Fulminant necrotising enterocolitis immediately following change to low birth weight formula feeds.

INTRODUCTION: The aim of this study was to investigate how low birth weight formula (LBWF) feeds may be implicated in the pathogenesis of a particularly fulminant form of necrotising enterocolitis (NEC). MATERIALS AND METHODS: A retrospective case note review was undertaken of cases of fulminant NEC between 1997 and 2003 with particular regard to the feeding history. RESULTS: Nine preterm infants were stable and already tolerating full enteral feeds for a median of seven days prior to developing fulminant NEC within a median of 24 hours following the introduction of LBWF. CONCLUSIONS: Although fortification of feeds undoubtedly benefits many premature neonates, there may be a tendency for LBWF feeds to preempt the development of fulminant NEC. This possible temporal association between LBWF and fulminant NEC requires further investigation.

Shorter anogenital and anoscrotal distances correlate with the severity of hypospadias: A prospective study.

INTRODUCTION: Anogenital distance (AGD) is a recognised marker of in utero androgen action. OBJECTIVE: This study aimed to evaluate the relationship between severity of hypospadias and AGD. STUDY DESIGN: Boys undergoing hypospadias repair in a single tertiary centre between May 2012 and February 16 were included in the study. Anogenital distance was measured from the centre of the anus to the base of the penis, and anoscrotal distance (ASD) from the centre of the anus to the junction between the smooth perineal skin and scrotal skin. Trained paediatric urologists made all measurements using digital callipers. RESULTS: Fifty-nine boys with hypospadias and 31 age-matched controls undergoing circumcision (median age 1.37 years, range 1.01-1.96) had AGD and ASD measured under anaesthetic. The patients were divided into two groups, according to hypospadias severity: group 1 - distal penile/subcoronal/glandular (n = 40); and group 2 - perineal/penoscrotal/midshaft (n = 19). The median AGD for controls was 74.0 mm (range 53.2-87.8) and for hypospadias it was 72.3 mm (range 50.7-90.0) (P = 0.816). The median ASD for controls was 42.3 mm (range 31.0-56.1) and for hypospadias it was 39.4 mm (range 20.7-77.0) (P = 0.224). Considering severity of hypospadias, the median AGD for group 1 and group 2 was 73.7 mm (range 50.7-90.0) and 63.3 mm (range 53.6-77.0), respectively (P < 0.001). The median ASD was also higher in group 1, at 41.3 mm (range 20.7-65.0), compared to 35.2 mm (range 23.5-77.0) in group 2 (P = 0.119) (Summary Fig.). DISCUSSION: This study showed that more severe forms of hypospadias are associated with shorter AGD and ASD. These findings agree with two previous studies that identified reduced AGD in boys with hypospadias. However, these studies did not investigate an association with severity of hypospadias. As hypospadias is multifactorial, only a small proportion of cases are thought to be associated with impaired in utero androgen exposure. The shorter AGD in boys with severe hypospadias compared with mild hypospadias would indicate that AGD is a marker of the severity of androgen production. This may also suggest that less severe forms of hypospadias have a different aetiology involving a later stage of development, and that they are not the result of reduced androgen exposure in the male programming window between the 8-14 weeks gestation. CONCLUSION: This study identified that boys with more severe hypospadias are more likely to have a shorter AGD and ASD than boys with mild hypospadias. This may indicate that there is a more profound impairment of in utero androgen action in severe hypospadias.

'Targeted top down' approach for the investigation of UTI: A 10-year follow-up study in a cohort of 1000 children.

INTRODUCTION: Investigations following urinary tract infection (UTI) aim to identify children who are prone to renal scarring, which may be preventable. In 2002, in an attempt to reduce unnecessary intervention, the present institution standardised the investigation of children with a confirmed UTI. OBJECTIVE: This study aimed to identify the significance of urological abnormalities on investigations following a UTI in children, prior to the introduction of the National Institute for Health and Care Excellence (NICE) guidelines. METHODS: Clinical information on the first 1000 patients was retrieved from a prospective UTI hospital database. The follow-up period was 10 years. RESULTS: There were 180 males and 820 females (M:F = 1:4.5). The median age of presentation was 5 years (range 11 days-16 years). A renal ultrasound (US) was performed on all patients, and was normal in 93% of cases (n = 889) (see Figure). Of the 7% who had an abnormal US (n = 71), 54 were female and 17 male (M:F = 1:3). A total of 372 DMSA scans were requested and 350 attended their appointment. Of these, 278 cases (79%) were reported as normal, while 72 had an abnormality documented. Of these 72 patients with abnormalities on DMSA scan, 49 had a repeat DMSA scan: 30 demonstrated permanent scarring, while the DMSA scan became normal in 19. Sixteen of the 278 patients whose DMSA scan was initially normal had a repeat DMSA scan due to symptoms, and all scans were normal. Twelve (1.2%) patients required surgical intervention: three underwent circumcision for recurrent UTIs; three underwent endoscopic treatment of VUR; one had a PUV resection; one underwent a cystoscopy; three had a pyeloplasty for pelvi-ureteric junction obstruction; and one had a ureteric reimplantation for vesico-ureteric junction obstruction. After initial investigations and management, 936 patients were discharged from the UTI clinic: 47 of them re-presented - 40 with recurrent UTIs and seven with dysuria. Thirty-five of the 47 children who re-presented with urological symptoms underwent a DMSA scan, which showed scarring in three (6%). DISCUSSION: Only 12% of children have a significant radiological abnormality picked up on investigation following a UTI. The present investigation approach differed from the NICE guidelines, where imaging is based on patient age and characteristics of the UTI. All children had a renal US, while DMSA scans were reserved for those children <1 year of age or those with upper tract symptoms. The present protocol recommended a renal US in all children presenting with a UTI. This promptly identified those with pelvi-ureteric junction obstruction and those with PUV, who all presented >6 months of age with a single UTI and, therefore, based on the NICE guidelines would not have undergone a renal US. Of the children who re-presented with further UTIs, a significant number were found to have dysfunctional voiding. As this link is well reported, it may be appropriate to screen for this in older children at initial presentation. Only three patients, who had a US at presentation, were subsequently found to have scarring on DMSA. After 10 years of follow-up, this could represent a false negative rate of 0.3% for the screening programme. None of the girls were found to have VUR or needed any surgical intervention, which suggested that early identification of the scarring might not have altered management. Few patients required surgical intervention, all of whom were identified early. No patient who re-presented required intervention. This would suggest that the present protocol is effective at picking up abnormalities that require surgical management. CONCLUSION: This study suggested that after a childhood UTI, the liberal use of renal ultrasound and a focused 'top down' approach to investigation is likely to identify the vast majority of children who require intervention.

Emerging trends in the management of the impalpable testis.

BACKGROUND: The management of the impalpable undescended testis is controversial. The study examines emerging trends in the management of this problem. METHODS: Two groups of boys were treated consecutively and recorded prospectively from 1974 to 1984 and from 1990 to 1998 inclusive. A consistent policy of using the preperitoneal approach for impalpable testis was adopted during both time intervals but during the second study period examination under anaesthesia and diagnostic laparoscopy were introduced to ascertain testicular presence and location. RESULTS: Some 919 boys were treated for cryptorchidism during the study period. Ninety boys in the first group (23 per cent) underwent preperitoneal explorations for impalpable testes. Anorchia was present in 18 and orchidectomy was performed in two boys. Thirty boys in the later group (5 per cent) were diagnosed as having impalpable testes. Fifteen boys underwent successful preperitoneal orchidopexy, anorchia was present in 11 and four underwent orchidectomy, carried out for high intra-abdominal testes. CONCLUSION: Examination under anaesthesia and subsequent laparoscopic assessment for all impalpable testes has reduced the need for preperitoneal exploration for the impalpable undescended testis. In this large series, division of the testicular vessels in order to secure scrotal placement of the testis was required in one instance only.

MACE or caecostomy button for idiopathic constipation in children: a comparison of complications and outcomes.

The Malone antegrade enema (MACE) and the caecostomy button (CB) are two methods of achieving colonic lavage in constipated children with faecal soiling. We reviewed our experience with the MACE and CB, aiming to compare results, complications, and outcomes. Between June 1998 and August 2002, 37 children (15 boys) underwent MACE and 12 children (9 boys) underwent CB for idiopathic constipation that had failed conventional treatment. Rectal biopsy was ganglionic in all cases. Mean age at surgery was 9.9 years for the MACE patients and 9.8 years for the CB patients. All children are under continuous review, and mean follow-up is 18 months. Statistical analysis of proportions used Fisher's exact test. Soiling stopped completely in 30 children with MACE and in 9 with CB. Occasional soiling is still present in two children with a CB and in one with MACE. One child with a CB had resumed regular bowel activity, and the CB was removed. MACE failed in 5 (14%) patients because of ineffective colonic lavage, and in one patient (3%) the appendix was replaced by a CB because of perforation of the appendicostomy. CB failed in one patient (8%) because of faecal leak around the button; the child was subsequently converted to MACE (P = >0.5). Complications requiring operative intervention were seen in 9 (24%) of the 37 patients who underwent MACE and none of the 12 patients who underwent CB (P = 0.09). The main complication requiring surgical intervention was stoma stenosis (11%). Complications not requiring operative intervention were seen in 7 (19%) patients after MACE and 11 (92%) of the 12 patients who underwent CB (P < 0.001). The MACE and CB procedures are reliable and effective with high success rates. The MACE has a higher incidence of complications requiring operative intervention. Conversely, complications not requiring operative intervention are more frequent with CB. CB is a safe and effective alternative to MACE in children with faecal soiling.

Prognostic value of laparoscopic ultrasound in patients with gastro-esophageal cancer.

Forty-four patients with gastro-esophageal tumors regarded as resectable by conventional staging underwent laparoscopic ultrasonography (LUS). Following LUS, seven were found to be irresectable and were managed by palliative therapies. Thirty-seven patients proceeded to surgical exploration and 36 were resected (R0 80%, R1 11%, and R2 9%). All patients were reviewed until death or for a minimum of 24 months. Patients undergoing resection had a 62% 1-year survival (median 17 months; confidence intervals, CI 6-28). LUS defined nodal status indicated a trend toward prolonged survival in the node-negative group, median 22 months (CI 5-39), compared with 13 months (CI 6-20) in the node-positive group. Disease-free survival was greater in LUS node-negative patients at 29 months (CI 23-35) compared with node-positive patients at 13 months (CI 5-21) P=0.0083. LUS staging allows prediction of the likelihood of recurrence of gastro-esophageal malignancies. This may prove useful for the appropriate allocation of patients to primary and adjuvant therapies.

Interleukin 2 receptor expression and interleukin 2 localisation in human solid tumor cells in situ and in vitro: evidence for a direct role in the regulation of tumour cell proliferation.

Frozen sections of 52 human solid tumours (38 malignant and 14 benign) of varied histogenesis were immunohistochemically stained with well characterised monoclonal antibodies (MAbs) to human interleukin 2 (IL-2) and the alpha and beta chains of its receptor (R). In all malignant specimens, the tumour cells expressed the IL-2R beta subunit (p75) but not the IL-2R alpha subunit (CD25). In 36 of 38 malignant tumours examined, there was conspicuous staining for IL-2 in the tumour cell nuclei/nucleoli and perinuclear cytoplasm. In the human solid tumour cell lines G361 (melanoma), A549 (lung), MCF-7 (breast) and WiDR (colorectal), both subunits of the IL-2R appeared to be expressed, although the alpha subunit only weakly. Exogenous addition of human recombinant (r) interleukin 2 altered cell numbers in 3 of the 4 cell lines (WiDR was refractory). When grown in the absence of exogenously added rIL-2, IL-2 staining was observed in all cell lines. The pattern of distribution was similar to that exhibited by the tumour cells in situ (i.e., a nuclear/nucleolar localisation). In G361 melanoma cells, this IL-2 staining was present in proliferating cells but disappeared as the cultures approached confluence. Addition of an IL-2R beta subunit blocking antibody to growing G361 cultures (grown in the absence of rIL-2) resulted in a significant reduction in cell numbers. We propose, therefore, that the presence of immunoreactive IL-2 and IL-2R expression is characteristic of human malignant cells and that IL-2 may play a role in the autocrine stimulation of proliferation of malignant cells, such as G361 melanoma cells.