Dhanya Mullassery

Value of liver herniation in prediction of outcome in fetal congenital diaphragmatic hernia: a systematic review and meta‐analysis

Intrathoracic liver herniation (ILH) is being used to estimate prognosis and hence guide antenatal interventions in fetal congenital diaphragmatic hernia (CDH). However, the literature regarding its utility in this role is conflicting. This review systematically examines the currently available evidence of ILH use in fetal CDH.

Neuroblastoma: contemporary management

Neuroblastoma is the most frequently diagnosed extracranial solid tumour in childhood. While a subset of tumours show spontaneous regression or complete remission following conventional treatment, a substantial number remain resistant to intensive multimodal therapies. Survival rates approaching 40% place high-risk neuroblastoma as one of the greatest challenges in paediatric oncology. This contemporary review provides an update on the diagnosis, risk stratification and management for this enigmatic tumour. Neuroblastoma is the most common extracranial solid tumour in childhood and the most frequently diagnosed neoplasm during infancy.1 This malignant tumour consists of undifferentiated and/or differentiating cells originating from neural crest-derived sympathoadrenal precursors. Neuroblastoma is often described as “enigmatic” and “unpredictable” because of the broad spectrum of clinical behaviour ranging from life-threatening progression despite intensive treatment to complete spontaneous regression. Although outcome for certain subsets of patients has improved over the past few decades, children with high-risk disease continue to have less than 40% long-term survival.2 New therapeutic options are being sought through advances in basic science and translational clinical research. Neuroblastoma accounts for more than 7% of malignancies in patients younger than 15 years and around 15% of all paediatric oncology deaths.3 The incidence of neuroblastoma in predominantly Caucasian populations is 9–12 per million children.4 A family history of neuroblastoma has been reported in 1% to 2% of patients5 and follows an autosomal dominant pattern of inheritance. Supporting the Knudson two-mutation hypothesis, the median age at diagnosis for familial neuroblastoma cases is 9 months compared to 18 months in sporadic cases.3 Associations with Hirschsprung disease and congenital central hypoventilation syndrome6 with a shared PHOX2b mutation proposed to explain this link7 have been reported, as has neurofibromatosis type 1.8 At present, genetic predisposition to neuroblastoma appears to be heterogeneous and hence tumourigenesis is postulated …

Diagnosis, incidence, and outcomes of suspected typhlitis in oncology patients—experience in a tertiary pediatric surgical center in the United Kingdom

BACKGROUND Typhlitis is clinically defined by the triad of neutropenia, abdominal pain, and fever. Radiologic evidence of colonic inflammation supports the diagnosis. We report a single United Kingdom tertiary center experience with management and outcome of typhlitis for 5 years. METHODS Hospital computerized records were screened for ultrasound or computerized tomographic scan requests for abdominal pain for all oncology inpatients (2001-2005). Retrospective case note analysis was used to collect clinical data for patients with features of typhlitis. RESULTS The incidence of typhlitis among oncology inpatients was 6.7% (40/596) among oncology inpatients and 11.6% (40/345) among those on chemotherapy. Eighteen children had radiologically confirmed typhlitis, and 22 had clinical features alone. Most (93%) patients responded to conservative management. Eighteen children had a variable period of bowel rest, including 12 patients who were supported with total parenteral nutrition. Three patients had laparotomy that revealed extensive colonic bowel necrosis (1), perforated gastric ulcer (1), and a perforated appendix (1). A single child died of fulminant gram-negative sepsis without surgical intervention. CONCLUSIONS The diagnosis of typhlitis was based on clinical features, supported by radiologic evidence in almost half of the study group. Surgical intervention should be reserved for specific complications or where another surgical pathologic condition cannot reasonably be ruled out.

Single live-cell imaging for systems biology.

Understanding how mammalian cells function requires a dynamic perspective. However, owing to the complexity of signalling networks, these non-linear systems can easily elude human intuition. The central aim of systems biology is to improve our understanding of the temporal complexity of cell signalling pathways, using a combination of experimental and computational approaches. Live-cell imaging and computational modelling are compatible techniques which allow quantitative analysis of cell signalling pathway dynamics. Non-invasive imaging techniques, based on the use of various luciferases and fluorescent proteins, trace cellular events such as gene expression, protein-protein interactions and protein localization in cells. By employing a number of markers in a single assay, multiple parameters can be measured simultaneously in the same cell. Following acquisition using specialized microscopy, analysis of multi-parameter time-lapse images facilitates the identification of important qualitative and quantitative relationships-linking intracellular signalling, gene expression and cell fate.

Surgical practice for infantile hypertrophic pyloric stenosis in the United Kingdom and Ireland—a survey of members of the British Association of Paediatric Surgeons

PURPOSE Operative strategy and antibiotic policy in treating infantile hypertrophic pyloric stenosis (IHPS) may vary widely. This study surveys current practice in the United Kingdom and Ireland among members of the British Association of Paediatric Surgeons. METHODS The study used postal and email survey of consultant pediatric surgeons. RESULTS One hundred five questionnaires were distributed, and 94 replies (90% response) were received. Umbilical pyloromyotomy is performed exclusively by 57 surgeons. Fourteen surgeons (15%) use laparoscopy, whereas 5 (randomized trial in progress) use the umbilical or laparoscopic route. Eight reported that the umbilical or classical right upper quadrant (RUQ) incision is undertaken at their institution according to surgeons preference. Ten surgeons only deploy an RUQ incision. Antibiotic practice showed that 40 (70%) using the umbilical incision prescribe prophylactic therapy, whereas only 6 adopting other operative techniques (RUQ incision or laparoscopy) found this policy beneficial. More than 50% surveyed do not routinely recommend antibiotics. CONCLUSION Umbilical pyloromyotomy is used by most pediatric surgeons in the United Kingdom and Ireland. Laparoscopy is increasingly popular in minimally invasive centers. The RUQ incision is used by a minority of surgeons. Antibiotic prophylaxis was common with the umbilical incision only. The superior cosmetic results offered by umbilical pyloromyotomy and laparoscopy are a benchmark for surgeons currently providing contemporary care for babies with IHPS.

Does Aggressive Surgical Resection Improve Survival in Advanced Stage 3 and 4 Neuroblastoma? A Systematic Review and Meta-analysis

The role of surgery in the management of advanced staged neuroblastoma (NBL) is controversial. A systematic review and meta-analysis is reported to address robust evidence for curative “gross total tumor resection” (GTR) in Stage 3 and Stage 4 neuroblastoma. Studies were identified using Medline, Embase, and Cochrane databases using pre-specified search terms. Primary outcomes were 5-year overall (OS) and disease-free survival (DFS) after GTR and subtotal resection (STR) in Stage 3 or 4 NBL. Data were analyzed using Review Manager. The Mantel-Haenszel method and a random effects model was utilized to calculate odds ratios (95% CI). Fifteen studies (five Stage 3 and 13 Stage 4) met full inclusion criteria. The pooled odds ratio for 5 year OS in Stage 3 following GTR compared to STR was 2.4 (95% CI 1.19–4.85). In Stage 4 disease, the pooled odds ratio for 5 year overall survival (OS) following GTR compared to STR was 1.65 (95% CI 0.96–1.91); a pooled odds ratio for 5 year DFS following GTR compared to STR was 1.55 (95% CI 1.12–2.14). A clear survival benefit is shown for GTR over STR in Stage 3 NBL only. Though some advantage can be demonstrated for GTR as defined by DFS in Stage 4 NBL GTR did not significantly improve OS in Stage 4 disease.

Neuroblastoma: A 20-year experience in a UK regional centre†

The role of surgery in the management of neuroblastoma yields conflicting reports. We report a 20‐year experience from a UK centre in the context of evolving cancer therapies for neuroblastoma.

'Exploitation of chick embryo environments to reprogram MYCN-amplified Neuroblastoma cells to a benign phenotype, lacking detectable MYCN expression'

Neuroblastoma is a paediatric cancer that arises from the sympathetic ganglia (SG) or adrenal gland. Tumours that occur in patients under 18 months of age have a particularly good prognosis and frequently undergo spontaneous regression. This led to the hypothesis that developmental cues in the youngest patients may prompt belated differentiation and/or apoptosis of the tumour cells. To test our hypothesis, we have injected MYCN-amplified neuroblastoma cells into the extra embryonic veins of chick embryos at embryonic day 3 (E3) and E6 and analysed the response of these Kelly cells at E10 and E14. Amplification of the MYCN gene occurs in up to 30% of tumours and is normally associated with a very poor prognosis. Kelly cells injected at E3 follow neural crest pathways and integrate into neural locations such as SG and the enteric nervous system although never into the adrenal gland. Additionally they migrate to non-neural locations such as the heart, meninges, jaw regions and tail. The cells respond to their respective microenvironments and in SG, some cells differentiate, they show reduced cell division and crucially all cells have undetectable MYCN expression by E10. In non-neural locations, cells form more rapidly dividing clumps and continue to express MYCN. The downregulation of MYCN is dependent on continuous and direct interaction with the sympathetic ganglion environment. We propose that the MYCN-amplicon in the Kelly cells retains the ability to correctly interpret the environmental cues leading to downregulation of MYCN.

Laparoscopic repair of late presenting congenital diaphragmatic hernia

Congenital diaphragmatic hernia usually presents in the neonatal period, with delayed presentation being uncommon. Traditionally repair was performed by laparotomy or thoracotomy. We have performed laparoscopic repair of a previously undiagnosed congenital diaphragmatic hernia that presented acutely in a 10-year-old male. Laparoscopic repair of late-presenting congenital diaphragmatic hernia is a safe and effective approach even in an emergency. The laparoscopic approach has advantages including reduced hospital stay, excellent visualisation of the defect even for obese patients, and improved cosmesis.

Simple fundoplication versus additional vagotomy and pyloroplasty in neurologically impaired children — a single centre experience

BACKGROUND AND AIMS Gastrooesophageal reflux disease (GERD) is a significant problem in children with neurological impairment (NI) with high failure rates for fundoplication. Fundoplication with vagotomy and pyloroplasty (FVP) can improve the outcome by altering the sensory or motor dysfunction associated with the reflux. We report our comparative outcomes for simple fundoplication (SF) and FVP in NI children. METHODS Case records of all patients having fundoplication under a single consultant at a tertiary UK paediatric surgical centre between January 1997 and December 2012 were retrospectively assessed for recurrent symptoms and redo surgery. The data were collected using a Microsoft Excel database and analysed on Graphpad prism software program. Data are median (range). P value<0.05 was considered significant. RESULTS Data were available for 244 out of 275 patients who underwent fundoplication during this period (157 SF and 87 FVP). Neurological disease or known syndromes were recorded in 158 patients. Thirty-five children had congenital anatomical abnormalities. Laparoscopic fundoplication was done in 37 cases. Revisional surgery for recurrent symptoms was performed in 22 patients. In the neurologically normal children, all of whom had SF, the revision rate was 6.5%. In the NI children the revision rates were 18.5% for SF and 3.9% for FVP, respectively (Fishers exact, P<0.05). The median time to redo surgery was 10 (1-63) months, and the median time to follow up was 19.5 (2-177) months. CONCLUSIONS There appears to be a significantly lower need for redo surgery following FVP than SF in children with NI.