Comparative study of open, laparoscopic and endoscopic treatments of intermediate grade vesicoureteral reflux in children.

BACKGROUND: Low-grade vesicoureteral-reflux (VUR) are rather treated by endoscopic injection, whereas open or laparoscopic procedures are mainly performed for high-grade VURs. Management of intermediate grades is controversial and no study focused on grade III to date. This study aims to compare the results of open, laparoscopic, and endoscopic approaches in children with grade III VUR. METHODS: A multicenter comparative retrospective study included children with grade III VUR operated for febrile urinary tract infections (UTIs) from 2007 to 2016. Children without UTI, with reflux of other grades, neurological bladder, duplex system, posterior urethral valves, and bladder exstrophy were excluded. Success was defined as no recurrence of febrile UTI and was presented as event-free survival curves. RESULTS: Out of 806 children operated of VUR, 171 met the inclusion criteria (114 females). Seventy-seven children (45%) underwent an open Cohen procedure, 35 (21%) a laparoscopic Lich-Gregoir and 59 (34%) a submucosal endoscopic injection according to the centers' preference. The mean follow-up was 64 months (24-132). Groups were not different for age, sex, and circumcision status. Compared to Cohen procedure, recurrences of febrile UTI were more frequent after laparoscopic treatment (p = 0,02, 8/35) and endoscopic treatment (p = 0.001, 16/59). Redosurgery was also more frequent after laparoscopy (n = 2) and endoscopic injection (n = 14) than after open surgery (n = 0, p < 0.001). CONCLUSION: Recurrent febrile UTIs and redosurgery are more frequent after endoscopic and laparoscopic procedures in grade III VUR than open reimplantation. Whether the lower morbidity of laparoscopic or endoscopic approaches balances the risk of recurrent febrile UTI remains to be determined for intermediate grade reflux.

Circumcision and Risk of Febrile Urinary Tract Infection in Boys with Posterior Urethral Valves: Result of the CIRCUP Randomized Trial.

BACKGROUND: Boys with posterior urethral valves (PUVs) have an increased risk of febrile urinary tract infections (fUTIs). Circumcision is believed to reduce the risk of fUTIs in boys, although there are no randomized trials demonstrating this. OBJECTIVE: To determine the effect of circumcision on the risk of fUTIs in boys with PUVs. DESIGN, SETTING, AND PARTICIPANTS: A clinical randomized trial that ran between August 2012 and July 2017 was conducted. The trial was multicentric, including 13 referral centers for pediatric urology. Male boys, aged 1-28 d, diagnosed with posterior urethral valves, confirmed by voiding cystogram, were included. The exclusion criteria included presence of a genital malformation contraindicating performing a circumcision. INTERVENTION: Participants were randomized to neonatal circumcision + antibiotic prophylaxis (CATB) or antibiotic prophylaxis alone (ATB), and followed for 2 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was a risk of presenting fUTIs in each group. An fUTI was defined as fever (>38.5 °C) with evidence of pyuria and culture-proven infection on urinalysis, obtained by urethral catheterization or suprapubic aspiration. A bivariate analysis of the primary outcome was performed using the Kaplan-Meier method. RESULTS AND LIMITATIONS: In total, 91 patients were included: 49 in group CATB and 42 in group ATB. The probability of presenting an fUTI was 20% in group ATB versus 3% in group CATB. The hazard ratio of presenting an fUTI within 2 yr in the ATB group compared with that in the CATB group was 10.3 (95% confidence interval: 1.3-82.5). Sixty-four children (70.3%) had a complete follow-up at 2 yr of age. CONCLUSIONS: Circumcision significantly decreases the risk of presenting an fUTI in boys with PUVs. PATIENT SUMMARY: In this report, we compared, in a multicentric trial, the number of febrile urinary tract infections (UTIs) in boys with posterior urethral valves who had either antibiotic prophylaxis alone or antibiotic prophylaxis and circumcision. We found that those who had a circumcision had a significantly lower risk of febrile UTIs.

A chemogenomic approach to identify personalized therapy for patients with relapse or refractory acute myeloid leukemia: results of a prospective feasibility study.

Targeted next-generation sequencing (tNGS) and ex vivo drug sensitivity/resistance profiling (DSRP) have laid foundations defining the functional genomic landscape of acute myeloid leukemia (AML) and premises of personalized medicine to guide treatment options for patients with aggressive and/or chemorefractory hematological malignancies. Here, we have assessed the feasibility of a tailored treatment strategy (TTS) guided by systematic parallel ex vivo DSRP and tNGS for patients with relapsed/refractory AML (number NCT02619071). A TTS issued by an institutional personalized committee could be achieved for 47/55 included patients (85%), 5 based on tNGS only, 6 on DSRP only, while 36 could be proposed on the basis of both, yielding more options and a better rationale. The TSS was available in <21 days for 28 patients (58.3%). On average, 3 to 4 potentially active drugs were selected per patient with only five patient samples being resistant to the entire drug panel. Seventeen patients received a TTS-guided treatment, resulting in four complete remissions, one partial remission, and five decreased peripheral blast counts. Our results show that chemogenomic combining tNGS with DSRP to determine a TTS is a promising approach to propose patient-specific treatment options within 21 days.

Malignancy after Augmentation Enterocystoplasty: A Nationwide Study of Natural History, Prognosis and Oncogene Panel Analysis.

PURPOSE: We report the natural history and prognosis of tumors after augmentation enterocystoplasty, with a molecular analysis using an oncogene panel to search for potential targeted therapies. MATERIALS AND METHODS: This multicenter, nationwide, retrospective study included 16 patients. A panel of 21 clinically relevant oncogenes was tested on archival tumor specimens using next-generation sequencing. Survival rate was the main clinical outcome and sequences were compared to the reference genome for the genetic outcome. RESULTS: Augmentation enterocystoplasties were performed mainly for congenital neurogenic bladder and bladder exstrophy at a median patient age of 17 years (range 4 months to 45 years). Most of the malignancies were diagnosed because of clinical manifestations, with a median latency period of 20 years. Adenocarcinomas were mainly found after gastrocystoplasty, whereas urothelial cell carcinomas were typically found after colocystoplasty. Of the 16 patients 13 were diagnosed at an advanced stage of the disease (positive lymph nodes in 7, distant metastases in 6). The overall 1-year survival rate was 56%. Only 3 patients remained disease-free at a median followup of 70 months. Of the 9 tumors with analyzable DNA 4 were wild-type and 5 harbored missense mutations (KIT-p.Pro573Ser, PDGFRA-p.Glu587Lys, KRAS-p.Gly12Asp, ERBB4p.Arg484Lys, CTNNB1-p.Ser37Phe and p.Ser47Asn). CONCLUSIONS: Malignancy after augmentation enterocystoplasty is diagnosed late with frequent metastases and a very low 1-year survival rate. More than half the tested samples harbored missense mutations in oncogenes accessible to targeted therapies. An international collaboration to enlarge the genetic panel analysis of these tumors may offer new therapeutic hope to patients.

Management of patients presenting with generalized musculoskeletal pain and a suspicion of Lyme disease.

Lyme disease is caused by bacteria of the B. burgdorferi sensu lato complex, and can give polymorphic clinical manifestations that can affect several organs such as the skin, the central nervous system, or the joints. In recent years, patients' associations and physicians have been supporting the hypothesis that this infection would manifest as chronic generalized musculoskeletal pain symptoms, named "chronic Lyme disease". Fibromyalgia is a clinical presentation characterized by chronic generalized musculoskeletal pain with a major impact on quality of life and social and psychological functioning. We analyzed existing literature data on pain syndromes associated with Lyme disease (post-treatment Lyme disease syndrome) or tick bites (polymorphic symptoms after a tick bite). We also analyzed existing data on the diagnosis, pathophysiology, and treatment of fibromyalgia. Our review shows that post-treatment Lyme disease syndrome has characteristics very close to post-infectious fibromyalgia. On the other hand, patients presenting for Lyme disease screening because of chronic generalized musculoskeletal pain symptoms after a tick bite should also be screened for fibromyalgia to allow appropriate management. Antibiotics are not recommended here.

Biliary cirrhosis and sepsis are two risk factors of failure after surgical repair of major bile duct injury post-laparoscopic cholecystectomy.

BACKGROUND: Major bile duct injury (MBDI) remains frequent after laparoscopic cholecystectomy (LC) reaching 0.3 to 0.6 % and is associated with a significant mortality rate. The aim of this study was to retrospectively analyze the factors likely to influence the long-term results of surgical repair for MBDI occurring after LC. METHODS: Medical records of patients referred to our referral center from January 1992 to January 2010 for management of bile duct injury following LC were retrospectively analyzed, and patients with MBDI were identified. Clinicopathological factors likely to influence long-term results after surgical repair were assessed by univariate and multivariable analysis. RESULTS: During the study period, 38 patients were treated for MBDI. These 38 patients underwent Roux-en-Y hepaticojejunostomy (HJ) or HJ revision in 25 (66 %) and 13 (34 %) cases, respectively. The median follow-up period was 93 (26-204) months. A Clavien-Dindo post-operative morbidity class >3 occurred in 10 (26 %) cases and was independently associated with a surgical repair performed during a sepsis period (OR = 102.5; IC 95 % [7.12; 11,352], p < 0.007). Long-term results showed that biliary strictures occurred in 5 (13 %) cases and were associated with sepsis (p < 0.006), liver cirrhosis (p < 0.002) and post-operative complications (p < 0.012). Multivariate analysis revealed that only liver cirrhosis remained predictive of stricture (OR = 26.4, 95 % CI [2; 1,018], p < 0.026). CONCLUSION: When MBDI occurs following LC, HJ seems to be the optimal treatment but should not be performed during a sepsis period. Long-term results are significantly altered by the presence of a biliary cirrhosis at time of repair.

[Post-traumatic necrotizing fasciitis]. / Fasciite nécrosante post-traumatique.

We are reporting the case of a 39-year-old male, without notable previous history except for an important alcoholic and tobacco consumption, who suffered a bicycle accident resulting in a minor wound on the left elbow. The neglected wound evolved extremely rapidly towards a necrotizing fasciitis, which underwent further complications consisting of a heat shock and multivisceral failure that necessitated reanimation procedures. The patient benefited a triple antibiotic therapy (amoxicillin-clavulanic acid, ornidazole and levofloxacin) and an extensive surgical debridement. The progression was then slow but favourable. The patient is now in functional reeducation. This observation illustrates the rate of evolution of the lesions caused by necrotizing fasciitis and reminds on the importance of prompt therapy.

[Low dose helical CT pelvimetry: evaluation of radiation dose and image processing]. / Pelviscanner hélicoïdal en basse dose: évaluation de la dose d'irradiation et du traitement d'images.

PURPOSE: to estimate from phantom measurements the radiation dose and the accuracy of helical ct pelvimetry. MATERIALS AND METHODS: Eight helical CT acquisitions using different tube current (100, 50, 25 or 10mAs) and pitch factor (1.125 or 1.375) settings but identical collimation (2mm) and kilovoltage (120 kVp) were evaluated using a four-channel MDCT scanner and compared with conventional CT pelvimetry including a single scout and two transverse images. A plexiglas phantom combined with an ionization chamber was used to calculate the CTDIw and DLP for each acquisition. Then, an ex vivo phantom of bony pelvis was used to evaluate the accuracy of helical acquisitions for the measurement of pelvic diameters (i.e. the antero-posterior inlet, the transverse inlet and the interspinous distance). Reconstructions of helical acquisitions were performed using 2D MPR, 3D MIP and 3D SSD algorithms. RESULTS: CTDIw and DLP of conventional pelvimetry were 26 mGy and 42 mGy.cm respectively. The radiation dose of helical acquisitions decreased linearly with tube current (CTDIw: from 13 to 1.3 mGy, DLP: from 218.3 to 18.7 mGy.cm). Compared to conventional CT, the dose was nearly similar at 25 mAs and reduced at 10 mAs. Helical acquisitions provided accurate measurements of pelvic diameters with a pitch of 1.125 and a 2D MPR algorithm to evaluate the AP inlet and a 3D MIP algorithm to evaluate the transverse inlet and the interspinous distance. Variations of tube current did not influence the accuracy of pelvic diameter measurement. CONCLUSION: Our results suggest that accurate low-dose helical CT pelvimetry using 10-25 mAs and a pitch factor of 1.125 combined with 2D MPR and 3D MIP reconstructions is possible.

Differential expression of apoptosis-associated genes post-hepatectomy in cirrhotic vs. normal rats.

Liver regeneration after partial hepatectomy or liver injury is controlled by a wide variety of growth factors that are proven activators or inhibitors of hepatocyte proliferation. Liver regeneration post-hepatectomy has been proven to be decreased and delayed in cirrhotic vs. normal liver. Apoptosis seems to play an important role in cellular proliferation and in liver regeneration. Therefore, this study has analyzed the expression of apoptosis-associated genes following 2/3 hepatectomy in cirrhotic vs. normal rats. Cirrhosis was induced by a weekly intragastric administration of CCl4 for 16 weeks followed by hepatectomy and histological examination of the resected liver. Rats were sacrificed at 6 h, 12 h, 24 h, or 72 h after liver resection. The expression of proapoptotic (Bad, Bak, Bax) and antiapoptotic (Bcl-2, Bcl-XL) genes was analyzed by quantitative RT-PCR. We have observed an early increase in antiapoptotic mRNA levels and a delayed increase in proapoptotic mRNA levels in normal liver following hepatectomy. Before resection, proapoptotic mRNA levels were significantly higher in cirrhotic vs. normal liver. After hepatectomy, apoptotic mRNA levels were decreased and delayed as compared with that observed following hepatectomy in normal liver. These results indicate that apoptosis takes place in liver during CCl4-induced cirrhosis and could participate in the impaired regenerative response observed in cirrhotic liver.