International Society of Paediatric Surgical Oncology (IPSO): A Short History, Developments, and Current Status.

The International Society of Paediatric Surgical Oncology (IPSO) was officially inaugurated in 1991 through the creativeness and inspiration of a collective dynamic group of paediatric surgeons committed to advancing childhood cancer. This article traces the origins and birth of IPSO tracking its modern day development to a growing world community of paediatric surgeon oncology members. LEVEL OF EVIDENCE: 5.

Treatment and outcomes of high-risk neuroblastoma in Southeast Asia: a single-institution experience and review of the literature.

Introduction: In Europe and North America, the majority of children with high-risk neuroblastoma survive the disease. Elsewhere, the treatment outcomes are poor. Methods: A retrospective review of children treated for high-risk neuroblastoma in a single institution in Singapore from 2007 to 2019 was carried out. Treatment consisted of intensive chemotherapy, surgery aimed at gross total resection of residual disease after chemotherapy, consolidation with high-dose therapy followed by autologous stem cell rescue, and radiotherapy to the primary and metastatic sites followed by maintenance treatment with either cis-retinoic acid or anti-disialoganglioside monoclonal antibody therapy. Survival data were examined on certain clinical and laboratory factors. Results: There were 57 children (32 male) treated for high-risk neuroblastoma. Their mean age was 3.9 (range 0.7-14.9) years. The median follow-up time was 5.5 (range 1.8-13.0) years for the surviving patients. There were 31 survivors, with 27 patients surviving in first remission, and the five-year overall survival and event-free survival rates were 52.5% and 47.4%, respectively. On log-rank testing, only the group of 17 patients who were exclusively treated at our centre had a survival advantage. Their five-year overall survival rate compared to patients whose initial chemotherapy was done elsewhere was 81.6% versus 41.1% (P = 0.011), and that of event-free survival was 69.7% versus 36.1% (P = 0.032). Published treatment results were obtained from four countries in Southeast Asia with five-year overall survival rates from 13.5% to 28.2%. Conclusion: Intensified medical and surgical treatment for high-risk neuroblastoma proved to be effective, with superior survival rates compared to previous data from Southeast Asia.

International Society of Paediatric Surgical Oncology (IPSO) Surgical Practice Guidelines.

Most children with tumors will require one or more surgical interventions as part of the care and treatment, including making a diagnosis, obtaining adequate venous access, performing a surgical resection for solid tumors (with staging and reconstruction), performing procedures for cancer prevention and its late effects, and managing complications of treatment; all with the goal of improving survival and quality of life. It is important for surgeons to adhere to sound pediatric surgical oncology principles, as they are closely associated with improved local control and survival. Unfortunately, there is a significant disparity in survival rates in low and middle income countries, when compared to those from high income countries. The International Society of Paediatric Surgical Oncology (IPSO) is the leading organization that deals with pediatric surgical oncology worldwide. This organization allows experts in the field from around the globe to gather and address the surgical needs of children with cancer. IPSO has been invited to contribute surgical guidance as part of the World Health Organization Initiative for Childhood Cancer. One of our goals is to provide surgical guidance for different scenarios, including those experienced in High- (HICs) and Low- and Middle-Income Countries (LMICs). With this in mind, the following guidelines have been developed by authors from both HICs and LMICs. These have been further validated by experts with the aim of providing evidence-based information for surgeons who care for children with cancer. We hope that this initiative will benefit children worldwide in the best way possible. Simone Abib, IPSO President Justin T Gerstle, IPSO Education Committee Chair Chan Hon Chui, IPSO Secretary.

The feasibility of adrenal-sparing surgery in bilateral adrenal neuroblastoma.

PURPOSE: Loss of adrenal function is a major concern in the treatment of children with bilateral adrenal neuroblastoma (BAN). We aimed to evaluate the feasibility of adrenal-sparing surgery in this unique subgroup. METHOD: Retrospective review of our center's neuroblastoma database was conducted. Patients with synchronous BAN confirmed at surgery were included. Their demographic data and clinical charts were analyzed. RESULTS: Five patients were confirmed with BAN. Mean age at diagnosis was 0.89 (0.39-1.32) years; male:female ratio was 4:1. They were stratified as stages M (n = 2), MS (n = 1), L1 (n = 1) and L2 (n = 1). MYCN amplification was present in 1 patient (stage M) and was stratified as high-risk group. All patients except one received preoperative chemotherapy. Among the 10 adrenal gland tumors, 2 underwent tumor adrenalectomy (TA) and 8 had adrenal-sparing tumorectomy (AST). After chemotherapy, 3 patients underwent single-stage bilateral AST and 1 patient underwent 2-stage TA-AST. One patient underwent upfront single-stage TA-AST, where lack of preoperative chemotherapy rendered the adrenal gland indistinguishable. The high-risk patient received autologous hematopoietic cell transplantation for consolidation. No patients required adrenal replacement therapy. All patients were alive without evidence of disease with mean follow-up 5.5 (2.6-8.5) years. CONCLUSION: Adrenal-sparing surgery is feasible in patients with BAN. LEVEL OF EVIDENCE: Level IV (case series with no comparison group).

Trapdoor anterior thoracotomy for cervicothoracic and apical thoracic neuroblastoma in children.

PURPOSE: Cervicothoracic and apical thoracic neuroblastoma pose unique surgical challenges. We report our experience with the trapdoor anterior thoracotomy (TAT) approach to overcome these difficulties. METHODS: Retrospective review of our centre's neuroblastoma database was conducted. Patients who underwent TAT at our centre were included, their demographic data and clinical reports were analyzed. RESULTS: A total of 21 patients underwent TAT for neuroblastoma, mean age at surgery of 3.5 (0.3-7.9) years, male to female ratio was 11:10. Fifteen patients had cervicothoracic tumors while 6 had apical thoracic tumors. All except 2 were primary tumors. They were stage M (n = 12), MS (n = 1), and L2 (n = 8). At pre-operative assessment, 19 patients had image-defined risk factor (IDRF), including dual compartmental involvement (n = 15), trachea/bronchus compression (n = 4), encasement of carotid (n = 5), subclavian (n = 11), and vertebral arteries (n = 6). Four underwent upfront surgery while 17 received pre-operative chemotherapy of 2-8 (mean 3.9) cycles. All patients accomplished gross total resection. None had MYCN amplification. The postoperative complications included Horner's syndrome (n = 21), Klumpke's palsy (n = 1), winged scapula (n = 1), phrenic nerve palsy (n = 1), and bronchomalacia (n = 2). CONCLUSION: Gross total resection of cervicothoracic and apical thoracic neuroblastoma can be accomplished by TAT with minimal morbidity.

Bilateral Ovarian Burkitt's Lymphoma: Successful Treatment with Preservation of Ovarian Function.

BACKGROUND: Bilateral ovarian Burkitt's lymphoma was diagnosed in a 10-year-old girl who presented with abdominal pain, constipation, and signs of ovarian torsion. CASE: Left salpingo-oopherectomy and biopsy of the right ovary were carried out as initial surgical intervention. She remained well in first complete remission at 25 months after multiagent chemotherapy, with pubertal development on clinical examination, hormonal measurements, and pelvic sonography. SUMMARY AND CONCLUSION: Although rare, Burkitt's lymphoma should be included in the differential diagnosis of bilateral ovarian tumors in childhood, and more conservative surgical management is indicated to preserve ovarian function and fertility.

Mesenteric lymphatic ligation in the prevention of chylous fistulae in abdominal neuroblastoma surgery.

PURPOSE: We evaluated the effectiveness of prophylactic mesenteric lymphatic ligation in preventing iatrogenic chylous fistulae in abdominal neuroblastoma surgery. METHOD: All patients who underwent resection of abdominal neuroblastoma between years 2002 and 2013 were included. A change in surgical strategy commenced from August 2010 when routine meticulous mesenteric lymphatic ligation (MLL) before abdominal closure was included in the primary surgery, thereby forming two study groups (Group A: before routine MLL; Group B: after routine MLL). Patients' demographics, disease characteristics, operative techniques, postoperative management and outcome were reviewed. RESULTS: There were 64 patients in Group A and 35 patients in Group B. Ten (15.6%) patients from Group A compared to none from Group B developed chylous fistulae (p = 0.01). No significant morbidity was associated with MLL. Patients' and disease characteristics in both groups were not statistically different. Patients who developed chylous fistulae were managed with combinations of dietary modifications or complete bowel rest, total parenteral nutrition and prolonged abdominal drainage. Two patients underwent laparotomy and ligation of the chylous fistulae. CONCLUSION: Chylous fistulae complicating abdominal neuroblastoma surgery disrupt neuroblastoma treatment. Meticulous MLL can be preventative if performed routinely before abdominal closure in the primary surgery.

Abdominal neuroblastoma in a child with inferior vena cava anomaly.

Congenital anomalies of the inferior vena cava are rare. Such anomalies pose great challenges to the surgeon in neuroblastoma surgery, especially when unrecognised preoperatively. We report the first case of an abdominal neuroblastoma detected in a child with a developmental anomaly of the left-sided inferior vena cava. The patient underwent surgical resection after good response to preoperative chemotherapy.

Surgical management of complications of multimodal therapy.

Multimodality therapies that include surgery, chemotherapy, radiotherapy, and various newer forms of targeted therapies have been commonly applied in childhood cancers. Such modalities are associated with complications that may adversely affect the outcome of cancer treatment. Acute complications that require surgical management form the focus of our discussion. These patients are often compromised by immunosuppression, thrombocytopenia, and malnutrition. The complications discussed include typhlitis, invasive aspergillosis (IA), pancreatitis, hemorrhagic cystitis, gastrointestinal hemorrhage, necrotizing skin and soft-tissue infections, and perianal infection. Familiarity with the spectrum of complications and their appropriate management approaches will minimize the patients' morbidity.

Pediatric risk of malignancy index for preoperative evaluation of childhood ovarian tumors.

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.

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

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.

Gene expression of TRK neurotrophin receptors in advanced neuroblastomas in Singapore--a pilot study.

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.

Perforation: a rare complication of choledochal cysts in children.

PURPOSE: Spontaneous perforation is a rare complication of choledochal cyst (CDC) which is difficult to diagnose due to its nonspecific clinical presentation. The surgical treatment can be either single-staged cyst excision or two-staged procedure with an initial drainage followed by delayed cyst excision. Both biliary duct obstruction and irritation due to refluxed pancreatic juice have been proposed as possible aetiology. In this report, we describe six cases of CDC perforation in hope to have a better understanding on the clinical features and cause of this complication. METHODS: Medical records of six patients whose diagnoses of perforated CDC were confirmed with intra-operative findings were retrospectively reviewed. Clinical data, investigation results and post-operative outcomes were analysed. RESULTS: Vomiting and abdominal pain were the most common complaints. Few patients present with clinical jaundice. Overt sign of peritonitis was absent. Both single-staged and two-staged approach offered satisfactory outcome. CONCLUSION: Hyperbilirubinaemia and remote free intra-peritoneal fluid allude the diagnosis of perforated CDC. When presenting with cholangitis, it warrants timely surgical intervention to prevent perforation. Single-staged or two-staged surgical approach would depend on stability of patient and surgical expertise available. Reversible dilatation of intra-hepatic duct suggests that increased intra-ductal pressure is a contributing factor to the perforation.

Peritoneal metastases after laparoscopic nephron-sparing surgery for localized Wilms tumor.

A 2-year-old girl was referred for the management of the progression of her localized Wilms tumor. She had undergone laparoscopic nephron-sparing surgery for her right Wilms tumor 3 months earlier. Postoperative chemotherapy was commenced 6 weeks later. Subsequent computer tomographic evaluation 12 weeks postsurgery showed local recurrence and peritoneal tumors. These findings were confirmed at laparotomy. We report the first case of peritoneal tumor dissemination after laparoscopic nephron-sparing surgery for localized Wilms tumor.

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.

Appendicitis in immunosuppressed children: Still a diagnostic and therapeutic dilemma?

Acute appendicitis in the immunosuppressed patients are often difficult to diagnose and are associated with increased morbidity and mortality. Recent debates on primary appendicitis and typhlitis-associated appendicitis have contributed to the diagnostic and therapeutic dilemma. We retrospectively reviewed all our immunosuppressed patients with appendicitis. The most frequent presenting symptom was fever followed by non-specific intermittent abdominal pain. The median delay in diagnosis was 4 days. CT scan was useful in making the diagnosis, but the presence of adjacent bowel thickening has contributed to the dilemma in diagnosis and treatment.

"Chinese fan spread" distraction technique of laparoscopic reduction of intussusception.

OBJECTIVE: The "Chinese Fan Spread" (CFS) distraction technique for laparoscopic reduction of intussusception is herein described and its outcome and benefits are evaluated. METHODS: A retrospective review was performed of all patients who underwent attempts at laparoscopic reduction of intussusception at our center. The CFS distraction technique was consistently applied in all cases. RESULTS: Fourteen patients were identified. Median age was 2.4 years (range, 4 months to 10.3 years). Indications for surgery included (1) failed pneumatic reduction (n=11), (2) need to evaluate for lead point in a patient with 4 recurrences (n=1), (3) need to biopsy the lead point in a patient with suspected lymphoma (n=1), and (4) diagnostic laparoscopy for evaluation of hematochezia (n=1). Two patients who failed laparoscopic reduction by the CFS distraction technique also failed open manual reduction, requiring right hemicolectomy. Of the 12 (86%) who were successfully reduced laparoscopically, pathologic lead points were identified in 5 (2 acute appendicitis, 1 Meckel's diverticulum, 1 harmatomatous polyp, and 1 Burkitt's lymphoma). Lead points were excised laparoscopically or via a vertical transumbilical incision. There were no complications. CONCLUSION: Laparoscopic reduction of intussusception by the CFS distraction technique is effective and safe. Lead points may be dealt with together either laparoscopically or via a transumbilical incision.

Nonrhabdomyosarcoma soft tissue sarcoma (NRSTS).

Nonrhabdmyosarcoma soft tissue sarcoma (NRSTS) is a heterogenous group of tumors analyzed as a unique group because of the rarity of each histopathological subtype. Initial information available has been obtained from adult series or pediatric case studies. Recent reports by several multi-center groups have been published that evaluated prognostic factors and treatment protocols. Established prognostic factors include tumor grade, invasiveness, size, and intergroup rhabdomyosarcoma study (IRS) group. Identification of sarcoma-specific chromosomal translocations has allowed for more accurate definitive diagnosis. Some may have prognostic significance and may offer as potential therapeutic targets. Surgery remained important, as many of the tumors are scarcely chemosensitive. With the development of multimodalities, surgical management has evolved over the years. Patients with localized unresectable disease are managed with surgery +/- radiotherapy with very good results. Localized unresectable disease is intermediate in behavior and prognosis. Patients are treated with neoadjuvant chemotherapy, +/- radiotherapy, followed by delayed surgical resection. Prognosis in patients with metastatic disease has been poor despite combination chemotherapy with surgical resection. The addition of ifosfamide and doxorubicin in the chemotherapy regimes has provided some improvement. With the lack of new active agents, we will depend on advances in molecular techniques to develop novel targeted therapies, better molecular markers and histology-specific trials to evaluate this group of tumors.