Ovarian Tissue Collection for Fertility Preservation in Children: The Need for Standardised Surgical Practice Guidance.

BACKGROUND: Chemotherapy, pelvic radiotherapy (including total body irradiation) and novel compounds used to treat children and teenagers with benign or malignant diseases can lead to impaired fertility. For prepubertal female patients at high risk of treatment-related infertility, upfront storage of ovarian tissue is increasingly being recognised as standard of care. No surgical guidelines exist to ensure best practice technique. We reviewed current UK practice to assess surgical management. METHODS: A ten-item, anonymous multiple-choice survey was distributed to the lead surgeons in all paediatric centres in England/Wales undertaking ovarian procurement for cryopreservation. RESULTS: There are currently 18 centres in England and Wales that provide ovarian procurement for cryopreservation. Responses were received from 100% of the invited paediatric surgical oncology centres in England and Wales. 39.3% of participants stated that in their centre <10 cases of ovarian harvest are performed annually. In 32.1% of centres >20 cases are undertaken per year. In 64% of centres surgery is performed by a paediatric surgeon with interest in oncology or fertility preservation. The majority of cases were performed by a Consultant or Senior Registrar (89%). Regarding the surgical technique, 82% of respondents stated they gain access to the abdominal cavity using standard 3-port laparoscopy, 7% use single-port laparoscopy. Most frequently used energy devices for ovary/ovarian tissue resection were Ligasure™ (44%) and Harmonic Scalpel™ (18.5%). 96% of respondents perform a total oophorectomy, 1 respondent stated they perform a hemi-oophorectomy. 53% stated they place the ovary into a retrieval bag only if the ovary was too big for easy removal via the camera port, 28.5% always place it in a retrieval bag. Most surgeons use the umbilical port site for retrieval (82%). CONCLUSION: This national survey shows significant heterogeneity in the surgical management of ovarian procurement for cryopreservation. To ensure best outcomes, research into the various surgical methods is necessary to provide data for a standardised best practice approach. LEVEL OF EVIDENCE: This is a level II evidence study. In itself, it is a national survey of specialists, which was undertaken in a prospective manner.

Sacrococcygeal teratoma: Long-term outcomes. A UK CCLG Surgeons Group Nationwide Study.

AIM: Sacrococcygeal teratoma (SCT) is a rare paediatric germ cell tumour (1:40,000). Long-term data regarding urinary tract and bowel function after SCT resection is limited to few studies. A UK Children's Cancer and Leukaemia Group (CCLG) Surgeons multicentre study aimed to critically analyse long-term functional outcomes in patients following resection of SCT. METHODS: Nationwide study of UK paediatric surgical oncology centres using a standardised data collection form. All index cases of newborn infants and children <16 years with SCT diagnosis during 2005-2015 were included. RESULTS: 165 SCT patients treated at 14 UK paediatric surgical oncology centres were included. Median age at presentation was 1 day [interquartile range, IQR: 0-25]; median age at surgery was 10 days [IQR: 4-150]. One hundred seventeen (70%) were female and 48 (30%) male. Antenatal diagnosis was made in 44% index cases. Total 59% of patients were Altman Stage I or II lesions. Follow-up data were available in 83% cases. Tumour recurrence occurred in 13 (7%) patients at median age 13 months [IQR: 8.75-30 months]. Fifty-nine (36%) of 165 patients had documented adverse bladder or bowel dysfunction. Twenty-two (37%) cases required urinary clean intermittent catheterisation (CIC) urology health care, with eight patients (14%) needing operative intervention to control management of bowel dysfunction. CONCLUSION: This UK CCLG study showed 36% of SCT patients develop bladder or bowel dysfunction after primary tumour resection. Functional assessment of bladder and bowel function is mandatory during after-care follow-up of all SCT patients. A multidisciplinary care pathway, with surgeon speciality groups including surgical oncology, paediatric urology and paediatric colorectal specialists, is strongly advised to facilitate 'best practice' monitoring of long-term health and improve patient quality of life (QoL) into adulthood.

Standardizing the surgical management of benign ovarian tumors in children and adolescents: A best practice Delphi consensus statement.

AIM: No widely agreed consensus protocols exist for the management of benign ovarian tumors (BOT) in children. This presents a substantial risk for suboptimal management. We aimed to generate multispecialty consensus guidance to standardize surgical management and provide a clear follow-up protocol for children with BOTs. METHODS: Prospective two-round confidential e-Delphi consensus survey distributed among multispecialty expert panel; concluded by two semistructured videoconferences. MAIN RESULTS: Consensus was generated on these core outcome sets: preoperative/intraoperative management; follow-up; adolescent gynecology referral. (1) Children with BOTs should receive the same management as other patients with potentially neoplastic lesions: Preoperative discussion at a pediatric oncology multidisciplinary meeting to risk stratify tumors, and management by health professionals with expertise in ovarian-sparing surgery and laparoscopy. (2) Ovarian-sparing surgery for BOTs should be performed wherever possible to maximize fertility preservation. (3) Ovarian masses detected during emergency laparoscopy/laparotomy should be left in situ wherever feasible and investigated appropriately (imaging/tumor markers) before resection. (4) Follow-up should be undertaken for all patients after BOT resection. Patients should be offered referral to adolescent gynecology to discuss fertility implications. CONCLUSION: This best practice Delphi consensus statement emphasizes the importance of managing children with BOTs through a well-defined oncological MDT strategy, in order to optimize risk stratification and allow fertility preservation by ovarian-sparing surgery wherever possible.

Recurrence and Metachronous Disease in Children with Benign Ovarian Tumors: A Systematic Review of the Literature.

AIM: The majority of ovarian tumors in children are benign, with good prognosis following complete resection. Little is published on the incidence of tumor recurrence and metachronous disease, and follow-up management of children with benign ovarian tumors (BOTs) remains a matter of debate. This systematic review aimed to evaluate the incidence and timing of recurrence and metachronous disease in children with BOTs in pediatric literature. METHODS: Comprehensive literature searches of the English literature (PubMed, OVID, EMBASE databases) from inception to present according to the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. Outcomes for tumor recurrence and metachronous disease were synthesized. RESULTS: Nineteen studies comprising 1,069 patients with BOTs were included in the analysis. All studies were retrospective cohort studies of children less than 18 years old. A total of 56 events of recurrence or metachronous disease were reported in these patients. The overall risk of recurrence/metachronous event occurrence was 5.2%/2.9%. Seventy-five percent of events occurred within the first 4 years following resection. CONCLUSION: Although the studies identified are few and heterogeneous, they demonstrate a significant risk of tumor recurrence and metachronous disease for children following resection of a BOT.Especially following total unilateral oophorectomy, these children are at risk of losing the contralateral ovary in case of metachronous disease.Immediate discharge from follow-up, therefore, does not appear safe. The majority of events occurred within the first 4 years following resection. Follow-up for children following resection of a BOT should, therefore, be continued for a minimum of 4 years following surgery. Larger, long-term prospective studies are required to more accurately determine the true incidence and long-term outcomes for children and adolescents with these tumors.

Congenital oesophageal stenosis in oesophageal atresia: underrecognised and often missed?

PURPOSE: Congenital oesophageal stenosis (COS) is characterised by an intrinsic oesophageal narrowing that is present, but not necessarily symptomatic at birth. Small studies report an association of COS with oesophageal atresia (OA) in up to 14% of OA cases. Although OA is usually appreciated shortly after birth, the diagnosis of a concomitant COS is frequently delayed. This risk may be increased with the current movement away from routine postoperative upper gastrointestinal (GI) contrast study following OA repair. We performed a systematic review of the literature to assess the timing of diagnosis of COS in patients with COS and OA and how this impacted on patient outcomes. METHODS: A systematic review in accordance with PRISMA guidelines was undertaken. Only patients with OA associated with COS were included. Delayed diagnosis was defined as presentation > 1 month of age. RESULTS: 14 full-text studies with a total of 131 patients were included. Diagnosis of COS was delayed in 62/131 (47%) patients. These children presented with symptoms of dysphagia and aspiration at a median age of 13.5 months (IQR 7-30 months). In total, 18/131 patients were identified at the initial operation, due to difficulty passing a tube distally into the stomach. The data on timing of contrast studies were provided in 60/131 (46%) patients. A routine postoperative contrast study was performed in 39/60 (65%) of these, of which COS was identified immediately in 28/39 (72%). A diagnosis of COS could also be made on retrospective review of the early contrast study in a further 6/39 patients, giving an overall sensitivity of 87%. CONCLUSION: The association of COS and OA may be underrecognised and diagnosis delayed if routine contrast study is not performed. Contrast studies, performed in the neonatal period are effective at detecting a concomitant COS (sensitivity > 87%). This review supports routine early contrast study after OA repair with specific consideration of the presence of COS.

Early Enteral Nutrition Following Gastrointestinal Surgery in Children: A Systematic Review of the Literature.

OBJECTIVE: To investigate the safety and effectiveness of early enteral feeding versus traditional enteral feeding after gastrointestinal (GI) anastomosis in children in the pediatric literature. SUMMARY OF BACKGROUND DATA: Prolonged postoperative fasting has been the traditional model of care following pediatric GI surgery. In contrast, early feeding has become well established in the adult population, where meta-analyses have shown early introduction of enteral feeds to be beneficial to hospital stay and patient outcomes. METHODS: Comprehensive literature searches of the English literature search (PubMed, Ovid, Embase databases) from inception to present according to the PRISMA guidelines. Included studies were assessed according to the MINORS criteria. Outcomes for time to first feed and full feeds, and discharge, and risk of major complications were synthesized. RESULTS: Ten studies comprising 451 patients were included in the analysis. All studies aimed at investigating the safety of early feeding in pediatric GI surgery, with or without a fast-track program. Only 4 studies compared the study group to a control group in which patients were fed in a traditional way (traditional feeding).Most studies defined early feeding as feeds commenced ≤24 hours postoperatively (range 2-72 hours). Mean time to first feed was significantly lower in the early feeding group, but not significantly lower for the mean time to full feeds and mean hospital stay. Bowel obstruction and anastomotic breakdown were classed as major complications. There was no significant difference in their occurrence in both groups. CONCLUSIONS: Although the studies identified are few and heterogeneous, they demonstrate that there is no clear advantage of keeping children "nil by mouth" and no clear disadvantage of providing early enteral nutrition following elective gastrointestinal surgery. Larger randomized controlled trials are required to assess the true impact on postoperative complications, health care associated costs, and to investigate patient-reported outcome measures.

Operative management of pediatric ovarian tumors and the challenge of fertility-preservation: Results from the UK CCLG Surgeons Cancer Group Nationwide Study.

BACKGROUND: Ovarian tumors in the pediatric age group are rare. A significant number of children with ovarian mass lesions present "out of hours "as surgical emergencies, and surgical management does not always involve a surgical oncologist. This multicenter study reports how the mode of clinical presentation may influence (i) operation (conventional open vs minimally invasive surgery (MIS)) and (ii) examines if young females presenting as surgical emergency(s) are more likely to undergo total oophorectomy or ovarian sparing surgery. METHODS: Retrospective multicenter study amongst UK pediatric surgical oncology centers. Females <16 years with diagnosis of ovarian tumor from 2006 to 2016 were included. Functional/neonatal ovarian cysts were excluded. RESULTS: Three hundred ten patients with ovarian tumors treated at 12 surgical oncology centers were identified. Mean age at surgery was 11 years [IQR 8-14]. Most common diagnosis were mature teratoma (57%, 177 cases), immature teratoma (10.9%, 34 cases) and cystadenoma (12%, 36 cases). Seventy percent (217) of cases were performed as open procedures. Thirty percent (94) of children underwent MIS. Tumors were significantly smaller in children who underwent MIS. Median tumor size in the laparoscopic group was 6 cm compared to 11 cm in the open group (p < 0.00001). Children who underwent MIS were significantly more likely to have ovary sparing surgery. CONCLUSION: This UK nationwide study demonstrates that ovary-sparing surgery and minimally invasive surgery are still infrequently deployed by pediatric surgeons in the UK. Patients with smaller tumors were more likely to undergo MIS, and more frequently underwent ovary-sparing surgery. In view of the implications on fertility and hormonal health caused by unilateral oophorectomy, it is time to review this current practise and agree consensus guidelines to reduce rates of unnecessary oophorectomy. LEVEL OF EVIDENCE STATEMENT: This is a level II evidence study. It is a retrospective multicentre collaborative study, which summarizes data from a national cohort of children.

Paediatric Horner's syndrome: is investigation for underlying malignancy always required?

OBJECTIVE: Horner's syndrome (HS) is characterised by a triad of ocular miosis, ptosis and anhidrosis. HS may be a subtle sign of occult pathology in otherwise asymptomatic children, neuroblastoma (NBL) being the the most common associated malignant tumour. Despite such knowledge, the incidence of underlying malignancy in children with HS remains unclear and robust evidence to guide best clinical practice is sparse. We performed a systematic review of the literature with the aim of identifying the incidence of NBL in children with HS of unknown aetiology, and establishing if screening for NBL should be routinely performed in this patient population. METHODS: Systematic review of the literature (PubMed and Ovid/Medline database, 1961-2018). RESULTS: The initial search identified 334 manuscripts, of which 8 studies were included in the final analysis. All reports were single-centre retrospective studies without control groups and included a total of 152 patients (age range 0-20 years). All studies investigated patients with HS but without previously established diagnosis. In the studies included, 17 out of a total of 152 patients were diagnosed with a space-occupying lesion. 12 out of the 152 patients were subsequently detected with NBL. CONCLUSION: HS in children may be the first sign of occult malignancy. We report the first systematic review that comprehensively investigates the incidence of malignancy in this unique patient cohort. We show that HS of unknown aetiology in children warrants further investigation(s) to exclude an underlying space-occupying lesion. This should include cross-sectional imaging of the brain, neck and thorax, plus urinary catecholamines for prompt diagnosis and treatment.

Controversies in the management of ovarian tumours in prepubertal children - A BAPS and UK CCLG Surgeons Cancer Group National Survey.

BACKGROUND: No clear treatment and follow-up protocols have been established for prepubertal patients with ovarian tumours. The lack of adequate prospective data in the literature includes all aspects of their management. A significant number of children with ovarian masses present out of hours as a surgical emergency and are initially managed by paediatric surgeons without special interest in surgical oncology. Clear guidance on the management of such tumours is therefore fundamental. We hypothesised that - owing to the lack of clear guidelines - the current approach to prepubertal ovarian tumours amongst paediatric surgeons is highly heterogenous. METHODS: An eleven-item multiple choice questionnaire was distributed amongst all BAPS consultant paediatric surgeons in the UK and simultaneously to all paediatric surgical oncology members of the UK Children's Cancer and Leukaemia Group in order to survey the management of ovarian masses in children. We aimed to compare the management approaches in both groups. RESULTS: 63 consultants participated in the survey; 49% with a special interest in surgical oncology, 48% with different subspecialty interests. The majority of participants (56%) performed 1-5 operations on ovarian tumours per year. Preoperative imaging of choice for the oncology surgeons was US and MRI (77.3%) versus 41.4% in the group of surgeons with different special interests. Surgeons with different special interests were more likely to request Ca125 as a preoperative tumour marker (62.1% vs 32.3%). 19.3% of oncology surgeons, and 27.6% of surgeons with other special interest stated they would never remove an ovarian tumour via the laparoscopic approach. Follow-up practise was highly variable amongst survey participants in both surgeon groups regarding frequency, duration and further investigations during follow-up. Almost 50% of participants follow their patients up according to personal practice protocols. CONCLUSION: This first national survey on the management of prepubertal ovarian tumours demonstrates great heterogeneity in the current approach amongst UK paediatric surgeons. Better evidence is needed to formulate clear guidance for the management of such tumours. We propose instigation of a multicentre registry for ovarian tumours to generate prospective data and clarify guidance for the future. LEVEL OF EVIDENCE STATEMENT: This is a level II evidence study. In itself it is a retrospective study, with the literature review including one large, high-quality prospective cohort study, and further prospective cohort studies of ordinary quality.

Implications of a negative abdominal CT in the management of pediatric blunt abdominal trauma.

BACKGROUND: No consensus exists on management of children with a negative trauma CT following blunt abdominal trauma (BAT). Asymptomatic children are frequently "admitted for observation" following negative CT owing to concerns about missing an intraabdominal injury (IAI) without evidence for this practice. We aimed to investigate the feasibility of discharge following a negative CT scan in children sustaining blunt abdominal trauma. METHODS: Retrospective audit at a UK paediatric major trauma center and review of the literature. RESULTS: 108 patients were included (median age 11y; 60% male). Commonest mechanisms of injury: road traffic collisions (61 patients; 56%) and falls from a height (37; 34%). 40 (37%) had a normal CT scan, of whom 6 (15%) were discharged from ED. The remaining 34 patients were admitted, of whom 14 (41%) were discharged within 24h. The other 20 children were admitted for other specialty input. None of the 108 children had a missed IAI or reattended with suspicion of IAI. The NPV for CT to detect IAI was 100% (95% CI: 96%-100%). The literature search identified 3 observational cohort studies and 2 patient groups contained in a systematic review (total of 9149 patients with normal CT abdomen after BAT). Only 9 (<0.1%) patients required operative intervention for missed IAI. The NPV for CT to detect IAI was 99.6%-99.8% (95% CI 99%-100%). CONCLUSION: Our study and literature review demonstrate that asymptomatic children with a normal abdominal CT scan in the ED are very unlikely to have IAI and that the NPV of CT is very high (96%-100%). Direct discharge from the ED is possible for asymptomatic children with a negative CT following blunt abdominal trauma, as long as no other reasons for admission exist and should be accompanied by safety-net advice. LEVEL OF EVIDENCE STATEMENT: This is a level II evidence study. In itself it is a retrospective study, with the literature review including one large, high-quality prospective cohort study, and further prospective cohort studies of ordinary quality.

Management of Familial Ovarian Teratoma: The Need for Guidance.

Ovarian teratomas in prepubertal females are uncommon, but familial ones are exceedingly rare. We report an ovarian teratoma in an 8-year-old girl, her mother, and her maternal grandmother. The risk of a metachronous tumor and subsequent complications (such as torsion) in the contralateral ovary remain unclear. There is no clear guidance on follow-up management of patient and family members in the literature. We have reviewed the literature and discuss the challenges for the pediatric surgeon arising from such cases.

Improving outcomes in pilonidal sinus disease.

BACKGROUND: Optimal surgical treatment for pilonidal sinus disease remains controversial. Studies in children are uncommon with overall high postoperative recurrence and infection rates (20%). Our unit adopted a technique for excision of the pilonidal sinus with primary midline closure using a full-thickness flap. We present our results of this technique in the pediatric age group. METHODS: Single-center retrospective review and telephone follow-up was performed, including all children undergoing pilonidal sinus excision from 2005 to 2014 using the same operative technique and preoperative/postoperative care. RESULTS: 19 children were identified. Median age was 15years, and 47% were male. All had previously infected sinuses, with 5 requiring abscess drainage. Median follow-up was 13months (3.5-67months). Histology confirmed pilonidal sinus in 18/19 cases (one developmental malformation excluded from subsequent analysis). Recurrence requiring further surgery occurred in 4/18 (22%) patients at a median of 9months (range 8-36), wound dehiscence in 8/18 (44%), and wound infection in 5/18 (28%) cases. Laser hair removal of the natal cleft was performed in 7/18 (39%) patients with no further recurrence. CONCLUSION: This is the first report of this technique in children which showed a higher incidence of complications than a comparable adult study. Our study underlines the importance of accurate long-term outcomes when introducing new techniques to evaluate operation-associated morbidity. Our preliminary results of laser hair removal are promising but need to be evaluated with a prospective study.

Atypical Henoch-Schonlein purpura? Consider polyarteritis nodosa!

We describe the case of a previously healthy 12-year-old boy admitted to a tertiary paediatric centre with the clinical diagnosis of Henoch-Schonlein purpura (HSP). Symptoms on admission included a generalised rash, colicky abdominal pain, hypertension, proteinuria and fresh rectal bleeding. Abdominal pain and distension worsened and serial ultrasounds suggested bowel ischaemia. He underwent repeat laparotomy and bowel resection, with slow improvement after the second laparotomy. The severity of systemic involvement (gastrointestinal, cardiac, renal and skin) made the initial diagnosis of HSP questionable. Immunohistochemistry of skin biopsies was negative for HSP. Histopathology of the bowel specimen revealed features of necrotising small and medium vessel vasculitis in keeping with polyarteritis nodosa.

Transparent cap colonoscopy versus standard colonoscopy: a systematic review and meta-analysis.

Due to the increasing demand for colonoscopy, devices to advance examination techniques are highly sought after. Several studies have examined the use of a transparent cap attached to the tip of the colonoscope, but the data are inconsistent. The aim of our study was to establish whether transparent cap colonoscopy is beneficial in the improvement of caecal intubation rate, time and polyp detection. We undertook a systematic review and meta-analysis in the form of a Cochrane review to evaluate these outcomes. We included fourteen randomised controlled trials that have been published to date. Transparent cap colonoscopy demonstrates a significant reduction in caecal intubation time, by an average of 48 s, when compared to standard colonoscopy. There was no significant difference in caecal intubation rate or polyp detection between the two groups. Despite a significant difference in caecal intubation time, the clinical significance of the transparent cap remains to be seen. We believe further research is needed to investigate this adjunct.

Transparent cap colonoscopy versus standard colonoscopy to improve caecal intubation.

BACKGROUND: Colonoscopy is considered the gold-standard investigation for screening and diagnosis of colorectal cancer. It is also becoming increasingly desirable for assessment, management, diagnosis and follow-up of other colorectal diseases, such as inflammatory bowel diseases and acute diverticulitis. Hence, due to the increasing demand for colonoscopy, devices to advance examination techniques are highly sought-after and the colonoscope with the transparent cap could be one of these. OBJECTIVES: To identify and review all relevant data in order to determine whether colonoscopy with a transparent cap is a more effective diagnostic tool than colonoscopy. SEARCH METHODS: We searched the MEDLINE, EMBASE and CINAHL databases, and the Cochrane Central Register of Controlled Trials for all randomised controlled trials (RCTs) comparing the use of colonoscopy with a transparent cap with standard colonoscopy. SELECTION CRITERIA: Studies were included if they were randomised controlled trials which compared the use of colonoscopy with a transparent cap with standard colonoscopy. DATA COLLECTION AND ANALYSIS: Data on study methods, participants, interventions used and outcomes measured was extracted from each study. Data was entered into the Cochrane Review Manager software (RevMan 5.0, 2008) and analysed using Cochrane MetaView. MAIN RESULTS: In the present meta-analysis, we considered 14 randomised controlled trials so far published. The findings of our work indicate that colonoscopy with transparent cap has a faster caecal intubation time when compared with standard colonoscopy. Reviewing studies individually would also seem to favour colonoscopy with transparent cap for polyp detection rate and pain during procedure but due to lack of comparable data meta-analysis was not feasible. AUTHORS' CONCLUSIONS: This review suggests that a transparent cap on the end of the colonoscope may give a marginally faster caecal intubation time compared with standard colonoscopy. It also suggests that there is a better polyp detection rate and less pain with the cap. However, the authors feel that further randomised controlled trials in this area would provide more clinically significant information on this adjunct to colonoscopy.

Sphingosine 1-phosphate-induced motility and endocytosis of dendritic cells is regulated by SWAP-70 through RhoA.

The phospholipid mediator sphingosine 1-phosphate (S1P) enhances motility and endocytosis of mature dendritic cells (DCs). We show that in vitro migration of Swap-70(-/-) bone marrow-derived DCs (BMDCs) in response to S1P and S1P-induced upregulation of endocytosis are significantly reduced. S1P-stimulated movement of Swap-70(-/-) BMDCs, specifically retraction of their trailing edge, in a collagen three-dimensional environment is impaired. These in vitro observations correlate with delayed entry into lymphatic vessels and migration to lymph nodes of skin DCs in Swap-70(-/-) mice. Expression of S1P receptors (S1P(1-3)) by wild-type and Swap-70(-/-) BMDCs is similar, but Swap-70(-/-) BMDCs fail to activate RhoA and to localize Rac1 and RhoA into areas of actin polymerization after S1P stimulus. The Rho-activating G protein Gα(i) interacts with SWAP-70, which also supports the localization of Gα(13) to membrane rafts in BMDCs. LPS-matured Swap-70(-/-) BMDCs contain significantly more active RhoA than wild-type DCs. Preinhibition of Rho activation restored migration to S1P, S1P-induced upregulation of endocytosis in mature Swap-70(-/-) BMDCs, and localization of Gα(13) to membrane rafts. These data demonstrate SWAP-70 as a novel regulator of S1P signaling necessary for DC motility and endocytosis.