儿童高胆红素血症

儿童高胆红素血症常表现为黄疸,是儿童特别是婴幼儿普遍存在的一种症状,各种病理生理学、解剖学、感染性、自身免疫性疾病及遗传代谢性因素及疾病均可引起黄疸。不同的原因导致的黄疸其严重程度及预后不同,并且有不同的时间敏感性和不同的治疗计划。早期诊断和评估、并给予个性化的优化治疗至关重要。随着分子检测技术的发展,二代测序技术使临床医生能够快速有效的对临床实践中无法通过常规血液检查直接诊断的疾病进行分子学诊断,进而精准治疗。文章主要介绍儿童高胆红素血症常见病因及其诊治策略。     

基于DWI的影像组学列线图预测部分肝切除术后肝内胆管癌辅助化疗获益价值

目的 探讨基于弥散加权成像（DWI）的影像组学列线图（RN）预测肝内胆管癌（ICC）肝部分切除术（HPx）后辅助化疗（AC）获益人群的应用价值。方法 回顾性分析2018年1月—2022年1月我院行HPx的85例ICC患者的MRI和临床病理资料,分为训练集60例和验证集25例。用随机森林算法行基于DWI的影像组学特征筛选并建立预测早期复发（ER）的影像组学模型（RS）,并计算的影像组学评分。多因素Logistic回归法筛选临床、病理、常规影像中与ER相关变量建立临床-病理-影像（CPR）模型。筛选出的变量与影像组学评分构建临床-影像组学列线图（RN）,评估并验证上述模型的辨别度和校准度。用Kaplan Meier法和log-rank检验分析不同组预后差异。结果 验证集中,基于DWI的RS与CPR模型在预测ER有相似的区分性能（AUC：0.762 vs 0.624,P=0.271）,而RN模型（AUC：0.833）预测效能显著优于RS（P=0.012）。RN模型预测的ER高危组患者中,行手术+AC患者的OS与DFS较仅行接受手术治疗患者显著延长（DFS,P=0.035;OS,P=0.020)。结论 基于DWI的RN模型不仅可有效预测ICC患者术后发生ER,还可有效筛选术后AC获益人群     

肝内胆管癌患者术后预后研究

目的 探讨影响肝内胆管癌（ICC）患者术后生存的因素。方法 2011年12月~2015年2月我院诊治的ICC患者94例,对其中35例行姑息性治疗,即肝内扩张胆管置管引流术,对另59例行根治性肿瘤切除术。采用单因素分析和多因素回归分析影响ICC患者术后生存的因素。结果 经随访,本组94例ICC患者生存期为3~35个月,平均为（26.1±4.6）个月;1 a生存率为76.6%,2a生存率为7.4%;单因素分析显示,ICC肿瘤数目、直径、肿瘤分化、血清CEA、CA19-9和是否发生淋巴结转移和远处转移以及手术方法为影响术后患者生存的因素（P<0.05）;经多因素回归分析,发现肿瘤多发、低程度分化、血清CEA大于25 μg/L、血清CA19-9大于182 U/ml、手术切除组织边缘肿瘤细胞阳性、淋巴结转移和姑息性手术是影响ICC患者术后生存的危险因素（P<0.05）。结论 ICC患者预后差,很多患者在诊断时已失去根治性切除肿瘤的机会,即使获得肿瘤切除而根治的患者仍存在很多影响预后的危险因素,临床医生需认真研究这些因素,而给予相应的处理。     

基于“肠道菌群–胆汁酸代谢”探讨茵栀黄颗粒对胆汁淤积症小鼠的改善作用及其机制

目的 探讨茵栀黄颗粒治疗小鼠胆汁淤积症的作用及其机制。方法 将8周龄C57BL/6小鼠给予含1%胆酸的饲料2周,构建小鼠胆汁淤积症模型,将小鼠分为对照组、模型组、熊去氧胆酸（0.1 g/kg）组以及茵栀黄颗粒（5、10、20 g/kg）组,各组分别ig相应药物,对照组和模型组大鼠ig同体积生理盐水,连续给药4周。分别给予收集小鼠血清,全自动生化仪测定肝功能相关指标,超高效液相色谱串联质谱（UPLC-MS/MS）测定胆汁酸成分;收集小鼠肝组织,苏木精–伊红（HE）染色观察肝脏组织病理变化;RT-qPCR检测肝组织炎症因子和胆汁酸代谢关键基因的m RNA表达水平;Western blotting检测肝组织胆汁酸代谢关键蛋白的表达情况;收集小鼠盲肠内容物,Illumina Miseq测序平台对V3～V4可变区进行扩增和测序,对小鼠肠道菌群结构进行分析。结果 与模型组相比,茵栀黄颗粒各组小鼠血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、碱性磷酸酶（ALP）水平均显著降低（P<0.05、0.01、0.001）;且能够显著改善小鼠肝组织损伤。与模型组相比,茵栀黄颗粒各剂量组小...     

降黄合剂Ⅱ号对肝内胆汁淤积大鼠肝损伤及肝组织中NTCP和BSEP表达的影响

目的探讨降黄合剂Ⅱ号对复合因素诱导的阴黄证肝内胆汁淤积模型大鼠肝损伤及钠-牛黄胆酸盐共转运多肽(NTCP)、胆盐输出泵(BSEP)表达的影响。方法将60只SD雄性大鼠随机分为正常组、模型组、降黄合剂Ⅱ号高剂量组、降黄合剂Ⅱ号中剂量组、降黄合剂Ⅱ号低剂量组,每组12只。正常组大鼠予常规饲养;其余各组大鼠造模阶段施以寒湿条件、大黄煎剂灌胃及高糖高脂饮食,造模3周,第22天时模型组及降黄合剂Ⅱ号各组给予0.5%的ANIT 20 mg/100 g灌胃1次,正常组予以相同体积生理盐水灌胃,建立阴黄证肝内胆汁淤积大鼠模型。降黄合剂Ⅱ号各组于造模第8天开始每天下午给相应剂量的降黄合剂Ⅱ号灌胃,一直到造模后14 d,共用药28 d,正常组和模型组均予相同剂量生理盐水灌胃。观察各组大鼠一般状态,检测干预结束后各组大鼠血清碱性磷酸酶(ALP)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBil)水平,镜下观察各组大鼠肝组织病理变化,采用Western blot法检测各组大鼠肝组织中BSEP、NTCP蛋白表达水平。结果正常组大鼠饮食量、活动量、被毛、体质量、排便排尿情况均正常;模型组大鼠形体均较消瘦,饮食量减少,大便增多,尿液明显变黄、增多,被毛枯黄、粗糙且易脱毛,精神状态不佳;降黄合剂Ⅱ号各组大鼠干预后情况均较模型组明显好转,以大剂量组最为明显。模型组大鼠血清ALP、ALT、AST、TBil水平均明显高于正常组(P均<0.05);降黄合剂Ⅱ号大剂量组和降黄合剂Ⅱ号中剂量组上述指标水平均明显低于模型组(P均<0.05),且降黄合剂Ⅱ号大剂量组各指标水平均明显低于降黄合剂Ⅱ号小剂量组(P均<0.05),其中血清ALP、ALT、TBil水平明显低于降黄合剂Ⅱ号中剂量组(P均<0.05)。HE染色显示降黄合剂Ⅱ号大、中剂量组肝组织较模型组中炎细胞浸润减少,毛细胆管淤堵减轻,肝细胞肿胀缓解,细胞核清晰,形态较完整,可见少量炎性细胞。模型组大鼠肝组织中NTCP、BSEP相对表达量均明显低于正常组(P均<0.05);降黄合剂Ⅱ号大剂量组和降黄合剂Ⅱ号中剂量组大鼠肝组织中NTCP、BSEP相对表达量均明显高于模型组(P均<0.05),降黄合剂Ⅱ号小剂量组与模型组比较差异均无统计学意义(P均>0.05)。结论降黄合剂Ⅱ号可改善阴黄证肝内胆汁淤积模型大鼠肝损伤,机制可能与上调NTCP和BSEP表达有关。     

两种静脉脂肪乳剂对早产儿静脉营养相关胆汁淤积的影响

目的:研究两种静脉脂肪乳剂对早产儿静脉营养相关胆汁淤积的影响.方法:通过回顾性病例对照研究,选取某院于2018年4月～2020年2月监护室收治的早产儿140例,将所有早产儿按照随机数字表法划分为对照组(采用豆油静脉脂肪乳剂)与研究组(采用鱼油静脉脂肪乳剂)各70例,观察比较两组早产儿经静脉营养支持后胆汁淤积发生情况.结...     

Intrahepatic cholangiocarcinoma as a rare secondary malignancy after allogeneic hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia: A case report

Secondary malignancies are a significant cause of non‐relapse mortality in patients who undergo allogeneic HCT. However, secondary liver cancer is rare, and ICC following HCT has never been reported in the literature. Secondary solid cancers typically have a long latency period, and cholangiocarcinoma is classically a malignancy occurring in older individuals. Here, we report the first case of secondary ICC, which presented just 3 years after HCT in a young adult with a history of childhood ALL. A 26‐year‐old male with history of precursor B‐cell ALL presented with asymptomatic elevated liver function tests 3 years after HCT. Laboratories were indicative of biliary obstruction. ERCP showed focal biliary stricturing of the common and left hepatic ducts. MRCP revealed left intrahepatic duct dilatation, suggestive of intrahepatic obstructing mass. Additional workup lead to a clinical diagnosis of ICC. The patient underwent left hepatectomy with extrahepatic bile duct resection and portal lymphadenectomy. Surgical pathology was consistent with moderately differentiated cholangiocarcinoma. Our case illustrates a rare SMN following HCT for ALL. It is the first case report of ICC occurring as a secondary cancer in this patient population. Although cholangiocarcinoma is characteristically diagnosed in the older population, it must remain on the differential for biliary obstruction in post‐HCT patients.     

The role of genetic mutations in intrahepatic cholestasis of pregnancy

ObjectiveIntrahepatic cholestasis of pregnancy (ICP) is a liver disorder of pregnancy characterized by pruritus, elevated liver enzymes and fasting serum bile acids. Genetic predisposition has been suggested to play a role in its etiology and mutations in the ATP8B1(OMIM 1602397) (FIC1), ABCB11(OMIM 1603201) (BSEP), and ABCB4(OMIM 1171060) (MDR3) genes have been implicated.In the present study, we aimed to investigate the possible role of ATP8B1, ABCB11, and ABCB4 gene mutations in the patients with ICP.Materials and methodsA total of 25 patients who were diagnosed with ICP were included in the study. Genetic test results and mutation status of the patients as assessed by the next-generation sequencing technology were retrospectively retrieved from the hospital database.ResultsOf all patients, significant alterations in the ATP8B1 (n = 2), ABCB11 (n = 1), and ABCB4 (n = 7) genes were observed in 10 patients using the molecular analysis testing. All these alterations were heterozygous. Of these alterations, four were reported in the literature previously, while six were not. Using the in-silico parameters, there was a pathogenic alteration in the ABCB4 gene in one patient, while there was no clinically relevant alteration in the other gene mutations in the remaining nine patients.ConclusionConsidering the fact that the alterations were compatible with clinical presentations of the ICP patients and the incidence of these mutations is low in the general population, we believe that our study results are clinically relevant. Further molecular genetic tests in ICP patients and functional studies supporting the results would shed light into the clinical importance of these alterations.     

Outcomes of vascular resection associated with curative intent hepatectomy for intrahepatic cholangiocarcinoma

Background and aimsWe aimed to investigate the impact of vascular resection (VR) on postoperative outcomes and survival of patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC).MethodsA retrospective analysis of a multi-institutional series of 270 patients with resected ICC was carried out. Patients were divided into three groups: portal vein VR (PVR), inferior vena cava VR (CVR) and no VR (NVR). Univariate and multivariate analysis were applied to define the impact of VR on postoperative outcomes and survival.ResultsThirty-one patients (11.5%) underwent VR: 15 (5.6%) to PVR and 16 (5.9%) to CVR. R0 resection rates were 73.6% in NVR, 73.3% of PVR and 68.8% in CVR. The postoperative mortality rate was increased in VR groups: 2.5% in NVR, 6.7% in PVR and 12.5% in CVR. The 5-years overall survival (OS) rates progressively decreased from 38.4% in NVR, to 30.1% in CVR and to 22.2% in PVR, p = 0.030. However, multivariable analysis did not confirm an association between VR and prognosis. The following prognostic factors were identified: size ≥50 mm, patterns of distribution of hepatic nodules (single, satellites or multifocal), lymph-node metastases (N1) and R1 resections. In the VR group the 5-years OS rate in patients without lymph-node metastases undergoing R0 resection (VRR0N0) was 44.4%, while in N1 patients undergoing R1 resection was 20% (p < 0.001).ConclusionVascular resection (PVR and CVR) is associated with higher operative risk, but seems to be justified by the good survival results, especially in patients without other negative prognostic factors (R0N0 resections).