Ovarian tissue cryopreservation for fertility preservation in 418 girls and adolescents up to 15 years of age facing highly gonadotoxic treatment. Twenty years of experience at a single center.

INTRODUCTION: The preservation of fertility is an integral part of care of children requiring gonadotoxic treatments for cancer or non-malignant diseases. In France, the cryopreservation of ovarian tissue has been considered and has been offered as a clinical treatment since its inception. The aim of this study is to review 20 years of activity in fertility preservation by ovarian tissue cryopreservation (OTC) for children and the feasibility of oocyte isolation and cryopreservation from the ovarian tissue at a single center. MATERIAL AND METHODS: Retrospective study including patients aged 15 years or younger who underwent OTC, combined for some with oocyte cryopreservation of isolated oocytes, before a highly gonadotoxic treatment for malignant or non-malignant disease was initiated. We describe the evolution of activities in our program for fertility preservation and patient characteristics at the time of OTC and follow up. RESULTS: From April 1998 to December 2018, 418 girls and adolescents younger than 15 years of age underwent OTC, representing 40.5% of all females who have had ovarian tissue cryopreserved at our center. In all, 313 patients had malignant diseases and 105 had benign conditions. Between November 2009 and July 2013, oocytes were isolated and also cryopreserved in 50 cases. The mean age of patients was 6.9 years (range 0.3-15). The most frequent diagnoses in this cohort included neuroblastoma, acute leukemia and hemoglobinopathies; neuroblastoma being the most common diagnosis in very young patients. During follow up, three patients requested the use of their cryopreserved ovarian tissue. All had undergone ovarian tissue transplantation, one for puberty induction and the two others for restoring fertility. So far, no pregnancies have been achieved. Eighty-four patients who had OTC died. CONCLUSIONS: Ovarian tissue cryopreservation is the only available technique for preserving fertility of girls. To our knowledge this is the largest series of girls and adolescents younger than 15 years so far reported on procedures of OTC before highly gonadotoxic treatment in a single center.

First liver transplantation for biliary atresia in children: The hidden effects of non-centralization.

The aim of our study was to determine the impact of initial orientation for medical and surgical care of children with BA on procedures and outcomes of the first LT. We retrospectively analyzed charts of children with BA who underwent first LT between 2006 and 2015. Patients were divided into two groups for comparison: a single-center management group (from diagnosis to transplantation) and a secondarily referred group (children referred after failure of KP). We focused analysis on disease severity at transplantation, blood transfusion, and overall survival. One hundred and eighty-five children were included. The median delay between pretransplant check-up and transplantation was shorter in patients secondarily referred. A severe undernutrition was observed in 23.7% of children secondarily referred compared to 11.1% in children with a single-center management (P = .024). At transplantation, INR and factor V level were higher in single-center group patients (respectively, 67% vs 55%, P < .001 and 61% vs 49%, P = .002). The total of red blood cell and fresh frozen plasma administrated during procedure was two times higher in patients secondarily referred. Finally, patients with a single-center management had a higher overall 12 months of survival rate (92.1% vs 83.1%, P = .033). In a country without low-density population issues, the authors advocate an early referring to transplant center to further improving LT outcomes in children with BA.

Testicular transposition in children undergoing brachytherapy for bladder and/or prostate rhabdomyosarcoma.

BACKGROUND/PURPOSE: Fertility preservation is a major goal in treatment of children with cancer. We describe a new technique of testicular transposition (TT) in patients treated with pulse-dose-rate (PDR) brachytherapy as part of the multimodal conservative treatment of bladder neck and/or prostate rhabdomyosarcoma (BP RMS). METHODS: Medical records of consecutive patients treated between September 2016 and August 2017 were studied. These patients underwent a TT performed during BP RMS surgery by the same suprapubic incision. The external oblique aponeurosis was not incised. The spermatic cord was mobilized up to the external inguinal ring, and the gubernaculum attachments were severed from the scrotum. The testis was then flipped over with care taken to avoid injury of the vessels or the vas, wrapped in a silicone material and sutured under the abdominal skin with a transfixing stitch facing the anterior superior iliac spine. At the end of brachytherapy, the testis was relocated in the scrotum and during the same general anesthesia, plastic tubes and stents were removed. Surgical outcome and dosimetric parameters were examined. RESULTS: Eight patients were identified. Median age was 24 months (range 11-80 months). All had embryonal BP RMS and received chemotherapy according to RMS 2005 protocol prior to local treatment. All patients underwent conservative surgery followed by brachytherapy (60 Gy) and had testicular transposition of one testis. None had surgical complications. After converting doses to biologically equivalent doses in 2-Gy fractions (EQD2), the dose delivered to 75% of the transposed testis was 1.5 GyEQD2 (1-3 GyEQD2), versus 5.4 GyEQD2 (3.9-9.4 Gy EQD2) for the untransposed testis (p < 0.001). CONCLUSION: Testicular transposition is feasible in order to potentially preserve fertility and future quality of life in children undergoing brachytherapy for BP RMS. TYPE OF STUDY: Level IV Treatment Study: Case Study with no Comparison Group.

Current perspectives in robot-assisted surgery.

From classical surgery to robot-assisted surgery (RAS), there has been a long way allowed by the improvements achieved in minimally invasive surgery (MIS). The last three decades have witnessed a prodigious development of MIS, and especially in the field of laparoscopic pediatric surgery but there are several limitations in the use of conventional laparoscopic surgery and RAS was developed to relieve these drawbacks. This new technology enables today the performance of a wide variety of procedures in children with a minimally invasive approach. As for all new technologies, an objective evaluation is essential with the need to respond to several questions: is the technology feasible?, is the technology safe?, is the technology efficient?, does it bring about benefits compared with current technology?, what are the procedures derived from most benefits of robotic assistance?, how to assume the transition from open surgery to minimally invasive access for RAS? In the first part of this article, some details are provided about technical concerns. Then, the implementation process with its organization, pitfalls, successes, and issues from human resources and financial standpoints is described. The learning curve is also analyzed, and a special focus on small children weighing less than 15 kg is developed. Finally, the concept of evaluation of this emerging technology is evocated and financial concerns are developed.

Rhabdoid tumor of the liver: Report of 6 pediatric cases treated at a single institute.

BACKGROUND: Rhabdoid tumors (RTs) of the liver are rare, aggressive and nonsecreting malignancies occurring mainly during the first year of life. Definition of RT relies on characteristic morphology and on the inactivation of the SMARCB1 tumor suppressor gene. The aim of this study was to analyze clinical data, treatments and outcomes in our patients. PATIENTS AND METHODS: 6 cases of patients treated in our institution for RT of the liver between January 2007 and January 2015 are reported. Variables examined included age at diagnosis, tumor stage, treatment and long-term survival. RESULTS: Median age at diagnosis was 5months (range: 4-23). Normal for age serum AFP levels was observed in all patients. No patient presented with metastasis at diagnosis. The diagnosis of RT based on the loss of SMARCB1 was made early in 4 patients. The 2 others were initially diagnosed as nonsecreting hepatoblastomas. Median follow-up was 6years (range: 2-9). All patients received chemotherapy, with variable regimens depending on initial diagnosis, followed by surgical resection. Three patients (50%) died of disease. Two of them were mistaken for nonsecreting hepatoblastomas at diagnosis and had recurrence shortly after completion of treatment. The third one presented a cardiac right atrium thrombus. Three patients (50%) are long-term survivors; they received multimodal therapy including chemotherapy according to protocol EpSSG NRSTS consisting of doxorubicin and surgical removal of the tumor performed within 3months after diagnosis. One patient had adjuvant radiotherapy. CONCLUSION: According to our results, search of SMARCB1 mutation or alternatively immunohistochemical assay for SMARCB1 in nonsecreting hepatoblastomas is mandatory to exclude RT. Chemotherapy according to EpSSG NRSTS protocol together with a surgical treatment seems justified to improve long-term survival. TYPE OF STUDY: Retrospective study. LEVEL OF EVIDENCE: Level IV.

Pulsed-dose rate brachytherapy for pediatric bladder prostate rhabdomyosarcoma: Compliance and early clinical results.

OBJECTIVE: No data are available on the feasibility of pulsed dose rate (PDR) brachytherapy in very young children. Our experience of PDR brachytherapy for bladder prostate (BP) rhabdomyosarcoma (RMS) is reported, with focus on compliance and dosimetric parameters. MATERIALS AND METHODS: Treatment parameters and outcome of consecutive BP RMS patients treated in our center were examined. Treatment was carried out as part of a multimodal conservative radio-surgical treatment. Four single leader plastic tubes were implanted under perioperative guidance, encompassing the prostate/bladder neck. Tubes were systematically sutured to the bladder wall. Treatment planning was based on a computed tomography and followed Paris system rules. Continuous hourly pulses of 0.42Gy were delivered, to a total dose of 60Gy. RESULTS: 32 patients were treated, median age 2.6years (10months-12years). Median duration of each pulse was 8.5min (3.8-17.4min). The minimal dose in the most irradiated 1cm3 of rectum was 44.7Gyα/ß=3 (range: 4.1-77.3Gyα/ß=3). Brachytherapy was conducted without significant compliance concern in all but two patients, 24 and 25months-old, who pulled out plastic tubes before treatment completion. Another child needed re-planning because of slight tube displacement. With median follow-up of 14.4months (15days-75months), all patients were free from any relapse after local treatment. Four grade 3 acute urinary complications were encountered. All long-term side effects were grade 2 or less. CONCLUSION: PDR brachytherapy is feasible in very young patients, and associated with acceptable acute toxicity rates. Longer follow-up is required to ensure that local control and long-term side effects profile are comparable to the results of low dose rate brachytherapy.

Brachytherapy Combined With Surgery for Conservative Treatment of Children With Bladder Neck and/or Prostate Rhabdomyosarcoma.

PURPOSE: To report the results of a conservative strategy based on partial surgery combined with brachytherapy in a prospective cohort of children with bladder-prostate rhabdomyosarcoma (BP RMS). METHODS AND MATERIALS: We prospectively documented the outcome of children treated in our department between 1991 and 2015 for BP RMS and undergoing a multimodal approach combining conservative surgery (partial cystectomy and/or partial prostatectomy) and perioperative interstitial low-dose-rate or pulse-dose-rate brachytherapy. Before brachytherapy, children had received chemotherapy with modalities depending on their risk group of treatment. RESULTS: A total of 100 patients were identified, with a median age of 28 months (range, 5.6 months-14 years). According to the Intergroup Rhabdomyosarcoma Study (IRS) group, 84 were IRS-III, and 12 were IRS-IV tumors. Four patients were treated at relapse. The median number of chemotherapy cycles before local therapy was 6 (range, 4-13). After surgery, 63 patients had a macroscopic tumor residuum. Five patients underwent a brachytherapy boost before pelvic external beam radiation therapy because of nodal involvement, and 95 had exclusive brachytherapy. Median follow-up was 64 months (range, 6 months-24.5 years). Five-year disease-free and overall survival rates were 84% (95% confidence interval 80%-88%) and 91% (95% confidence interval 87%-95%), respectively. At last follow-up most survivors presented with only mild to moderate genitourinary sequelae and a normal diurnal urinary continence. Five patients required a secondary total cystectomy: 3 for a nonfunctional bladder and 2 for relapse. CONCLUSION: Brachytherapy is effective as part of a conservative strategy for BP RMS, with a relatively low delayed toxicity as compared with previously published studies using external beam radiation therapy. Longer follow-up is required to ensure that the functional results are maintained over time.

[Specificities of carcinomas in adolescents and young adults]. / Carcinomes des adolescents et jeunes adultes : quelles spécificités ?

Carcinomas are rare tumors of the adolescent-young adult (AYA) with a different spectrum from those of adults. The most common sites outside of the thyroid is the nasopharynx, salivary gland, colon-rectum and ovaries. If nasopharyngeal carcinoma or salivary gland tumors are good prognosis, others are more reserved prognosis, such as digestive carcinomas, gynecological or midline. The revelation modes are non-specific and depend on the location: mass, tumor syndrome, pain, impaired general condition. The unusual of pediatric carcinomas led to propose a systematic oncogenetic exploration. The medical history of the family, the symptoms and the type of the carcinoma should guide the analysis. In the absence of guidance, analysis of TP53 gene and, for carcinomas of the expanded spectrum of the hereditary non-polyposis colorectal cancer (HNPCC) syndrome, the search for mutation of MMR genes (mismatch repair) seems essential. Because of the rarity of these diseases and the absence of homogeneous recommendations, members of the rare tumors committee of the SFCE recommended for the management of these AJA, an histological review by a pathologist familiar with carcinomas of the adult, a double discussion between pediatric and adult oncologists, analysis of adult standards with adaptation to pediatric data, especially in terms of risk of side effects. An advice to a national opinion (by a member of FRACTURE group) or European (group EXPERT) is sometimes necessary in the most complex situations.

Surgical Management of Neuroendocrine Tumors of the Appendix in Children and Adolescents: A Retrospective French Multicenter Study of 114 Cases.

BACKGROUND: Right hemicolectomy (RHC) in patients with neuroendocrine tumors (NET) of the appendix has been advocated for tumors more than 2 cm, or with mesoappendix/vessel invasion, or with raised mitotic activity. No study demonstrated prolonged survival with RHC over appendectomy alone. The aim of this study was to contribute to define guidelines for secondary surgery in children or adolescents with NET of the appendix. PROCEDURE: We contacted all French pediatric surgeons and oncologists by mail, and reviewed the records of patients under 18 with NET of the appendix from 1988 until 2012. RESULTS: A total of 114 patients were recorded with a female/male ratio of 1.6. Median age at presentation was 12 years (range: 5-17 years). Ten patients had a tumor more than 2 cm. Twenty patients had evidence of extension into the mesoappendix, including five with blood or lymph vessels' invasion. Solely, one patient had a tumor with a high proliferative index. Incomplete resection was observed in three cases. Eighty-five patients had no criterion for secondary surgery. Twenty-nine patients had criteria for RHC but only 10 underwent surgery. None of the resected specimens showed carcinoid tumor. Three patients had positive lymph nodes. At the last follow-up, all patients were alive and disease free. CONCLUSION: Appendectomy alone seems to be curative of these tumors with no influence on life expectancy. Follow-up is not only unnecessary, but its means, whether clinical, radiological or biological, are ineffective.

[Preservation of fertility in children with cancer]. / La préservation de la fertilité dans les cancers de l'enfant.

Preserving fertility is a requisite for any child undergoing gonadotoxic treatment for cancer. Techniques vary depending on the age, sex of the patient and nature of the treatment. Boys undergoing irradiation have testicular protection or transposition. Post-pubertal boys undergoing chemotherapy can have semen cryopreservation like adults. However, fertility preservation for pre-pubertal boys undergoing chemotherapy implies testicular tissue cryopreservation. Research concentrates on germ cell transplantation, autotransplantation of testicular tissue or in vitro spermatogonial maturation in order to later restore spermatogenesis. Ovarian transposition can be undergone in case of brachytherapy or external beam radiotherapy in girls and has published success rates of 80%. Ovarian cryopreservation has been developed since 1995 for pre-pubertal and post-pubertal girls undergoing chemotherapy. The ovary is retrieved surgically and ovarian cortical segments are frozen. Thawing and transplantation of gonadal tissue are the next steps to restoring fertility. However, immature oocytes will have to be matured either in vivo or in vitro in order to restore fertility. Fertility preservation must be offered to children with cancer even if maturation of immature germ cells is uncertain for research 20 to 30 years from now will probably enable fertility restoration.

A new surgical approach of temporary ovarian transposition for children undergoing brachytherapy: technical assessment and dose evaluation.

PURPOSE: We developed a new technique of temporary ovarian transposition (OT) for prepubertal girls undergoing brachytherapy. The aim of this study was to describe it, assess its feasibility and safety and calculate the dose delivered to the ovary in order to prove its efficacy. METHODS: Sixteen prepubertal patients underwent temporary OT for brachytherapy at our center from March 2001 to December 2012. OT was done either by laparotomy or by laparoscopy. In all patients, the ovaries were grasped with an atraumatic forceps and mobilized above the iliac crest level as high as possible without any dissection or division of the ovarian ligaments or of the fallopian tube. They were sutured to the anterior abdominal wall by a transfixing stitch of non-dissolvable suture knotted on the outside of the patient on a pledget. RESULTS: Median age at surgery was 3 years (range: 2-9 years). The integrity of the fallopian tube was respected and not a single ligament was dissected or divided. None of the patients had intraoperative or postoperative complications. The stitches were retrieved after completion of irradiation and the ovaries in all the patients fell back into the pelvis. The calculated median radiation dose to the ovary was 1.4 Gy (range: 0.4-2.4 Gy). CONCLUSIONS: This surgical technique is simple and safe, either by laparotomy or by laparoscopy. It meets the radiation and physical constraints in prepubertal girls with vaginal or bladder RMS. However, longer follow-up is required to assess the ovarian function.

Laparoscopic treatment of renal cancer in children: a multicentric study and review of oncologic and surgical complications.

OBJECTIVE: The aim was to report a multicentric study with a longer follow-up to evaluate the laparoscopic radical nephrectomy in children with renal cancer. MATERIAL AND METHODS: This was a retrospective multicentric study, from October 2005 to January 2012, of children who underwent a laparoscopic radical nephrectomy for small renal malignant tumors. RESULTS: Seventeen children were included in this study. Sixteen underwent chemotherapy before surgery according the SIOP (Société Internationale d'Oncologie Pédiatrique) protocol and one was treated by surgery only for a carcinoma. All except one could be treated by laparoscopy; the biggest tumoral size was 8 cm. The median hospital stay was 3 days (2-10). The pathologic examination showed 15 Wilms' tumors, one clear cell sarcoma and one TFE3 renal cell carcinoma. With a median follow-up of 42 months (range 12 and 77 months) after laparoscopic radical nephrectomy, 15 children had no oncological complications (port site or local recurrence, pulmonary metastasis) and one had a local recurrence without intraoperative tumoral rupture. The child with TFE3 renal cell carcinoma died 4 years after surgery from brain and lung metastases without local recurrence. No small bowel obstruction occurred. CONCLUSIONS: Radical nephrectomy in children for Wilms' tumor or other renal cancer can be safely performed laparoscopically and our indications can be summarized, for trained laparoscopic surgeons, by small tumors under about 8 cm diameter, especially without crossing the lateral edge of the vertebra on the CT scan at the time of surgery.

[Guidelines for diagnosis of acute appendicitis in childhood]. / Conduite du diagnostic d'une appendicite aiguë chez l'enfant.

Facing a child with suspected acute appendicitis it is important to remind that a child is not a smaller adult. The main risk is to over-diagnose acute appendicitis in elder children and to misdiagnose it in preschool children and infants because it is less frequent, with early complications, and/or confusing symptoms in these age groups. Careful anamnesis and examination of the whole child--not only the belly--are mandatory. Biological findings of bacterial infection and US findings suggesting acute appendicitis are helpful. In doubtful cases the best help is offered by observation of the patient, symptoms and signs worsening necessarily in case of an acute appendicitis.

How to successfully implement a robotic pediatric surgery program: lessons learned after 96 procedures.

BACKGROUND: Both our teams were the first to implement pediatric robotic surgery in France. The aim of this study was to define the key points we brought to light so other pediatric teams that want to set up a robotic surgery program will benefit. METHODS: We reviewed the medical records of all children who underwent robotic surgery between Nov 2007 and June 2011 in both departments, including patient data, installation and changes, operative time, hospital stay, intraoperative complications, and postoperative outcome. The department's internal organization, the organization within the hospital complex, and cost were evaluated. RESULTS: A total of 96 procedures were evaluated. There were 38 girls and 56 boys with average age at surgery of 7.6 years (range, 0.7-18 years) and average weight of 26 kg (range, 6-77 kg). Thirty-six patients had general surgery, 57 patients urologic surgery, and 1 thoracic surgery. Overall average operative time was 189 min (range, 70-550 min), and average hospital stay was 6.4 days (range, 2-24 days). The procedures of 3 patients were converted. Median follow-up was 18 months (range, 0.5-43 months). Robotic surgical procedure had an extra cost of 1934 compared to conventional open surgery. CONCLUSIONS: Our experience was similar to the findings described in the literature for feasibility, security, and patient outcomes; we had an overall operative success rate of 97 %. Three main actors are concerned in the implementation of a robotic pediatric surgery program: surgeons and anesthetists, nurses, and the administration. The surgeon is at the starting point with motivation for minimally invasive surgery without laparoscopic constraints. We found that it was possible to implement a long-lasting robotic surgery program with comparable quality of care.

Surgical experimental jejunoileal atresia in rat embryo.

PURPOSE: Jejunoileal atresia represents about 40% of intestinal atresia. After surgical repair, intestinal motility disorders are burdened with the postoperative outcome, and the origin of these troubles remains unclear. To specify the physiopathologic feature of jejunoileal atresia, we developed an experimental surgical model in fetal rat. METHODS: Time-dated pregnant rats were operated on at 18 days of gestational age. Hysterotomy was performed, followed by fetal wall incision. The exteriorization of the bowel loop was obtained by saline injection; the intestine was ligated and returned to the abdominal cavity before incisions were closed. Fetal intestine was excised at day 21, after cesarean delivery. RESULTS: Twenty-one pregnant rats underwent operation with 90% maternal survival rate. Among the 56 fetuses successfully operated on, 49 survived (87%). In fetuses with atresia, the mean birth weight (4.5 +/- 0.6 g) and the mean intestinal length (12.8 +/- 1.3 cm) were significantly lower compared to sham fetuses and controls. CONCLUSION: The rat model offers the advantage of a low-expense mammal model with a wide panel of probes and reagents available for the study of the gut. This model of jejunoileal atresia could be used to study the consequences of prenatal intestinal obstruction on fetal gut.