Safety and efficacy of Kaffes intraductal self-expanding metal stents in the management of post-liver transplant anastomotic strictures

BACKGROUND Endoscopic management is the first-line therapy for post-liver-transplant anas-tomotic strictures.Although the optimal duration of treatment with plastic stents has been reported to be 8-12 months,data on safety and duration for metal stents in this setting is scarce.Due to limited access to endoscopic retrograde cholan-giopancreatography(ERCP)during the coronavirus disease 2019 pandemic in our centre,there was a change in practice towards increased usage and length-of-stay of the Kaffes biliary intraductal self-expanding stent in patients with suitable anatomy.This was mainly due to the theoretical benefit of Kaffes stents allowing for longer indwelling periods compared to the traditional plastic stents.METHODS Adult liver transplant recipients aged 18 years and above who underwent ERCP were retrospectively identified during a 10-year period through a database query.Unplanned admissions post-Kaffes stent insertion were identified manually through electronic and scanned medical records.The main outcome was the incidence of complications when stents were left indwelling for 3 months vs 6 months.Stent efficacy was calculated via rates of stricture recurrence between patients that had stenting courses for≤120 d or>120 d.RESULTS During the study period,a total of 66 ERCPs with Kaffes insertion were performed in 54 patients throughout their stenting course.In 33 ERCPs,the stent was removed or exchanged on a 3-month interval.No pancreatitis,perfor-ations or deaths occurred.Minor post-ERCP complications were similar between the 3-month(abdominal pain and intraductal migration)and 6-month(abdominal pain,septic shower and embedded stent)groups-6.1%vs 9.1%respectively,P=0.40.All strictures resolved at the end of the stenting course,but the stenting course was variable from 3 to 22 months.The recurrence rate for stenting courses lasting for up to 120 d was 71.4%and 21.4%for stenting courses of 121 d or over(P=0.03).There were 28 patients that were treated with a single ERCP with Kaffes,21 with removal after 120 d and 7 within 120 d.There was a significant improvement in stricture recurrence when the Kaffes was removed after 120 d when a single ERCP was used for the entire stenting course(71.0%vs 10.0%,P=0.01).CONCLUSION Utilising a single Kaffes intraductal fully-covered metal stent for at least 4 months is safe and efficacious for the management of post-transplant anastomotic strictures.

Bile duct cyst in adults:Interventional treatment,resection,or transplantation?

Cystic dilatations of the bile ducts may be found along the extrahepatic biliary tree,within the liver,or in both of these locations simultaneously.Presentation in adults is often associated with complications.The therapeutic possibilities have changed considerably over the last few decades.If possible,complete resection of the cyst(s)can cure the symptoms and avoid the risk of malignancy.According to the type of bile duct cyst,surgical procedures include the Roux-en-Y hepaticojejunostomy and variable types of hepatic resection.However,the diffuse forms of Todani type Ⅴ cysts(Caroli disease and Caroli syndrome)in particular remain a therapeutic problem,and liver transplantation has become an important option.The mainstay of interventional treatment for Todani typeⅢbile duct cysts is via endoscopic retrograde cholangiopancreatography.The diagnostic term"bile duct cyst"comprises quite different pathological and clinical entities.Interventional therapy,hepatic resection,and liver transplantation all have their place in the treatment of this heterogeneous disease group.They should not be seen as competitive treatment modalities,but as complementary options.Each patient should receive individualized treatment after all of the clinical findings have been considered by an interdisciplinary team.

Association of extraintestinal manifestations of inflammatory bowel disease in a province of western Hungary with disease phenotype:Results of a 25-year follow-up study

AIM:IBD is a systemic disease associated with a large number of extraintestinal manifestations (EIMs).Our aim was to determine the prevalence of EIMs in a large IBD cohort in Veszprem Province in a 25-year follow-up study. METHODS:Eight hundred and seventy-three IBD patients were enrolled (ulcerative colitis/UC/:619,m/f:317/302, mean age at presentation:38.3 years,average disease duration:11.2 years;Crohn's disease/CD/:254,m/f:125/129, mean age at presentation:32.5 years,average disease duration:9.2 years).Intestinal,extraintestinal signs and laboratory tests were monitored regularly.Any alteration suggesting an EIMs was investigated by a specialist. RESULTS:A total of 21.3% of patients with IBD had EIM (UC:15.0%,CD:36.6%).Age at presentation did not affect the likelihood of EIM.Prevalence of EIMs was higher in women and in CD,ocular complications and primary sclerosing cholangitis (PSC) were more frequent in UC.In UC there was an increased tendency of EIM in patients with a more extensive disease.Joint complications were more frequent in CD (22.4% vsUC 10.2%,P<0.01).In UC positive family history increased the risk of joint complications (OR:3.63).In CD the frequency of type-1 peripheral arthritis was increased in patients with penetrating disease (P=0.028).PSC was present in 1.6% in UC and 0.8% in CD.Dermatological complications were present in 3.8% in UC and 10.2% in CD,the rate of ocular complications was around 3% in both diseases.Rare complications were glomerulonephritis,autoimmune hemolytic anaemia and celiac disease. CONCLUSION:Prevalence of EIM in Hungarian IBD patients is in concordance with data from Western countries.The high number of EIM supports a role for complex follow-up in these patients.

Endoscopic management of biliary strictures after liver transplantation

Bile duct strictures remain a major source of morbidity after orthotopic liver transplantation (OLT). Biliary strictures are classifi ed as anastomotic or non-anastomotic strictures according to location and are defi ned by distinct clinical behaviors. Anastomotic strictures are localized and short. The outcome of endoscopic treatment for anastomotic strictures is excellent. Nonanastomotic strictures often result from ischemic and immunological events, occur earlier and are usually multiple and longer. They are characterized by a far less favorable response to endoscopic management, higher recurrence rates, graft loss and need for retransplantation. Living donor OLT patients present a unique set of challenges arising from technical factors, and stricture risk for both recipients and donors. Endoscopic treatment of living donor OLT patients is less promising. Current endoscopic strategies for biliary strictures after OLT include repeated balloon dilations and placement of multiple side-by-side plastic stents. Lifelong surveillance is required in all types of strictures. Despite improvements in incidence and long term outcomes with endoscopic management, and a reduced need for surgical treatment, the impact of strictures on patients after OLT is signifi cant. Future considerations include new endoscopic technologies and improved stents, which could potentially allow for a decreased number of interventions, increased intervals before retreatment, and decreased reliance on percutaneous and surgical modalities. This review focuses on the role of endoscopy in biliary strictures, one of the most common biliary complications after OLT.

Risk factors of choledocholithiasis formation after liver transplantation

Systematic study of risk factors for biliary stone post-liver transplantation is rarely performed. To investigate the risk factor of choledocholithiasis formation after liver transplantation, we c onducted a case-control study. Fourteen patients were selected into a study group. The stones of the bile duct of the patients were confirmed and treated successfully by endoscopic retrograde cholangiopancreatography. For univariate analysis, we selected carefully some potential risk factors such as cold ischemia time, warm ischemia time, and biliary stricture. The results revealed that cold ischemia time and biliary stenosis were significant predictors. But multivariate analysis revealed that only biliary stenosis was a significant risk factor. In conclusion, biliary stenosis is a risk factor of bile duct stones formation after liver transplantation. Endoscopic retrograde cholangiopancreatography is effective and safe in the diagnosis or treatment of bile duct stones after liver transplantation.

Donation after cardio-circulatory death liver transplantation

The renewed interest in donation after cardio-circulatory death (DCD) started in the 1990s following the limited success of the transplant community to expand the donation after brain-death (DBD) organ supply and following the request of potential DCD families. Since then, DCD organ procurement and transplantation activities have rapidly expanded, particularly for nonvital organs, like kidneys. In liver transplantation (LT), DCD donors are a valuable organ source that helps to decrease the mortality rate on the waiting lists and to increase the availability of organs for transplantation despite a higher risk of early graft dysfunction, more frequent vascular and ischemia-type biliary lesions, higher rates of re-listing and re-transplantation and lower graft survival, which are obviously due to theinevitable warm ischemia occurring during the declaration of death and organ retrieval process. Experimental strategies intervening in both donors and recipients at different phases of the transplantation process have focused on the attenuation of ischemia-reperfusion injury and already gained encouraging results, and some of them have found their way from pre-clinical success into clinical reality. The future of DCD-LT is promising. Concerted efforts should concentrate on the identification of suitable donors (probably Maastricht category Ⅲ DCD donors), better donor and recipient matching (high risk donors to low risk recipients), use of advanced organ preservation techniques (oxygenated hypothermic machine perfusion, normothermic machine perfusion, venous systemic oxygen persufflation), and pharmacological modulation (probably a multi-factorial biologic modulation strategy) so that DCD liver allografts could be safely utilized and attain equivalent results as DBD-LT.

Magnetic resonance cholangiopancreatography image enhancement for automatic disease detection

AIM:To sufficiently improve magnetic resonance cholangiopancreatography(MRCP) quality to enable reliable computer-aided diagnosis(CAD).METHODS:A set of image enhancement strategies that included filters(i.e.Gaussian,median,Wiener and Perona-Malik),wavelets(i.e.contourlet,ridgelet and a non-orthogonal noise compensation implementation),graph-cut approaches using lazy-snapping and Phase Unwrapping MAxflow,and binary thresholding using a fixed threshold and dynamic thresholding via histogram analysis were implemented to overcome the adverse characteristics of MRCP images such as acquisition noise,artifacts,partial volume effect and large inter-and intra-patient image intensity variations,all of which pose problems in application development.Subjective evaluation of several popular pre-processing techniques was undertaken to improve the quality of the 2D MRCP images and enhance the detection of the significant biliary structures within them,with the purpose of biliary disease detection.RESULTS:The results varied as expected since each algorithm capitalized on different characteristics of the images.For denoising,the Perona-Malik and contourlet approaches were found to be the most suitable.In terms of extraction of the significant biliary structures and removal of background,the thresholding approaches performed well.The interactive scheme performed the best,especially by using the strengths of the graphcut algorithm enhanced by user-friendly lazy-snapping for foreground and background marker selection.CONCLUSION:Tests show promising results for some techniques,but not others,as viable image enhancement modules for automatic CAD systems for biliary and liver diseases.

基于CT图像的纹理分析鉴别肝脏实性局灶性病变

目的 CT是鉴别肝脏实性局灶性病灶的常用检查方法,但其对不典型病灶的鉴别诊断仍有较大的经验依赖性,而纹理分析可以提供客观、定量的图像描述特征。本研究旨在探讨基于CT图像的纹理分析在肝脏实性局灶性病变鉴别诊断中的价值。资料与方法回顾性分析258例经病理证实或临床确诊的肝脏局灶性病变患者的CT图像,其中肝脏局灶性结节增生（FNH）34例,血管瘤（HEM）60例,肝细胞肝癌（HCC）60例,肝内胆管细胞癌（ICC）44例,转移瘤（MET）60例。所有患者均行腹部CT平扫与三期增强扫描。以Ma Zda软件生成CT图像的纹理特征并进行特征筛选,进行各组病灶的判别。结果 258例患者中,基于增强CT图像的纹理分析对于肝脏实性局灶性病变的鉴别诊断错判率（4.26%~37.80%）低于基于平扫图像的纹理分析（9.57%~39.02%）。对于良恶性病变的鉴别,门静脉期图像纹理分析错判率最低（13.57%）;对于FNH与HEM的鉴别,动脉期及门静脉期图像纹理分析效果相当（错判率为4.26%）;对于恶性肿瘤间的鉴别纹理分析错判率相对较高,若于恶性肿瘤间两两鉴别则错判率可降低（错判率最低为HCC与MET,约11.67%）。结论基于CT图像的纹理分析可以作为肝脏实性局灶性病灶鉴别诊断的辅助手段,尤其是FNH与HEM、良性病灶与恶性病灶、恶性病灶间的两两鉴别;其中基于三期增强扫描的纹理分析较基于平扫图像者效果更优。

慢性肝病胆小管增生与肝纤维化的关系

目的 探讨慢性肝病胆小管增生与肝纤维化的关系．方法 用ＬＤＰ 法观察７７ 例同时进行肝活组织学检查及血清纤维化标志检测的慢性肝病患者肝穿组织及１０ 例肝癌和２ 例正常人手术标本的ＣＫ－ １９ 单克隆抗体表达情况，并与肝病分级分期及血清纤维化标志等进行比较．结果 随ＣＫ－ １９ 表达强度从＋ 到＋＋＋＋ ，４ 项纤维化标志均逐步升高，尤其透明质酸与ＣＫ － １９ 表达强度的同步性最好，各组间比较均有显著性差异；ＣＫ － １９ 表达强度与肝病分级分期等显著相关（χ２ 分别为６５－６ ，６９－７ ，Ｐ 均＜ ０－０１） ；ＣＫ － １９ 染色还能显示胆小管破坏及淋巴细胞浸润．结论 ＣＫ－ １９ 染色对判断肝纤维化程度及肝炎相关的自身免疫现象有一定作用．

兔胆总管部分结扎肝硬化模型的建立

目的:探讨通过手术造成胆总管狭窄制备兔胆汁性肝硬化模型的可行性。方法:分离并部分结扎新西兰兔胆总管,结扎时分别与不同孔径的硬塑料管共同结扎或不用塑料管垫衬,结扎后将导管抽出,形成孔径分别为0、0.6mm、1.0mm和1.6mm的狭窄胆总管。存活兔于结扎14周后处死,观察其胆道系统变化情况。结扎前及结扎术后根据兔存活情况于1、2、4、11周经耳中央动脉抽血1.5mL测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBIL)、直接胆红素(DBIL)、总蛋白(TP)、白蛋白(ALB)。结果:兔胆总管部分结扎后有2种现象,一为肝内胆管形成球囊样扩张伴有胆石沉积,此类无明显肝纤维化表现;二为胆总管自狭窄以上呈不同程度扩张,有的呈现串珠样扩张,但无包裹性胆石沉积,此类肝纤维化程度较重。术后第1周,ALT、AST、TBIL、DBIL明显升高,第2周,ALT、AST、TP、ALB下降,TBIL、DBIL降至正常。结论:对新西兰兔进行胆总管部分结扎术可建立胆管阻塞型肝硬化模型。

超声造影观察肝移植术后缺血性胆管病变的肝脏血流灌注

目的用超声造影(CEUS)技术观察肝移植术后缺血性胆管病变(ITBL)的肝脏血流灌注特征。方法收集肝移植术后临床确诊为ITBL的患者39例,根据二维超声检查是否有肝内胆管扩张分为无胆管扩张缺血组(22例)和胆管扩张缺血组(17例),对照组为恢复正常的肝移植患者。分别对ITBL患者及对照组患者行CEUS检查,比较各组之间造影参数的差异,分析ITBL患者的肝脏血流灌注特征。结果胆管扩张缺血组与对照组肝实质峰值增强强度差异无统计学意义(P>0.05),峰值斜率差异有统计学意义(P<0.01),无胆管扩张缺血组与对照组肝实质峰值增强强度和峰值斜率差异均有统计学意义(P均<0.05)。结论肝移植术后发生ITBL的患者较肝移植后正常的患者肝实质血流灌注有所减低,CEUS可较常规超声更为敏感地检测到这种改变,CEUS是一种早期诊断ITBL的有前景的新技术。

腹腔镜联合手术

目的探讨腹腔镜联合手术的临床应用价值。方法回顾分析165例胆囊疾病病人经腹腔镜胆囊切除联合手术的临床资料,其中加做阑尾切除术29例,肝囊肿切除术38例,肝脏手术13例,胆总管切开取石术64例,胃肠手术4例,胰腺被膜切开术1例,泌尿系手术16例。结果165例腹腔镜联合手术中,2例中转,1例术后胆漏,1例再手术,其余161例均获成功,并顺利恢复。结论腹腔镜联合手术能够安全、有效、经济地处理多种腹部疾病,使患者能够充分享受微创外科手术的优越性,值得进一步开展普及。

犬胆道梗阻后肝脏超氧化物歧化酶及过氧化脂质的变化

通过犬胆道梗阻模型，动态观察了胆道梗阻后不同时相肝组织内超氧化物歧化酶（ＳＯＤ）及丙二醛（ＭＤＡ）含量变化。结果发现：犬胆道梗阻后２周其肝组织ＭＤＡ含量较对照组明显升高（Ｐ＜０．０１），梗阻后３周ＳＯＤ含量亦有显著下降（Ｐ＜０．０５），且二者变化随着梗阻时间的延长而加重。表明胆道梗阻后肝脏对自由基的清除能力下降，脂质过氧化反应增强，可能是胆道梗阻导致肝损伤的原因之一。

胆道梗阻再通后肝线粒体CCO及SDH活力的变化

通过建立犬胆道梗阻再通模型，对肝细胞线粒体琥珀酸脱氢酶（ＳＤＨ）及细胞色素氧化酶（ＣＣＯ）活力在胆道梗阻再通前后的变化进行了测定。结果表明：胆道梗阻对ＳＤＨ及ＣＣＯ活力可产生明显的抑制作用，再通后二酶活力在各组的恢复程度与再通前的梗阻时间成反比，与再通后的恢复时间成正比。提示：早期解除梗阻有利于肝细胞线粒体呼吸抑制的恢复。

MRCP诊断肝脏移植术后胆管狭窄

目的:探讨MRCR探查肝脏移植术后胆管狭窄的可行性。方法:19例原位肝脏移植术后3～10月临床怀疑胆管狭窄病人行MRCP检查,其中16例在1周内行ERCP检查确诊,3例经临床和实验室检查随访2月作出最后诊断。MRCP征象与ERCP、临床最终结果对照分析了解MRCP诊断胆管狭窄的价值及局限性。结果:15例病人确诊为胆管狭窄并植入支架,包括1例MRCP正常而ERCP考虑吻合口狭窄,随访半月症状加重也实施支架植入术,其中吻合口狭窄2例,非吻合口狭窄13例。1例供受体胆管不称误诊为吻合口狭窄。3例胆管无狭窄病人诊断为胆管炎。MRCP诊断胆管狭窄敏感性为93%,特异性为75%。本组资料显示碱性磷酸酶和γ-谷氨酰酶升高常提示胆管狭窄。结论:MRCP能够正确诊断肝脏移植术后胆管狭窄,但与ERCP相比由于分辨率较低病变细节不够清晰,往往会夸大狭窄程度,我们认为动态观察碱性磷酸酶和γ-谷氨酰酶、MRCP能够早期作出诊断。

化浊降逆和胃汤对胆汁反流性胃炎模型大鼠血清胃泌素、胃窦黏膜前列腺素E_2的影响

目的观察化浊降逆和胃汤对胆汁反流性胃炎模型大鼠血清胃泌素、胃窦黏膜前列腺素(PG)E2的影响,并探讨其作用机制。方法将40只Wistar大鼠随机分为4组,即空白对照组、模型对照组、化浊降逆和胃汤组及阳性药对照组,每组10只。除空白对照组外,其余3组均制备胆汁反流性胃炎大鼠模型。化浊降逆和胃汤组、阳性药对照组分别予化浊降逆和胃汤、甲氧氯普胺各6.7 mL/kg灌胃,空白对照组和模型对照组予等容积蒸馏水灌胃。每日2次,连续4周。检测血清胃泌素,刮取胃窦黏膜,检测PGE2。结果模型对照组血清胃泌素、胃窦黏膜PGE2均较空白对照组降低(P<0.05),提示造模成功。化浊降逆和胃汤组、阳性药对照组血清胃泌素、胃窦黏膜PGE2较模型对照组升高(P<0.01)。化浊降逆和胃汤组与阳性药对照组血清胃泌素、胃窦黏膜PGE2比较差异无统计学意义(P>0.05)。结论化浊降逆和胃汤通过改善胃分泌功能促进黏膜血液循环,营养胃黏膜等途径,恢复其分泌胃泌素的能力;同时化浊降逆和胃汤能通过提高胃窦黏膜PGE2含量,增强胃黏膜抵抗力,产生细胞保护作用。

防御素2在肝内胆管结石病中的抗菌作用

目的探讨人防御素2(HBD2)在肝胆管结石病中的抗菌作用。方法应用免疫组织化学方法和RT-PCR检测肝内胆管结石患者手术切除肝组织标本HBD2的表达情况。比较胆汁培养为革兰阴性及阳性菌组的HBD2表达的强弱,左右肝组织HBD2表达的强弱,分析HBD2表达与急性生理功能和慢性健康状况评分系统(ARACHEⅡ)评分的关系。结果 HBD2在部分肝内胆管结石的胆管间质细胞胞浆中表达,革兰阴性菌组的肝组织HBD2表达强于革兰阳性菌组,左肝部位HBD2的表达强于右肝部位,ARACHEⅡ高分组的HBD2表达强于低分组。结论 HBD2在肝胆管结石病肝组织中起到抗菌作用,其表达强度与革兰阴性菌和ARACHEⅡ评分正相关。

移植肝缺血型胆道病变的研究进展

肝移植术后胆道并发症影响移植肝的长期存活,而移植肝缺血型胆道病变日益成为胆道并发症的主要类型,并严重影响肝移植患者的5年生存率。本文对肝移植术后缺血型胆道病变的发病机制、临床表现、诊治等研究进展进行综述。

小儿肝胆超声声像图特点

小儿肝胆疾病,究其病因、先天发育特点、以及病理生理特点有其特殊性,不同于成人肝胆疾病,其超声影像学检查因此亦不同于成人超声影像特点。根据病因分为5类,(1)感染相关疾病;(2)先天发育异常疾病;(3)代谢性疾病;(4)肝脏占位性病变;(5)肝脏血管疾病。本文从这5个方面系统回顾儿科肝胆疾病超声特点,并对特征性疾病超声特点给予阐述。

完全梗阻性黄疸持续时间对大鼠肝切除术后肝再生的影响

目的探讨术前完全梗阻性黄疸的持续时间对大鼠肝切除术后肝再生的影响。方法建立完全梗阻性黄疸大鼠模型,测定梗阻不同时相的胆红素水平;选取梗阻0,1,3,7d分为4组,即正常肝切除组(A组)、梗阻1d肝切除组(B组)、梗阻3d肝切除组(C组)及梗阻7d肝切除组(D组),观察肝切除(肝切除量约70%)术后各组大鼠死亡率,检测肝切除术后0,12,24,48,72,168h的肝功能指标,免疫组织化学检测残肝组织PCNA标记指数,RT-PCR法检测肝组织HGF基因的表达,检测术后7d残肝质量/体质量的比值。结果B组在肝切除术后死亡率、肝功能恢复、PCNA标记指数、HGF mRNA表达及肝质量/体质量的比值等方面均优C组及D组,差别均有统计学意义(P<0.05)。结论术前高胆红素血症可明显抑制大鼠肝切除术后的肝再生;术前梗阻时间短、胆红素处于较低水平,扩大肝叶切除术才可能相对安全地进行。