Prognostic impact of pre-referral tumor resection in unilateral Wilms tumor: A single-institute experience from a lower middle-income country.

INTRODUCTION: The objectives of this study were to evaluate the prognostic impact of pre-referral surgical resection of Wilms tumor (WT) performed at non-oncology centers, and to strategize an improved care plan for this very curable pediatric tumor. METHODS: In this study conducted in a large pediatric cancer center in Pakistan, we retrospectively reviewed the electronic medical records (EMR) of 149 patients with unilateral WT from September 2008 to August 2017. Based on treatment approach, patients were categorized into two groups: (i) pre-referral tumor resection (PTR: n = 75), and (ii) post-neoadjuvant chemo nephrectomy (PCN: n = 74). RESULTS: The proportion of metastatic disease in PTR and PCN groups was 33.3% and 35.1%, respectively. In the PTR subset, median time to admission after PTR was 5 weeks (mean 11, SEM 2.8, range: 2-202) weeks, with 53.3% (n = 40) presenting more than 4 weeks after PTR. Twenty patients had no cross-sectional imaging prior to PTR and underwent surgery after abdominal ultrasound only. On baseline imaging at our center, 58.7% (n = 44) of the PTR group had radiologically evaluable disease (four metastases only, 19 local residual tumor only, 21 both localized tumor and visible metastases). Disease staging was uncertain in 23 patients because of no or inadequate histology specimens and/or lymph node sampling in patients with no evaluable disease. Statistically significant differences were recorded for the two subsets regarding tumor volume, extent and nodularity, renal vein and renal sinus involvement, lymph node status, tumor rupture and histopathologic features, and tumor stage, with a 10-year event-free survival (EFS) for PCN and PTR of 74.3% and 50.7%, respectively (p < .001). In the PTR group, EFS for those presenting within 4 weeks and later was 91.4% versus 15.0%, respectively (p < .0001). CONCLUSION: Suboptimal pre-referral surgical intervention results in poor survival outcomes in unilateral WT. Our findings highlight the need for a comprehensive action plan for educating healthcare professionals engaged in WT diagnosis and referral process. PCN in a multidisciplinary team approach can reduce surgical morbidity and seems to be a better strategy to improve the survival rates in low-resource settings.

Case Report: Expanding the Phenotypic Spectrum of Timothy Syndrome Type 1: A Sporadic Case With a de novo CACNA1C Pathogenic Variant and Segmental Ileal Dilatation.

Background: Long QT syndactyly syndrome (long QT syndrome type 8), also known as Timothy Syndrome (TS) was first described in 1994 with still <50 case reported in the literature. The full spectrum of the syndrome is not yet known. Results: Here we report a girl who presented with new onset refractory seizures and an undiagnosed cause of intermittent abdominal distention. She also had syndactyly of her fingers and toes and was found to have prolonged QT. Upon further investigations she was found to have a de novo pathogenic variant in CACNA1C, along with Segmental Ileal Dilatation (SID), and subsequently diagnosed with Timothy syndrome. Conclusion: To our knowledge, the association of Timothy Syndrome with Segmental Ileal Dilatation, was not described before.

Prophylactic Antibiotics for Reducing Central Line-associated Blood Stream Infection in Children with Totally Implantable Venous Access Devices.

OBJECTIVE: To analyse the need of prophylactic antibiotic before the insertion of totally implantable venous access devices (TIVADs) in terms of preventing central line-associated blood stream infection (CLABSI) in early postoperative period in pediatric oncology patients. STUDY DESIGN: A cohort study. PLACE AND DURATION OF STUDY: Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore from January 2005 to June 2016. METHODOLOGY: A total of 645 consecutive children with malignancy, who were implanted with TIVAD, were included in the study. The data were collected retrospectively and divided into two groups on the basis of prophylactic antibiotic administration (Group A) received the antibiotic; and Group B did not receive the antibiotic. Both the groups were compared in terms of positive central blood cultures in the absence of any other clinical source of infection during the early postoperative period of 30 days. RESULTS: The overall infection rate was 12.54% (35 out of 279) in Group B (did not receive prophylactic antibiotic) and 11.68% (41 out of 351) in Group A (received prophylactic antibiotic) without any significant difference (p = 0.741). CONCLUSION: There was no advantage of the use of prophylactic antibiotic before TIVAD insertion in preventing early postoperative CLABSI.

Absence of the TRIP13 c.1060C>T Mutation in Wilms Tumor Patients From Pakistan.

BACKGROUND AND AIM: Wilms tumor (WT) is the most common childhood malignant renal tumor. Germline mutations in several WT predisposition genes have been identified. However, the fundamental cause of most WT patients remains unexplained. Recently, a founder mutation, c.1060C>T (p. Arg254X) in a mitotic spindle checkpoint gene, TRIP13, was reported in 5 unrelated children with WT from the United Kingdom, of Pakistani descent from Azad Kashmir region. This observation suggests other children with WT in Pakistan may also harbor this mutation. We conducted the first study to assess the contribution of TRIP13 c.1060C>T mutation to WT in Pakistan. MATERIALS AND METHODS: Constitutional genomic DNA from 68 Pakistani individuals including unrelated WT cases (n=26) and one (n=10) or both (n=32) of their parent(s) were screened for the TRIP13 c.1060C>T mutation using DNA sequence analysis. We also included positive controls in the analyses. RESULTS: The median age of WT diagnosis was 3.0 years (range, 0.75 to 10). The TRIP13 c.1060C>T mutation was not found in any WT patient (n=26) or their parents (n=42). Twenty-four patients (92.4%) presented with unilateral tumor and 2 patients (7.7%) were diagnosed with synchronous bilateral WT. Thirteen patients (50%) reported parental consanguinity. Thirteen patients (50.0%) belonged to the Punjabi ethnicity and 1 patient (3.8%) had a Kashmiri background. Four patients (16.7%) reported a family history of WT or other malignancies. The predominant histologic subtype was stromal (46.2%). The majority of patients presented with >5 cm of tumor size (81%). None of the patients had a personal or family history of congenital anomalies, or associated genetic syndromes. CONCLUSIONS: Our findings suggest that TRIP13 c.1060C>T mutation may be infrequent in Pakistani WT cases. Further evaluation of this mutation in a large number of WT patients of Kashmiri heritage and various ethnic backgrounds from Pakistan is warranted.

Short term surgical outcomes of Wilms tumour from a single institute.

Wilms tumour is the commonest solid tumour of childhood in Pakistan. In developed world the long-term outcome of Wilms tumour have significantly improved reaching up to 98% long term survival. We have no National data of prevalence, treatment and survival of this condition in Pakistan. Surgical treatment also varies in various parts of the country. We have studied our patients presenting with a diagnosis of Wilms tumour to our institute from Jan 2014 to April 2016. A total of 42 patients were operated for Wilms tumour. The most common symptoms were abdominal mass (75%), pain (28%) and fever (19%). A total of 48 tumour resections were performed, 45 total nephrectomies and 3 had nephron sparing surgery (NSS). Mean operative time was 225±78.7 minutes. Mean blood loss was 165±223.5ml. Mean size of the tumour was 102±48.4mm and mean weight of the tumour was 433±400.7gm. Ninety percent patients had a favourable histology. Mean high dependency unit (HDU) stay was 1.16±1.2 day and mean hospital stay was 6.89±3.47 days. Complications were observed in 8 patients. Surgery remains a major part of treatment for Wilms tumour.

I-131 mIBG Scintigraphy Curie Versus SIOPEN Scoring: Prognostic Value in Stage 4 Neuroblastoma

Objective: I-131 mIBG scan semi-quantitative analysis with modified Curie and the International Society of Pediatric Oncology Europe Neuroblastoma (SIOPEN) scoring systems is helpful in the evaluation of disease extent and has prognostic impact in stage 4 neuroblastoma. Methods: Retrospective, cross-sectional analysis of baseline I-131 mIBG scans in 21 patients with stage 4 or 4S neuroblastoma diagnosed between January 2007 and December 2015. All scans were assessed for Curie and SIOPEN scores. Distribution of scores was evaluated for risk factors i.e. age at diagnosis (>18 months) and early relapse (within 12 months). A curie score <2 and SIOPEN score <4 at diagnosis were correlated with event-free survival (EFS) and overall survival (OS). Results: The data set comprised of 12 (57%) males and 9 (43%) females. Patients with age >18 months (n=9) at diagnosis or early relapse (n=9) had higher Curie [mean 5+7.5 standard deviation (SD), p=0.004] and SIOPEN (mean 5.2+10.8 SD, p=0.02) scores. Patients with a Curie score <2 and a SIOPEN score of <4 had better EFS and OS than patients with higher scores. Curie: 5-year EFS=Curie <2 (79%) versus Curie >2 (33%) (p=0.03); 5-year OS=Curie <2 (56%) versus Curie >2 (36%) (p=0.01). SIOPEN: 5-year EFS=SIOPEN <4 (70%) versus SIOPEN >4 (17%) (p=0.002); 5-year OS=SIOPEN <4 (58%) versus SIOPEN >4 (17%) (p=0.04). There was no statistically significant difference between the two scoring systems in terms of survival predictive value (Hazard ratio 2.38, 95% CI: 0.33-16.9, p=0.38). Conclusion: I-131 mIBG Curie and SIOPEN scores have prognostication value in stage 4 neuroblastoma and should be routinely applied. Higher scores predict unfavorable prognosis.

Early multifocal recurrence of hepatoblastoma in the residual liver after R0 liver resection with ALPPS procedure: a case report.

Associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been successfully employed in adults to avoid potential liver insufficiency in patient with small future liver volume (FLV) when subjected to conventional right trisectionectomy. We are reporting an infant with hepatoblastoma, who underwent a technically successful ALPPS procedure with R0 resection. However he developed very early recurrence within the first month after the procedure. We present this report with a view to share our unexpected finding of early multifocal recurrence of hepatoblastoma in the residual liver after ALPPS procedure in a very young patient.

Clinical profile, treatment and survival outcomes of peadiatric germ cell tumours: A Pakistani perspective.

Germ Cell Tumours (GCTs) are rare tumours. Generally 80% are benign and 20% malignant with a bimodal age distribution. The retrospective study was conducted at Shaukat Khanum Cancer Hospital, Lahore, Pakistan, and comprised all paediatric patients below 18 years of age who received treatment for histology-proven GCT from 2006 to 2014. Of the 207 patients, 98(42.3%) were males and 109(52.7%) were females. The most common GCT was yolk sac tumour in 90(43.5%) children followed by mixed GCT in 40(19.3%) and dysgerminoma in 34(16.4%). Gonads were most commonly involved in 165(79.7%) patients with metastasis in 24(11.6%) at presentation and recurrence in 26(12.5%) patients. Overall, 133(64.3%) patients are well and followed up at regular intervals and 55(26.5%) have been lost to follow-up with an expected overall 5-year median survival of 45%. Despite the distinct clinical profile of paediatric GCT, survival can be improved by early diagnosis, regimented treatment according to set guidelines, protocols and by improving follow-up.

Endoscopic cystogastrostomy: minimally invasive approach for pancreatic pseudocyst.

Pancreatic pseudocysts in children are not uncommon. Non-resolving pseudocysts often require surgical intervention. Endoscopic cystogastrostomy is a minimally invasive procedure which is recommended for this condition. We report a large pancreatic pseudocyst in a 4-year old child, which developed following therapy with PEG-Asparaginase for acute lymphoblastic leukemia. It was managed with minimally invasive procedure.

Urinary schistosomiasis in children in the United Kingdom.

We report on two patients with urinary schistosomiasis, who both presented within a fortnight to our hospital with similar symptoms of persistent painless haematuria. Ultrasound, cystoscopic biopsies and histology were used to confirm diagnosis. Treatment with praziquantel was given. Symptoms of urinary schistosomiasis can easily be missed in non-endemic areas and possibly confused with a more sinister pathology. A thorough history and awareness of disease can avoid interventional investigations.

Combined laparoscopic and thoracoscopic excision of pheochromocytoma and functional paraganglioma.

In this paper, we report an 11-year-old girl who underwent a combined laparoscopic adrenalectomy procedure and thoracoscopic excision of a paravertebral mass. To our knowledge, this is the first such report in the English literature.

Wandering spleen: a rare cause of mesenteroaxial gastric volvulus.

Gastric volvulus is a rare cause of acute abdomen in children. Usually it is associated with defects such as diaphragmatic hernia, hiatal hernia, eventration, and paralysis of the diaphragm. We report an extremely rare case presenting with acute intractable vomiting and abdominal distention. Passage of a nasogastric tube relieved the symptoms. A history of the ingestion of a large bolus of chewing gum and a suboptimal contrast study were misleading, and there was a delay in diagnosis of 3 days. Later, repeat upper GI fluoroscopy with contrast medium identified mesenteroaxial volvulus of the stomach. Exploratory laparotomy additionally revealed a wandering spleen. Derotation of the stomach with anterior gastropexy was performed. To our knowledge, wandering spleen in association with gastric volvulus has been mentioned only three times before in the literature.

Separation of xiphi-omphalo-ischiopagus tetrapus twins with favorable internal anatomy.

Conjoined twinning is a rare occurrence, and ischiopagus variety is even more rare. So far, only 20 cases have been reported. The incidence is 1 in 500,000. Because of its rarity and variable anatomy, no definite line of treatment can be adapted. Time of operation and mode of treatment have to be tailored according to the local circumstances and organ sharing in each individual pair. The twins in this report were xi phi-omphalo-ischiopagus tetrapus conjoined twins. Although several internal organs were fused and shared, they were complete mirror image sets for each twin. In this case report, details of anatomy and more importantly, preoperative investigations, preparations, and organizational aspects that were designed to suit local conditions are described. Operative details, postoperative care, and short and long-term progress also has been highlighted.