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Osteosarcoma is the commonest malignant bone tumor of children and adolescents and is characterized by a high risk of recurrence despite multimodal therapy, especially in metastatic disease. This suggests the presence of clinically undetected cancer cells that persist, leading to cancer recurrence. We sought to evaluate the utility of peripheral blood exosomes as a more sensitive yet minimally invasive blood test that could aid in evaluating treatment response and surveillance for potential disease recurrence. We extracted exosomes from the blood of pediatric osteosarcoma patients at diagnosis (n=7) and after neoadjuvant chemotherapy (n=5 subset), as well as from age-matched cancer-free controls (n=3). We also obtained matched tumor biopsy samples (n=7) from the cases. Exosome isolation was verified by CD9 immunoblot and characterized on electron microscopy. Profiles of 780 cancer-related transcripts were analysed in mRNA from exosomes of osteosarcoma patients at diagnosis and control patients, matched post-chemotherapy samples, and matched primary tumor samples. Peripheral blood exosomes of osteosarcoma patients at diagnosis were significantly smaller than those of controls and overexpressed extracellular matrix protein gene THBS1 and B cell markers MS4A1 and TCL1A. Immunohistochemical staining of corresponding tumor samples verified the expression of THBS1 on tumor cells and osteoid matrix, and its persistence in a treatment-refractory patient, as well as the B cell origin of the latter. These hold potential as liquid biopsy biomarkers of disease burden and host immune response in osteosarcoma. Our findings suggest that exosomes may provide novel and clinically-important insights into the pathophysiology of cancers such as osteosarcoma., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CL is a co-founder of Biolidics, Singapore. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: Gross total resection of neuroblastoma is associated with lymphatic leaks that can delay postoperative resumption of treatment. To prevent postoperative lymphatic leak, we introduced systematic lymphatic repair (SLR), which involved oversewing the entire edge of the disrupted lymphatic plane after neuroblastoma resection. We sought to study the impact of SLR on postoperative lymphatic leak and time to return to treatment., Methods: We reviewed 60 neuroblastoma patients who underwent gross total resection at KK Women's and Children's Hospital. Patient, disease, and operative factors were correlated with surgical drainage, treatment delay and length of stay (LOS). Among patients with sufficient records, the interaction between variables associated with drainage, delay and LOS outcomes were compared in 14 patients who had SLR versus 35 historical controls who had targeted lymphatic repair (TLR)., Results: Postoperative drain duration and volume were significantly higher in tumors with ≥2 image-derived risk factors (IDRFs, P = 0.005 and P = 0.013, respectively) or vessel encasement (P = 0.031 and P = 0.024, respectively). Longer LOS was significantly associated with ≥2 IDRFs (P = 0.006). All forms of suture repair of lymphatics and use of Tachosil™ were associated with significantly longer postoperative drain duration (P < 0.05); the former was also associated with significantly higher total drain volume (P < 0.05) - indicating appropriate use of these adjuncts in patients at risk of chyle leak. In patients who had suture repair of lymphatics, SLR was significantly associated with reduced postoperative interval to chemotherapy resumption (P = 0.014, two-way ANOVA)., Conclusion: A systematic approach to repair of lymphatic channels following neuroblastoma resection can significantly reduce time to postoperative resumption of treatment., Type of Study: Clinical Research., Level of Evidence: III., Competing Interests: Conflicts of interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: New histomolecular subtypes of rhabdomyosarcoma have recently been defined but their corresponding clinical characteristics are not well described. Also, these clinical phenotypes vary greatly by age and ethnicity but have not been profiled in Asian populations. Thus, we sought to determine the landscape of rhabdomyosarcoma subtypes in a national Asian cohort and compare clinical characteristics among age groups and molecular subtypes., Methods: We performed a retrospective population-based study of all rhabdomyosarcoma patients in Singapore public hospitals from 2004 to 2014 (n = 67), and assigned histomolecular subtypes according to the updated 2020 WHO classification of soft tissue tumors following central pathology review and molecular profiling., Results: Age-specific prevalence followed a tri-modal peak. There were significantly more embryonal and alveolar (p = 0.032) and genitourinary (non-bladder/prostate) tumors (p = 0.033) among children. Older age was associated with complete resection among spindle cell/sclerosing tumors (p = 0.027), with the omission of chemotherapy among embryonal tumors (p = 0.001), and with poorer survival among embryonal and alveolar tumors (p = 0.026, p = 0.022, respectively). Overall survival differed with stage, group, and surgical resection, adjusted for age group (p = 0.004, p = 0.001, p = 0.004, respectively). Spindle-cell/sclerosing tumors showed an indolent phenotype with a significantly lower incidence of nodal metastasis (p = 0.002), but two of 15 patients with MYOD1 mutations had a contrastingly aggressive disease., Conclusion: Disease and treatment response profiles of rhabdomyosarcoma subtypes vary significantly between adults and children, especially surgical resectability. In our Asian population, poorer outcomes were observed in adults with embryonal and alveolar tumors, while activating mutations influence the behavior of otherwise favorable spindle cell/sclerosing tumors., (© 2023 The Authors. Asia-Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.)

Perivascular epithelioid cell tumours (PEComa) are rare tumours of mesenchymal origin. We report a 39-year-old patient who presented with painful defecation secondary to an anorectal mass. The diagnosis of anorectal PEComa was confirmed following excision and histopathological examination. We review the literature and discuss the management of this uncommon entity., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A lack of consensus exists as to the timing of kidney biopsy in children with steroid-dependent nephrotic syndrome (SDNS) where minimal change disease (MCD) predominates. This study aimed at examining the applicability of a biomarker-assisted risk score model to select SDNS patients at high risk of focal segmental glomerulosclerosis (FSGS) for biopsy., Methods: Fifty-five patients with SDNS and biopsy-proven MCD (n = 40) or FSGS (n = 15) were studied. A risk score model was developed with variables consisting of age, sex, eGFR, suPAR levels and percentage of CD8 + memory T cells. Following multivariate regression analysis, total risk score was calculated as sum of the products of odds ratios and corresponding variables. Predictive cut-off point was determined using receiver operator characteristics (ROC) curve analysis., Results: Plasma suPAR levels in FSGS patients were significantly higher, while percentage of CD45RO + CD8 + CD3 + was significantly lower than in MCD patients and controls. ROC analysis suggests the risk score model with threshold score of 16.7 (AUC 0.84, 95% CI 0.72-0.96) was a good predictor of FSGS on biopsy. The 100% PPV cut-off was >24.0, while the 100% NPV was <13.3., Conclusion: A suPAR and CD8 + memory T cell percentage-based risk score model was developed to stratify SDNS patients for biopsy and for predicting FSGS.

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., Competing Interests: FINANCIAL SUPPORT AND CONFLICTS OF INTEREST Zhang'e Choo and the project is supported by the National Medical Research Council, Singapore New Investigator Grant awarded to Zhi Xiong Chen. Susanne Schlisio is supported by grants from the Swedish Children Cancer Foundation and the Swedish Research Council. In addition, all authors declare that there is no conflict of interest.

Background: Osteosarcoma (OS) and the Ewing sarcoma family of tumors (ESFT) are the most common primary pediatric bone malignancies. We sought to assess the diagnostic accuracy of initial tumor biopsies in patients with OS or ESFT at a pediatric cancer center., Methods: All biopsies performed at initial presentation of patients with OS or ESFT at our institution from 2003 to 2012 were retrospectively reviewed. Diagnostic accuracy and incidence of complications were correlated with study variables using logistic regression analysis., Results: One hundred forty-two biopsies were performed in 105 patients (median age 13.4years, range: 1.8-23.0), 104 (73.2%) OS and 38 (27.8%) ESFT. Thirty-one (21.8%) were performed on metastatic sites. Eighty-five (76.6%) of 111 primary site biopsies were open procedures, and 26 were percutaneous (23.4%). Primary site biopsies were successful in 94.1% of open and 73.1% of percutaneous procedures. Odds of obtaining a successful diagnostic specimen were 7.8 times higher with open approach (CI: 1.6-36.8). Metastatic site biopsies were successful in 66.7% of percutaneous and 100% of open and thoracoscopic procedures., Conclusion: Biopsy of metastatic sites was equal to primary site in obtaining diagnostic material with the added benefit of accurate staging, with few adverse events and high diagnostic yield., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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., (2015 BMJ Publishing Group Ltd.)

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.

Background: Tumor biopsies are central to the diagnosis and management of cancer and are critical to efforts in personalized medicine and targeted therapeutics. In the current study, the authors sought to evaluate the safety and accuracy of biopsies in children with cancer., Methods: All biopsies performed in children at the study institution with a suspected or established diagnosis of cancer from 2003 through 2012 were reviewed retrospectively. Patient characteristics and disease-related and procedure-related factors were correlated with procedure-related complications and diagnostic accuracy using logistic regression analysis., Results: A total of 1073 biopsies were performed in 808 patients. Of 1025 biopsies with adequate follow-up, 79 (7.7%) were associated with an adverse event, 35 (3.4%) of which were minor (grade 1-2) and 32 (3.1%) of which were major (grade 3-4) (grading was performed according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). The most common major adverse events were blood transfusion (>10 mL/kg; 24 cases) and infection requiring intravenous antibiotics (6 cases). Eleven deaths (1.4%) occurred within 30 days after the procedure, but the procedure may have contributed to the outcome in only 2 cases. A total of 926 biopsies (90.3%) provided definitive histologic diagnoses. Using multivariable analysis, biopsy site, preprocedure hematocrit level, and body mass index were found to be associated with the risk of postprocedural complications (P<.0001, P<.0001, and P =.0029, respectively). Excisional biopsy and biopsy site were found to be independently associated with obtaining a diagnostic result (P =.0002 and P =.0008, respectively)., Conclusions: Tumor biopsies in children with cancer are associated with a low incidence of complications and a high rate of diagnostic accuracy. The predictive factors identified for adverse outcomes may aid in risk assessment and preprocedural counseling., (© 2014 American Cancer Society.)

Background: 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., Procedure: We conducted a retrospective review of outcomes in children and adolescents with newly diagnosed osteosarcoma from 1986 to 2012, where bony resection margins for limb-sparing surgeries were decreased serially from 5 to 1.5 cm. The association between bony margins and other surgicopathological factors with survival and recurrence outcomes was determined., Results: In 181 limb-sparing surgeries in 173 patients, planned and actual bony resection margins were not significantly associated with local recurrence-free survival (LRFS), event-free survival (EFS), and overall survival (OS)-at median 5.8 years follow-up, decreasing planned bony resection margins from 5 to 1.5 cm did not significantly decrease survival outcomes. Multivariable analysis showed that the presence of distant metastases at diagnosis was associated with decreased LRFS, EFS, and OS (P = 0.002, 0.005, and <0.0001, respectively). Post-chemotherapy tumor necrosis ≤90% was associated with decreased EFS and OS (P = 0.001 and 0.022, respectively). Earlier years of treatment and pathologic fractures were associated with decreased OS only (P = 0.018 and 0.008, respectively); previous cancer history and male gender were associated with decreased EFS only (P = 0.043 and 0.023, respectively)., Conclusion: We did not observe significant increase in adverse survival outcomes with reduction of longitudinal bony resection margins to 1.5 cm. Established prognostic factors, particularly histologic response to chemotherapy and metastases at diagnosis, remain relevant in limb-sparing patients. Pediatr Blood Cancer 2015;62:246-251. © 2014 Wiley Periodicals, Inc., Competing Interests: STATEMENT No conflicts of interest to declare., (© 2014 Wiley Periodicals, Inc.)

The application of thoracoscopic surgical techniques to pediatric solid tumors represents an important adjunctive tool for the surgical management of childhood cancer. Nearly four decades has passed since the introduction of minimally invasive chest surgery in children, and although the adoption of minimally invasive surgery in general pediatric surgical practice is better recognized, its role in pediatric oncology is still considered a developing field. As no consensus exists regarding the use of thoracoscopy for pediatric thoracic solid tumors, the purpose of this article is to review the current literature surrounding the use of thoracoscopic interventions in pediatric oncology and examine established indications, procedures, and technologic advances.

The application of minimally invasive surgical techniques to pediatric abdominal tumors is a controversial application towards the surgical management of childhood cancer. Although general pediatric surgeons practice minimally invasive surgery techniques in a vast array of abdominal cases, its role in pediatric oncology is still developing, with no consensus in North America about its use for pediatric solid abdominal tumors. The purposes of this article are to review the current literature about the use of minimally invasive surgery in pediatric abdominal oncology and to examine established indications, procedures and technologic advances., (Published by Elsevier Inc.)

Background: The optimal management of locally recurrent pediatric osteosarcoma is not established, especially after prior limb-sparing surgery. We describe our experience in the management of these patients and identify prognostic indicators of post-recurrence survival., Methods: We conducted a retrospective, single-institution review of patients with locally recurrent osteosarcoma after limb-salvage surgery who were treated between October 1989 and January 2012. The management of each recurrence was evaluated, and patient, disease, and treatment factors were correlated with post-recurrence survival (PRS)., Results: Of 200 patients who underwent limb-sparing procedures, 18 (9 %) had biopsy-proven local recurrence. Recurrences occurred in soft tissue in 15 patients (83.3 %). Six patients (33.3 %) were amenable to repeat limb-sparing surgery. Median time to local recurrence was 1.4 (range 0.6-10.4) years. Median PRS was 11.8 months (range 3.7 months-12.1 years). Post-recurrence survival was significantly associated with the length of resection margins and was longer when recurrent tumors were resected with margins of ≥1 cm, compared with subcentimeter or positive margins (P = 0.03). Median PRS was longer in patients who underwent amputations (2.44 years) than those who underwent repeat limb-sparing surgery (0.86 years), and in patients who had distant metastases resected (2.7 years) than those who did not (0.85 years); however, differences were not significant., Conclusions: Local management of recurrent osteosarcoma in a previously reconstructed limb is highly individualized. A sufficiently wide resection is important for local control of recurrences, independent of the type of surgery. Maintaining control of distant metastases may also contribute to improved survival.

Purpose: To evaluate the diagnostic accuracy of preoperative serum alpha-fetoprotein (AFP) levels in predicting malignancy risk in children and adolescents presenting with ovarian neoplasms., Methods: In 110 girls aged 18 and below diagnosed with ovarian neoplasms, we retrospectively correlated preoperative serum AFP levels with histological diagnosis of germ cell tumor or immature teratoma (GCT/IT) versus non-GCT/IT, and benign versus non-benign. We determined area under receiver-operating characteristic curves (AUC), sensitivity, specificity, and likelihood ratios., Results: Twenty patients (18.2 %) had non-benign ovarian neoplasms, of which 12 had GCT/IT (10.9 %). In diagnosing GCT/IT versus non-GCT/IT, specificity of preoperative serum AFP was 87.8 %, sensitivity 66.7 %, and AUC 0.853. Excluding infants to remove the effects of increased variance in AFP in this group, specificity improved (92.0 %), but not sensitivity (66.7 %); AUC was 0.926. Increasing AFP cutoff to two times upper normal limit improved specificity (94.9 %), but not sensitivity (66.7 %). For benign versus non-benign tumors, AFP specificity was only 88.9 % and sensitivity 50.0 %., Conclusion: The diagnostic accuracy of preoperative serum AFP for detecting GCT/IT in girls was limited by poor sensitivity and positive predictive value. Excluding infants and raising cutoff levels improved specificity marginally. Clinicians should be aware of these limitations when using AFP in the preoperative evaluation of childhood ovarian neoplasms.

Children with solid tumors represent a unique population. Recent improvements in pediatric solid tumor survival rates have been confined to low- and moderate-risk cancers, whereas minimal to no notable improvement in survival have been observed in high-risk and advanced-stage childhood tumors. Treatments for patients with advanced disease are rarely curative, and responses to therapy are often followed by relapse, which highlights the large unmet need for novel therapies. Recent advances in cancer treatment have focused on personalized therapy, whereby patients are treated with agents that best target the molecular drivers of their disease. Thus, a better understanding of the pathways that drive cancer or drug resistance is of critical importance. One such example is the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway, which is activated in many solid cancer patients and represents a target for therapy. PI3K/Akt/mTOR pathway activation has also been observed in tumors resistant to agents targeting upstream receptor tyrosine kinases (RTKs). Agents that target this pathway have the potential to shut down survival pathways, and are being explored both in the setting of pathway-activating mutations and for their ability to restore sensitivity to upstream signaling targeted agents. Here, we examine the role of the PI3K/Akt/mTOR pathway in pediatric solid tumors, review the novel agents being explored to target this pathway, and explore the potential role of the inhibition of this pathway in the clinical development of these agents in children.

Background: 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., Procedure: Natural logarithm of delay was retrospectively described for 390 newly diagnosed tumors reported to the Singapore Childhood Cancer Registry from 1997 to 2007. Delay was correlated with socio-demographic, disease and healthcare-system factors using multivariate linear regression, and with event-free survival (EFS) using Cox regression analysis., Results: Total median delay was 5.3 weeks (range 0.1-283.1). Shorter delay was independently associated with younger patient age (P = 0.006), abdominal and pelvic sites (P < 0.001 and P = 0.036, respectively), incidental diagnoses by healthcare staff (P = 0.002), and when pediatric emergency units were the first contacted healthcare facilities and the first to raise suspicion of malignancy (P = 0.034, and P = 0.018, respectively). These factors explained only a small percentage of variance in delay times (21%). Delay was not associated with EFS and disease stage, with 24% of tumors presenting in stage 4., Conclusions: Diagnostic delay was independently associated with age and site of presentation, and points of first symptom detection, first healthcare contact, and first suspicion of malignancy. The broad range of clinical variables analyzed could only account in a small way for differences in delay times observed. While overall delay times were short, they did not influence disease stage at presentation and eventual outcome., (Copyright © 2011 Wiley Periodicals, Inc.)

Purpose: This study aimed to develop and provisionally validate a novel scoring index for preoperative cancer-risk prediction in childhood ovarian tumors., Methods: Fifty-five girls aged 18 and below underwent surgery for ovarian masses between 2004 and 2009. Benign or non-benign histological diagnoses (the latter including all malignant and borderline tumors and tumors containing immature components) were correlated with clinical and biochemical parameters, and blinded scores of ultrasound and computed-tomography using multivariate logistic regression. Regression coefficients were used as weighting factors to create an additive index. This index was validated prospectively against 23 consecutive adnexal masses operated in 2010., Results: In total, 67 tumors were benign and 11 non-benign. Non-benign diagnosis was independently associated with the maximum diameter of the largest solid component (score = value in cm), the presence of sex hormone-related symptoms (score = +6), and enhancement or flow in a septum or solid papillary projection (score = +4). The novel scoring index was calculated as the total score of these three parameters. A cutoff score of 7 gave a specificity of 97.9% and sensitivity of 87.5% for the training data set, and specificity and sensitivity of 100% for the pilot testing set., Conclusion: The novel pediatric risk-of-malignancy index is able to accurately discriminate between benign and non-benign ovarian tumors in children and adolescents. Its preoperative application may guide surgical management decisions before the availability of histological confirmation.

The clinical hallmark of neuroblastoma is heterogeneity. Biologically, ploidy and N-Myc amplification are currently the only 2 features used to define risk group and to determine therapy. Tyrosine kinase neurotrophin receptors (Trks, including TrkA, TrkB, and TrkC) are important in the clinical and biological behavior of neuroblastomas. The authors aim to study Trks gene expression in their local population of advanced neuroblastoma patients. Multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) assay on the expression of TrkA, TrkB, TrkB-truncated, and TrkC was performed on a total of 19 advanced neuroblastoma archival tumors, diagnosed in KK Women's and Children's Hospital between 2003 and 2007. Of the 19 tumors investigated, Trks expression was present in 14 (73.6%) cases. Of these cases, 8 (42.1%), 10 (52.6%), 7 (36.8%), and 6 (31.6%) expressed TrkA, TrkB, TrkB-truncated, and TrkC receptor mRNAs, respectively. Subsequently, the authors compared Trks expression with N-Myc amplification status of the 19 patients. N-Myc was amplified in 5 (26.3%) of the cases. Within the non-N-Myc-amplified group, Trks expression was present in 9 (64%) of the 14 cases. The significant expression of Trk isoforms among advanced neuroblastoma cases as evident from this study support their role as possible risk assessment tools alongside N-Myc amplification status.

Introduction: The purpose of this case series was to determine the sonographic features of neonatal ovarian torsion., Materials and Methods: Seven surgically proven cases of neonatal ovarian cysts were included in this retrospective study. The patients were divided into 2 groups, torsion and non-torsion. These 7 patients were evaluated for the clinical presentation, sonographic features, surgical and pathological findings. The findings on follow-up sonography after surgery were also noted., Results: The sonographic appearance was variable. Of the 4 cases with torsion, 2 lesions had internal echoes with 'fi sh-net appearance'. The other 2 lesions were predominantly cystic on the sonography with internal echoes and echogenic nodule. A calcific focus was present in 1 of these echogenic nodules. One of the cysts had fluid-fluid level. In the non-torsion group, only 1 lesion had mixed echogenic appearance. The other 2 lesions were cystic with low level internal echoes in 1 of the cysts. The surgical procedure performed in the torsion group was salpingo-oophorectomy in 2 patients and oophorectomy in 1 patient. In 1 patient, cystectomy was attempted without success. In the non-torsion group, only cystectomy was performed with preservation of normal ovaries, which was confirmed on follow-up sonography., Conclusion: The sonographic features of cysts with 'fish-net appearance', fluid-debris level and cysts with echogenic nodule favour torsion. The former sign has so far not been described as a sonographic predictor for neonatal ovarian torsion.

Colonic perforation is an uncommon cause of acute abdomen in paediatric patients, and can present a diagnostic enigma as well as management challenge to the paediatric surgeon. An adolescent developed multiple colonic perforations following a short course of oral indomethacin, requiring emergency hemicolectomy. This is the youngest known case of enteral non-steroidal anti-inflammatory drug (NSAID)-mediated large bowel injury. We review current evidence on NSAID-related enteropathy, and postulate potentiating mechanisms that may have accounted for the unusually rapid clinical course of our patient.

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.

Introduction: While benign prostatic hyperplasia (BPH) incidence has been shown to vary by race and ethnicity, data is lacking among Asians. This study aimed to describe the baseline symptom profile and response to medical therapy in a multiracial Singaporean cohort with BPH., Materials and Methods: International Prostate Symptom Score (IPSS), uroflowmetry and prostate specific antigen (PSA) levels were retrospectively analysed for 887 men at presentation and on follow-up 1 year later. Following diagnosis, 150 men were managed conservatively and 586 men with drugs; 151 received surgery., Results: Overall median IPSS scores were 9.0 at baseline. Malay men most often had severe symptoms (17.3%), compared to other groups (Chinese 11.7%, Others 11.1%, Indians 10.7%). Indians most frequently showed improvement in the Quality of Life (QOL) score following intervention (64.3%). Malays had the poorest initial mean peak-flow rates (9.6 mL/s) and Chinese, the highest (12.0 mL/s). Initial post-void residual urine volume was highest in Malays (100.1 mL) but showed greatest reduction with medical treatment. Median IPSS scores decreased from 10.5 below 50 years old to 7.0 above 80 years old. Peak-flow rates were 12.6 to 7.2 mL/s respectively, with a corresponding upward trend in RU. Treatment with a combination of 5-alpha-reductase inhibitor and alpha-blocker yielded the greatest improvement in IPSS and QOL scores, and residual urine volume (71.4%, 60% and 68.8%, respectively). Indians had the lowest initial and follow-up PSA (1.5 and 1.2, P = 0.8 and 0.6, respectively)., Conclusions: Inter-ethnic differences in symptom perception and quantitative assessment of BPH were evident among our multiracial urban study cohort, as well as varied degrees of response to the medical treatments instituted.

The kidneys can be damaged by a large number of therapeutic agents. The aim of this article is to discuss the pathological features of drug-induced renal disease as diagnosed by kidney biopsy. The literature is reviewed and cases seen by the authors that have a known drug association are analysed. Mechanisms of injury are varied and all renal structures may be affected. The tubulointerstitial compartment is most frequently involved, but glomerular and vascular lesions are seen in a significant proportion of cases.

Background: Mazabraud's syndrome was first described, by Mazabraud et al. as a rare disease, associated with single or multiple intramuscular myxomas with monostotic or polyostotic forms of fibrous dyplasia,, Purpose: Reports of this syndrome is rare and usually associated with myoxomatas. The authors would want to report the occurrence of this rare case associated with a hamartoma as basis for record and future studies., Method: An adult male came to the institution 4 years ago complaining of a right unilateral proptosis that he had since childhood. However, proptosis progressed in a month's time accompanied by right eye redness. Right eye was congested with a palpable firm mass on the right lower lid. Best corrected visual acuity was 6/15-2. Pupillary examination revealed the presence of RAPD on the right eye. Exophthalmometry revealed a 10 mm proptosis. EOMS were restricted on the right eye and diplopia was noted in all gazes. Ishihara test showed 14/15 for the right eye. CT SCAN and MRI confirmed a mild inflammatory extraconal or intramuscular mass in the right obito-retrobulbar region. Bony changes seen in the right zygoma, sphenoid bone and squamous part of the temporal bone with extensive bone mineralization. The patient underwent a right lateral orbitotomy with biopsy and debulking of the inferior orbital mass. Histopathology revealed a hamartomatous lesion., Conclusion: Due to the associated soft tissue lesion with multiple craniofacial bone changes, this case may be considered a variant of Mazabraud's Syndrome. The associated hamatomatous lesion may be a rare occurrence that should be noted.

Background: Unnecessary delay of insertion of Port-A-Cath indwelling venous catheters in thrombocytopenic patients may result from fear of potential morbidity. This study sought to compare the morbidity of Port-A-Cath insertions in acute leukemic patients with platelet counts below and above 50 x 10(9)/L., Method: Incidence and profile of catheter-related bloodstream infections (CRBSIs) and other complications were determined in 80 consecutive Port-A-Cath insertions in pediatric patients with acute leukemia from January 2002 to December 2004. Subgroup analysis was performed for patients with platelet levels below and above the recommended safe level of 50 x 10(9)/L., Results: Twenty-two (27.5%) patients had insertions performed at platelet levels below the recommended level (median, 35.3; range, 10-49 x 10(9)/L); postoperative counts were correspondingly higher (median, 66.0; range, 20-207 x 10(9)/L) with perioperative platelet transfusion. Catheter-related bloodstream infection incidence was similar in patients with platelets less than and greater than the recommended threshold (18.2% vs 17.2%, respectively), and likewise for CRBSIs encountered in the immediate 30 postoperative days (4.6% and 5.2%, respectively). Only 2 episodes of postoperative bleeding occurred, both in the group with platelet counts greater than 50 x 10(9)/L, with an equally low incidence of other local and mechanical complications in both subgroups. Patient demographics and other preoperative blood parameters did not differ significantly., Conclusion: Preoperative thrombocytopenia was not associated with increased incidence of postoperative complications for Port-A-Cath insertions in acute leukemic children.

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.

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.

Introduction: We report a case of sudden death due to granulomatous myocarditis and propose that cardiac sarcoid could have been the underlying aetiology. This is the first case reported in Singapore. The differential diagnoses for granulomatous myocarditis including sarcoidosis and its cardiac manifestations as well as idiopathic giant cell myocarditis are discussed., Clinical Picture: A 53-year-old Indian woman died suddenly and autopsy revealed bilateral hilar adenopathy and myocardial infiltrates which proved to be granulomatous in nature., Conclusion: Sarcoidosis may not be a rarity here and it is important to recognise the different clinical manifestations.