicalyceal system. DISCUSSION: Pediatric urologists should be aware of forniceal rupture based on the presence of extravasation of contrast during endourological procedures especially when they have difficulties to reach lower caliceal stone in small patient. CONCLUSION: URS in patients aged of 5 years or less, is a complex minimally invasive procedure with reasonable efficacy and low morbidity. Intrarenal stones treated by RIRS in young children carries the risk of additional procedures to complete stone clearance.

Evaluating the impact of pop-off mechanisms in boys with posterior urethral valves.

Introduction: Posterior urethral valves are urethral leaflets that cause Lower Urinary Tract Obstruction (LUTO) in boys and are associated with congenital renal dysplasia and abnormal bladder function. They affect 1:4,000 to 1:25,000 births and can be responsible for End-Stage Renal Failure in childhood. There have been several studies on the effect of pop-off mechanisms in boys with posterior urethral valves, but results are contradictory. We aimed to assess and discuss the effect of pop-off mechanisms on renal function in a large cohort of patients. Patients and method: Boys with PUV with and without pop-off mechanisms (urinoma, VURD or giant bladder diverticula) were divided into three severity groups for renal function according to their nadir creatinine (low-risk NC < 35 µmol/L, intermediate-risk NC between 35 and 75 µmol/L, and high-risk NC > 75 µmol/L). We compared children with and children without pop-off mechanisms for mean renal function as well as patient distribution within each severity group. Results: We included 137 boys of which 39 had a pop-off mechanism. Patients had complete data for at least 5 years follow-up. Though there was no significant statistical difference in mean renal function between the pop-off and non-pop-off group, patient distribution within each severity group varied according to whether patients had a pop-off mechanism or not. Conclusion: Though there was no significant difference in mean renal function between boys with and without pop-off mechanisms, it is possible that these are two different patient populations and direct comparison is not possible.

Nadir creatinine predicts long-term bladder function in boys with posterior urethral valves.

INTRODUCTION: Posterior urethral valves (PUV) cause lower urinary tract obstruction leading to increased intravesical pressure during fetal urinary tract development. Though the bladder and kidneys are separate organs, with different embryological origins, they are complementary and influence each other both before and after birth. We aimed to assess the relationship between renal and bladder function in boys with PUV and whether early renal markers could predict future bladder function. PATIENTS AND METHODS: We included all boys with prenatally suspected lower urinary tract obstruction, born between 2000 and 2013, in two University Hospitals, with at least 5 years follow-up. We excluded patients who presented a Lower Urinary Tract Obstruction other than PUV, children who presented multiple birth defects and neonatal deaths and those with incomplete long-term renal or bladder function data. We included data on nadir creatinine (NC), long-term renal function and long-term bladder function (defined by Uroflow parameters). Boys with PUV were divided into three severity groups for renal function according to their NC and three severity groups for bladder function as determined by Uroflow. RESULTS: We included 73 boys. Average nadir creatinine was 43.4 ± 26.1 µmol/L. Twenty-nine boys (49.3%) presented a NC < 35 µmol/L, thirty-eight (52.1%) a NC between 35 and 75 µmol/L, and 6 (8.2%) a NC > 75 µmol/L. Thirty-eight (52.1%) presented normal bladder function, 23 (31.5%) presented moderately impaired bladder function and 12 (16.4%) presented severely impaired bladder function. 41.4% of boys with NC < 35 had abnormal bladder function vs 46.2% of those with an NC between 35 and 75 µmol/L and 83.3% of boys with NC > 75 µmol/L. Nadir creatinine both predicted both bladder function and renal status (table 1). Correlation between presence of grade 3-5 CKD and poor uroflow was also significant (p < 0.005). DISCUSSION: Nadir creatinine was significantly correlated to bladder function at 5 years of age. What this study suggests is that as nadir creatinine increases so does the risk of severe bladder dysfunction. Our results, though limited to flowmeter and renal function, could help pediatric urologist tailor bladder function monitoring, and indicate which patients could benefit from more aggressive bladder therapy. CONCLUSION: Bladder and renal function are linked in boys with posterior urethral valves. Boys with high nadir creatinine could benefit from early bladder function evaluation and management.

Testicular prostheses in children: Is earlier better?

INTRODUCTION: The absence of a testis occurs for various reasons in children, but testicular prosthesis implantation in children is uncommon. The optimal time for prosthesis placement is still unclear, and its complication rate has been poorly studied in children. OBJECTIVE: The aim of this study was to determine the risk factors of complications in cases of testicular prosthesis implantation in children. STUDY DESIGN: A monocentric, retrospective review was performed of children implanted with a testicular prosthesis between 2008 and 2014. All implantations were performed through an inguinal incision with a standardized procedure. Children were divided into two groups depending on the interval after orchiectomy: (A) early implantation (delay between surgeries <1 year); and (B) delayed surgeries (delay ≥1 year). Statistical analysis was performed with Student and Fisher tests. RESULTS: Twenty-six patients (A, 15; B, 11) had a total of 38 testicular prostheses placements. Mean follow-up was 36.2 months. First surgery was performed at the mean age of 11.8 years (range 0-17.9) (A, 14.1; B, 8.1; P = 0.01) and testicular prosthesis implantation at the mean age of 14.7 years (range 9-18) (A, 14.3; B, 14.6) with a mean delay of 36.1 months (A, 1.3; B, 80.3). Indications were mainly spermatic cord torsion (27%), bilateral anorchia (27%), and testicular atrophy after cryptorchidism surgery (19.2%). Complications (10.5%) included two cases of extrusion, one infection and one migration. Patient 1 had a history of acute lymphoblastic leukemia with testicle relapse 2 years after induction therapy. High-dose chemotherapy, total body irradiation and bilateral orchiectomies were performed, and bilateral prostheses were implanted 12 years after the end of chemotherapy. Complications happened 85 days after surgery. Patient 2 was followed-up for a proximal hypospadias. The tunica vaginalis flap, which was used during a redo urethroplasty, lead to testicular atrophy. Thirteen years after the last penile surgery, a testicular prosthesis was placed through an inguinal incision, and extrusion occurred 203 days after surgery. Bacterial cultures of the prostheses were sterile and histological review showed no sign of granuloma or graft rejection. The complication rate was significantly higher if the delay between the two surgeries exceeded 1 year (P = 0.01). Indications of orchiectomy, prior scrotal incision, and prosthesis size were not risk factors. CONCLUSIONS: Testicular prosthesis implantation was relatively safe in a pediatric cohort. The complication rate was significantly higher if the delay between the orchiectomy and the prosthetic placement exceeded 1 year. These results suggest that reducing the delay between orchiectomy and prosthesis implantation may lead to fewer complications.

Lessons learnt from two pediatric motor vehicle accidents resulting in anal canal, rectal and gluteal muscle wrenching.

Ano-rectal trauma is common in motor vehicle accidents involving children. Inadequate initial assessment of the extent of lesions may be life threatening. We describe two cases where children were struck by buses that subsequently rolled over them in the prone position, resulting in ano-rectal and gluteal muscle wrenching. The first patient was inadequately assessed. Initial management did not include a diverting stoma, leading to life-threatening necrosis and septic shock. The second benefitted from our previous experience and recovery was uneventful. The distinctive mechanism of trauma in true gluteal muscle and anal canal wrenching is discussed. Gluteal muscle, anal canal and rectal wrenching as a result of rolling force from a motor vehicle is a very serious condition requiring immediate intestinal diversion with a stoma. Immediate repair may be attempted at the same time as stoma creation if the patient is stable. Broad-spectrum antibiotics and close wound monitoring are necessary to avoid muscle necrosis and serious complications.

[Hemorrhagic ascites revealing duodenal duplication]. / Une ascite hémorragique révélant une duplication duodénale.

Duodenal duplication is a rare congenital disorder of the gastrointestinal tract. The presentation is highly variable. We report a case of duodenal duplication presenting with hemorrhagic ascites in a 3-month-old girl. The diagnosis of duodenal duplication can be made preoperatively by resonance magnetic imaging. Surgical resection of the duplication was performed. Microscopic examination of the specimen confirmed the duodenal duplication. To our knowledge, this is the 1st reported case of hemorrhagic ascites caused by duodenal duplication and demonstrated by resonance magnetic imaging.

Long-term outcome of laparoscopic Nissen, Toupet, and Thal antireflux procedures for neurologically normal children with gastroesophageal reflux disease.

BACKGROUND: Nissen fundoplication is the most popular laparoscopic operation for the management of gastroesophageal reflux disease (GERD). Partial fundoplications seem to be associated with a lower incidence of postoperative dysphagia, and thus a better quality of life for patients. The aim of this study was to compare the long-term outcome in neurologically normal children who underwent laparoscopic Nissen, Toupet, or Thal procedures in three European centers with a large experience in laparoscopic antireflux procedures. METHODS: This study retrospectively analyzed the data of 300 consecutive patients with GERD who underwent laparoscopic surgery. The first 100 cases were recorded for each team, with the first team using the Toupet, the second team using the Thal, and the third team using the Nissen procedure. The only exclusion criteria for this study was neurologic impairment. For this reason, 66 neurologically impaired children (52 Thal, 10 Nissen, 4 Toupet) were excluded from the study. This evaluation focuses on the data for the remaining 238 neurologically normal children. The patients varied in age from 5 months to 16 years (median, 58 months). The median weight was 20 kg. All the children underwent a complete preoperative workup, and all had well-documented GERD. The position of the trocars and the dissection phase were similar in all the procedures, as was the posterior approximation of the crura. The short gastric vessels were divided in only six patients (2.5%). The only difference in the surgical procedures was the type of antireflux valve created. RESULTS: The median duration of surgery was 70 min. There was no mortality and no conversion in this series. A total of 12 (5%) intraoperative complications (5 Nissen, 5 Toupet, 2 Thal) and 13 (5.4%) postoperative complications (3 Toupet, 4 Nissen, 6 Thal) were recorded. Only six (2.5%) redo procedures (2 Thal, 2 Toupet, 2 Nissen) were performed. After a minimum follow-up period of 5 years, all the children were free of symptoms except nine (3.7%), who sometimes still require medication. The incidence of complications and redo surgery for the three procedures analyzed with the Mann-Whitney U test are not statistically significant. CONCLUSIONS: For pediatric patients with GERD, laparoscopic Nissen, Toupet, and Thal antireflux procedures yielded satisfactory results, and none of the approaches led to increased dysphagia. The 5% rate for intraoperative complications seems linked to the learning curve period. The authors consider the three procedures as extremely effective for the treatment of children with GERD, and they believe that the choice of one procedure over the other depends only on the surgeon's experience. Parental satisfaction with laparoscopic treatment was very high in all the three series.

Dairy products, calcium and phosphorus intake, and the risk of prostate cancer: results of the French prospective SU.VI.MAX (Supplémentation en Vitamines et Minéraux Antioxydants) study.

Although dairy products have been found to be associated with an elevated risk of prostate cancer, studies investigating the potential effect of Ca are limited, and findings are inconsistent. The objective of the present study was to test the relationship between the risk of prostate cancer and consumption of dairy products and Ca. The analysis included 2776 men from the French SU.VI.MAX (Supplementation en Vitamines et Minéraux Antioxydants) prospective study, among whom sixty-nine developed prostate cancer during the follow-up period (median: 7.7 years). Food consumption was assessed at inclusion from repeated 24 h records and nutrient intake was calculated using a food composition table. A higher risk of prostate cancer was observed among subjects with higher dairy product (relative risk (RR; 95 % CI), 4th quartile v. 1st: 1.35 (1.02, 1.78), P = 0.04) and Ca intake (RR (95 % CI), 4th quartile v. 1st: 2.43 (1.05, 5.62), P = 0.04). Nevertheless, we identified a harmful effect of yoghurt consumption upon the risk of prostate cancer (RR (95 % CI), increment 125 g/d: 1.61 (1.07, 2.43), P = 0.02) independently of the Ca content. Our data support the hypothesis that dairy products have a harmful effect with respect to the risk of prostate cancer, largely related to Ca content. The higher risk of prostate cancer with linear increasing yoghurt consumption seems to be independent of Ca and may be related to some other component.

[Contribution of simultaneous multiple immunoassays to biology]. / Apport des immunoanalyses multiple simultanées á la biologie.

During the last years, research in the area of immunoanalysis has been oriented towards the marketing of more reliable, faster and low cost kits. In this field, simultaneous multiple immunoanalysis that offer long-time ignored original and specific advantages, has undergone tremendous improvements triggered by striking technological innovations and the advent of lanthanide chelate based markers. Simultaneous multiple immunoassays have turned from semi-quantitative methods restricted to pharmacology to quantitative methods for medical biology. We chose first to describe several commercial systems among the most representative then we stressed on the main emerging systems based on optical or electrochemical detection as well as some immunosensor devices. The array of simultaneous multiple immunoassays currently available appears attractive enough so as to take a significant area within the analytical arsenal at the biologist disposal.

The effect of age on the pharmacokinetics of valsartan.

Twelve young (mean age 23 years, range 18-28) and 12 elderly (mean age 76 years, range 65-89) volunteers were given a single oral dose of 80 mg valsartan after an overnight fast. Each group consisted of six male and six female subjects. Mean systemic exposure to valsartan was higher in the elderly when compared with the young (AUC(0-24 h), 52% increase and AUC(0-infinity), 70% increase). Variability, as shown by the coefficient of variation (CV), was larger for the elderly subjects and ANOVA of the log transformed AUC showed a significant difference between the two groups. This difference was largely brought about by five elderly subjects (one male, four females), whose AUC was about 2-fold higher than the rest of the group. For the remaining elderly subjects, plasma valsartan AUC was similar to that observed for the young volunteers. This higher systemic exposure in five of the elderly subjects is not thought to be of clinical relevance when data from the patient population are considered. Other covariates--such as body weight, comedication, creatinine clearance, valsartan kinetics (absorption rate, distribution, and elimination)--did not explain the higher AUC in this subset of the elderly group. Data from the present study were compared with population kinetic data obtained from larger clinical trials including hypertensive patients in all age groups. Using this population approach, there was no difference in the pharmacokinetics of valsartan between male and female patients. Also, a relationship between plasma clearance of valsartan and age was established. The median age of patients in the hypertensive pool was 55 years. For an average 70-year-old patient, plasma clearance of valsartan is predicted to fall by 22% compared with an average 55-year-old. For the population this difference is not sufficient to warrant initial dose adjustment based on age per se. The covariate age, does not completely explain the variability in the pharmacokinetics of valsartan within the general population. The treatment was well tolerated.

Absolute bioavailability of letrozole in healthy postmenopausal women.

Letrozole is a new non-steroidal inhibitor of the aromatase enzyme system. It is currently under development for the treatment of postmenopausal women with advanced breast cancer. Absolute bioavailability of letrozole when given orally as one 2.5 mg film-coated tablet in comparison to the same dose given intravenously as a bolus injection was studied in 12 healthy postmenopausal women. Letrozole absolute systemic bioavailability after p.o. administration was 99.9 +/- 16.3%. Elimination of letrozole was slow. Total-body clearance of letrozole from plasma after i.v. administration was low (2.21 L h-1). The calculated distribution volume at steady state (1.87 L kg-1) suggests a rather high tissue distribution. Biotransformation of letrozole is the main elimination mechanism with the glucuronide conjugate of the secondary alcohol metabolite being the predominant species found in urine. The two study treatments were tolerated equally well.

An incremental method for the study of the absorption of drugs whose kinetics are described by a two-compartment model: estimation of the microscopic rate constants.

A method is proposed for estimating the overall absorption kinetics of drugs (expressed as percent of total amount absorbed versus time) from plasma data. It is applicable to the study of drugs whose kinetics can be described by linear one- or two-compartment models. Use is made of an iterative process based on the differential equations of the model and on linear interpolation of plasma data. The method does not require that the overall absorption kinetics should be apparent first-order and/or that the model parameters should be estimated from a previous experiment. It was tested for the influence of data scatter: added noise (CV = 10%) resulted in a variability of percent absorbed versus time of the same order of magnitude. During the calculations, the microscopic rate constants are estimated and optimalized. Data scatter resulted in wide variations in the estimates of the two-compartment model parameters. However, when a sufficiently large number of plasma concentration-time curves were studied, an average model could be determined with a reasonable precision. Model kinetics calculated from the related parameter estimates were in agreement with the theory. The method permits the exploitation of the various plasma concentration-time curves which are available after the development of an orally administered drug.

Clinical pharmacology studies with acenocoumarol.

In two different studies, the relation between plasma concentrations of acenocoumarol and apparent prothrombin levels (Quick test) was investigated, using a new specific analytical method for the assay of the drug. The prothrombin level appeared independent of the plasma concentration of the drug, which is higher in old patients (over 70 years) than in younger patients (under 51 years).