Debasish Sahoo

and 8 more

Background Chemotherapy related mucosal toxicity is a major hindrance to successful therapy in pediatric cancers. The role of gut dysbiosis in modulation of chemotherapy related gastrointestinal toxicity is poorly understood. Methods Pediatric cancer patients with neutropenia and gastrointestinal symptoms were evaluated for neutropenic enterocolitis (NEC) with CECT abdomen. Clinical features, fecal calprotectin and microbiological data were analysed. Fecal Gut microbiota was evaluated in children with NEC and compared with children where NEC was excluded and healthy controls using conventional culture method. Results Of 590 children receiving chemotherapy during study period, 44 were diagnosed with NEC. Significantly higher frequency of isolation of Bacteroides was observed in children with NEC (42%) as compared to non- NEC group (14%) and healthy controls (13%). Isolation of Lactobacilli was infrequent in NEC group (26%) than non- NEC group (74%) and healthy controls (80%). There was nonsignificant trend towards higher isolation of Clostridium in children with NEC. Clostridiodes difficle or Clostridium septicum were not identified in any group. Isolation of other bacterial flora was similar in the sub groups. No significant association of survival with gut dysbiosis could be established. Isolation of Lactobacilli was associated with reduction in duration of intravenous alimentation by 2.4 days, whereas isolation of Bacteroides prolonged the requirement of bowel rest by 2.2 days. Conclusion Gut dysbiosis was significantly higher in NEC group and associated with higher morbidity suggesting its role in pathogenesis. This highlights role of interventions towards gut dysbiosis like prebiotics and probiotics in pediatric cancer patients.

Debasish Sahoo

and 7 more

Background Neutropenic enterocolitis (NEC) is a dreaded complication of chemotherapy. There is scant literature regarding incidence, clinical features, and determinants. The understanding of gut dysbiosis in NEC and pediatric cancer is evolving. Methods Pediatric cancer patients with neutropenia and gastrointestinal symptoms were evaluated for NEC with CECT abdomen. Clinical, imaging, and laboratory features were analysed. Fecal samples were analysed for fecal calprotectin by sandwich ELISA and gut microbiota by conventional culture and compared with healthy controls and children without NEC. Results NEC was diagnosed in 44 children based on clinical and imaging features with incidence of 7.4% (Four had recurrent episodes). Common manifestations included fever(98%), pain abdomen(88%), and diarrhoea(83%). Hypoalbuminemia was observed in 78% patients. Large bowel involvement(94%) with diffuse bowel involvement(63%) and pancolitis(64%) were common. Fecal calprotectin was significantly elevated in NEC group than non-NEC group and healthy controls (median 87, 53, and 42 µg/g respectively). Higher degree of gut dysbiosis was observed in children with NEC with higher isolation of Bacteroides and infrequent isolation of Lactobacilli.. Mortality rate of 23% was observed. Only presence of free fluid predicted higher mortality. Though levels of fecal calprotectin and gut dysbiosis were higher in NEC, they didn’t increase mortality. Isolation of Bacteroides and absence of Lactobacilli predicted longer duration of intravenous alimentation. Conclusion NEC caused significant morbidity and mortality in pediatric cancer patients. Gut dysbiosis was significantly higher in NEC group suggesting role in pathogenesis and influencing outcome. This highlights role of targeted interventions towards gut dysbiosis like prebiotics and probiotics.

Praneetha Mude

and 7 more

Background: Childhood cancer survivors are 8.8 times more likely to die of pulmonary causes when compared to general population: an aspect of concern. Pulmonary dysfunction is the third leading cause of non recurrence related cause of death among Hodgkin lymphoma survivors. Methods: A cross section study on Hodgkin lymphoma survivors in complete remission, who completed treatment within last 5 years was done. All children were subjected to detail history including drugs, past history of respiratory illnesses, physical and respiratory system examination followed by spirometry and three minute step test under supervision. Pulmonary dysfunction was determined as presence of obstructive, restrictive or mixed pattern on spirometry or abnormality in three minute step test. Subclinical pulmonary dysfunction was determined as patients who were clinically asymptomatic but had pulmonary dysfunction Results: A total of 60 children were enrolled (Mean age of 11.3 years and 53 were boys) Abnormal pulmonary function tests were documented in 11 (18.3%) of HL survivors at a median time of 2 years (IQR 1,3) from treatment completion. Restrictive pattern was documented in 10 (16.67%) and obstructive pattern in only one patient (1.67%), mostly mild in severity. Older age at start of chemotherapy and radiotherapy and past history of respiratory illness were found to be significantly associated with pulmonary dysfunction. Conclusion: Majority of Hodgkin lymphoma survivors had subclinical pulmonary dysfunction at median follow up of 2 years from treatment completion. Hodgkin lymphoma survivors require long term follow up for timely detection of pulmonary dysfunction and improve quality of life.

Vishwa CR

and 7 more

BACKGROUND: Neurocognitive deficits are an important late effect in survivors of acute lymphoblastic Leukemia(ALL). Data from low middle income countries is scarce and highly influenced by biological and cultural variations. Such data would be useful for highlighting the importance of early intervention in an already disadvantaged population. PROCEDURE: 70 consecutive survivors of childhood ALL were evaluated for neurocognitive deficits by the Indian adaptation of Wechsler Intelligence Scale for Children-Fourth Edition(WISC-INDIA). Prevalence of neurocognitive deficits was calculated based on Full Scale Intelligence Quotient(FSIQ) and scores in discrete domains like Verbal Comprehension, Perceptual Reasoning, Working Memory and Processing Speed were calculated and compared to baseline characteristics, chemotherapy and radiation dose received. RESULTS: The mean FSIQ was 86.1 ± 20.5, with significant neurocognitive deficit(FSIQ <90) being prevalent in 50%(95% CI 38% to 62%) of the cohort. The proportion of survivors with deficits in individual domains of verbal comprehension, perceptual reasoning, working memory and processing speed were 49%, 50%, 47% and 44% respectively. The odds of having deficits in neurocognitive function was higher when a child belonged to lower socioeconomic strata, had parents with less than primary school education and whose birth order was higher(All p<0.05). Age at diagnosis, current age at assessment, receiving lower or higher dose of radiotherapy, high dose methotrexate or cytarabine did not have a direct impact on neurocognitive function. CONCLUSIONS AND RELEVANCE: The current need is to develop country specific neurocognition assessment tools to initiate early screening and develop culturally appropriate preventive and rehabilitative interventions.

Satya Prakash

and 6 more

Background and aims: Oral mucositis (OM) is common and distressing toxicity in children on chemotherapy. There is limited number of safe and effective therapeutic options available for OM. Ketamine oral rinse has shown promising results in few studies in adults. This randomized, double-blind placebo-controlled trial aimed to test the efficacy of ketamine mouthwash in reducing chemotherapy-induced severe OM pain in children. Methods: Children aged 8-18 years with severe OM were randomized to a single dose of ketamine mouthwash (4 mg/ml solution; dose 1 mg/kg) or a placebo. A sample size of 44 patients was determined. Pain score (6-point faces scale) was noted at baseline and 15, 30, 45, 60, 120, 180, and 240 min. The outcome variables were a reduction in pain score, need for rescue medications, and adverse events. Results: The baseline characteristics were comparable in the two groups. The mean OM pain at 60 min decreased by 1.64 points (CI 1.13-2.14) in the ketamine group and 1.32 points (CI 0.76-1.87) in the placebo group (p=0.425), with a group difference of 0.32 points. Rescue pain medication (at 60 min) was required in 13.6% in the ketamine group and 18.2% in the placebo group (p=1.000). There were no significant adverse events observed. Conclusions: Among children on cancer chemotherapy with severe OM, ketamine mouthwash at a dose of 1 mg/kg did not significantly reduce OM pain. It did not decrease the need for rescue pain medications. Further research is warranted to test higher doses of ketamine for a clinically significant effect.