Cystic tumors of the liver:A practical approach

Biliary cyst tumors(cystadenoma and cystadeno-carcinoma) are an indication for liver resection. They account for only 5% of all solitary cystic lesions of the liver,but differential diagnosis with multiloculated or complicated biliary cysts,atypical hemangiomas,hamartomas and lymphangiomas may be difficult. The most frequent challenge is to differentiate biliary cyst tumors from hemorrhagic cysts. Computerized tomography(CT) and magnetic resonance imaging(MRI) are often not diagnostic and in these cases fine needle aspiration(FNA) is used to confirm the presence of atypical biliary cells. FNA,however,lacks adequate sensitivity and specificity and should always be used in conjunction with imaging. Pre-operative differentiation of cystadenoma from cystadenocarcinoma is impossible and surgery must be performed if a biliary cyst tumor is suspected. When multiple cystic lesions are observed throughout the liver parenchyma,it is important to exclude liver metastasis,of which colonic cancer is the most common primary site. Multiple biliary hamartomas(von Meyenburg complex) can appear as a mixture of solid and cystic lesions and can be confused with cystic metastasis. Strong and uniform T2 hyperintensity on MRI is usually diagnostic,but occasionally a percutaneous biopsy may be required.

Simultaneous liver mucinous cystic and intraductal papillary mucinous neoplasms of the bile duct:A case report

Cystic hepatic neoplasms are rare tumors,and are classified into two separate entities:mucinous cystic neoplasms(MCNs)and intraductal papillary mucinous neoplasms of the bile duct(IPMN-B).We report the case of a 56-year-old woman who presented with abdominal pain and jaundice due to the presence of a large hepatic multilocular cystic tumor associated with an intraductal tumor.Partial hepatectomy with resection of extrahepatic bile ducts demonstrated an intrahepatic MCN and an intraductal IPMN-B.This is the first report of the simultaneous occurrence of these two histologically distinct entities in the liver.

Rare cystic liver lesions: A diagnostic and managing challenge

Cystic formations within the liver are a frequent finding among populations.Besides the common cystic lesions,like simple liver cysts,rare cystic liver lesions like cystadenocarcinoma should also be considered in the differential diagnosis.Thorough knowledge of each entity’s nature and course are key elements to successful treatment.Detailed search in PubMed,Cochrane Database,and international published literature regarding rare cystic liver lesions was carried out.In our research are included not only primary rare lesions like cystadenoma,hydatid cyst,and polycystic liver disease,but also secondary ones like metastasis from gastrointestinal stromal tumors lesions.Up-to date knowledge regarding diagnosis and management of rare cystic liver lesions is provided.A diagnostic and therapeutic algorithm is also proposed.The need for a multidisciplinary approach by a team including radiologists and surgeons familiar with liver cystic entities,diagnostic tools,and treatment modalities is stressed.Patients with cystic liver lesions must be carefully evaluated by a multidisciplinary team,in order to receive the most appropriate treatment,since many cystic liver lesions have a malignant potential and evolution.

Cystic fibrosis associated liver disease in children

Cystic fibrosis(CF)is an autosomal recessive disorder caused by mutations in the CF transmembrane conductance regulator gene.CF liver disease develops in 5%-10%of patients with CF and is the third leading cause of death among patients with CF after pulmonary disease or lung transplant complications.We review the pathogenesis,clinical presentations,complications,diagnostic evaluation,effect of medical therapies especially CF transmembrane conductance regulator modulators and liver transplantation in CF associated liver disease.

Mucinous cystic neoplasm of the liver: A case report

BACKGROUND Mucinous cystic neoplasm of the liver(MCN-L)is a cyst-forming epithelial neoplasm.The most distinguishing feature is the ovarian-type subepithelial stroma on pathological examination.CASE SUMMARY An abdominal ultrasound incidentally revealed a liver tumor in a 32-year-old woman.Physical and laboratory examination results did not reveal any abnormalities.Enhanced abdominal computed tomography(CT)revealed a cystic space measuring 7.2 cm×5.4 cm in the liver.Subsequent CT showed an increase in tumor size.Thus,we performed surgical resection of the tumor and gallbladder.Postoperative histopathological examination confirmed the diagnosis of MCN-L.At the 6-mo of follow-up,no recurrence was observed on ultrasound or CT.CONCLUSION Since preoperative diagnosis of MCN-L is difficult,active surgery is recommended and helpful for the diagnosis and treatment of MCN-L.

Risk factors for hepatic steatosis in adults with cystic fibrosis: Similarities to non-alcoholic fatty liver disease

AIM To investigate the clinical, biochemical and imaging characteristics of adult cystic fibrosis(CF) patients with hepatic steatosis as compared to normal CF controls.METHODS We performed a retrospective review of adult CF patients in an academic outpatient setting during 2016. Baseline characteristics, genetic mutation analysis as well as laboratory values were collected. Abdominal imaging(ultrasound, computed tomography, magnetic resonance) was used to determine presence of hepatic steatosis. We compare patients with hepatic steatosis to normal controls.RESULTS Data was collected on 114 patients meeting inclusion criteria. Seventeen patients(14.9%) were found to have hepatic steatosis on imaging. Being overweight(BMI > 25)(P = 0.019) and having a higher pp FEV1(75 vs 53, P = 0.037) were significantly associated with hepatic steatosis. Patients with hepatic steatosis had a significantly higher median alanine aminotransferase level(27 vs 19, P = 0.048). None of the hepatic steatosis patients had frank CF liver disease, cirrhosis or portal hypertension. We found no significant association with pancreatic insufficiency or CF related diabetes.CONCLUSION Hepatic steatosis appears to be a clinically and phenotypically distinct entity from CF liver disease. The lack of association with malnourishment and the significant association with higher BMI and higher pp FEV1 demonstrate similarities with non-alcoholic fatty liver disease. Long term prospective studies are needed to ascertain whether CF hepatic steatosis progresses to fibrosis and cirrhosis.

Identification of a gene engineering antibody against cystic echinococcosis in liver

OBJECTIVE: To identify a gene engineering antibody against cystic echinococcosis in liver. METHODS: A single chain of variable fragment of human antibodies (ScFvs) was selected from the library by using affinity selection technique with the recombinant antigen on solid surface. The positive clones were demonstrated by ELISA and their DNA sequences were also determined. RESULTS: The DNA sequence data showed that the antibody gene is composed of 768bp. In addition, a specific combination capacity with recombinant Echinococcus granulosus antigen B (r-EgB) was demonstrated by ELISA. CONCLUSION: The obtained gene engineering antibody against r-EgB may have potential implications in immunological treatment and drug targeting delivery.

Prevalence and outcomes of pancreatic cystic neoplasms in liver transplant recipients

AIM To determine the prevalence,characteristics and clinical course of pancreatic cystic neoplasms(PCNs) in liver transplantation(LT) recipients.METHODS We retrospectively studied consecutive patients who underwent LT between January 1998 to April 2016. Clinical and laboratory data were obtained from patient medical records. Imaging findings on computed tomography and magnetic resonance cholangiopancreatography were reviewed by two radiologists.RESULTS During the study period,872 patients underwent cadaveric LT. Pancreatic cysts were identified in 53/872(6.1%) and 31/53(58.5%) were PCNs [28 intraductal papillary mucinous neoplasm(IPMN),2 mucinous cystic neoplasm(MCN),1 serous cystadenoma]. Patients with PCNs exhibited less male predominance(55% vs 73%,P = 0.03) compared to patients without pancreatic cysts. Thirteen patients(42%) were diagnosed with PCN pre-LT while 18 patients(58%) developed PCN post-LT. The median size of PCNs was 13 mm [interquartile range(IQR) 10-20 mm]. All IPMNs were side-branch type. Most PCNs were found in the head and body of pancreas(37% each),followed by the tail(25%). Five patients underwent further evaluation with endoscopic ultrasound. Progress imaging was performed on 81% of patients. PCNs remained stable in size and number in all but 2 patients. During a median follow up of 39 mo(IQR 26-58 mo),the 2(6%) patients with MCN underwent pancreatectomy. No PCN patient developed pancreatic adenocarcinoma,while 5 died from illnesses unrelated to the PCN. Among patients without PCN,1/841(0.1%) developed pancreatic adenocarcinoma.CONCLUSION The prevalence of PCNs in LT recipients was similar to the general population(3.6%,31/872). Side-branch IPMNs do not appear to have accelerated malignant potential in post-LT patients,indicating the current surveillance guidelines are applicable to this group.

Recurrent renal cell carcinoma leading to a misdiagnosis of polycystic liver disease: A case report

BACKGROUND Polycystic liver disease(PCLD) with a large cystic volume deteriorates the quality of life of patients through substantial effects on the adjacent organs,recurrent cyst infections, cyst rupture, and hemorrhage. Surgical or radiological intervention is usually needed to alleviate these symptoms. We report a rare case of the cystic metastasis of renal cell carcinoma(RCC), which was misdiagnosed as PCLD, as a result of the clinical and radiological similarity between these disorders.CASE SUMMARY A 74-year-old female who had undergone nephrectomy for papillary-type RCC(PRCC) was suffering from abdominal pain and the recurrent intracystic hemorrhage of multiple cysts in the liver. Imaging studies and aspiration cytology of the cysts showed no evidence of malignancy. With a diagnosis of autosomal dominant polycystic liver disease, the patient received hepatectomy for the purpose of mass reduction and infectious cyst removal. Surgery was performed without complications, and the patient was discharged on postoperative day 14. Postoperatively, the pathology revealed a diagnosis of recurrent PRCC with cystic formation.CONCLUSION This case demonstrates the importance of excluding the cystic metastasis of a cancer when liver cysts are observed.

肝脏黏液性囊性肿瘤的MRI特征及分型

目的:探讨肝脏黏液性囊性肿瘤的MRI特征及分型。方法:回顾性分析复旦大学附属中山医院和日照市人民医院2010年6月至2023年1月经病理证实的55例肝脏黏液性囊性肿瘤患者的资料,图像分析包括病灶的位置、边界、数目、大小、形态、有无分隔、壁结节、有无胆管扩张、囊壁及囊腔在T1WI、T2WI、DWI及ADC图像上的信号特征,病灶的囊壁、分隔及壁结节的强化特点,根据形态学特点分为微囊型、寡囊型、混合型3组,分析3组病灶的MRI特征差异有无统计学意义。结果:55例患者中有55个病灶,所有病灶均为单发,微囊型6例,寡囊型20例,混合型29例,病灶大小为1.6~23(8.8±4.7)cm;3组间在病灶大小、有无壁结节的比较差异有统计学意义(P<0.05),在年龄、性别、有无临床症状、形态、病灶位置、边界、实验室指标、有无浸润性、囊液信号、有无分隔、壁结节强化方式及壁结节是否扩散受限、囊腔数量及上游胆管有无扩张的比较差异无统计学意义(P>0.05)。结论:不同类型的肝脏黏液性囊性肿瘤的MRI表现有一定的特征,MRI有助于该病的诊断与鉴别诊断。

肝脏原发性腺样囊性癌一例并文献复习

目的通过报告肝脏原发性腺样囊性癌的病例,增进医学界对这种疾病的认识。方法针对我院1例肝脏原发性腺样囊性癌患者进行鉴别分析,描述其组织病理学特征和免疫组化概况及整个诊疗过程,并回顾了相关文献。结果判定本例患者确定是肝脏原发腺样囊性癌,国内外仅有2例类似病例。结论肝脏原发性腺样囊性癌早期临床表现无特异性,易延误诊治,远处转移对患者生存影响较大,早期明确诊断后应及时行手术治疗。

Evaluation of hepatic cystic lesions

Hepatic cysts are increasingly found as a mere coincidence on abdominal imaging techniques, such as ultrasonography (USG), computed tomography (CT) and magnetic resonance imaging (MRI). These cysts often present a diagnostic challenge. Therefore, we performed a review of the recent literature and developed an evidence-based diagnostic algorithm to guide clinicians in characterising these lesions. Simple cysts are the most common cystic liver disease, and diagnosis is based on typical USG characteristics. Serodiagnostic tests and microbubble contrast-enhanced ultrasound (CEUS) are invaluable in differentiating complicated cysts, echinococcosis and cystadenoma/cystadenocarcinoma when USG, CT and MRI show ambiguous findings. Therefore, serodiagnostic tests and CEUS reduce the need for invasive procedures. Polycystic liver disease (PLD) is arbitrarily defined as the presence of > 20 liver cysts and can present as two distinct genetic disorders: autosomal dominant polycystic kidney disease (ADPKD) and autosomal dominant polycystic liver disease (PCLD). Although genetic testing for ADPKD and PCLD is possible, it is rarely performed because it does not affect the therapeutic management of PLD. USG screening of the liver and both kidneys combined with extensive family history taking are the cornerstone of diagnostic decision making in PLD. In conclusion, an amalgamation of these recent advances results in a diagnostic algorithm that facilitates evidence-based clinical decision making.

Lumacaftor/ivacaftor therapy is associated with reduced hepatic steatosis in cystic fibrosis patients

BACKGROUND Hepatic steatosis is a common form of cystic fibrosis associated liver disease(CFLD)seen in an estimated 15%-60%of patients with cystic fibrosis(CF).The pathophysiology and health implications of hepatic steatosis in cystic fibrosis remain largely unknown.In the general population,hepatic steatosis is strongly associated with insulin resistance and type 2 diabetes.Cystic fibrosis related diabetes(CFRD)impacts 40%-50%of CF adults and is characterized by both insulin insufficiency and insulin resistance.We hypothesized that patients with CFRD would have higher levels of hepatic steatosis than cystic fibrosis patients without diabetes.AIM To determine whether CFRD is associated with hepatic steatosis and to explore the impact of lumacaftor/ivacaftor therapy on hepatic steatosis in CF.METHODS Thirty patients with CF were recruited from a tertiary care medical center for this cross-sectional study.Only pancreatic insufficient patients with CFRD or normal glucose tolerance(NGT)were included.Patients with established CFLD,end stage lung disease,or persistently elevated liver enzymes were excluded.Mean magnetic resonance imaging(MRI)proton density fat fraction(PDFF)was obtained for all participants.Clinical characteristics[age,sex,body mass index,percent predicted forced expiratory volume at 1 s(FEV1),lumacaftor/ivacaftor use]and blood chemistries were assessed for possible association with hepatic steatosis.Hepatic steatosis was defined as a mean MRI PDFF>5%.Patients were grouped by diabetes status(CFRD,NGT)and cystic fibrosis transmembrane conductance regulator(CFTR)modulator use(lumacaftor/ivacaftor,no lumacaftor/ivacaftor)to determine between group differences.Continuous variables were analyzed with a Wilcoxon rank sum test and discrete variables with a Chi square test or Fisher’s exact test.RESULTS Twenty subjects were included in the final analysis.The median age was 22.3 years(11.3-39.0)and median FEV1 was 77%(33%-105%).Twelve subjects had CFRD and 8 had NGT.Nine subjects were receiving lumacaftor/ivacaftor.The median PDFF was 3.0%(0.0%-21.0%).Six subjects(30%)had hepatic steatosis defined as PDFF>5%.Hepatic fat fraction was significantly lower in patients receiving lumacaftor/ivacaftor(median,range)(2.0%,0.0%-6.4%)than in patients not receiving lumacaftor/ivacaftor(4.1%,2.7-21.0%),P=0.002.Though patients with CFRD had lower PDFF(2.2%,0.0%-14.5%)than patients with NGT(4.9%,2.4-21.0%)this did not reach statistical significance,P=0.06.No other clinical characteristic was strongly associated with hepatic steatosis.CONCLUSION Use of the CFTR modulator lumacaftor/ivacaftor was associated with significantly lower hepatic steatosis.No association between CFRD and hepatic steatosis was found in this cohort.

Treatment of liver hydatidosis:How to treat an asymptomatic carrier?

Liver hydatidosis is the most common clinical presentation of cystic echinococcosis(CE).Ultrasonographic mass surveys have demonstrated the true prevalence,including the asymptomatic characteristic of the majority of cases,providing new insight into the natural history of the disease.This raises the question of whether to treat or not to treat these patients,due to the high and unsuspected prevalence of CE.The high rate of liver/lung frequencies of cyst localization,the autopsy findings,and the involution of cysts demonstrated in long time follow-up of asymptomatic carriers contribute to this discussion.The decision to treat an asymptomatic patient by surgery,albendazole,or puncture aspiration injection and reaspiration or to wait and watch,is based on conflicting reports in the literature,the lack of complications in untreated patients over time,and the spontaneous disappearance and involution of cysts.All these points contribute to difficulties of individual clinical decisions.The patients should be informed of the reasons and the risks of watchful/waiting without treatment,the possibility of complications,and the risks of the other options.As more information on the natural history of liver hydatidosis is acquired,selection of the best treatment will be come easier.Without this knowledge it would be very difficult to establish definitive rules of treatment.At present,it is possible to manage these patients over time and to wait for the best moment for treatment.Followup studies must be conducted to achieve this objective.

Cystic fibrosis patients on cystic fibrosis transmembrane conductance regulator modulators have a reduced incidence of cirrhosis

BACKGROUND Cystic fibrosis transmembrane conductance regulator(CFTR)modulators significantly improve pulmonary function in patients with cystic fibrosis(CF)but the effect on hepatobiliary outcomes remains unknown.We hypothesized that CF patients on CFTR modulators would have a decreased incidence of cirrhosis compared to patients not on CFTR modulators or on ursodiol.AIM To investigate the effect of CFTR modulators on the development of cirrhosis in patients with CF.METHODS A retrospective analysis was performed using Truven MarketScan from January 2012 through December 2017 including all patients with a diagnosis of CF.Patients were excluded if they underwent a liver transplantation or if they had other etiologies of liver disease including viral hepatitis or alcohol use.Subjects were grouped by use of CFTR modulators,ursodiol,dual therapy,or no therapy.The primary outcome was development of cirrhosis.Kaplan-Meier curves estimated the incidence of cirrhosis and log-rank tests compared incidence curves between treatment groups.RESULTS A total of 7201 patients were included,of which 955(12.6%)used a CFTR modulator,529(7.0%)used ursodiol,105(1.4%)used combination therapy,and 5612(74.3%)used neither therapy.The incidence of cirrhosis was 0.1%at 1 year and 0.7%at 4 years in untreated patients,5.9%and 10.1%in the Ursodiol group,and 1.0%and 1.0%in patients who received both therapies.No patient treated with CFTR modulators alone developed cirrhosis.Patients on CFTR modulators alone had lower cirrhosis incidence than untreated patients(P=0.05),patients on Ursodiol(P<0.001),and patients on dual therapy(P=0.003).The highest incidence of cirrhosis was found among patients treated with Ursodiol alone,compared to untreated patients(P<0.001)or patients on Ursodiol and CFTR modulators(P=0.01).CONCLUSION CFTR modulators are associated with a reduction in the incidence of cirrhosis compared to other therapies in patients with CF.

Paediatric cholestatic liver disease:Diagnosis,assessment of disease progression and mechanisms of fibrogenesis

Cholestatic liver disease causes significant morbidity and mortality in children.The diagnosis and management of these diseases can be complicated by an inability to detect early stages of fibrosis and a lack of adequate interventional therapy.There is no single gold standard test that accurately reflects the presence of liver disease,or that can be used to monitor fibrosis progression,particularly in conditions such as cystic fibrosis.This has lead to controversy over how suspected liver disease in children is detected and diagnosed.This review discusses the challenges in using commonly available methods to diagnose hepatic fibrosis and monitor disease progression in children with cholestatic liver disease.In addition,the review examines the mechanisms hypothesised to be involved in the development of hepatic fibrogenesis in paediatric cholestatic liver injury which may ultimately aid in identifying new modalities to assist in both disease detection and therapeutic intervention.

Cystic Degeneration of Peripheral Intrahepatic Cholangiocarcinoma: An Atypical Presentation

Cholangiocarcinomas are primary malignant tumors of the liver that arises from the epithelium lining the small intra and extrahepatic bile ducts, and has numerous histologic types and growth patterns. At computed tomography (CT) and magnetic ressonance (MR), it has various appearences which motivated the present study;we present a case within an atypical presentation. The objective is to show the variety of differential diagnoses before an atypical aspect and the importance of the imaging methods for the diagnosis. Cholangiocarcinoma is still an uncommon neoplasm, and CT and MR are crucial for accurate diagnosis and for differentiation from other hepatic tumorous and nontumorous lesions.

MRI诊断肝脏囊性占位性病变的价值

目的:评价MRI诊断肝脏囊性占位性病变的价值。方法:选择2021年5月至2022年12月间本院收治的196例疑似肝脏囊性占位性病变患者,都接受MRI、螺旋CT检查,以病理检查结果为标准,比较MRI、CT的诊断效能,并且评价核磁共振ADC值定量鉴别各种肝脏囊性占位性病变的效果。结果:病理检查结果表明,187例为肝脏囊性占位性病变。MRI与螺旋CT诊断肝脏囊性占位性病变的准确度、特异度、敏感度均无显著差异(P>0.05)。螺旋CT鉴别炎症性囊性病变的符合率为86.27%(44/51),MRI为98.04%(50/51),显著高于螺旋CT(P<0.05);两种方法鉴别肝囊肿、肝血管瘤、肝肿瘤囊变或坏死的符合率则无显著差异(P>0.05)。4种肝脏囊性占位性病变的囊区ADC值、实区ADC值、综合ADC值均有统计学差异(P<0.05)。结论:MRI可以准确诊断肝脏囊性占位性病变,并且有效区分肝囊肿、肝脓肿、肝血管瘤、肝肿瘤囊变或坏死,具有较高的应用价值。

《2022年欧洲肝病学会临床实践指南:囊性肝病的管理》摘译

放射增强成像技术的问世对囊性肝病的诊断助益很大,与此同时,该疾病的治疗在既往数十年里日益成熟。因此,有必要提供全面的临床指南。本指南涵盖肝囊肿、肝脏黏液性囊性肿瘤、多囊肝病、先天性肝内胆管囊状扩张症、先天性胆管扩张综合征、胆道错构瘤和胆管周围囊肿的诊断和治疗。在深度文献复习的基础上,本指南给出了解决临床难题的建议及其支持性文件。根据牛津循证医学中心系统对证据水平进行分级,并将推荐意见等级分为“弱推荐”和“强推荐”。本指南目标为提供最佳证据,为临床医师对此类患者的临床决策提供参考。

阿苯达唑片联合腹腔镜根治术治疗肝囊型包虫病的效果及对肝功能的影响

目的探讨阿苯达唑片联合腹腔镜根治术治疗肝囊型包虫病的效果及对肝功能的影响。方法前瞻性选取2019年1月至2022年1月喀什地区第一人民医院收治的100例肝囊型包虫病患者作为研究对象,按照随机数字表法将其分为观察组与对照组,每组50例。对照组患者立即采取腹腔镜根治术治疗,观察组患者口服阿苯达唑片3个月后采取腹腔镜根治术治疗。对比两组患者手术时间、术中出血量、住院时间、治疗费用以及围手术期病死率,对比两组患者手术前和手术3 d后的肝功能指标[碱性磷酸酶(ALP)、丙氨酸转移酶(ALT)、天冬氨酸转移酶(AST)]与炎症细胞因子[C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-2(IL-2)]水平,并比较两组患者术后并发症发生率以及1年包虫复发率。结果两组患者治疗费用、围手术期病死率比较,差异均无统计学意义(P>0.05),观察组患者手术时间、住院时间分别为(117.25±23.12)min、(4.36±1.12)d,均短于对照组[(142.27±32.82)min、(5.46±1.37)d],术中出血量为(81.27±15.18)mL,少于对照组[(98.31±12.27)mL],差异均有统计学意义(P<0.05)。手术后,两组患者ALP、ALT、AST水平均较手术前升高,但观察组ALP、ALT、AST水平分别为(249.62±28.24)U/L、(136.26±46.42)U/L、(48.41±3.35)IU/L,均低于对照组[(282.85±43.32)U/L、(174.51±48.37)U/L、(52.00±5.58)IU/L],差异均有统计学意义(P<0.05)。手术后,两组患者CRP、TNF-α水平均较手术前升高,IL-2水平均较手术前降低,但观察组患者CRP、TNF-α水平分别为(161.12±16.12)μg/mL、(13.63±2.52)mg/L,均低于对照组[(196.21±13.93)μg/mL、(15.68±3.12)mg/L],IL-2水平为(3.02±1.25)μg/L,高于对照组[(2.32±0.32)μg/L],差异均有统计学意义(P<0.05)。观察组患者的总复发率为4.00%,明显低于对照组(28.00%),差异有统计学意义(P<0.05)。结论阿苯达唑片联合腹腔镜根治术治疗肝囊型包虫病疗效显著,能够减轻患者术中损伤,减少住院时间,且能够减轻患者手术带来的肝功能损伤,降低机体炎症因子水平,减少远期复发,值得临床应用推广。