Gestational trophoblastic neoplasia with concurrent metastasis to the mother and child: a systematic literature review.

Gestational trophoblastic neoplasia (GTN) arising in the placenta and presenting as a metastatic disease concurrently in the mother and the baby is extremely rare. GTN poses a diagnostic dilemma to the treating clinicians. In the current review, an electronic search of Scopus, PubMed, Embase and other databases was conducted for case reports and case series of GTN co-existing or metastatic to both the mother and the baby, published to date. Globally, a total of twenty-two cases of GTN with metastasis to both the mother and baby was found. The previous history of histopathology confirmed molar pregnancy was present in 4/22 cases. The median time to diagnose GTN in the mother was six weeks post-partum. In the majority of cases, diagnosis of maternal disease was made after the infant presented with clinical manifestation. Overall survival was reported in 17/22 mothers up to varying latest follow-up and in 6/22 infants. A knowledge of the varied clinical presentation, eliciting a history of previous pregnancy loss/term pregnancy and serum beta human chorionic gonadotrophin (ß-hCG) estimations were helpful for early diagnosis. The concurrent presence of GTN in the mother and baby is a rare entity and poses a diagnostic dilemma. Diagnosis in the mother often follows diagnosis in the baby after an infant presents with clinical manifestations. GTN is a highly chemo-sensitive tumour, but the main prognostic factors determining survival are the time to diagnosis following previous pregnancy and serum ß-hCG levels.

Diagnostic Accuracy of Cord Bilirubin to Predict the Need for Phototherapy in Healthy Neonates >35-Week Gestational Age: A Systematic Review and Meta-Analysis.

Objective: Early discharge puts neonates at risk of delayed detection of jaundice and resulting neurological injury. In these neonates, we can use cord bilirubin to make predictions. In this meta-analysis, we assessed the diagnostic accuracy of cord bilirubin in predicting the need for phototherapy (AAP-2004 or NICE-2010 charts). Methods: We searched the databases of PubMed, Embase, Cochrane Library, Google Scholar, and Index Medicus for Southeast Asian Region. We included all observational studies that assessed the diagnostic accuracy of cord bilirubin. A bivariate model was used to pool the data in prespecified range of cord bilirubin levels (<1.5 mg/dl, 1.5-2.0 mg/dl, 2.0-2.5 mg/dl, 2.5-3.0 mg/dl, and >3.0 mg/dl). Data were pooled separately for studies including all neonates (no risk stratification), high-risk neonates (Rh and/or ABO incompatibility only), and low-risk neonates (excluded Rh and ABO incompatibility). Results: Of the 1990 unique records, we studied 153 full texts and included 54 studies in the meta-analysis. For all the three groups of studies, the highest diagnostic odds ratio was noted for a cord bilirubin cut-off of 2.5-3.0 mg/dl (all neonates: 22.5, 95% CI: 21.1, 22.9; high-risk neonates: 75.5, 95% CI: 63, 85.7; low-risk neonates: 91.9; 95% CI: 64, 134.14). Using the same cut-off, the studies including all neonates without risk stratification had a pooled sensitivity of 0.31 (95% CI: 0.18, 0.47) and a pooled specificity of 0.98 (0.96, 0.99) in predicting the need for phototherapy. In studies on high-risk neonates, the pooled sensitivity was 0.8 (0.39, 0.96) and pooled specificity was 0.95 (0.78, 0.99). In studies on low-risk neonates, the pooled sensitivity was 0.74 (0.39, 0.93) and pooled specificity of 0.97 (0.91, 0.99). We noted significant heterogeneity and a high risk of bias in the index test's conduct. Conclusion: A cord bilirubin cut-off of 2.5-3 mg/dl has good diagnostic accuracy in predicting the need for phototherapy in neonates. Registration number: CRD42020196216.

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.

Microalbuminuria and Urinary Neutrophil Gelatinase-associated Lipocalin (uNGAL) in Human Immunodeficiency Virus Infected Children.

Introduction: Renal dysfunction and progression to end stage renal disease is well known in human immunodeficiency virus (HIV) infection. We studied the role of microalbuminuria and urinary NGAL levels in children with HIV infection for the prediction of renal dysfunction. Design and Methods: A cross-sectional study was carried out and 60 HIV infected children, aged (18 months to 15 years) were screened for microalbuminuria by nephelometry and for uNGAL by ELISA. Thirty healthy children were screened for uNGAL for normative data in Indian children. Results: The prevalence of microalbuminuria in studied population was 3.3%. The mean uNGAL and uNGAL/creatinine in study population was higher than controls (26.94 ± 93.12 ng/ml vs. 88.94 ± 345.20 mcg/g, and 15.53 ± 37.52 ng/ml vs. 30.12 ± 78.66 ng/ml; P = 0.003, P = 0.002). Children with lower CD4 counts had significant higher mean Albumin Creatinine Ratio (ACR) and mean uNGAL; P = 0.03, P = 0.01. Conclusions: uNGAL and urine microalbumin are useful biomarkers of early tubular and glomerular injury in children with HIV infection.

Outcome and prognostic factors in childhood B non-Hodgkin lymphoma from India: Report by the Indian Pediatric Oncology Group (InPOG-NHL-16-01 study).

The literature on B-non-Hodgkin lymphoma (NHL) in India is restricted to individual hospital data. The study aimed to evaluate the epidemiology and outcome of B-NHL in our country. One hundred and ninety-one patients of B-NHL from 10 centers diagnosed between 2013 and 2016 were analyzed retrospectively. B/T lymphoblastic lymphoma and patients with inadequate data were excluded. The median age was 88 months (IQR: 56, 144) with an M:F ratio of 5.6:1. Undernourishment and stunting were seen in 36.5% and 22%. Primary site was abdomen in 66.5%. Hypoalbuminemia was noted in 82/170 (48.2%). Histological subtypes: Burkitt lymphoma (BL): 69.6%, Burkitt-like: 10.4%, and diffuse large B cell lymphoma (DLBCL): 13.6%, unclassified and others (6.4%). Stage distribution: I/II, 33 (17.3%), III, 114 (59.7%), and IV, 44 (23%). One-eighty-six patients took treatment. Protocols used were LMB and BFM in 160/186 (86%). At a median follow-up of 21.34 (IQR: 4.34, 36.57) months, the disease-free-survival (DFS) was 74.4% and event-free-survival (EFS) was 60.7%. Treatment-related mortality (TRM), relapse/progression and abandonment were 14.3%, 14.5%, and 8.4%, respectively. Bone marrow positivity, stage IV disease, and lactate dehydrogenase (LDH) > 2,000 U/l predicted inferior EFS. Stage IV disease, LDH > 2,000 U/l, bone marrow positivity, tumor lysis syndrome and low albumin predicted TRM; LDH retained significance on multivariate analysis for EFS and TRM [OR: 4.54, 95% CI: 1.14-20, p 0.03; OR 20, 95%CI: 1.69-250, p 0.017]. BL was the main histological subtype. High TRM and relapse/progression are hampering survival. An LDH > 2,000 U/l was adversely prognostic. These data demonstrate a need to develop a national protocol that balances toxicity and potential for cure.

Congenital hypothyroidism in India: A systematic review and meta-analysis of prevalence, screen positivity rates, and etiology.

Background: Congenital hypothyroidism (CH) is the leading cause of preventable mental retardation, which is currently not universally screened in India. Knowledge of the country-specific prevalence of the disease can guide in establishing a universal screening program. Methods: We performed a systematic review and meta-analysis to assess the prevalence, screen positivity rates, compliance to recall and etiology of CH in India. The databases of PubMed, Embase, Google scholar and IMSEAR were searched on 1st October 2021. All observational studies reporting at least one of the outcomes of interest were included. Two reviewers independently extracted the data and appraised the quality of studies using the Joanna Briggs tool for prevalence studies. Estimates were pooled using a random-effects model with double arcsine transformation (MetaXL software). PROSPERO database registration number was CRD42021277523. Findings: Of the 2 073 unique articles retrieved, 70 studies were eligible for inclusion. The prevalence of CH (per 1 000 neonates screened) was 0·97 (95% confidence intervals/CI: 0·9, 1·04) in non-endemic areas (54 studies and 819 559 neonates), 79 (95% CI: 72, 86) in endemic areas (3 studies, 5 060 neonates), 50 (95% CI: 31, 72) in neonates born to mothers with thyroid disorders, and 14 (95% CI: 8, 22) in preterm neonates. At thyroid stimulation hormone cut-off of 20 mIU/L, the screen positivity rates were 5·6% (95% CI: 5·4%, 5·9%) for cord blood samples and 0·19% (95% CI: 0·18%, 0·2%) for postnatal sample. About 70% (95% CI: 70, 71) of screen positive neonates were retested with diagnostic tests. Among neonates with permanent hypothyroidism, thyroid dysgenesis 56·6% (95% CI: 50·9%, 62·2%) was more common than dyshormonogenesis 38·7% (95% CI: 33·2%, 44·3%). Interpretation: The prevalence of congenital hypothyroidism in India is higher than global estimates. Screen positivity rate was higher for cord blood screening when compared to postnatal screening. Compliance with confirmatory testing was higher for cord blood screening. Funding: The study was not funded by any source.

Acute neurological complications during acute lymphoblastic leukemia therapy: A single-center experience over 10 years.

BACKGROUND: Acute neurological complications occur in 3.6-11% of children treated for acute lymphoblastic leukemia (ALL). This analysis aimed to evaluate the profile of acute neuro-toxicity and its etiology in children with ALL. METHODS: A retrospective case analysis of central nervous system events in children treated for ALL at our center was performed. Details of events were retrieved from the case records (January 2006-December 2015) and analyzed. RESULTS: Ninety (9.5%) neurological events occurred in 923 patients treated for ALL. Phase of therapy were: induction (38), consolidation (5), interim maintenance (5), intensification (15) and maintenance (27). Seizures and neurological deficits were the presenting features in 64 and 40 children, respectively. Events included : neuro-infections in 18, posterior reversible encephalopathy syndrome (PRES) in 7, epilepsy in 6, intracranial bleed in 5, systemic infection with neurological complication in 4, hydrocephalus and aseptic meningitis in 3 each, methotrexate encephalopathy and metabolic seizures in 2 children each. Seizures and status epilepticus of unknown etiology and neurological deficits of unknown etiology was observed in 26 and 13 children, respectively. Seizures occurred mainly in induction (12) and intensification phase (9). Status epilepticus transpired in maintenance phase in 9/14 patients. Induction phase was complicated by PRES in 7, intracranial bleed in 5 and cerebral sinus venous thrombosis in 1 patient. Neuroimaging was done in 86% of events. There were 18 (20.6%) deaths: neuro-infections (8), status epilepticus (6), systemic infection (2), bleed (1), and unexplained encephalopathy (demyelination)(1). At last follow-up, 53 patients were well and 7 children persist to have a neurological disability. CONCLUSION: Ten percent of children on treatment for ALL suffered an acute neuro-toxicity. Morbidity and high-incidence of neuroinfections are major concerns.

Copy Number Variations in Wilms Tumor: A Pilot Study From India.

BACKGROUND: The prognostic role of copy number variation is upcoming in Wilms tumor, and its identification will help in tailored therapy for improved cure. STUDY DESIGN: This was a retrospective, nested case-control, pilot study. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded blocks of nephrectomy specimens were retrieved for the study and control groups (children with relapse and survivors for ≥2 y). Multiplex ligand probe amplification (MRC-Holland probe-mix P 380 A1) was performed, with 3 reference samples of normal kidney DNA run for every 7 cases. RESULTS: At least 1 variation was detected in 41 (97.8%) specimens. Loss of heterozygosity 1p was not observed. Loss of 16q, 1q gain, and MYCN gain were observed in 5 (11.9%), 29 (69%), and 39 (92.9%) specimens, respectively. The occurrence of copy number variations was similar in both groups: 1q gain: 15 versus 14 (P=1.0), 16q loss: 4 versus 1 (P=0.34), MYCN gain: 19 versus 20 (P=1.0). The gain of 1q, 16p loss, and MYCN gain did not differ across stage or age. CONCLUSIONS: The gain of 1q, MYCN gain, and 16p loss were identified. A higher occurrence of 1q gain and MYCN gain and a lack of difference in the distribution of variations among survivors and those with a relapse suggest a different molecular profile of Wilms tumor in Indian children.