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小儿癌症患者中性粒细胞减少性小肠结肠炎的结局与决定因素

Outcome and Determinants of Neutropenic Enterocolitis in Pediatric Cancer Patients.

作者信息

Sahoo Debasish, Seth Rachna, Chaudhry Rama, Naranje Priyanka, Ahuja Vineet, Dwivedi Sada N, Gupta Aditya K, Meena Jagdish P

机构信息

Division of Pediatric Oncology, Department of Pediatrics.

Departments of Microbiology.

出版信息

J Pediatr Hematol Oncol. 2022 Oct 1;44(7):376-382. doi: 10.1097/MPH.0000000000002422. Epub 2022 Apr 22.

Abstract

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 contrast-enhanced computed tomography abdomen. Clinical, imaging, and laboratory features were analyzed. Fecal samples were analyzed for fecal calprotectin by sandwich enzyme-linked immunoassay 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% (4 had recurrent episodes). Common manifestations included fever (98%), pain abdomen (88%), and diarrhea (83%). Hypoalbuminemia was observed in 78% of 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). A 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 the presence of free fluid predicted higher mortality. Though levels of fecal calprotectin and gut dysbiosis were higher in NEC, they did not increase mortality. Isolation of Bacteroides and absence of Lactobacilli predicted a longer duration of intravenous alimentation.

CONCLUSIONS

NEC caused significant morbidity and mortality in pediatric cancer patients. Gut dysbiosis was significantly higher in NEC group suggesting a role in pathogenesis and influencing outcome. This highlights the role of targeted interventions towards gut dysbiosis like prebiotics and probiotics.

摘要

背景

中性粒细胞减少性小肠结肠炎(NEC)是化疗令人恐惧的并发症。关于其发病率、临床特征和决定因素的文献很少。对NEC和儿童癌症中肠道微生物群失调的认识正在不断发展。

方法

对患有中性粒细胞减少症和胃肠道症状的儿童癌症患者进行腹部增强计算机断层扫描以评估是否患有NEC。分析临床、影像学和实验室特征。通过夹心酶联免疫吸附测定法分析粪便样本中的粪便钙卫蛋白,并通过传统培养法分析肠道微生物群,并与健康对照和无NEC的儿童进行比较。

结果

根据临床和影像学特征,44名儿童被诊断为NEC,发病率为7.4%(4名有复发发作)。常见表现包括发热(98%)、腹痛(88%)和腹泻(83%)。78%的患者观察到低白蛋白血症。大肠受累(94%),弥漫性肠受累(63%)和全结肠炎(64%)很常见。NEC组的粪便钙卫蛋白明显高于非NEC组和健康对照(中位数分别为:87、53和42μg/g)。在患有NEC的儿童中观察到更高程度的肠道微生物群失调,拟杆菌分离率更高,乳酸杆菌分离率较低。观察到死亡率为23%。只有存在游离液体预示着更高的死亡率。虽然NEC中粪便钙卫蛋白水平和肠道微生物群失调较高,但它们并未增加死亡率。拟杆菌的分离和乳酸杆菌的缺乏预示着静脉营养的持续时间更长。

结论

NEC在儿童癌症患者中导致了显著的发病率和死亡率。NEC组的肠道微生物群失调明显更高,表明其在发病机制中起作用并影响预后。这突出了针对肠道微生物群失调的靶向干预措施(如益生元和益生菌)的作用。

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