Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Children Aged ⩾6 Years with Cystic Fibrosis and at Least One F508del Allele: A Phase 3, Open-Label Clinical Trial.

Rationale: A 24-week, phase 3, open-label study showed elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was safe and efficacious in children aged 6-11 years with cystic fibrosis (CF) and one or more F508del-CFTR alleles. Objectives: To assess long-term safety and efficacy of ELX/TEZ/IVA in children who completed the pivotal 24-week phase 3 trial. Methods: In this phase 3, two-part (part A and part B), open-label extension study, children aged ⩾6 years with CF heterozygous for F508del and a minimal function CFTR mutation (F/MF genotypes) or homozygous for F508del (F/F genotype) who completed the 24-week parent study received ELX/TEZ/IVA based on weight. Children weighing <30 kg received ELX 100 mg once daily/TEZ 50 mg once daily/IVA 75 mg every 12 hours, whereas children weighing ⩾30 kg received ELX 200 mg once daily/TEZ 100 mg once daily/IVA 150 mg every 12 hours (adult dose). The 96-week analysis of part A of this extension study is reported here. Measurements and Main Results: Sixty-four children (F/MF genotypes, n = 36; F/F genotype, n = 28) were enrolled and received one or more doses of ELX/TEZ/IVA. Mean (SD) period of exposure to ELX/TEZ/IVA was 93.9 (11.1) weeks. The primary endpoint was safety and tolerability. Adverse events and serious adverse events were consistent with common manifestations of CF disease. Overall, exposure-adjusted rates of adverse events and serious adverse events (407.74 and 4.72 events per 100 patient-years) were lower than in the parent study (987.04 and 8.68 events per 100 patient-years). One child (1.6%) had an adverse event of aggression that was moderate in severity and resolved after study drug discontinuation. From parent study baseline at Week 96 of this extension study, the mean percent predicted FEV1 increased (11.2 [95% confidence interval (CI), 8.3 to 14.2] percentage points), sweat chloride concentration decreased (-62.3 [95% CI, -65.9 to -58.8] mmol/L), Cystic Fibrosis Questionnaire-Revised respiratory domain score increased (13.3 [95% CI, 11.4 to 15.1] points), and lung clearance index 2.5 decreased (-2.00 [95% CI, -2.45 to -1.55] units). Increases in growth parameters were also observed. The estimated pulmonary exacerbation rate per 48 weeks was 0.04. The annualized rate of change in percent predicted FEV1 was 0.51 (95% CI, -0.73 to 1.75) percentage points per year. Conclusions: ELX/TEZ/IVA continued to be generally safe and well tolerated in children aged ⩾6 years through an additional 96 weeks of treatment. Improvements in lung function, respiratory symptoms, and CFTR function observed in the parent study were maintained. These results demonstrate the favorable long-term safety profile and durable clinical benefits of ELX/TEZ/IVA in this pediatric population. Clinical trial registered with www.clinicaltrials.gov (NCT04183790).

Comparison of the Surgical Outcomes in Neonates with Left-sided Congenital Diaphragmatic Hernia with Only Skin Closure versus Abdominal Muscle Closure.

Aim: This study aims to compare the outcome of neonatal left congenital diaphragmatic hernia (CDH, Bochdalek type) repair through laparotomy with and without abdominal muscle closure. Materials and Methods: This retrospective study was conducted between January 2012 and May 2021 at a neonatal surgical unit of a Tertiary Care Center. Demographic details, preoperative management, Two-dimensional-echo, intra-operative findings, postoperative course, and follow-up data were collected and analyzed. Results: The study group comprised 50 neonates with a mean standard deviation (SD) age at admission: 4.44 (5.12) days, male: female ratio of 3:2, and mean (SD) weight: 2.73 (0.51) kg. Following repair of the diaphragmatic defect through laparotomy, 26 (52%) underwent skin closure alone, whereas 24 (48%) underwent abdominal muscle closure. Postoperatively, there was a significant fall in the level of platelets (P = 0.021), increase in pressure support by at least 4-5 cm H2O (P = 0.027), and increase in the blood urea (P < 0.001), creatinine (P = 0.005), lactate (P = 0.019), and acidosis (P = 0.048) in the muscle closure group. Although not statistically significant, there was a fall in the urine output and blood pressure in this group. There was no significant difference in the duration of inotropes. Mortality was 8 (32%) in the skin closure group, and 14 (61%) in the muscle closure group (P = 0.05). Conclusions: Neonates undergoing left CDH repair through the abdominal route with skin closure alone, had better survival, as well as hematological, renal, and ventilatory parameters than those who underwent muscle closure. It is a useful surgical modification to improve outcome in centers with limited facilities.

A higher tumor volume and undernutrition at diagnosis adversely affect the survival of children with Wilms tumor: A study of 200 patients.

BACKGROUND: Distinct prognostic factors for Wilms tumor (WT) in low- and middle-income countries need identification. METHODS: Retrospective study of patients with WT managed by the International Society of Pediatric Oncology (SIOP) approach for over 11 years (2005-2016) at a single center in Chandigarh, India. RESULTS: The study included 200 patients (median age: 33.5 months). The tumor stage (SIOP) distribution included stage I (30%), II (36%), III (14%), IV (17%), and V (3%). The histology-risk groups were low (8%), intermediate (84%), and high risk (9%). At diagnosis, 68 out of 190 (36%) patients were underweight. The median tumor volume at diagnosis was 481 ml (interquartile ratio [IQR]: 306.9, 686.8, n = 146). Following neoadjuvant chemotherapy, it reduced to 110 ml (IQR: 151.2, 222, n = 77). Treatment was abandoned in 20.5% of the patients. Treatment-related mortality occurred in 13 of 179 (7.2%) patients. Relapse occurred in 26 of 158 (16.5%) patients. The 3-year overall survival (OS) and event-free survival (EFS) of patients who completed therapy were 78.3 and 72%, respectively. The stage (p = .013) and histology (p = .023) influenced OS. A lower OS in stage II (75.4%) versus stage III disease (83.7%) suggested understaging. Patients with a higher tumor volume at diagnosis (p = .005; odds ratio [OR]: 0.99; 95% confidence interval [CI]: 0.99-1.00) or a lower weight-for-age z-score (p = .002; OR: 1.68; 95% CI: 1.21-2.33) had an increased risk of death or relapse. CONCLUSIONS: The 3-year OS and EFS of children who completed therapy were 78.3 and 72%, respectively. A higher tumor volume and lower weight-for-age z-score at diagnosis were identified as distinct adverse prognostic factors. A likely suboptimal lymph node assessment (intraoperative and histopathology) contributed to the understaging of stage III to II disease and reduced survival.

Procalcitonin and C-reactive protein for diagnosing post-operative sepsis in neonates.

AIM: To determine whether serum procalcitonin (PCT) or C-reactive protein (CRP) can diagnose post-operative sepsis among neonates undergoing major non-cardiac surgery. METHODS: In this diagnostic study, we included neonates who underwent major non-cardiac surgery and were monitored for post-operative sepsis. We excluded pre-existing septic, inflammatory or life-threatening conditions. Subjects either had 'definite' (culture-positive, n = 14), 'probable' (clinical sepsis, culture-negative, n = 25) or no sepsis (n = 31). We measured serum CRP and PCT at 48 ± 6 h, 72 ± 6 h and 96 ± 6 h post-operatively and compared 'definite or probable sepsis' with 'no sepsis'. RESULTS: Median (Q1, Q3) CRP (mg/L) in 'definite or probable' sepsis group was higher than 'no sepsis' at 72 h (91.48 (57.87, 143.50) vs. 51.32 (33.0, 80.1); P = 0.009) and 96 h (87.51 (45.19, 128.22) vs. 31.00 (25.3, 45.2); P < 0.001). Median (Q1, Q3) PCT (ng/mL) in 'definite or probable' sepsis was higher than 'no sepsis' at 72 h (4.22 (2.04, 12.73) vs. 1.78 (0.9, 6.4); P = 0.01) and 96 h (3.54 (1.96, 9.65) vs. 0.97 (0.4, 3.0); P < 0.001). Ninety-six-hour CRP and PCT cut-offs (based on Youden's index) were 74.16 mg/L and 1.65 ng/mL, respectively. If both CRP and PCT were positive, specificity was 100% (95% confidence interval: 88.78-100). If either one was positive, sensitivity was 88.89% (95% confidence interval: 73.94-96.89). CONCLUSIONS: Septic neonates have significantly higher serum CRP and PCT compared to non-septic neonates at 72 and 96 h post-operatively. If both CRP and PCT are positive at 96 h after surgery, it has 100% specificity, and if either one is positive, 89% sensitivity.

Outcome of pediatric germ cell tumor with comparison of carboplatin and cisplatin based regimens: A 10-year analysis.

Carboplatin is being advocated more frequently for treatment of childhood germ cell tumors (GCT), due to less long-term toxicity, and demonstrable equivalence in outcome as compared to cisplatin. This analysis presents the survival of GCT in a low middle-income country and compares two different chemotherapeutic regimens. A retrospective analysis of patient case records was carried out over 10-years (January 2007-December 2016). Chemotherapy regimen used was bleomycin, etoposide, and cisplatin (PEb) for initial 6-½ years and carboplatin, etoposide, and bleomycin (CEb) subsequently. Ninety patients with GCT were treated over 10-years. Malignant GCT was diagnosed in 69 (77%) patients, with 21(23%) having teratoma. The chemotherapy protocol was PEb in 38 (42%), CEb in 28 (31%) patients, while 24 patients were treated with surgery only. Stage 4 tumor was observed in 19 (21%) patients. Relapse or disease progression was seen in 11(12%). Overall and event-free survival at 5-years for the entire cohort was 77% and 73%, being similar with PEb (OS:77%; EFS:72.5%) vs. CEb (OS:69%; EFS: 69%). Significantly better overall survival was noted for patients with gonadal GCT) and non-stage 4 disease, while event-free survival was significantly better in patients with non-stage 4 disease. The chemotherapeutic regimen (PEb vs. CEb), very high AFP (value ≥10,000 IU/L), and risk stratification (low, intermediate, or high-risk disease) did not affect survival significantly. Carboplatin-based strategy was equivalent in our cohort to cisplatin-based strategy, and could be used safely in the LMIC set-up. The overall survival is suboptimal, with delayed presentation, abandonment, and relapse being barriers to survival.

Duodenal and Pyloric Web in Children: Clinical Presentation and Management.

Background: Duodenal and pyloric web (DW/PW) can present at any age, symptoms depend upon the location of the web along with the presence and size of the opening in the web. The surgical management is not straightforward always. Here, in this study, we aim to assess clinical characteristics, management, and outcome of children with DW/PW. Materials and Methodology: This was a retrospective study from 2005 to 2019, and data were collected from record registers. All children of DW/PW presented between this duration were included in this study. Results: A total of 45 patients (age range = 1 day to 11 years) included in the study, 40 had DW while 5 had PW. Seven patients were diagnosed antenatally and 20 patients had associated congenital anomalies. Most patients presented with vomiting either bilious or nonbilious. Plain X-ray was sufficient for the diagnosis in 60% of patients, the rest diagnosed on contrast study. The web excision and pyloroplasty were done for PW. The web excision and Heineke-Mikulicz type enteroplasty was the preferred surgery for DW but some patients were required Kimura's duodeno-duodenostomy. For postoperative nutrition, enteral feeding was established through the placement of a feeding tube beyond anastomosis. Ten patients died due to septicemia and associated anomalies. Four patients had a minor leak which was managed by conservative means. Four patients required redo surgery, adhesive obstruction was the most common indication. During follow-up, all 35 patients were doing well with no major complaints. Conclusion: DW/PW has different presentations as compared to other intestinal atresia and can present at any age. A contrast study confirms the diagnosis when plain X-ray is inconclusive. Associated anomalies and septicemia are the poor prognostic indicators. Postoperative enteral feeding helps in maintaining adequate nutrition and improves the outcome even in children with a minor anastomotic leak.

Outcome Analysis of Reduction and Nonreduction Dismembered Pyeloplasty in Ureteropelvic Junction Obstruction: A Randomized, Prospective, Comparative Study.

Objectives: The objective of this study is to compare the changes in renal function and drainage following open dismembered pyeloplasty with and without renal pelvis reduction. Materials and Methods: Randomized prospective study of children with ureteropelvic junction obstruction undergoing pyeloplasty with (Group 1) and without (Group 2) pelvis reduction over an 18-month period. Postoperative function and drainage were assessed by ethylene dicysteine (EC) scan and intravenous urography (IVU) and renal pelvis size by ultrasonography. Results: Forty-two patients (2 months-11 years) participated. The mean preoperative EC scan function was Group 1: 45.88% ± 14.42% (5%-80%) and Group 2: 39.22% ± 9.75% (21%-53%). (P = 0.117). The mean postoperative EC scan function of Group 1 was 42.64% ± 9.62% (17%-54%) and 43.75% ± 9.88% (17%-58%) and of Group 2 was 44.77% ± 12.82% (20%-68%) and 42.25% ± 8.56% (23%-58%) at 3 months (P = 0.584) and ≥ 1year (P = 0.385), respectively, with no significant difference. None required re-do pyeloplasty. The number of patients with slow drainage, especially at 3 months and also at ≥1-year postoperative period on EC scan was slightly higher in Group 2 compared to Group 1 but did not attain statistical significance. There was postoperative improvement in function and drainage on IVU with no significant difference between the two groups, (P = 0.214; P = 0.99, respectively). At a mean follow-up of 45.5 months, Group 2 also showed significant reduction in pelvis size on ultrasound (P = 0.011). Conclusion: Postoperative function remained stable in both groups. More number of patients achieved unobstructed drainage by 3 mo postoperative after reduction pyeloplasty but drainage patterns were mostly similar between reduction and nonreduction of pelvis group in late follow-up.

Outcome of Patients with Antenatally Diagnosed hydronephrosis with Respect to Postnatal Diagnosis and Need for Surgical Intervention.

Aims: This study aims to determine the etiology of antenatal hydronephrosis (ANH) and predict need for surgical intervention based on antenatal renal pelvis anteroposterior diameter (APD). Materials and Methods: Combined prospective and retrospective study (2012-2018) of ANH cases with postnatal follow-up. Surgical intervention was correlated with the degree of hydronephrosis (HDN) and pelvis APD measured at the 2nd trimester, 3rd trimester, and postnatal 6-week follow-up. Results: One hundred and sixty-five patients were studied with a total of 219 ANH units. Transient HDN was seen in 116 units. Surgical intervention included pyeloplasty (n = 76), sub ureteric dextranomer injection (n = 8) and nephrectomy (n = 1). Chances of requiring surgery based on the degree of HDN in 2nd and 3rd trimester respectively were mild: 11.32% and 9.52%, moderate: 34.21% and 37.03% and severe: 85.71% and 86.27%. The mean increase in APD between the 2nd and 3rd trimester (n = 50) was lesser in conservatively managed (3.548 ± 4.219 mm) than surgically managed (8.261 ± 5.857 mm) patients (P = 0.002). In another subset (n = 37), the mean increase in APD between the 2nd trimester and postnatal period was less in conservatively managed (1.432 ± 0.612 mm) (P = 0.088) than surgically managed patients (12.91 ± 3.247 mm) (P = 0.004). The area under the receiver operating characteristic (ROC) curve showed that an APD of 8.2 mm in the 2nd trimester and 12.85 mm in the 3rd trimester correlated with the requirement of postnatal surgery. Conclusion: Apart from the degree of HDN, significant changes in APD between 2nd and 3rd trimester and cut off value suggested by the ROC curve will help during antenatal counseling with regard to requirement of postnatal surgery.

Unusual manifestations of Peutz-Jegher's syndrome in children.

PeutzJegher's syndrome (PJS) is a rare, autosomal dominant disease, characterized by gastrointestinal (GI) polyps and perioral hyperpigmentation along with the increased risk of certain malignancies. In children, the most common presentation is recurrent intussusception due to polyps. These polyps can involve any part of the GI tract and can present with a variety of clinical presentations. Usually, these polyps can be removed endoscopically but often require surgical excision also. In this report, we discuss two children of PJS with uncommon presentations, one presented with retrograde intussusception and another with gastric outlet obstruction. The first child underwent laparoscopy and another required open surgery with intraoperative enteroscopy.

Primary Repair of Pediatric Posttraumatic Complete Bladder Neck Horizontal Transection: Our Experience.

Complete transverse transection just below the bladder neck is extremely rare. We present two such cases with associated pelvic fracture following trauma. Both underwent early primary vesicourethral anastomosis with no postoperative complications and are continent in the follow-up.

Reverse Gastric Tube Esophagoplasty with and without Lower Esophageal Stump Wrap - Comparison of Outcome.

Aim and Objectives: The aim of the study is to compare the outcome in children born with long-gap esophageal atresia following reverse gastric tube esophagoplasty (RGTE) with or without the lower esophageal stump as a "fundoplication" wrap. Materials and Methods: All children who underwent RGTE between 2008 and 2018 were retrospectively analyzed. Patients in whom the lower esophagus (LE) had been excised as is done routinely in RGTE (Group 1) were compared with those where the LE was wrapped partially or completely around the intraabdominal neo-esophagus (Group 2). Both vagal nerves were preserved to the extent possible. Complications and final outcome, including weight and height centiles were assessed. Follow-up upper gastrointestinal contrast study and reflux scans were studied. Results: Nineteen patients (mean age: 15.78 ± 5.02 months [range 10-30 months] at RGTE) were studied; nine in Group 1 and ten in Group 2. Both groups had similar early postoperative complications as well as the requirement of dilatation for anastomotic stricture. Dysphagia for solids was noticed in two patients with complete lower esophageal wrap (n = 4), one requiring removal. More patients in Group 2 had absent reflux (n = 7) compared to Group 1 (n = 3) (P = 0.118). At a mean follow-up period of 45.75 ± 18.77 months (14-84 months), Group 2 children reached better height and weight percentiles compared to Group 1. Conclusion: We have described a novel method of using the LE as a "fundoplication" wrap following RGTE. Vagi should be preserved. Those with complete esophageal wrap may develop dysphagia to solids and this is, therefore, not recommended. Lower esophageal wrap patients appeared to have a better outcome in terms of growth and less reflux.

Abdominal Wall Yolk Sac Tumor in a Child.

Midline vascular abdominal wall lesions are likely to be mistaken for vascular malformations in young children. We report a case of large yolk sac tumor located in the anterior abdominal wall just below xiphisternum in a 20-month-old girl diagnosed by raised serum alpha fetoprotein levels and fine-needle aspiration cytology. Preoperative chemotherapy helped in reducing its size allowing wide resection and primary wound closure. This case is reported for the unusual location and role of chemotherapy in management.

Diagnostic accuracy and cytomorphological spectrum of Wilms tumour in fine needle aspiration biopsy cytology samples supplemented with cell blocks.

OBJECTIVE: Paediatric malignant renal neoplasms are subjected to neoadjuvant chemotherapy as per Societe Internationale d'Oncologie Pediatrique; International Society of Pediatric Oncology (SIOP) protocol. An accurate tissue diagnosis is required prior to institution of chemotherapy, and hence the aim of this study was to evaluate the diagnostic accuracy of fine needle aspiration biopsy cytology (FNABC) along with cell block histology. MATERIALS AND METHODS: A retrospective audit of all paediatric renal neoplasms diagnosed by FNABC between 2015 and 2019 was performed. Histopathology correlation was done wherever available. WT cases were subjected to detailed cytomorphological evaluation. RESULTS: A total of 121 cases of paediatric renal neoplasms including 109 WT, four clear cell sarcoma, one malignant rhabdoid tumour and three mesoblastic nephroma were evaluated. The age range was 4 weeks to 8 years. FNABC samples were adequate for diagnosis in 120 of 121 cases (99.18%) and a definitive cytological diagnosis was achieved in 117 cases (96.7%). The specificity and sensitivity for a cytopathological diagnosis of WT were 98.7% and 97.4%, respectively. On detailed cytomorphological analysis of 68 histopathology-proven WT, 40 (58.8%) cases were triphasic, 23 (35.3%) were biphasic and four were composed of blastema only. The corresponding cell blocks provided additional information over the conventional smears in 23 (33.8%) cases, with epithelial or mesenchymal elements recognised and evidence of rhabdomyoblastic differentiation. CONCLUSION: FNABC along with cell block histology is highly accurate for diagnosis of WT and other malignant paediatric renal neoplasms and is recommended as the technique of choice in centres with cytopathology expertise for establishing a cellular diagnosis prior to commencement of neoadjuvant chemotherapy.

Survival in patients with high-risk neuroblastoma treated without autologous stem cell transplant or dinutuximab beta.

The majority of patients with high-risk neuroblastoma (HR-NB) in low- and middle-income countries (LMIC) do not have access to autologous stem cell transplant (ASCT) and dinutuximab. Consolidation with nonmyeloablative chemotherapy is not well-defined, and the outcomes are variable. We report a single-center outcome of patients with HR-NB, treated with nonmyeloablative consolidation. A tabulated compilation of similar reports is included. A retrospective chart review of patients with HR-NB was performed from January 2009 till June 2016. Patients were treated on the backbone of HR-NBL1/SIOPEN protocol. Treatment included induction with rapid-COJEC, surgery, followed by consolidation. Consolidation involved 4 cycles of topotecan, vincristine, and doxorubicin (TVD) instead of ASCT. Infusion of vincristine and doxorubicin were modified for ease and to enable administration in the clinic. Subsequent treatment included radiotherapy to the primary tumor and differentiation therapy with isotretinoin. Over 7½ years, 28 patients with HR-NB were treated. Two (7%) patients had therapy-related mortality. A relapse or disease progression occurred in 11 (39%) patients at a median duration of 17 months (IQR: 5, 18). Treatment abandonment was observed in 4 (14%) patients. The median follow-up of disease-free patients was 49 months (IQR: 45, 79). Patients with relapse were not treated further. A 4-year EFS of 29.3% was observed when 4-cycles of TVD were administered instead of ASCT in patients with HR-NB. The study and the review will aid decision-making for care of patients in LMIC while considering the options of treatment for HR-NB if access to ACST and dinutuximab is lacking.

Congenital Parotid Fistula: Surgical Management in Two Infants and Review of Literature.

Congenital salivary gland fistulas are uncommon. They develop as a result of abnormalities of the first and second branchial arches. Operative and nonoperative methods of management have been described. We report two rare cases of congenital parotid fistula presenting to us in infancy that were managed surgically.

Benign Renal Tumors in Pediatric Age Group: Retrospective Analysis.

BACKGROUND: Benign renal tumors are extremely rare and were studied here. This series also includes a renal teratoma in a horseshoe kidney, probably only the second in the pediatric literature. MATERIALS AND METHODS: Retrospective review of children with benign renal tumors operated between 2006 and 2018 at one center. RESULTS: Twelve patients (M:F ratio 10:2), age range 3 weeks (31-week gestation) to 13 years presented with large palpable renal swelling (n = 12) and hematuria (n = 3). Computed tomography (CT) scan showed features typical of the tumor. Final histopathology (age group [mean]) showed: multilocular cystic nephroma (MLCN) - n = 5 (41.7%), (11-16 months [13.6]); congenital mesoblastic nephroma (CMN) - n = 4 (33.3%) (classic 1, cellular 3) (0.75-5 months [2.125]); mature cystic teratoma - n = 1 (8.3%): (48 months, in a horseshoe kidney), and angiomyolipoma (AML) - n = 2 (16.7%) (144 months [sporadic] and 156 months [tuberous sclerosis]) One patient with cystic teratoma with no calcification on CT scan received pre-operative chemotherapy as fine-needle aspiration cytology (FNAC) reported malignant small blue cell tumor. Nephroureterectomy with Gerota's fascia could be done easily in all without intraoperative complications. Delay in presentation in MLCN and CMN led to increased symptoms and CT scan changes. All patients did well in 1.5-12 years (median 3 years) follow-up including cellular mesoblastic nephroma. CONCLUSIONS: Benign renal tumors often occur in specific age groups but may overlap that of Wilms tumor. Proper interpretation of clinical presentation, CT scan, and FNAC findings help in avoiding preoperative chemotherapy. Upfront nephroureterectomy is curative. Histopathological findings decide further treatment. Children with AML and tuberous sclerosis need lifelong follow-up.

Autologous stem cell transplant for high-risk neuroblastoma: Achieving cure with low-cost adaptations.

BACKGROUND: The majority of patients in low- and middle-income countries (LMIC) are unable to receive optimal therapy, including autologous stem cell transplant (ASCT) for high-risk neuroblastoma. Management is intensive and multidisciplinary; survival is often poor. We report a single-center outcome of high-risk neuroblastoma, with adaptations optimized for LMIC. PROCEDURE: The study was retrospective. Patients were treated on the backbone of the high-risk neuroblastoma study-1 of SIOP-Europe (HR-NBL1/SIOPEN) protocol with ASCT. Adaptations incorporated to decrease cost, requirement for inpatient admission, infections, and faster engraftment included (a) optional outpatient administration for rapid-COJEC, (b) two sessions of stem-cell apheresis, (c) storing stem cells at 2-6°C without cryopreservation for up to 7 days, (d) no central lines, (e) no antibacterial/antifungal/antiviral prophylaxis, (f) omitting formal assessment of cardiac/renal/pulmonary functions before ASCT, and (g) administration of pegylated granulocyte colony-stimulating factor on Day +4. RESULTS: Over 5 years 9 months, 35 patients with high-risk neuroblastoma were treated. Rapid-COJEC was administered over a median duration of 80 days (interquartile range: 77, 83). Conditioning regimen included melphalan (n = 7), oral busulfan-melphalan (Bu/Mel; n = 6), or intravenous Bu/Mel (n = 22). The median viability of stem cells stored for 6 days (n = 28) was 93% (range: 88-99). Two (5.7%) patients had ASCT-related mortality. The 3-year overall and event-free survival was 41% and 39%, respectively. A relapse occurred in 20 (57%) patients. Treatment abandonment was observed in one (3%) patient. CONCLUSIONS: Administration of therapy in a disciplined time frame along with low-cost adaptations enables to manage high-risk neuroblastoma with low abandonment and an encouraging survival in LMIC. Stem cells can be stored safely without cryopreservation for up to 7 days.

Modified Duhamel's Two-Staged Procedure for Hirschsprung's Disease: Further Modifications for Improved Outcomes.

AIMS AND OBJECTIVES: We studied the short- and long-term outcomes and quality of life (QOL) in patients undergoing a two-staged modified Duhamel's procedure for Hirschsprung's disease. MATERIALS AND METHODS: Patients who had undergone this modified procedure, with initial Hartmann's procedure based on contrast enema, followed by bowel preparation and low colo-anal anastomosis below the dentate line were included. The patient who underwent this procedure over 10 years with a minimum 2-year follow-up were analysed based on an interview-based questionnaire. RESULTS: Of the 152 patients, 69 responded. Mean age at the time of interview was 7.72 ± 3.04 years with mean follow-up of 4.9 years (2-11 years). Perineal excoriation and soiling was present in 60.9% and 36.2% of patients initially which reduced to 0 and 4.3% by the end of 2 years. In the first 6 months, postoperative period, 15.9% of patients had constipation and 78.2% had altered stool consistency. Good fecal continence score was present in 97.1% of patients in the long term. About 95.4% had good QOL scores. There was no mortality in this series. CONCLUSIONS: Although short-term outcomes showed altered bowel function, soiling, and perineal excoriation, this improved significantly in the long term, with good QOL scores in the majority.

Type IV Congenital Pouch Colon in Male Children: Anatomical Variations and a Proposed New Subclassification.

BACKGROUND: Congenital pouch colon (CPC) is a rare variant of anorectal malformation. In male patients, CPC communicates distally with the urogenital tract by a large fistula. The CPC cases which do not fulfill the criteria as mentioned in the classical description are reported along with the pertinent literature review. MATERIALS AND METHODS: This was a retrospective study from January 2004 to December 2017 of male children with Type IV CPC. We evaluated clinical presentation, primary management, anatomical relationship, previous surgical intervention, definitive management, result, and outcome in terms of continence status on Templeton score. RESULTS: Fifty-one children were included in the study among whom 36 children (Group 1) had a colovesical fistula and 15 children (Group 2) had no communication of the pouch with the genitourinary tract. In Group 2 children, the clinical presentations and management were varied: 4 underwent primary pull-through procedure, whereas 11 underwent staged procedure. Group 2 included three children in whom a narrow and thin-walled anal canal or anal canal with lower rectum was present, which was incorporated during the pull-through procedure. On continence assessment, only one child in Group 1 had "good" continence score compared to four children (three having anal canal) in Group 2. CONCLUSION: CPC Type IV can present without genitourinary tract communication (fistula), contrary to its emblematic description. Awareness about anatomical variations and adaptation of surgical technique accordingly is vital. The identification of the anal canal with or without the lower part of the rectum (even though apparently narrow and thin walled) and incorporation of this in bowel continuity lead to better outcomes in terms of continence.

Clinical Presentation and Surgical Management of Neonatal Tumors: Retrospective Analysis.

AIMS: Neonatal tumors (NTs) include a group of diverse neoplasms. In this study, we reviewed our data for clinical presentations, management options, and outcome. MATERIALS AND METHODS: All patients from 0- to 1-month age presenting with solid tumors, from 2006 to 2018 were studied. The gender, presentation, location, type of tumor, and management were analyzed. The final diagnosis was made with histopathology in all cases. Hemangiomas and lymphangiomas were excluded from the study. RESULTS: A total of 32 neonates were studied. The most common tumor was sacrococcygeal teratoma (SCT,16) followed by teratoma at other sites including two cases of fetus-in-fetu, soft-tissue sarcoma (STS, 4), mesenchymal hamartoma (2), hemangioendothelioma (2), and other rare tumors. Three tumors were diagnosed antenatally; of whom, two were neither visible externally nor palpable. Complete surgical excision was done for all except in a case of ovarian cyst where near-total cystectomy was done. No patient received chemotherapy or radiotherapy. Six patients had postoperative complications, including two who had local recurrence requiring excision. There was one mortality. All the other patients are doing well during follow-up. CONCLUSION: NTs have varied presentations. SCT and STS were the most common benign and malignant tumor, respectively. Early diagnosis and complete surgical excision are often curative for all, regardless of the pathology with the minimal role of chemotherapy or radiotherapy.