Amos Hong Pheng Loh

Diagnostic delay in pediatric solid tumors: A population based study on determinants and impact on outcomes

Despite socioeconomic and clinical progress, pediatric tumors continue to present in advanced stage, and may be due to delays in diagnosis. This study aimed to identify factors associated with diagnostic delay (time between symptom onset and diagnosis) in pediatric tumors in a population‐based study, and to assess the impact of delay on subsequent outcome.

Delays in diagnosis of pediatric solid tumors in Singapore.

Objective To investigate social, clinical, and disease-related factors associated with diagnostic delay. Materials and Methods Two-hundred and 9 solid tumor cases reported to the Singapore Childhood Cancer Registry at KK Hospital between 1997 and 2007 were reviewed retrospectively. The natural logarithms of total delay times were correlated with social, clinical, and disease factors using univariate and multivariate analysis. Subanalysis was performed for the periods before and after first healthcare contact, which were defined as parental and physician delay, respectively. Results Mean total delay was 11.6 weeks. Mean parental and physician delay was 7.7 and 4.0 weeks, respectively. Shorter delay was associated with younger age (P<0.05), incidental detection by healthcare workers (P<0.001), and first presentations to pediatricians and nonpediatric emergency departments (P=0.01). Tumor type (P<0.01) and site (P=0.001) were also significantly related. After adjustment for other factors, extracranial germ cell tumors, abdominal tumors and first presentation to nonpediatric emergency departments were significantly associated with shorter total delay. Disease stage remained constant over time, with 30% presenting in stage 4. Conclusions Patient age, first healthcare contact, tumor type, and site were significantly related to diagnostic delay in pediatric solid tumors. Our findings reflect factors related to delay in an urban island-state with minimized confounding by healthcare access and geographic factors.

An Approach to Renal Masses in Pediatrics

Renal masses in children may be discovered during routine clinical examination or incidentally during the course of diagnostic or therapeutic procedures for other causes. Renal cancers are rare in the pediatric population and include a spectrum of pathologies that may challenge the clinician in choosing the optimal treatment. Correct identification of the lesion may be difficult, and the appropriate surgical procedure is paramount for lesions suspected to be malignant. The purpose of this article is to provide a comprehensive overview regarding the spectrum of renal tumors in the pediatric population, both benign and malignant, and their surgical management.

Novel Karyotypes and Cyclin D1 Immunoreactivity in Clear Cell Sarcoma of the Kidney

Pathological diagnosis of clear cell sarcoma of the kidney (CCSK) is challenging as it resembles blastemal Wilms tumor (WT) and other pediatric sarcomas, and does not have any distinctive immunophenotype. The YWHAE-FAM22 translocation t(10;17)(q22;p13) has been reported in a subset of CCSK. This translocation also occurs in high-grade endometrial sarcoma, in which it is associated with cyclin D1 overexpression. Hence we seek to determine YWHAE-FAM22 translocation status and cyclin D1 immunoreactivity in a series of local CCSK cases. Of 8 CCSK cases from 7 patients identified, no CCSK had the YWHAE-FAM22 fusion transcript by reverse transcriptase–polymerase chain reaction. Novel karyotypes were identified for 2 cases: 1 had t(2;13)(q13; q22) and the other t(3:17)(q29;p11.2). Excluding a case with poor tissue section antigenicity, 7 of 7 CCSKs (100%) showed diffuse and strong nuclear cyclin D1 staining. Cyclin D1 immunohistochemistry was also performed on tissue microarrays of other pediatric renal tumors: blastemal areas of 18 WT cases were negative; 6 rhabdoid tumors and 1 metanephric adenoma showed patchy and weak staining; 3 mesoblastic nephromas and 18 of 29 neuroblastomas had positive staining. Cyclin D1 immunohistochemistry helps distinguish CCSK from blastemal WT and metanephric adenoma and rhabdoid tumors, but not from neuroblastomas and mesoblastic nephromas. Cyclin D1 overexpression in CCSK is not contingent on YWHAE-FAM22 translocation, and cyclin D1 inhibition may potentially be explored as a targeted therapeutic strategy in CCSK.

Port-A-Cath Insertions in Acute Leukaemia and Childhood Malignancies

OBJECTIVE This retrospective case series sought to determine the incidence and profile of catheter-related complications associated with Port-A-Cath insertions in paediatric cancer patients, as well as predictive factors for infection-related port removals. METHODS Between January 2002 and December 2004, 175 consecutive Port-A-Cath insertions were followed for a total of 75,000 days (median, 407; range, 6-1,074). Incidence of catheter-related bloodstream infections (CRBSIs), other complications and CRBSI-related port removals were analysed for cases with acute leukaemia versus other malignancies. RESULTS A total of 33 CRBSIs were encountered in 26 cases (18.9%), an infection rate of 0.44 episodes per 1,000 catheter days. While mean preoperative platelet count was 125.34 x 10(9)/L in children with acute leukaemia and 392.11 x 10(9)/L in those with other malignancies (p < 0.01), the incidence of all complications were similar between both subgroups. Staphylococcus epidermidis (23.1%) and Klebsiella spp. (19.2%) were most commonly isolated from infected ports. Median patient age and duration of implantation in CRBSI-related port removals was 1.5 years and 111 days respectively, and 10.0 years and 414 days respectively in CRBSIs without port removal. CONCLUSION Minimal complications are associated with Port-A-Cath insertions, even in thrombocytopaenic leukaemic patients. The dominance of Gram-negative organisms in CRBSIs parallels the changing trend of nosocomial infectious agents involved in catheter-related infections.

Neonatal intestinal volvulus due to a persistent right vitelline artery

We report a case of neonatal intestinal volvulus around a persistent right vitelline artery, presenting as an aberrant parieto-mesenteric band on exploratory laparotomy. To our knowledge, this is the first case report in the English literature of a persistent right vitelline artery causing axial intestinal volvulus in a neonate. A review of the literature and the embryopathogenesis is discussed, as well as the importance of emergent diagnoses of such lesions.

XAF1 promotes neuroblastoma tumor suppression and is required for KIF1Bβ-mediated apoptosis.

Neuroblastoma is an aggressive, relapse-prone childhood tumor of the sympathetic nervous system. Current treatment modalities do not fully exploit the genetic basis between the different molecular subtypes and little is known about the targets discovered in recent mutational and genetic studies. Neuroblastomas with poor prognosis are often characterized by 1p36 deletion, containing the kinesin gene KIF1B. Its beta isoform, KIF1Bβ, is required for NGF withdrawal-dependent apoptosis, mediated by the induction of XIAP-associated Factor 1 (XAF1). Here, we showed that XAF1 low expression correlates with poor survival and disease status. KIF1Bβ deletion results in loss of XAF1 expression, suggesting that XAF1 is indeed a downstream target of KIF1Bβ. XAF1 silencing protects from NGF withdrawal and from KIF1Bβ-mediated apoptosis. Overexpression of XAF1 impairs tumor progression whereas knockdown of XAF1 promotes tumor growth, suggesting that XAF1 may be a candidate tumor suppressor in neuroblastoma and its associated pathway may be important for developing future interventions.

Influence of bony resection margins and surgicopathological factors on outcomes in limb-sparing surgery for extremity osteosarcoma

Limb‐sparing surgery for osteosarcoma requires taking wide bony resection margins while maximizing preservation of native bone and joint. However, the optimal bony margin and factors associated with recurrence and survival outcomes in these patients are not well established.

Re: External validation of the Paediatric Risk of Malignancy Index.

Sir, We appreciate the external validation of the Paediatric Risk of Malignancy Index (PRMI) reported by Hermans et al., and are pleased that the results of the index were reproducible in a different ethnic population. Interestingly, a higher rate of false positives was encountered due to large mature teratomas with large solid components (Table 1). This could be due to a difference in our definitions of what constitutes a solid component in these lesions. We recognised only soft tissue solid components in our measurements, and did not include hyperechoic contents as solid components. Posterior acoustic shadowing and solid hyperechoic components as described in common ultrasound terminology have been shown to be benign features that are negatively predictive for malignancy, and less specific for malignancy. Including bony structures or Rokitansky nodules that may be seen on computed tomography (CT) imaging as solid components may have accounted for these differences in results. To better understand these differences, we reviewed the impact of different definitions of the ‘solid component’ on the scores for mature teratomas in our original data set. In our original series, 22 of 78 (28.2%) masses were mature teratomas, comparable to the 18 of 78 (23.1%) masses in the paper by Hermans et al. The mature teratomas in our series were also large; median maximum lesional diameter was 9.15 cm (range: 3.4–15.0 cm). In our series, using our original definition, the mean maximum diameter of the largest solid component was 1.11 cm (SD 1.72 cm) in this group of tumours. This gave a median score of 1.0 (range: 0–6.4). Applying the alternative definition in this same group, the mean maximum diameter of the largest solid component was 2.38 cm (SD 2.02 cm), which gave a median score of 2.8 (range: 0–7.8). Using our original definition of the solid component, the PRMI score for all mature teratomas in the series fell below 7, predicting a benign histology. Using a wider definition that includes bony and echogenic components in mature teratomas resulted in an elevated PRMI score above the cut-off of 7. Thus, a wider definition of what constitutes a solid component can affect the rate of false positives, particularly when the PRMI is applied to mature teratomas.n References

Thyroglossal duct cyst carcinoma: diagnostic and management considerations in a 15-year-old with a large submental mass

A 15-year old boy presented with a 2-year history of a painless slowly enlarging submental neck mass. Head and neck imaging showed a multicystic mass with a central solid component that was closely applied to the hyoid bone. Core needle biopsy under general anaesthesia revealed a papillary thyroid neoplasm. The mass was resected and frozen section histology confirmed papillary carcinoma. Intraoperatively, enlarged cervical lymph nodes were palpable. Bilateral neck dissections and total thyroidectomy with parathyroid reimplantation were performed. On histological examination, the thyroid gland was not involved. The patient recovered uneventfully from the surgery and is planned for radioactive iodine therapy and thyroxine suppression, with subsequent follow-up with serum thyroid-stimulating hormone and thyroglobulin for surveillance. We review the literature and discuss challenges in the diagnosis and surgical management of this rare entity in the paediatric age group.