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BACKGROUND: The authors report the prospective evaluation of reduced dose alkylator chemotherapy combined with radiotherapy for European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) standard risk nonalveolar rhabdomyosarcoma (NA-RMS). PATIENTS AND METHODS: Localized node negative Intergroup Rhabdomyosarcoma Study (IRS) II/III NA-RMS at favorable sites (subgroup C), <25 years old, received five cycles of ifosfamide, vincristine, and dactinomycin (IVA) chemotherapy (30 g/m2 ifosfamide) and four cycles of vincristine and dactinomycin (if receiving radiotherapy), or nine cycles of IVA (54 g/m2 ifosfamide) ± radiotherapy. Delayed primary tumor excision was considered for IRS III tumors. The primary end points were event-free survival (EFS) and overall survival (OS). RESULTS: From October 2005 to December 2016, 359 evaluable patients were recruited: orbit, 164 (45.7%); head and neck nonparameningeal, 77 (21.4%); and genitourinary non-bladder/prostate, 118 (32.9%). EFS and OS were 77.4% (95% confidence interval [CI], 72.5-81.6) and 93.5% (95% CI, 90.1-95.8), respectively. Lower dose alkylator chemotherapy and radiotherapy achieved 5-year OS of 93.7% but the difference with higher dose alkylator chemotherapy +/- radiotherapy was not significant (p = 0.8003). Adjuvant radiotherapy improved EFS with 5-year estimates of 84.7% versus 65.2% for nonirradiated (p < .0001), but not OS (p = .9298). Omitting radiotherapy for orbital tumors reduced OS (5-year was 87.1% vs. 97.3% for irradiated, p = .0257). Following R0 resection (n = 60), radiotherapy did not significantly improve EFS or OS. CONCLUSIONS: Radiotherapy for local tumor control allows for reduction of cumulative dose of alkylators in EpSSG standard risk subgroup C RMS patients. The omission of radiotherapy did not affect OS in all patients except those with orbital RMS and was associated with inferior EFS.
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Congenital hyperinsulinism (CHI) is a condition characterised by severe and recurrent hypoglycaemia in infants and young children caused by inappropriate insulin over-secretion. CHI is of heterogeneous aetiology with a significant genetic component and is often unresponsive to standard medical therapy options. The treatment of CHI can be multifaceted and complex, requiring multidisciplinary input. It is important to manage hypoglycaemia in CHI promptly as the risk of long-term neurodisability arising from neuroglycopaenia is high. The UK CHI consensus on the practice and management of CHI was developed to optimise and harmonise clinical management of patients in centres specialising in CHI as well as in non-specialist centres engaged in collaborative, networked models of care. Using current best practice and a consensus approach, it provides guidance and practical advice in the domains of diagnosis, clinical assessment and treatment to mitigate hypoglycaemia risk and improve long term outcomes for health and well-being.
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Hiperinsulinismo Congênito , Criança , Lactente , Humanos , Pré-Escolar , Consenso , Hiperinsulinismo Congênito/diagnóstico , Hiperinsulinismo Congênito/genética , Hiperinsulinismo Congênito/terapia , Pancreatectomia , Reino UnidoRESUMO
Although survival after rhabdosarcoma treatment has improved over the years, one third of patients still develop locoregional relapse. This review aims to highlight developments pertaining to staging and local treatment of specific RMS tumor sites, including head and neck, chest/trunk, bladder-prostate, female genito-urinary, perianal, and extremity sites.
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Context: In focal congenital hyperinsulinism (CHI), localized clonal expansion of pancreatic ß-cells causes excess insulin secretion and severe hypoglycemia. Surgery is curative, but not all lesions are amenable to surgery. Objective: We describe surgical and nonsurgical outcomes of focal CHI in a national cohort. Methods: Patients with focal CHI were retrospectively reviewed at 2 specialist centers, 2003-2018. Results: Of 59 patients with focal CHI, 57 had heterozygous mutations in ABCC8/KCNJ11 (51 paternally inherited, 6 de novo). Fluorine-18 L-3,4 dihydroxyphenylalanine positron emission tomography computed tomography scan identified focal lesions in 51 patients. In 5 patients, imaging was inconclusive; the diagnosis was established by frozen section histopathology in 3 patients, a lesion was not identified in 1 patient, and 1 declined surgery. Most patients (n = 56) were unresponsive to diazoxide, of whom 33 were unresponsive or partially responsive to somatostatin receptor analog (SSRA) therapy. Fifty-five patients underwent surgery: 40 had immediate resolution of CHI, 10 had persistent hypoglycemia and a focus was not identified on biopsy in 5. In the 10 patients with persistent hypoglycemia, 7 underwent further surgery with resolution in 4 and ongoing hypoglycemia requiring SSRA in 3. Nine (15% of cohort) patients (1 complex surgical access; 4 biopsy negative; 4 declined surgery) were managed conservatively; medication was discontinued in 8 children at a median (range) age 2.4 (1.5-7.7) years and 1 remains on SSRA at 16 years with improved fasting tolerance and reduction in SSRA dose. Conclusion: Despite a unifying genetic basis of disease, we report inherent heterogeneity in focal CHI patients impacting outcomes of both surgical and medical management.
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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.
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Preservação da Fertilidade , Neoplasias Ovarianas , Adolescente , Criança , Técnica Delphi , Feminino , Humanos , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Estudos Prospectivos , Estudos RetrospectivosRESUMO
OBJECTIVE: To report a 20-year experience highlighting management and outcome(s) of paediatric testicular tumours. PATIENTS AND METHODS: All males (< 19 years) with an index diagnosis of testicular tumours during the era(s) 1998-2018 in North West England were identified. Data were collected regarding age at diagnosis, disease stage, surgical operations, tumour biology and outcome(s). RESULTS: A total of 34 male patients were identified. Median age at primary diagnosis was 94 months (range: 0-229 months). Eighteen tumours were benign and 16 malignant. Twenty cases (59%) were recorded in pre pubertal children and 14 (41%) in post pubertal males . In the pre pubertal group (0-11 years) - 15 cases of germ cell tumours (unrelated to germ cell neoplasia in situ - non-GCNIS derived) were recorded, including six yolk sac lesions, eight teratomas and one mixed teratoma/yolk sac tumour (pre-pubertal type). Four males with sex cord-stromal tumours included one juvenile granulosa cell tumour, two Sertoli cell tumours and one Leydig cell tumour. One miscellaneous type tumour notably a papillary cyst adenoma was also identified. In the post pubertal male cohort (>12 years) (n = 14) - four non-GCNIS derived tumours were identified (3 epidermoid cysts and one teratoma), eight cases of germ cell tumour derived from germ cell neoplasia in situ (GCNIS derived) included one teratoma, six with mixed germ cell tumours and one embryonal carcinoma. Two males had sex cord stromal tumours: (Leydig cell and granulosa cell biology). Twenty-eight patients underwent high radical inguinal orchidectomy(s) with one male also requiring retroperitoneal surgery to clear distant locoregional disease and a further single case thoracotomy and metastasectomy. Six patients had lesions suitable for 'testicular sparing' surgery. Six patients had metastatic disease at presentation (18%). Overall study survival was 97%. A single fatality occurred in an adolescent male with a mixed GCT harbouring liver, lung and para-aortic disease who died 48 months after initiating treatment. CONCLUSION: We highlight one of the largest study series of paediatric testicular tumours in the UK and Europe. Non-GCNIS derived tumours accounted for the most common tumour biology (56%). Survival for paediatric testicular tumours is reassuringly generally excellent. Delayed presentation however with a malignant testicular tumour may be associated with poor outcome(s).
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Tumor de Células de Leydig , Neoplasias Embrionárias de Células Germinativas , Teratoma , Neoplasias Testiculares , Adolescente , Criança , Humanos , Tumor de Células de Leydig/cirurgia , Masculino , Neoplasias Embrionárias de Células Germinativas/cirurgia , Orquiectomia , Teratoma/epidemiologia , Teratoma/cirurgia , Neoplasias Testiculares/epidemiologia , Neoplasias Testiculares/cirurgiaRESUMO
BACKGROUND: Congenital Hyperinsulinism (CHI) is an important cause of severe hypoglycaemia in infancy due to excessive, dysregulated insulin secretion. In focal CHI, a localised lesion within the pancreas hypersecretes insulin and, importantly, hypoglycaemia resolution is possible through limited surgical resection of the lesion. Diagnosis of focal CHI is based on a crucial combination of compatible genetics and specialised imaging. Specifically, a focal lesion arises due to a paternal mutation in one of the ATP-sensitive potassium channel genes, KCNJ11 or ABCC8, in combination with post-zygotic loss of maternal heterozygosity within the affected pancreatic tissue. 6-[18F]Fluoro-L-3,4-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET)/computed tomography (CT) imaging is used to detect and localise the lesion prior to surgery. However, its accuracy is imperfect and needs recognition in individual case management. CASE PRESENTATION: We report the case of an infant with hypoglycaemia due to CHI and a paternally inherited KCNJ11 mutation, c.286G > A (p.Ala96Thr), leading to a high probability of focal CHI. However,18F-DOPA PET/CT scanning demonstrated diffuse uptake and failed to conclusively identify a focal lesion. Due to unresponsiveness to medical therapy and ongoing significant hypoglycaemia, surgery was undertaken and a small 4.9 × 1.7 mm focal lesion was discovered at the pancreatic neck. This is the second case where this particular KCNJ11 mutation has been incorrectly associated with diffuse 18F-DOPA uptake, in contrast to the correct diagnosis of focal CHI confirmed by pancreatic biopsy. CONCLUSIONS: Identifying discrepancies between genetic and imaging investigations is crucial as this may negatively impact upon the diagnosis and surgical treatment of focal CHI. This case highlights the need for pancreatic biopsy when a strong suspicion of focal CHI is present even if 18F-DOPA imaging fails to demonstrate a discrete lesion.
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BACKGROUND: Paratesticular rhabdomyosarcoma (PT RMS) is rare compared to benign scrotal pathology. Inappropriate first surgery (InFS) required supplementary treatment to maintain excellent outcomes. Initial staging of regional lymph nodes is important. The aim of this study was to determine to what extent the quality of locoregional approach impacted on patient morbidity and survival. DESIGN/METHODS: Analysis was performed on all nonmetastatic PT RMS patients enrolled in the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 protocol. Aspects assessed were adherence to surgical guidelines and impact of protocol violations, relapse analysis, and survival outcomes. RESULTS: Analysis was performed on 237 patients, with median follow up of 67.1 months. Median age was 9.0 years. InFS occurred in 75 of 237 (32%) patients. InFS required intensified chemotherapy (10) and local therapy. After InFS, 61 required primary reexcision and five delayed surgery. Of 26 recurrences, the risk of relapse was higher in patients ≥10 years (21/26) and was mainly locoregional in 16 of 26 recurrences (± metastatic). Sixteen of 26 died with 14 of 16 patients ≥10 years. Nodal relapse neither occurred when N1 nodes were identified at diagnosis, nor after surgical staging. Five-year overall survival (OS) at age <10 years versus ≥10 years was 98.1 and 86.7%, respectively (P = .0013). Event-free survival (EFS) at age <10 years versus ≥10 years was 95.8 and 79.6%, respectively (P = .0004). OS and EFS did not highlight a significant difference in patients undergoing appropriate versus InFS (P = .8479, P = .2780, respectively). CONCLUSIONS: InFS required intensified therapy to maintain excellent OS and EFS, so better anticipation of malignancy is required. Surgical staging of the retroperitoneal lymph nodes should be performed in patients ≥10 years old.
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Fidelidade a Diretrizes , Rabdomiossarcoma , Neoplasias Testiculares , Adolescente , Adulto , Criança , Pré-Escolar , Intervalo Livre de Doença , Seguimentos , Humanos , Lactente , Masculino , Rabdomiossarcoma/mortalidade , Rabdomiossarcoma/terapia , Taxa de Sobrevida , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/terapiaRESUMO
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 <16â¯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 11â¯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 6â¯cm compared to 11â¯cm in the open group (pâ¯<â¯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.
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Preservação da Fertilidade , Neoplasias Ovarianas , Criança , Feminino , Humanos , Neoplasias Ovarianas/cirurgia , Ovariectomia , Estudos Retrospectivos , Reino Unido/epidemiologiaRESUMO
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.
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Síndrome de Horner/etiologia , Algoritmos , Neoplasias Encefálicas/diagnóstico , Catecolaminas/urina , Criança , Síndrome de Horner/diagnóstico , Humanos , Neoplasias/diagnóstico , Neuroblastoma/diagnósticoRESUMO
BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are rare tumors of childhood. The role of standard chemotherapy in unresectable MPNST is still unclear. We report the outcome and prognostic factors in the EpSSG risk-adapted prospective study for localized pediatric MPNST. METHODS: Patients were stratified into four treatment groups defined by surgical resection, tumor size, and tumor grade (G): (a) surgery-only group-resected tumors G1; (b) adjuvant radiotherapy group-R0/R1, G2 tumors; (c) adjuvant chemotherapy group-R0/R1, G3 tumors; and (d) neoadjuvant chemotherapy group-R2 resected tumors and/or nodal involvement. Chemotherapy consisted of four courses of ifosfamide-doxorubicin and two courses of ifosfamide concomitant with radiotherapy (50.4-54 Gy). RESULTS: Overall, the study included 51 patients. The 5-year event-free survival (EFS) and overall survival (OS) were 52.9% (95% confidence interval, 38.1-65.8) and 62.1% (46.7-74.3), respectively. The 5-year EFS was 92% (56.6-98.9) for treatment group 1 (N = 13), 33% (0.9-77.4) for treatment group 2 (N = 4), 29% (4.1-61.2) for treatment group 3 (N = 7), and 42% (23.1-60.1) for treatment group 4 (N = 27). Response rate to chemotherapy (partial response + complete response) in patients with measurable disease was 46%. The presence of neurofibromatosis type 1 (NF1; 51% of patients) was an independent poor prognostic factor for OS and EFS. CONCLUSION: The outcome for patients with resectable MPNST was excellent. Standard ifosfamide-doxorubicin for unresectable MPNST rendered the best reported outcome. Children with NF1 disease seem to have worse prognosis.
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Quimiorradioterapia Adjuvante/métodos , Neurofibrossarcoma/patologia , Neurofibrossarcoma/terapia , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Europa (Continente) , Feminino , Humanos , Lactente , Masculino , Neurofibrossarcoma/mortalidade , Prognóstico , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: To determine the impact of intra-operative Trans-anastomotic Tube (TAT) placement on the cost of post-operative nutrition in infants with congenital duodenal obstruction (CDO). METHODS: A retrospective analysis of patients undergoing corrective surgery for CDO, with birth-weight over 1.5 kg over a 10-year period. Data are presented as median (inter-quartile range) and analysed with Mann-Whitney U test and Fisher's exact test as appropriate. RESULTS: 59 patients were included. There was no difference between TAT and non-TAT groups for baseline characteristics, age at operation and abnormality. In the TAT group there was a significant reduction in the duration of post-operative parenteral nutrition (PN) [6 (0-11) vs 12 (8-19) days, p = 0.006], the cost of PN [£750 (0-1375) vs £1500 (1000-2375), p = 0.006] and the total cost of nutrition [£765.26 (38.36-1404) vs £1387.52 (1008.23-2363.08), p = 0.015], thereby demonstrating a median cost saving of £622.26 per patient. 14% experienced TAT displacement but no other TAT complications were encountered. CONCLUSION: The use of a TAT is a safe and effective way to reduce the duration of PN required in patients with CDO. This infers a significant cost saving per patient, a factor that cannot be overlooked in this period of austerity.
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Procedimentos Cirúrgicos do Sistema Digestório/métodos , Obstrução Duodenal/terapia , Estado Nutricional , Nutrição Parenteral Total/métodos , Procedimentos de Cirurgia Plástica/métodos , Anastomose Cirúrgica , Custos e Análise de Custo , Obstrução Duodenal/congênito , Obstrução Duodenal/diagnóstico , Feminino , Humanos , Recém-Nascido , Masculino , Nutrição Parenteral Total/economia , Estudos RetrospectivosRESUMO
Background: Congenital Hyperinsulinism (CHI) is an important cause of severe and persistent hypoglycaemia in infancy and childhood. The focal form (CHI-F) of CHI can be potentially cured by pancreatic lesionectomy. While diagnostic characteristics of CHI-F pancreatic histopathology are well-recognized, correlation with clinical phenotype has not been established. Aims: We aimed to correlate the diversity in clinical profiles of patients with islet cell organization in CHI-F pancreatic tissue. Methods: Clinical datasets were obtained from 25 patients with CHI-F due to ABCC8/KCNJ11 mutations. 18F-DOPA PET-CT was used to localize focal lesions prior to surgery. Immunohistochemistry was used to support protein expression studies. Results: In 28% (n = 7) of patient tissues focal lesions were amorphous and projected into adjoining normal pancreatic tissue without clear delineation from normal tissue. In these cases, severe hypoglycaemia was detected within, on average, 2.8 ± 0.8 (range 1-7) days following birth. By contrast, in 72% (n = 18) of tissues focal lesions were encapsulated within a defined matrix capsule. In this group, the onset of severe hypoglycaemia was generally delayed; on average 46.6 ± 14.3 (range 1-180) days following birth. For patients with encapsulated lesions and later-onset hypoglycaemia, we found that surgical procedures were curative and less complex. Conclusion: CHI-F is associated with heterogeneity in the organization of focal lesions, which correlates well with clinical presentation and surgical outcomes.
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Cuidados Paliativos/métodos , Procedimentos Cirúrgicos Operatórios/métodos , Síndrome da Trissomía do Cromossomo 18 , Tomada de Decisão Clínica , Feminino , Humanos , Recém-Nascido , Masculino , Seleção de Pacientes , Prognóstico , Estudos Retrospectivos , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Síndrome da Trissomía do Cromossomo 18/terapia , Reino UnidoRESUMO
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.
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Neoplasias Ovarianas/cirurgia , Guias de Prática Clínica como Assunto , Cirurgiões/estatística & dados numéricos , Criança , Estudos Transversais , Feminino , Humanos , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Several classification systems exist to predict mortality in oesophageal atresia, the most widely quoted of these being over 20 years old. No classification system exists to predict morbidity. We sought to test whether these classification systems remain relevant and to determine whether they can be useful to predict morbidity. In addition, we aimed to identify independent risk factors for predicting mortality and morbidity. METHODS: Neonates presenting with oesophageal atresia over a 20-year period (1990-2010) were retrospectively reviewed. Discriminative statistical analysis compared the performance of current classification systems. Stepwise logistic regression analysis of the influence of perioperative risk factors on mortality and duration of ventilatory support and intensive care unit stay were performed. RESULTS: All classification systems predicted mortality in this series of 248 neonates. Birth weight, cardiac anomalies and pre-operative pneumonia were independent risk factors for predicting mortality in oesophageal atresia. The Waterston classification is the most useful classification for predicting post-operative morbidity in terms of length of hospital stay and time spent ventilated. CONCLUSION: Despite advances in the neonatal care of the very low birth weight infant and those with congenital cardiac disease, these conditions remain relevant in predicting mortality and morbidity in oesophageal atresia.
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Atresia Esofágica/mortalidade , Complicações Pós-Operatórias , Peso ao Nascer , Análise Discriminante , Atresia Esofágica/classificação , Atresia Esofágica/cirurgia , Feminino , Cardiopatias Congênitas/complicações , Humanos , Lactente , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Modelos Logísticos , Masculino , Pneumonia/complicações , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Reino Unido/epidemiologiaRESUMO
Objectives: We aimed to characterize mosaic populations of pancreatic islet cells from patients with atypical congenital hyperinsulinism in infancy (CHI-A) and the expression profile of NKX2.2, a key transcription factor expressed in ß-cells but suppressed in δ-cells in the mature pancreas. Patients/Methods: Tissue was isolated from three patients with CHI-A following subtotal pancreatectomy. CHI-A was diagnosed on the basis of islet mosaicism and the absence of histopathological hallmarks of focal and diffuse CHI (CHI-D). Immunohistochemistry was used to identify and quantify the proportions of insulin-secreting ß-cells and somatostatin-secreting δ-cells in atypical islets, and results were compared with CHI-D (n = 3) and age-matched control tissues (n = 3). Results: In CHI-A tissue, islets had a heterogeneous profile. In resting/quiescent islets, identified by a condensed cytoplasm and nuclear crowding, ß-cells were reduced to <50% of the total cell numbers in n = 65/70 islets, whereas δ-cell numbers were increased with 85% of islets (n = 49/57) containing >20% δ-cells. In comparison, all islets in control tissue (n = 72) and 99% of CHI-D islets (n = 72) were composed of >50% ß-cells, and >20% δ-cells were found only in 12% of CHI-D (n = 8/66) and 5% of control islets (n = 3/60). Active islets in CHI-A tissue contained proportions of ß-cells and δ-cells similar to those of control and CHI-D islets. Finally, when compared with active islets, quiescent islets had a twofold higher prevalence of somatostatin/NKX2.2+ coexpressed cells. Conclusions: Marked increases in NKX2.2 expression combined with increased numbers of δ-cells strongly imply that an immature δ-cell profile contributed to the pathobiology of CHI-A.
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Hiperinsulinismo Congênito/genética , Hiperinsulinismo Congênito/patologia , Predisposição Genética para Doença , Ilhotas Pancreáticas/patologia , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Biópsia por Agulha , Pré-Escolar , Estudos de Coortes , Hiperinsulinismo Congênito/cirurgia , Feminino , Proteína Homeobox Nkx-2.2 , Proteínas de Homeodomínio , Humanos , Imuno-Histoquímica , Lactente , Ilhotas Pancreáticas/metabolismo , Masculino , Mosaicismo , Pancreatectomia/métodos , Prognóstico , Valores de Referência , Índice de Gravidade de Doença , Fator Nuclear 1 de TireoideRESUMO
BACKGROUND: Patients with Congenital Hyperinsulinism (CHI) due to mutations in K-ATP channel genes (K-ATP CHI) are increasingly treated by conservative medical therapy without pancreatic surgery. However, the natural history of medically treated K-ATP CHI has not been described; it is unclear if the severity of recessively and dominantly inherited K-ATP CHI reduces over time. We aimed to review variation in severity and outcomes in patients with K-ATP CHI treated by medical therapy. METHODS: Twenty-one consecutively presenting patients with K-ATP CHI with dominantly and recessively inherited mutations in ABCC8/KCNJ11 were selected in a specialised CHI treatment centre to review treatment outcomes. Medical treatment included diazoxide and somatostatin receptor agonists (SSRA), octreotide and somatuline autogel. CHI severity was assessed by glucose infusion rate (GIR), medication dosage and tendency to resolution. CHI outcome was assessed by glycaemic profile, fasting tolerance and neurodevelopment. RESULTS: CHI presenting at median (range) age 1 (1, 240) days resolved in 15 (71%) patients at age 3.1(0.2, 13.0) years. Resolution was achieved both in patients responsive to diazoxide (n = 8, 57%) and patients responsive to SSRA (n = 7, 100%) with earlier resolution in the former [1.6 (0.2, 13.0) v 5.9 (1.6, 9.0) years, p = 0.08]. In 6 patients remaining on treatment, diazoxide dose was reduced in follow up [10.0 (8.5, 15.0) to 5.4 (0.5, 10.8) mg/kg/day, p = 0.003]. GIR at presentation did not correlate with resolved or persistent CHI [14.9 (10.0, 18.5) v 16.5 (13.0, 20.0) mg/kg/min, p = 0.6]. The type of gene mutation did not predict persistence; resolution could be achieved in recessively-inherited CHI with homozygous (n = 3), compound heterozygous (n = 2) and paternal mutations causing focal CHI (n = 2). Mild developmental delay was present in 8 (38%) patients; adaptive functioning assessed by Vineland Adaptive Behavior Scales questionnaire showed a trend towards higher standard deviation scores (SDS) in resolved than persistent CHI [-0.1 (-1.2, 1.6) v -1.2 (-1.7, 0.03), p = 0.1]. CONCLUSIONS: In K-ATP CHI patients managed by medical treatment only, severity is reduced over time in the majority, including those with compound heterozygous and homozygous mutations in ABCC8/KCNJ11. Severity and treatment requirement should be assessed periodically in all children with K-ATP CHI on medical therapy.
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Hiperinsulinismo Congênito/tratamento farmacológico , Hiperinsulinismo Congênito/genética , Transportadores de Cassetes de Ligação de ATP/genética , Pré-Escolar , Hiperinsulinismo Congênito/metabolismo , Diazóxido/uso terapêutico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mutação/genética , Octreotida/uso terapêuticoRESUMO
OBJECTIVES: To quantify islet cell nucleomegaly in controls and tissues obtained from patients with congenital hyperinsulinism in infancy (CHI) and to examine the association of nucleomegaly with proliferation. METHODS: High-content analysis of histologic sections and serial block-face scanning electron microscopy were used to quantify nucleomegaly. RESULTS: Enlarged islet cell nuclear areas were 4.3-fold larger than unaffected nuclei, and the mean nuclear volume increased to approximately threefold. Nucleomegaly was a normal feature of pediatric islets and detected in the normal regions of the pancreas from patients with focal CHI. The incidence of nucleomegaly was highest in diffuse CHI (CHI-D), with more than 45% of islets containing two or more affected cells. While in CHI-D nucleomegaly was negatively correlated with cell proliferation, in all other cases, there was a positive correlation. CONCLUSIONS: Increased incidence of nucleomegaly is pathognomonic for CHI-D, but these cells are nonproliferative, suggesting a novel role in the pathobiology of this condition.
Assuntos
Núcleo Celular/patologia , Hiperinsulinismo Congênito/patologia , Ilhotas Pancreáticas/patologia , Núcleo Celular/ultraestrutura , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Ilhotas Pancreáticas/ultraestrutura , Masculino , Microscopia EletrônicaRESUMO
BACKGROUND: A variety of prosthetic materials are used in the pediatric population for abdominal and chest wall reconstruction. Pediatric experience of non-cross-linked porcine acellular dermal matrix is limited to patients following liver transplantation. We review our outcomes in patients in whom this matrix was used. METHODS: A retrospective analysis of patients who underwent abdominal and chest wall reconstruction with a non-cross-linked porcine acellular dermal matrix (Strattice TM) was performed to assess clinical outcomes. RESULTS: The tissue matrix was used in thirteen patients over a three-year period. Eleven had abdominal wall reconstruction and two underwent chest wall reconstruction. Seven procedures were contaminated at the time of surgery. Median age at insertion was 8.1years (5days-18years) with a median weight of 20.6kg (1.9kg-99kg). The tissue matrix failed in one patient with no unanticipated adverse events. CONCLUSION: Future growth and need for reoperation requires special consideration in pediatric patients undergoing abdominal or thoracic wall reconstruction. Non-cross-linked porcine acellular dermal matrix can be safely used for abdominal and chest wall reconstruction in the pediatric population with a number of advantages over previously utilized materials. In our study, children have a favorable risk profile as compared to published adult series.