Response assessment by positron emission tomography-computed tomography as compared with contrast-enhanced computed tomography in childhood Hodgkin lymphoma can reduce the need for radiotherapy in low- and middle-income countries.

INTRODUCTION: The InPOG-HL-15-01, a multicentric prospective study, used a risk-stratified and response-based approach with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) backbone to treat children and adolescents with newly diagnosed Hodgkin lymphoma (HL) and reduce the use of radiation therapy (RT). Children/adolescents with bulky disease or inadequate response at early response assessment (ERA) after two cycles of chemotherapy were assigned to receive RT. For ERA, positron emission tomography computed tomography (PET-CT) was recommended but not mandatory in view of limited access. This study aimed to compare the impact of using contrast-enhanced computed tomography (CECT) and PET-CT on treatment decisions and outcomes. METHODOLOGY: 396 patients were enrolled and 382 had an ERA at the assigned time point. Satisfactory response was defined as Deauville score 3 or less for patients undergoing PET-CT and complete response (CR)/very good partial response (VGPR) for patients undergoing CECT. Outcomes of interest incorporate 5 year event-free survival (EFS), EFS including abandonment (EFSa), and overall survival (OS). RESULTS: At ERA, satisfactory response was documented in 277 out of 382 (72.5%) participants and this was significantly higher in PET-CT (151 out of 186, 81.2%) as compared with CECT-based assessments (126 out of 196, 64.3%) respectively (p value < .001). Amongst the 203 patients with nonbulky disease (wherein the indication for RT was entirely dependent on ERA), 96 out of 114 (84.2%) and 61 out of 89 (68.5%) patients achieved a satisfactory response according to the PET-CT and CECT (p value = .008) respectively and hence a lesser proportion of patients in the PET-CT arm received RT. Despite a lower usage of RT the 5 year OS of both groups, ERA based on CECT (91.8%) versus PET-CT (94.1%) was comparable (p value = .391) and so was the 5 year EFS (86.7 vs. 85.5%, p value = .724). CONCLUSION: Use of PET-CT as the modality for ERA is more likely to indicate a satisfactory response as compared with CECT and thereby decreases the need for RT in response-based treatment algorithm for HL-afflicted children. The reduction in the application of RT did not impact the overall outcome and plausibly would lower the risk of delayed toxic effects.

Hodgkin Lymphoma in Children Under 5 Years: Do They Behave Differently?

The median age of presentation for Hodgkin lymphoma (HL) is lower in developing countries with a higher proportion under 5 years of age possibly attributable to the high prevalence of Epstein-Barr virus-driven disease. It is unclear whether the clinical presentation and outcomes of this cohort are different with concern regarding late effects being most pronounced in this age group. We report the outcome of children under 5 years of age enrolled in the InPOG-HL-15-01, the first multicentric collaborative study for newly diagnosed children and adolescents with HL from India. Thirty-five (9%) of the study population was younger than 5 years with a striking male preponderance of 34:1. They were less likely to have bulky disease, mediastinal or splenic involvement. The outcomes appear to be at least as favorable as in the older patient group. Efforts need to be made to evolve treatment strategies that spare this very young cohort from potential late effects.

Treating early-stage Hodgkin lymphoma in resource-limited settings: InPOG-HL-15-01 experience.

BACKGROUND: Hodgkin lymphoma (HL) in childhood is an eminently curable disease. Excellent outcomes can be achieved even in resource-limited settings and increasingly, the focus is on limiting long-term toxicity. Contemporary treatment incorporates a risk-stratified, response-adapted approach using multiagent chemotherapy with or without low-dose radiotherapy (RT). Many developing countries continue to use ABVD (adriamycin, bleomycin, vinblastin, and dacarbazine)-based regimen owing to limited acute toxicity, cost, and ease of delivery. We report outcomes of children with early-stage HL using limited cycles of ABVD-based treatment in the first prospective multicentric collaborative study from India InPOG-HL-15-01. METHODS: Children <18 years with biopsy-proven HL were enrolled. Patients with stages I and IIA with or without bulky disease were classified as having early-stage disease. Patients were planned to receive four cycles of ABVD subject to satisfactory early response assessment (ERA) scheduled after two cycles of chemotherapy. RT was limited to patients with bulky disease or those with suboptimal ERA. RESULTS: Four hundred ten patients were enrolled over 30 months from 27 centers. One hundred thirty-four were classified as having early-stage disease. Fifty-three (40%) of these had bulky disease. One hundred ten (83%) of this cohort achieved complete or very good partial ERA. Fifty-four (40%) received RT. At a median of 52 months since diagnosis, 5-year event-free survival (EFS) and overall survival (OS) is 94% and 95.5%, respectively. Treatment-related mortality and abandonment were <1%. CONCLUSION: Limited cycles of ABVD with RT to selected patients is a very effective option for patients with early-stage disease in resource-limited settings.

High soluble interleukin-2 receptor values in Indian paediatric & adult controls - Need for population-specific threshold in the diagnosis of haemophagocytic lymphohistiocytosis.

Background & objectives: Elevated soluble interleukin-2 receptor (sIL2R) is a diagnostic criterion for haemophagocytic lymphohistiocytosis (HLH). International guidelines propose a 2400 U/ml cut-off or individual laboratory-defined cut-off. However, sIL2R normal values are so far not known in Indians. So, this study was undertaken to measure sIL2R in healthy children and adults to establish age-related reference values. Methods: Healthy controls and cases (participants with persistent fever, organomegaly, cytopenias and biochemical markers of HLH) were prospectively enrolled. Serum sIL2R was measured by double-sandwich enzyme immunoassay in a standardization batch to determine the optimum cut-off value using receiver operator characteristic curve and was subsequently validated. Results: One hundred and forty six age- and sex-matched children (80 controls and 66 suspected HLH cases) and 55 adults (49 controls and 6 suspected HLH cases) were prospectively enrolled. The optimal sIL2R cut-off ≥23 ng/ml was defined as raised sIL2R in the standardization batch. No controls had sIL2R ≥23 ng/ml in the validation batch. In healthy controls, median sIL2R (interquartile range) decreased with increasing age from 9.0 ng/ml (6.6-13.4) below five years of age to 3.2 ng/ml (2.8-5.1) in adults. Proposed upper limit of normal value for sIL2R is 17.4 ng/ml in less than five year, 12.2 ng/ml in 5-9 yr, 6.7 ng/ml in 10-17 yr and 5.2 ng/ml in ≥18 yr. sIL2R accuracy to diagnose HLH marginally improved with age-appropriate cut-off. Interpretation & conclusions: Paediatric controls in India showed higher sIL2R levels than most studies conducted in other countries, except for some reports in Chinese and Russian populations. Age-appropriate reference values of sIL2R in a specific population may be considered to determine elevated sIL2R as a marker of HLH.

How the COVID-19 Pandemic Experience has Affected Pediatric Palliative Care in Mumbai.

INTRODUCTION: The COVID 19 pandemic has created difficulties for children registered under Children's Palliative Care in Mumbai. 2 hospitals who have started Services last year would like to share their experiences on difficulties faced by Children and their families and unique ways in which solutions were found to help them surmount all odds. RESULTS: Some difficulties faced included transport to visit hospitals for doctor's care and essential medications; for those in native place, unavailability of doctors and medications. Difficulty to return home for those from out of Mumbai and vice versa. Unavailability of rations for those who were not original Mumbai residents. CONCLUSIONS: Unique solutions were found for each family. These are presented in this paper.

Assessment of Risk Factors for a Sustainable "On-Table Extubation" Program in Pediatric Congenital Cardiac Surgery: 5-Year Experience.

OBJECTIVE: To delineate risk factors for failure of extubation in the operating room among pediatric cardiac surgery patients. DESIGN: Prospective, observational study. SETTING: Single center, tertiary care, teaching hospital. PARTICIPANTS: The study comprised 448 congenital cardiac surgery patients who were enrolled for intended extubation in the pediatric cardiac operating room over 5 years. INTERVENTIONS: The airways of enrolled patients were extubated in the operating room if predetermined suitability criteria were met. If the criteria were not met, patients were transferred to the intensive care unit with an endotracheal tube in situ. Patients whose airways were extubated successfully were followed up to determine specifically whether reintubation or use of noninvasive ventilation was necessary post-procedure. MEASUREMENTS AND MAIN RESULTS: The airways of 92% (412) patients were extubated in the operating room. Incidence of reintubation in the intensive care unit was 2.4%. There were 4 mortalities in the whole group. A 100% success rate for operating room extubation was achieved for patients in Risk Adjusted Congenital Heart Surgery category 1, and patients undergoing adult congenital cardiac disease surgery and redo sternotomy. The airways of 85% of patients with preoperative pulmonary hypertension were extubated in the operating room. Statistical analysis was applied to identify risk factors present in the group that made extubation in the operating room unachievable. CONCLUSIONS: Extubation in the operating room was successful in a majority of patients undergoing cardiac surgery. Multivariate analysis identified weight<5 kg, age<1 year, cardiopulmonary bypass time>120 minutes, and presence of significant noncardiac structural anomalies as significant factors affecting extubation in the operating room, with an adjusted odds ratio (95% confidence interval) of 10 (2.7-37), 7.2 (2-22), 5.5 (1.7-17.7), and 3.3 (1.2-9.3), respectively. Pulmonary hypertension, redo sternotomy, higher Risk Adjusted Congenital Heart Surgery category, and aortic clamp time>60 minutes did not achieve significance in the multivariate analysis as risk factors for extubation in the operating room.

Outcome of pediatric acquired aplastic anemia: a developing world experience.

INTRODUCTION: Outcome data of children with acquired aplastic anemia (AA) are lacking from the developing world. Here, we describe the same from a centre in North India. METHODS: Retrospective data regarding medical history, physical examination, complete blood count, bone marrow aspirate, and biopsy were retrieved for all children <18 years, with acquired AA admitted between January 2005 and June 2012. In addition, the outcome data after immunosuppressive therapy (IST) or bone marrow transplant (BMT) was obtained. RESULTS: A total of 61 children were diagnosed with AA (Inherited-18 and acquired-43). Among 43 children with acquired AA, 3 had nonsevere and 40 had severe. One patient with nonsevere AA died of sepsis and 2 recovered spontaneously. Of the 40 remaining children with severe AA, 10 refused therapy and 3 died due to severe sepsis prior to any therapy. Five underwent upfront matched sibling donor BMT and one post-IST failure. Four year overall survival (OS) and event free survival (EFS) for children undergoing BMT was 100% and 80 ± 17.9, respectively. Out of 22 treated with IST, 20 were evaluable for response. Seventeen received one course and 3 received two course of IST. The overall response to IST was seen in 14/20 (70%). Only two achieved complete response while remaining 12 had partial response. The 4-year estimated OS and EFS for children treated with IST was 74.4 ± 12.1% and 65.6 ± 12.2. CONCLUSION: Outcomes for children with AA are encouraging in the developing world although barriers like sepsis and treatment abandonment remain. BMT offers faster and complete recovery.

Empirical Antitubercular Treatment for Lymphadenopathy: Are We Missing Lymphoma?

OBJECTIVE: To evaluate the proportion of patients who received empirical treatment with antitubercular therapy (ATT) prior to the diagnosis of Hodgkin lymphoma (HL) in the first multicentric, prospective study on HL from India, and to assess its impact on extent of disease at diagnosis and outcomes. METHODS: Children < 18 y with biopsy proven HL were enrolled in InPOG-HL-15-01. Along with other clinical and epidemiological data, history of prior treatment with ATT was documented. All patients received treatment as per a risk-stratified, response-adapted strategy. RESULTS: Out of 396, 115 (29%) children had received ATT prior to establishing a definitive diagnosis of HL. This cohort presented with advanced-stage disease (p = 0.001) and B symptoms (p = 0.001) in a higher proportion of cases. Consequently, those children were more likely to receive 6 rather than 4 cycles of chemotherapy (p = 0.001). They were more likely to have infradiaphragmatic involvement (p = 0.001). Overall survival and event-free survival were not different. CONCLUSION: Empirical treatment with ATT in children presenting with lymphadenopathy continues to be practiced widely in India. The delay in diagnosis may contribute to children presenting with advanced-stage disease warranting more intensive treatment for successful outcomes.

Hepatic hemangioendothelioma in an infant with severe congenital neutropenia.

Severe congenital neutropenia (SCN) is a rare disorder caused by heterogeneous genetic mutations. We describe here a rare association of SCN caused by a novel ELANE mutation and infantile hepatic hemangioendothelioma. In a 2-month-old infant, an abdominal ultrasound performed for omphalitis revealed a hepatic tumor, which was resected. Histopathology confirmed the diagnosis of hemangioendothelioma. Postoperatively, severe neutropenia was noted. Bone marrow examination showed myeloid maturation arrest, diagnostic of SCN. Mutation analysis for the neutrophil elastase gene identified a novel heterozygous de novo ELANE missense mutation in exon 2 (c.215T>A, p.Val72Glu). He was managed successfully with broad-spectrum antibiotics and high-dose granulocyte colony-stimulating factor.

Risk based and response adapted radiation therapy for children and adolescents with newly diagnosed advanced stage Hodgkin lymphoma treated with ABVD chemotherapy: a report from the Indian pediatric oncology group study InPOG-HL-15-01.

This multi-centric prospective study (InPOG-HL-15-01) assessed epidemiological, clinical and outcome data of advanced stage Hodgkin Lymphoma (IIB, III and IV) in children and adolescents (N = 262). Chemotherapy regimen was ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and radiotherapy (RT) was restricted to patients with bulky disease at diagnosis or with suboptimal response at early response assessment (ERA). ERA revealed complete response in 175 (68.1%), partial response in 77 (29.9%), stable disease in 2 (0.8%), and progressive disease in 3 (1.2%) patients. RT was administered to 111 (97 bulky disease, 14 suboptimal response) patients. Five-year event free (EFS) and overall survival for the whole cohort was 81.1% and 90.8% respectively. On multivariate analysis, the only statistically significant predictor of EFS was use of RT (89% versus 74.2%; p-value <0.001). This study reinforces the benefit of consolidative RT in bulky disease and in those with suboptimal response at ERA on an ABVD backbone.

Dynamic Airway Driving Pressure and Outcomes in Children With Acute Hypoxemic Respiratory Failure.

BACKGROUND: Limited adult data suggest that airway driving pressure might better reflect the potential risk for lung injury than tidal volume based on ideal body weight, and the parameter correlates with mortality in ARDS. There is a lack of data about the effect of driving pressure on mortality in pediatric ARDS. This study aimed to evaluate the effect of driving pressure on morbidity and mortality of children with acute hypoxemic respiratory failure. METHODS: This retrospective cohort study was performed in a tertiary level pediatric ICU. Children who received invasive mechanical ventilation for acute hypoxemic respiratory failure (defined as [Formula: see text] < 300 within 24 h after intubation), in a 2-y period were included. The cohort was divided into 2 groups based on the highest dynamic driving pressure (ΔP, calculated as the difference between peak inspiratory pressure and PEEP) in the first 24 h, with a cutoff value of 15 cm H2O. RESULTS: Of the 380 children who were mechanically ventilated during the study period, 101 children who met eligibility criteria were enrolled. Common diagnoses were pneumonia (n = 51), severe sepsis (n = 24), severe dengue (n = 10), and aspiration pneumonia (n = 7). In comparison to the group with high ΔP (ie, ≥ 15 cm H2O), children in the group with low ΔP (ie, < 15 cm H2O) had significantly lower median (interquartile range) duration of ventilation (5 [4-6] d vs 8 [6-11] d, P < .001], ICU length of stay (6 [5-8] d vs 12 [8-15] d, P < .001], and more ventilator-free days at day 28 (23 [20-24] vs 17 [0-22] d, P < .001). Logistic regression analysis also suggested driving pressure as an independent predictor of morbidity after adjusting for confounding variables. However, there was no statistically significant difference in mortality between the 2 groups (17% in low ΔP vs 24% in high ΔP, P = .38). Subgroup analysis of 65 subjects who fulfilled ARDS criteria yielded similar results with respect to mortality and morbidity. CONCLUSIONS: Below a threshold of 15 cm H2O, ΔP was associated with significantly decreased morbidity in children with acute hypoxemic respiratory failure.

Effect of Albumin Addition to Cardiopulmonary Bypass Prime on Outcomes in Children Undergoing Open-Heart Surgery (EACPO Study)-A Randomized Controlled Trial.

BACKGROUND: There is a paucity of literature regarding the association of high oncotic priming solutions for pediatric cardiopulmonary bypass (CPB) and outcomes, and no consensus exists regarding the composition of optimal CPB priming solution. This study aimed to examine the impact of high oncotic pressure priming by the addition of 20% human albumin on outcomes. METHODS: Double-blinded, randomized controlled study was done in the pediatric cardiac intensive care unit of a tertiary care hospital. Consecutive children with congenital heart diseases admitted for open-heart surgery were randomized into two groups, where the study group received an additional 20% albumin to conventional blood prime before CPB initiation. RESULTS: We enrolled 39 children in the high oncotic prime (added albumin) group and 37 children in the conventional prime group. In the first 24-hour postoperative period, children in the albumin group had significantly lower occurrence of hypotension (28.2% vs 54%, P = .02), requirement of fluid boluses (25.6% vs 54%, P = .006), and lactate clearance time (6 vs 9 hours, P < .001). Albumin group also had significantly higher platelet count (×103/µL) at 24 hours (112 vs 91, P = .02). There was no significant difference in intra-CPB hemodynamic parameters and incidence of acute kidney injury. In subgroup analysis based on risk category, significantly decreased intensive care unit stay (4 vs 5 days, P = .04) and hospital stay (5 vs 7 days, P = .002) were found in the albumin group in low-risk category. CONCLUSION: High oncotic pressure CPB prime using albumin addition might be beneficial over conventional blood prime, and our study does provide a rationale for further studies.

Pediatric Hodgkin lymphoma presenting with pulmonary nodules and leukemoid reaction.

An 8-year-old female presented with fever and severe pain in the hipbones and legs for 2(1/2) months. Investigations revealed a leukemoid reaction and bilateral diffuse nodular opacities on chest X-ray. Supraclavicular lymph node biopsy was diagnostic of Hodgkin lymphoma (HL), mixed cellularity. Both pulmonary nodules and leukemoid reaction being present in the same patient with HL has not been reported.

Factors impacting referral of JIA patients to a tertiary level pediatric rheumatology center in North India: a retrospective cohort study.

BACKGROUND: JIA studies demonstrate that there is a "window of opportunity" early in the disease course during which appropriate management improves outcomes. No data is available regarding patients' pathway, before first pediatric rheumatology (PR) evaluation in India, a country where health-care costs are self- paid by patients and where a significant shortage of pediatric rheumatologists (PRsts) is known. This study aimed to describe time from onset of symptoms to first PR visit of JIA patients to a tertiary center in India and factors that impact this. METHODS: This retrospective study is from data collected at the PR center, Sir Ganga Ram Hospital (SGRH) in New Delhi. JIA patients fulfilling ILAR 2004 criteria and seen at least twice from 1st October 2013 to 30th September 2018 were included. Data collected were: demographic details, history of disease, referral practitioner, clinical and laboratory features, treatments. Mann-Whitney U-test, Chi square and logistic regression were used as appropriate to study factors that determined time to first PR visit. RESULTS: Five hundred and twenty patients were included: 396 were diagnosed at this PR center (group A), 124 were previously diagnosed as JIA and managed by non PRsts before first PR visit (group B). Median time from symptom onset to first PR visit was 4.1 months and median distance travelled 119.5 km. Despite ongoing treatment, group B patients had more aggressive disease and resided further away as compared to Group A patients. On univariate analysis, factors that predicted PR visit within 3 months were private patients, short distance to travel, family history of inflammatory disease, history of fever, history of acute uveitis or high ESR. On multivariate analysis all these factors were significant except high ESR and acute uveitis. CONCLUSION: Time to first PR assessment at this center was comparable to that seen in western countries. Cost of care and long distance to the center delayed consultation; acuity of complaints and family history of rheumatologic condition hastened referral. Possible solutions to improve referral to PR centers would be to increase the number of PRsts and to improve medical insurance coverage.

Low apoptotic index & bak expression in EBV-associated childhood classical Hodgkin lymphoma.

BACKGROUND & OBJECTIVE: Association of Epstein-Barr virus (EBV) with Hodgkin lymphoma (HL) is particularly high in low-income countries, and resistance to apoptosis might play a role in pathogenesis and survival. Data from previous studies are not consistent, and none is available in children. Thus this study was undertaken on Indian children with classical Hodgkin lymphoma to assess the significance of bcl-2, bak and p53 expression, and apoptotic index in relation with EBV status and treatment outcome with chemotherapy alone. METHODS: Children (age<15 yr) with classical HL (n=143) were included in the study. Bcl-2, bak, p53, Ki67 and latent membrane protein-1 (LMP1) were detected by immunohistochemistry in pre-treatment lymph node biopsies. Apoptotic index was assessed by TdT-dUTP nick-end labelling (TUNEL). RESULTS: Bcl-2, bak, p53 were expressed above positivity threshold in 83.3, 94.0 and 7.1 per cent of the cases respectively. More than 10 per cent of apoptotic tumour cells were seen in 60.4 per cent of the cases. 131 (91.6%) cases were EBV associated. EBV-positive cases had a significantly lower mean bak expression (p=0.001) and a lower apoptotic index, without higher proliferation index. Advanced stage showed a borderline association with bcl-2 expression in >25 per cent of tumour cells and p53 negative tumours. In univariate analysis, p53 positive cases, which were significantly associated with B symptoms, had a poorer overall survival (P=0.03) while low proliferation index was associated with poorer failure-free survival. Neither EBV status nor any of the apoptotic parameters studied showed independent association with survival. INTERPRETATION & CONCLUSION: EBV detection in children with classical Hodgkin lymphoma was associated with significant lower bak expression and with lower spontaneous apoptosis of H-RS cells suggesting that EBV-LMP1 might downregulate bak pro-apoptotic protein. this needs to be substantiated further.

Metabolic imaging patterns in posterior cortical atrophy and Lewy body dementia.

PURPOSE: To study the imaging patterns of Posterior cortical atrophy (PCA) and Dementia with Lewy bodies (DLB) on fluoro-deoxyglucose positron emission tomography computed tomography ([F]FDG PET/CT), identify areas of overlap and differences and to develop a prediction model to assist in diagnosis using univariate and multivariate analysis. METHODS: A retrospective analysis of 72 patients clinically suspected of having posterior dementia was done. All patients underwent [FF]FDG PET/CT of the brain and dopamine transporter imaging with [[Tc]TRODAT-1 SPECT scan on separate days. The patients were divided into PCA with normal TRODAT uptake (n=34) and DLB with abnormal TRODAT uptake (n=38). The FDG PET/CT uptake patterns were recorded and areas of significant hypometabolism by z score analysis were considered as abnormal. Receiver operator characteristics (ROC) curve analysis was used to determine cutoff z scores and binary logistic regression analysis was used to determine the Odds ratio of being in the predicted groups. RESULTS: Significantly hypometabolism was found in parieto-temporo-occipital association cortices and cingulate cortices in PCA patients. DLB patients showed significantly reduced uptake in the visual cortex. No significant difference was found between z score of occipital association cortex which showed hypometabolism in both groups. The cut-off z-score values derived from the ROC curve analysis were as follows- parietal association (cut-off-3, sensitivity-65.6%, specificity - 68.7%), temporal association (cut-off-2, sensitivity-78%, specificity-75%) and posterior cingulate (cut-off-0.5, sensitivity-93.7%, specificity-40.6%), their respective Odds ratio (with 95% confidence interval) for being in the PCA group as derived from univariate logistic regression were 3.66 (1.30-10.32), 10.71 (3.36-34.13) and 7.85 (1.57-39.17). The cut-off z score of primary visual cortex as derived from ROC curve was zero with sensitivity of 87.5%, specificity of 71.9%, and the Odds ratio for being the in the DLB group was 24.7 with 95% confidence interval of 5.99-101.85. CONCLUSION: [F]FDG PET may be useful as a non-invasive diagnostic modality in differentiating the two posterior cortical dementias, despite significant overlap. Primary visual cortical hypometabolism can serve as an independent diagnostic marker for DLB, even in the absence of TRODAT imaging.

Proliferative index and CD15 expression in pediatric classical Hodgkin lymphoma.

BACKGROUND: This study was conducted to assess the clinical and prognostic significance of lack of CD15 expression, proliferative index (PI), and expression of tumor suppressor protein p53 in pediatric classical Hodgkin lymphoma (CHL). PROCEDURE: Pre-treatment lymph node (LN) biopsies were studied by immunohistochemistry for immunophenotyping of the lymphoma and with Ki-67 (PI) and p53 antibodies. Expression of CD15 antigen on the Hodgkin and Reed-Sternberg (H-RS) cells, proliferation, and apoptosis parameters were correlated with clinical stage, response to chemotherapy alone, overall (OS) and failure-free survival (FFS). RESULTS: One hundred and twenty-one children with CHL were studied. Expression of Ki-67 and p53 in H-RS cells was seen in 100% and 89.9% of the cases, respectively. Loss of CD15 expression, seen in 12 (9.9%) cases, was significantly associated with p53 negativity and was an independent prognostic factor for poor OS and poor FFS. PI

Study of Proliferating cell nuclear antigen expression and Angiogenesis in Urothelial neoplasms: Correlation with tumor grade and stage.

BACKGROUND: Urinary bladder carcinoma ranks ninth in worldwide cancer incidence. About 74,000 new cases were diagnosed in 2015 alone and 16,000 persons died of the disease. Since histopathology is considered gold standard for diagnosis, it is prudent to look for potential tumor proliferation and predictive markers in such a prevalent malignancy so as to alert surgical and medical oncologists for timely intervention and provide better patient-tailored therapy. AIMS: This study is to analyze the role of potential biomarkers-proliferating cell nuclear antigen (PCNA) and angiogenesis using CD31 in urothelial neoplasms in relation to tumor grade and stage. METHODS: Histopathology slides were prepared from transurethral resection of bladder tumor chips and assessed by three independent observers as per the WHO/International Society of Urologic Pathology criteria 2016. Representative sections were subjected to immunohistochemistry. PCNA labeling index (PCNA LI) and mean vessel density (MVD) were calculated. STATISTICAL ANALYSIS: Tests of analysis were applied as appropriate. A statistical P < 0.05 was considered significant. RESULTS: Forty-nine patients were analyzed. PCNA LI increased with grade and stage. PCNA was significantly higher in noninvasive papillary urothelial carcinoma high grade (NIPUCHG) than in noninvasive papillary urothelial carcinoma low grade (NIPUCLG) and in infiltrating urothelial carcinoma as compared to NIPUCLG. MVD also increased with tumor grade and stage; however, a significant difference was observed only between infiltrating urothelial carcinoma and papillary urothelial neoplasm of low malignant potential. A cutoff value of 73% for PCNA and 49 vessels/high-power field for CD 31 showed 100% accuracy to differentiate between noninvasive papillary urothelial carcinoma high grade and NIPUCLG. No association was observed between tumor recurrence and PCNA or CD31 expression. CONCLUSION: PCNA and CD31 when used together are valuable markers to help classify urothelial neoplasms in limited tumor material. However, larger prospective studies are required for better prognostication.

Association between Altered Expression and Genetic Variations of Transforming Growth Factor ß-Smad Pathway with Chronic Myeloid Leukemia.

Background: Chronic myeloid leukemia (CML) is a hematological disorder caused by fusion of BCR and ABL genes. BCR-ABL dependent and independent pathways play equally important role in CML. TGFß-Smad pathway, an important BCR -ABL independent pathway, has scarce data in CML. Present study investigate the association between TGFß-Smad pathway and CML. Materials and Methods: Sixty-four CML patients and age matched healthy controls (n=63) were enrolled in this study. Patients were segregated into responder and resistant groups depending on their response to Imatinib mesylate (IM). TGFß1 serum levels were evaluated by ELISA and transcript levels of TGFß1 receptors, SMAD4 and SMAD7 were evaluated by Real-Time PCR. Sequencing of exons and exon-intron boundaries of study genes was performed using Next Generation Sequencing (NGS) in 20 CML patients. Statistical analysis was performed using SPSS version 16.0. Results:TGFß1 serum levels were significantly elevated (p = 0.02) and TGFßR2 and SMAD4 were significantly down-regulated (p = 0.012 and p = 0.043 respectively) in the patients. c.69A>G in TGFß1, c.1024+24G>A in TGFßR1 and g.46474746C>T in SMAD7 were the most important genetic variants observed with their presence in 10/20, 8/20 and 7/20 patients respectively. In addition, TGFßR1 transcript levels were reduced in CML patients with c.69A>G mutation. None of the genes differed significantly in terms of expression or genetic variants between responder and resistant patient groups. Conclusion: Our findings demonstrate the role of differential expression and genetic variants of TGFß-Smad pathway in CML. Decreased TGFßR2 and SMAD4 levels observed in the present study may be responsible for reduced tumor suppressive effects of this pathway in CML.