Morphological,Functional, and Tissue Characterization of Silent Myocardial Involvement in Patients With Primary Biliary Cholangitis

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Current standards and future perspectives in adjuvant treatment for biliary tract cancers

Biliary tract cancer, including cholangiocarcinoma (CCA) and gallbladder cancer (GBC) are rare tumours with a rising incidence. Prognosis is poor, since most patients are diagnosed with advanced disease. Only ~20% of patients are diagnosed with early-stage disease, suitable for curative surgery. Despite surgery performed with potentially-curative intent, relapse rates are high, with around 60–70% of patients expected to have disease recurrence. Most relapses occur in the form of distant metastases, with a predominance of liver spread. In view of high tumour recurrence, adjuvant strategies have been explored for many years, in the form of radiotherapy, chemo-radiotherapy and chemotherapy. Historically, few randomised trials were available, which included a variety of additional tumours (e.g. pancreatic and ampullary tumours); most evidence relied on phase II and retrospective studies, with no high-quality evidence available to define the real benefit derived from adjuvant strategies.Since 2017, three randomised phase III clinical trials have been reported; all recruited patients with resected biliary tract cancer (CCA and GBC) who were randomised to observation alone, or chemotherapy in the form of gemcitabine (BCAT study; included patients diagnosed with extrahepatic CCA only), gemcitabine and oxaliplatin (PRODIGE-12/ACCORD-18; included patients diagnosed with CCA and GBC) or capecitabine (BILCAP; included patients diagnosed with CCA and GBC). While gemcitabine-based chemotherapy failed to show an impact on patient outcome (relapse-free survival (RFS) or overall survival (OS)), the BILCAP study showed a benefit from adjuvant capecitabine in terms of OS (pre-planned sensitivity analysis in the intention-to-treat population and in the per-protocol analysis), with confirmed benefit in terms of RFS. Based on the BILCAP trial, international guidelines recommend adjuvant capecitabine for a period of six months following potentially curative resection of CCA as the current standard of care for resected CCA and GBC. However, BILCAP failed to show OS benefit in the intention-to-treat (non-sensitivity analysis) population (primary end-point), and this finding, as well as some inconsistencies between studies has been criticised and has led to confusion in the biliary tract cancer medical community.This review summarises the adjuvant field in biliary tract cancer, with evidence before and after 2017, and comparison between the latest randomised phase III studies. Potential explanations are presented for differential findings, and future steps are explored.     

原位肝移植术后缺血型胆道病变20例

目的探讨原位肝移植术后缺血型胆道病变（ITBL）的病因及预防、诊断和治疗的措施。方法回顾性分析1999年2月至2005年4月间291例次原位肝移植后发生ITBL患者的临床资料。结果291例次原位肝移植术后共发生ITBL 20例（6．9％）。术后发生ITBL的高危因素为：原发病为重型乙型肝炎、供受者ABO血型不符、供肝冷保存时间超过12h和术后肝动脉病变。其发生率分别为12．5％（9／71）、20．0％（2／10）、11．1％（9／81）和60％（3／5）。采用药物、经内镜逆行胰胆管造影（ERCP）介入、胆道外科手术及再次肝移植等方法治疗，有效率为80．0％（16／20）、治愈率为50．0％（10／20），与ITBL相关的病死率为10．0％（2／20），与ITBL相关的移植物功能丧失发生率为20．0％（4／20）。结论针对ITBL的高危因素进行相应处理是预防ITBL的有效措施。胆道造影和核磁共振胆胰管成像对诊断ITBL有很高的敏感性和特异性。根据不同的病因和病变程度采用适当的方法治疗ITBL，可获得良好的疗效。     

Preservation of Bile Ductules Mitigates Bile Duct Loss

The finer branches of the biliary tree (FBBT) contain a regenerative compartment. We hypothesized that preservation of the FBBT together with its microvasculature will lead to recovery of biliary damage and prolonged preservation of bile ductules during the development of chronic liver allograft rejection. The interlobular bile ducts, portal bile ductules and extraportal biliary cells with and without microvessels were studied in sequential biopsies in five patients who fulfilled the Banff criteria of early chronic rejection (CR) (imminence group). Biopsies of CR patients (n = 12) served as controls. Biopsies were double immunostained with CD34 (microvessels) and cytokeratin 7 (biliary structures). Proliferation and proangiogenic activity were assessed with Ki67 and VEGF-A immunostaining. Severe damage of bile ducts in the imminence group did not progress to significant bile duct loss. This was associated with a high proliferative activity in all biliary structures and preservation of the microvascular compartment. VEGF-A expression was increased in all but the reperfusion biopsies. In conclusion, both regenerative activity of the FBBT and an intact microvascular compartment are associated with less damage of the biliary tree and could therefore be prerequisites for biliary regeneration.     

耳穴脉冲刺激对Oddi括约肌张力及肌电活动的影响

目的　探讨耳穴脉冲电刺激治疗胆石症 ,胆绞痛的机制 .方法　选用 15条成年杂种犬 ,进行耳穴体表脉冲刺激与缩胆素 (CCK)对在体狗胆囊张力 ,Oddi括约肌张力及肌电活动影响的对比研究 .结果　耳穴脉冲电刺激对胆囊张力无明显影响 [(1.2 7± 0 .2 6 ) k Pa与 (1.2 4± 0 .2 2 ) k Pa,P<0 .0 5 ],CCK注射液能明显提高胆囊张力 [(1.2 7± 0 .2 6 ) k Pa与 (1.91± 0 .39) k Pa,P<0 .0 5 ],CCK注射液能明显降低Oddi括约肌张力 [(2 .2 4± 0 .5 5 ) k Pa与 (1.5 8± 0 .5 6 ) k Pa,P>0 .0 5 ]及肌电活动 .结论　耳穴脉冲电刺激同 CCK一样 ,均对 Oddi括约肌的张力有显著的降低作用 ,并减少 Oddi括约肌的肌电峰电位爆发波的频率与电压值 ,推测其对胆绞痛有治疗作用 ,并有助于胆结石的排石过程 .     

Sonographic evaluation of gallbladder kinetics: in vitro and in vivo comparison of different methods to assess gallbladder emptying.

In an in vitro study, 10 gallbladders of adult pigs and 6 gallbladders of lambs, all removed immediately after slaughtering, were stimulated in a water bath by electric means to induce active contraction. Gallbladder emptying was followed by ultrasonography employing five measurement procedures: (1) gallbladder width, (2) longitudinal planimetry, (3) transverse planimetry, (4) ellipsoid method, and (5) sum of cylinders method. In an in vivo investigation, gallbladder emptying of 30 volunteers (12 healthy subjects, 18 diabetics) was evaluated in the same way after ingestion of a fatty meal. Gallbladder width was found to be unsuitable to estimate the decrease in gallbladder volume due to a nonlinear relation of the parameters. Longitudinal planimetry tended to be less valid than transverse planimetry in assessing gallbladder volume reduction. The most valid estimation of gallbladder volume decreases was obtained by the two three-dimensional procedures. However, in neither in vitro nor in vivo could a significant difference between the sum of cylinders method and the ellipsoid method in determining relative volume reduction be established. We conclude that a three-dimensional measurement procedure should be used for valid assessments of gallbladder motility. However, according to our data there is no advantage in using the time-consuming sum of cylinders method compared to the simple ellipsoid method.     

急性胆源性胰腺炎的微创治疗

目的探讨应用十二指肠镜及腹腔镜治疗急性胆源性胰腺炎(ABP)的有效性。方法回顾性分析5年间对94例ABP患者进行微创治疗的临床资料。ABP合并胆囊结石的59例行行单纯腹腔镜胆囊切除术(LC);胆总管结石14例内镜下乳头括约肌切开取石术(EST),同时置入鼻胆管引流(ENBD),其中3例联合LC;对胆囊结石合并胆总管结石21例行ERCP EST,联合LC治疗。结果全组术后再次发作胰腺炎1例,胆道出血1例,均为ERCP EST患者;另肺部感染2例,切口感染1例,5例均经非手术治疗痊愈。全组有效率100%。结论十二指肠镜及腹腔镜联合应用于治疗ABP效果好。微创技术是目前ABP理想的治疗方法。     

Biliary stent causing colovaginal fistula: case report.

OBJECTIVES: Perforation of the bowel during placement of a biliary stent is a known complication of this procedure. We report the endoluminal loss of a biliary stent during routine stent extraction that ultimately led to a chronic colovaginal fistula. This case emphasizes the need for evaluation of fecal passage of stents in patients with a known dislodged prosthesis. CASE REPORT: A 65-year-old white female underwent biliary stent placement for an episode of choledocholithiasis. The stent was lost in the duodenum during routine extraction. The patient was managed expectantly. She denied ever passing this stent via the rectum and began to develop symptoms of colovaginal fistula. Evaluation found a retained biliary stent in the sigmoid colon and a fistula into the vagina. The patient underwent elective low anterior resection and colovaginal fistula repair. DISCUSSION: Reports exist of migration of stents that lead to acute colonic perforation and the need for emergent surgery. For this reason, it has been suggested that dropped or migrated stents be purposefully retrieved. However, if the option of expectant observation is used, it is important to clearly document the fecal passage of these stents and be prepared to retrieve these objects if they have a prolonged bowel transit time.     

Liver Transplantation Across Rh Blood Group Barriers Increases the Risk of Biliary Complications

Background Cold ischemia time and the presence of postoperative hepatic arterial thrombosis have been associated with biliary complications (BC) after liver transplantation. An ABO-incompatible blood group has also been suggested as a factor for predisposal towards BC. However, the influence of Rh nonidentity has not been studied previously. Materials Three hundred fifty six liver transplants were performed from 1995 to 2000 at our hospital. BC incidence and risk factors were studied in 345 patients. Results Seventy patients (20%) presented BC after liver transplantation. Bile leakage (24/45%) and stenotic anastomosis (21/30%) were the most frequent complications. Presence of BC in Rh-nonidentical graft–host cases (23/76, 30%) was higher than in Rh-identical grafts (47/269, 17%) (P = 0.01). BC was also more frequent in grafts with arterial thrombosis (9/25, 36% vs 60/319, 19%; P = 0.03) and grafts with cold ischemia time longer than 430 min (26/174, 15% vs 44/171, 26%; P = 0.01). Multivariate logistic regression confirmed that Rh graft–host nonidentical blood groups [RR = 2(1.1–3.6); P = 0.02], arterial thrombosis [RR = 2.6(1.1–6.4); P = 0.02] and cold ischemia time longer than 430 min [RR = 1.8(1–3.2); P = 0.02] were risk factors for presenting BC. Conclusion Liver transplantation using Rh graft–host nonidentical blood groups leads to a greater incidence of BC.     

肝移植术后并发胆道狭窄和胆泥淤积影像诊断及介入治疗

目的:评价肝移植术后胆道狭窄和胆泥淤积影像诊断及介入治疗的价值。方法:对39例肝移植术后并发胆道狭窄和胆泥淤积的影像诊断及介入治疗进行回顾性分析。结果:超声、T型管胆道造影、CT和MRI检查诊断胆道狭窄伴胆泥形成39例,38例介入治疗后胆道梗阻症状明显缓解;1例介入治疗后胆道梗阻症状未明显改善,后行外科胆管修补术。结论:T型管胆道造影或直接经皮胆道造影对肝移植术后胆道狭窄和胆泥淤积诊断特异性及敏感性最高,放射介入和内镜介入技术对其均发挥重要的治疗作用。