Scurvy: an unusual complication of paediatric cancer treatment.

Scurvy is a disease that is rarely encountered in modern medicine. A condition that was classically associated with sailors, its incidence has decreased dramatically since the discovery of its association with vitamin C deficiency. We present the case of a 2-year-old boy, whose treatment for neuroblastoma was complicated by gastrointestinal disease, which necessitated enteral feeding. While still undergoing treatment, he started to complain about increasing pain in his lower limbs, which appeared to be markedly tender on palpation. Radiographic findings suggested a diagnosis of scurvy, which was subsequently confirmed on serum biochemistry. This was an unexpected finding, as the child had been receiving adequate vitamin C in his enteral feeds. However, his absorption had become severely impaired due to pseudomembranous gastritis and enteritis, leading to his deficient state. He significantly improved after intravenous ascorbic acid replacement and demonstrated a full recovery, both clinically and radiologically. This case highlights the importance of considering scurvy in the differential diagnosis for at-risk patients. Early recognition can facilitate the simple treatment of this potentially serious condition.

Bevacizumab, Irinotecan, or Topotecan Added to Temozolomide for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON-Neuroblastoma Trial.

PURPOSE: Outcomes for children with relapsed and refractory high-risk neuroblastoma (RR-HRNB) remain dismal. The BEACON Neuroblastoma trial (EudraCT 2012-000072-42) evaluated three backbone chemotherapy regimens and the addition of the antiangiogenic agent bevacizumab (B). MATERIALS AND METHODS: Patients age 1-21 years with RR-HRNB with adequate organ function and performance status were randomly assigned in a 3 × 2 factorial design to temozolomide (T), irinotecan-temozolomide (IT), or topotecan-temozolomide (TTo) with or without B. The primary end point was best overall response (complete or partial) rate (ORR) during the first six courses, by RECIST or International Neuroblastoma Response Criteria for patients with measurable or evaluable disease, respectively. Safety, progression-free survival (PFS), and overall survival (OS) time were secondary end points. RESULTS: One hundred sixty patients with RR-HRNB were included. For B random assignment (n = 160), the ORR was 26% (95% CI, 17 to 37) with B and 18% (95% CI, 10 to 28) without B (risk ratio [RR], 1.52 [95% CI, 0.83 to 2.77]; P = .17). Adjusted hazard ratio for PFS and OS were 0.89 (95% CI, 0.63 to 1.27) and 1.01 (95% CI, 0.70 to 1.45), respectively. For irinotecan ([I]; n = 121) and topotecan (n = 60) random assignments, RRs for ORR were 0.94 and 1.22, respectively. A potential interaction between I and B was identified. For patients in the bevacizumab-irinotecan-temozolomide (BIT) arm, the ORR was 23% (95% CI, 10 to 42), and the 1-year PFS estimate was 0.67 (95% CI, 0.47 to 0.80). CONCLUSION: The addition of B met protocol-defined success criteria for ORR and appeared to improve PFS. Within this phase II trial, BIT showed signals of antitumor activity with acceptable tolerability. Future trials will confirm these results in the chemoimmunotherapy era.

Familial distal foregut atresia in a family with likely autosomal dominant inheritance pattern.

Familial occurrence of distal foregut atresia (DFA) (Type 1) is rare. Diagnosis is based upon the clinical symptomatology and confirmed by radiological studies, surgery and histology. A number of reports have described families in which several family members have been involved and suggested an autosomal recessive mode of inheritance. Little is known about the underlying genetic causes or indeed the likely pathogenic mechanism. We report a family in which there are five affected cases including three siblings where the DFA appears to be inherited in an autosomal dominant inheritance pattern with reduced penetrance.

Outcome in cystic fibrosis liver disease.

OBJECTIVES: Evidence suggests that cystic fibrosis liver disease (CFLD) does not affect mortality or morbidity in patients with cystic fibrosis (CF). The importance of gender and age in outcome in CF makes selection of an appropriate comparison group central to the interpretation of any differences in mortality and morbidity in patients with CFLD. METHODS: This is a 7-year follow-up of 42 children with CFLD and their age- and sex-matched controls. Participants were reviewed clinically, biochemically, and radiologically at follow-up. RESULTS: Overall, 85% (72 of 84) of the original cohort were included, 36 CFLD participants and 36 CF controls. There was no significant difference in the number of deaths/transplants between groups (7 of 36 (19.4%) CFLD participants, 3 of 36 (8.3%) CF controls). There was a tendency for participants with CFLD to die younger than their respective CF controls. There was no difference in height, weight, body mass index, or pulmonary function between the groups. Nutritional parameters (sum skinfold thickness 31.6 vs. 42.3, P=0.03; mean upper arm fat area 15.08 vs. 10.59, P=0.001; Shwachman score 43.7 vs. 32.1, P=0.001) were worse among CFLD participants than among CF controls. Cystic fibrosis-related diabetes was more common in CFLD participants (11 of 27 (40.7%) vs. 5 of 33 (15.2%), P=0.02). Eight children (22.2%) with evidence of CFLD at baseline had no clinical evidence of liver disease as adults. CONCLUSIONS: Patients with CFLD have a more severe CF phenotype than do CF patients without liver disease. However, a subgroup of children with CFLD will not manifest clinically significant liver disease as adults.

Bleeding meckel's diverticulum: A study of the accuracy of pertechnetate scintigraphy as a diagnostic tool.

BACKGROUND: The reported accuracy of pertechnetate scintigraphy (Meckel scan) in investigating children with a bleeding Meckel's diverticulum has increased steadily since it was first introduced into clinical practice in 1970. Recent studies have indicated that the examination has a sensitivity of up to 94% and a specificity of up to 97% in this scenario. There have also been several misleading reviews from Departments of Surgery, suggesting that the Meckel scan has a poor predictive value, and should not be relied upon to exclude a bleeding Meckel's Diverticulum (MD). OBJECTIVE: The aim of this study was to assess the accuracy of pertechnetate scintigraphy performed at Our Lady's Hospital for Sick Children, Crumlin (OLCHC) on children with clinical suspicion of a bleeding MD. METHOD: This was a retrospective study of all the Meckel scans performed over a 10year period (2005-2015) in OLCHC, 144 in total. RESULTS: Of the total 144 scans performed, 22 were considered to be positive, and all patients were found to have a MD at surgery. 122 were negative, and in 53 of these patients, an alternative cause for symptoms was found, often at endoscopy. In the remaining 69 patients, no cause was found, despite full medical work-up. In all of these cases, symptoms resolved, and have not yet recurred, making MD very unlikely. DISCUSSION: Pertechnetate scintigraphy, when performed using meticulous technique, can provide up to 100% sensitivity CI [85.1, 100.0] and 100% specificity CI [93.2, 100.0] in diagnosing a bleeding MD in a paediatric population. This examination is seldom of value in children with no history of rectal bleeding.

Primary desmoplastic small round cell tumor of bone: report of a case with cytogenetic confirmation.

We report a case of desmoplastic small round cell tumor occurring in the right ilium of a 13-year-old boy. Morphologically, the neoplasm consisted of small round cells of primitive appearance with a diffuse growth pattern replacing marrow space and eroding bone. Immunohistochemical staining was positive for vimentin, synapsin, CD99 (MIC2 protein), and FLI-1, prompting an initial diagnosis of Ewing sarcoma/primitive neuroectodermal tumor. However, a diagnosis of desmoplastic small round cell tumor was rendered after the detection by cytogenetic analysis of the reciprocal chromosomal translocation, t(11;22)(p13;q12), which is uniquely associated with this tumor. This is the first documented instance of desmoplastic small round cell tumor arising in bone.

Primitive myxoid mesenchymal tumor of infancy: a report of a further case with locally aggressive behavior.

We report a case of an 8-month-old child with a primitive myxoid mesenchymal tumor of infancy arising in the thenar eminence. The lesion recurred after conservative excision and was ultimately nonresponsive to chemotherapy, necessitating partial amputation. The patient remains free of disease 5 years after this radical surgery. This is the 1st report of such a tumor since it was initially described by Alaggio and colleagues in 2006. The pathologic differential diagnosis is discussed.

Wilms tumor arising in extracoelomic paravertebral soft tissues.

Extrarenal Wilms tumor (ERWT) is a well-established entity which most commonly arises within the genitourinary tract, including intracoelomic paranephric soft tissue. Rarely, ERWT arises within teratoma, and it tends to occur predominantly in distinct settings, such as females with spinal defects and males with testicular teratomas. We report a unique ERWT arising within an extracoelomic teratoma of the paraspinal musculature, thereby expanding the range of reported locations for this unusual tumor.

Abdominal pain: general imaging strategies.

Acute abdominal pain is the most common condition necessitating surgical admission to a paediatric hospital. The vast majority of cases are due to either appendicitis or acute non-specific abdominal pain; however, there are many other conditions presenting with acute abdominal pain in childhood which can mimic appendicitis. Some of these conditions are rarely encountered in adult practice. Plain abdominal radiographs are still obtained initially on many children presenting with abdominal pain. In the absence of associated symptoms such as vomiting however, ultrasonography (US) is more likely to elucidate the underlying cause of pain than plain-film radiography. While computed tomography (CT) is being used extensively in investigating adults with abdominal pain, its widespread use in children is to be avoided in the interest of radiation protection.

Non-invasive investigation and management of aortic saddle embolus in a 7-month-old infant.

There are few reports in the literature on the ultrasound appearance of aortic saddle embolus, and none relating to small children. This unusual condition is usually diagnosed angiographically. The purpose of this report is to show how effectively high-frequency ultrasound can identify a saddle embolus with its associated collateral circulation in a young child, and to demonstrate its usefulness in monitoring the efficacy of treatment. In this case the embolus occurred as a complication of parvovirus B19 myocarditis and was diagnosed and followed up entirely by ultrasound examination, with no invasive procedure performed. The early development of an extensive collateral circulation prevented distal tissue necrosis and allowed a conservative approach to management.

Multifocal infantile myofibromatosis and generalized fibromuscular dysplasia in a child: evidence for a common pathologic process?

Infantile myofibromatosis (IM) is a condition characterized by the formation of spindle cell tumors of skin, soft tissue, and viscera. Although small vessel involvement by the process is a frequently identified and indeed diagnostically useful histological finding, involvement of large vessels is not widely reported. Fibromuscular dysplasia (FMD) is a noninflammatory arteriopathy characterized by intimal, medial, and/or adventitial fibroplasias leading to luminal compromise and aneurysm formation. Although venous disease has been reported, involvement of arterioles and viscera has not been identified. We report a patient in whom IM was diagnosed, on the basis of multiple soft tissue tumors present from birth, who subsequently developed generalized and ultimately fatal FMD. These two conditions exhibit overlapping pathologic features, including pronounced intimal fibroplasia. Their occurrence in a single individual may provide insights into the pathogenesis of both conditions, suggesting that they represent part of the same spectrum of vascular myofibroblastic proliferations.

Langerhans' cell histiocytosis of the clivus: case report and literature review.

This report describes a 5-year-old girl with Langerhans' cell histiocytosis (LCH) of the clivus. To date only five patients, including our patient, have been described with LCH at this site. Our patient differs from those previously reported by her atypical clinical presentation with torticollis, but without a sixth nerve palsy. In addition, she is the first patient to present with concomitant disease elsewhere at the time of diagnosis, i.e. both femoral necks and left proximal humerus. Our patient thus presents unique features and underlines the importance of including LCH in the differential diagnosis of erosive lesions of the clivus.

Cystic fibrosis-associated liver disease: a population-based study.

OBJECTIVES: The aim of this study was to explore the clinical factors associated with the development of cystic fibrosis-associated liver disease (CFALD). STUDY DESIGN: This was a case-control study of all children (age 5-18 years) with established CFALD in the Republic of Ireland between January 1999 and June 2000. Each child was pair matched for age and sex with a patient with cystic fibrosis (CF) without evidence of liver disease. Only children with clinically overt liver disease were enrolled in the disease group. RESULTS: Patients with established CFALD (n = 42; 26 boys) were enrolled. Children with CFALD had worse forced expiratory volume in 1 second values than those without CFALD. However, chest radiography and clinical scores did not differ between groups. Height (mean difference, -4.2 cm [95% confidence interval [CI], -7.41 to -0.90], P =.014), weight (mean difference, -3.21 kg [95% CI, -6.03 to -0.40], P =.026), and mid-upper arm circumference (mean difference, -1.23 cm [95% CI, -2.35 to -0.12], P =.031) were significantly lower among children with CFALD. Children with CFALD were given diagnoses of CF later than children without liver disease. There were more children with meconium ileus in the control group (14 vs 4) than among those with CFALD. CONCLUSIONS: Children with established CFALD have impaired growth and nutrition, altered body composition, and worse forced expiratory volume in 1 second values. CFALD is associated with later age of diagnosis of CF.