Liver metastasis at diagnosis in children with nephroblastoma enrolled in SIOP2001 protocol: A French multicentric study.

BACKGROUND: Liver metastases are rare in children with Wilms tumor (WT), and their impact on the outcome is unclear. PATIENTS AND METHODS: The French cohort of patients with WT presenting liver metastases at diagnosis and enrolled in the International Society of Pediatric Oncology (SIOP) 2001 study was reviewed. RESULTS: From 2002 to 2012, 906 French patients were enrolled in the SIOP2001 trial. Among them, 131 (14%) presented with stage IV WT and 18 (1.9%) had liver metastases at diagnosis. Isolated liver metastases were displayed in four of them. After preoperative chemotherapy, persistent liver disease was reported in 14/18 patients, and 13 of them underwent metastasectomy after nephrectomy. In resected liver lesions, the same histology of the primary tumor was reported for three patients, blastemal cells without anaplasia were identified in one patient with DA-WT, and post-chemotherapy necrosis/fibrosis was identified for the other 10 patients. For the four patients who had liver and lung surgery, both sites had nonviable cells with post-chemotherapy necrosis/fibrosis. Six patients had hepatic radiotherapy. Sixteen patients achieved primary complete remission and were alive at the last follow-up (median follow-up: 6.4 years). The only two deceased patients presented diffuse anaplasia histology. The five-year EFS and OS were 83% (60%-94%) and 88% (66%-97%), respectively. CONCLUSION: Liver involvement does not appear to be an adverse prognostic factor in metastatic WT. The role of hepatic surgery and radiotherapy remains unclear, and should be carefully considered in case of persistent liver metastases, according to histology and radiological response to other metastatic sites.

A 16-year bicentric retrospective analysis of ovarian tissue cryopreservation in pediatric units: indications, results, and outcome.

Background: Cancer treatments of the last decades improve the survival rate of children and adolescents. However, chemo- and radiotherapy result in gonadal damage, leading to acute ovarian failure and sterility. The preservation of fertility is now an integral part of care of children requiring gonadotoxic treatments. Ovarian tissue cryopreservation (OTC) is an effective fertility preservation option that allows long-term storage of primordial follicles, subsequent transplantation, and restoration of endocrine function and fertility. The efficacy of this technique is well-demonstrated in adults but the data are scarce for pediatric patients. Currently, OTC represents the only possibility of preserving the potential fertility in prepubertal girls. Procedure: This is a retrospective study of OTC practice of two French centers from January 2004 to May 2020. A total of 72 patients from pediatric units underwent cryopreservation of ovarian tissue before gonadotoxic therapy for malignant or non-malignant diseases. The ovarian cortex was cut into fragments and the number of follicles per square millimeter was evaluated histologically. The long-term follow-up includes survival rate and hormonal and fertility status. Results: The mean age of patients at OTC was 9.3 years [0.2-17] and 29.2% were postpubertal; 51 had malignant diseases and 21 had non-malignant diseases. The most frequent diagnoses included acute leukemia, hemoglobinopathies, and neuroblastoma. Indication for OTC was stem cell transplantation for 81.9% (n = 59) of the patients. A third of each ovary was collected for 62.5% (n = 45) of the patients, a whole ovary for 33.3% (n = 24) of the patients, and a third of one ovary for 4.2% (n = 3) of the patients. An average of 17 fragments [5-35] per patient was cryoconserved. A correlation was found between the age of the patients and the number of fragments (p < 0.001). More fragments were obtained from partial bilateral harvesting than from whole ovary harvesting (p < 0.05). Histological analysis of ovarian tissue showed a median of 6.0 primordial follicles/mm2 [0.0-106.5] and no malignant cells were identified. A negative correlation was found between age and follicular density (p < 0.001). Median post-harvest follow-up was 92 months [1-188]. A total of 15 girls had died, 11 were still under treatment for their pathology, and 46 were in complete remission. Of all patients, 29 (40.2%) were subjected to a hormonal status evaluation and 26 were diagnosed with premature ovarian insufficiency (POI) (p < 0.001). One patient had undergone thawed ovarian tissue transplantation. Conclusion: OTC should be proposed to all girls with high risk of developing POI following gonadotoxic therapies in order to give them the possibility of fertility and endocrine restoration.

Management of refractory overactive bladder in children by transcutaneous posterior tibial nerve stimulation: A controlled study.

OBJECTIVE: To assess the objective efficacy of transcutaneous posterior tibial nerve stimulation in children presenting with overactive bladder resistant to well conducted treatment. MATERIAL AND METHOD: This was a randomized, double-blind, controlled study on 20 children with OAB. All patients were previously treated with anticholinergic drugs associated with detrusor rehabilitation, diet advice, bladder-voiding hygiene and constipation treatment, with poor clinical results. Patients were randomized into two groups: -Group A: treatment with PTNS (n = 11). -Group B: sham treatment (n = 9). The program lasted 12 consecutive weeks with two 30-minutes sessions a week. Each patient underwent pre-stimulation urodynamic testing to validate bladder overactivity followed by a post-stimulation testing. Pre- and post-stimulation urodynamic parameters were compared in order to objectively evaluate the treatment's efficacy. The patients noted their incontinence episodes for 7 consecutive days in a diary before the beginning of the program, in the middle and at the end of it: this led to computing an incontinence score (score ranged from 0 to 13, from good to poor). The difference between the pre-stimulation and post-stimulation score enabled to express clinical results in terms of poor (less than a 3-point decrease), medium (a 3 to 5-point decrease), good (6 to 8-point decrease), very good (final score ranged between 0 and 3). Children were questioned regarding their impression of being stimulated or not. RESULTS: In Group A, there were five very good clinical results (45%), one medium (10%) and five poor results (45%). In group B, nine very good results (66%) and three poor results (33%) were noted. Regarding urodynamic testing, volume voided during urgency (184 mL to 265 mL), maximal cystomanometry volume (215 mL to 274 mL) and volume at the onset of the first overactive detrusor contraction (ODC) (48 mL to 174 mL) were significantly increased in Group A (p = 0.002, p = 0.024 and p = 0.001) and maximal bladder pressure during ODC had decreased (61 to 46) (p = 0.042). 85% children in group A thought they were being stimulated vs. 70% in group B. CONCLUSION: Even though we noticed urodynamics improvements in group A, which objectively supports the efficacy of TCTPNS, clinical results remained the same between the two groups. In spite of the small size of our sample, this underlines the placebo effect of any type management in this pediatric population. Studying precisely the maximal useful voltage and duration of stimulation should then be relevant in order to yield maximal benefits from this easy-to-use procedure.

Hepatic proliferation and angiogenesis markers are increased after portal deprivation in rats: a study of molecular, histological and radiological changes.

BACKGROUND & AIMS: To determine the pathogenesis of liver nodules, and lesions similar to obliterative portal venopathy, observed after portosystemic shunts or portal vein thrombosis in humans. METHODS: We conducted an experimental study comparing portacaval shunt (PCS), total portal vein ligation (PVL), and sham (S) operated rats. Each group were either sacrificed at 6 weeks (early) or 6 months (late). Arterial liver perfusion was studied in vivo using CT, and histopathological changes were noted. Liver mRNA levels were quantified by RT-QPCR for markers of inflammation (Il10, Tnfa), proliferation (Il6st, Mki67, Hgf, Hnf4a), angiogenesis: (Vegfa, Vegfr 1, 2 and 3; Pgf), oxidative stress (Nos2, and 3, Hif1a), and fibrosis (Tgfb). PCS and PVL were compared to the S group. RESULTS: Periportal fibrosis and arterial proliferation was observed in late PCS and PVL groups. CT imaging demonstrated increased arterial liver perfusion in the PCS group. RT-QPCR showed increased inflammatory markers in PCS and PVL early groups. Tnfa and Il10 were increased in PCS and PVL late groups respectively. All proliferative markers increased in the PCS, and Hnf4a in the PVL early groups. Mki67 and Hnf4a were increased in the PCS late group. Nos3 was increased in the early and late PCS groups, and Hif1a was decreased in the PVL groups. Markers of angiogenesis were all increased in the early PCS group, and Vegfr3 and Pgf in the late PCS group. Only Vegfr3 was increased in the PVL groups. Tgf was increased in the PCS groups. CONCLUSIONS: Portal deprivation in rats induces a sustained increase in intrahepatic markers of inflammation, angiogenesis, proliferation, and fibrosis.