Radiofrequency and malignant biliary strictures:An update

Malignant biliary strictures are usually linked to different types of tumors,mainly cholangiocarcinoma, pancreatic and hepatocellular carcinomas. Palliative measures are usually adopted in patients with nonresectable or borderline resectable biliary disease. Stent placement is a well-known and established treatment in patients with unresectable malignancy. Intraductal radiofrequency ablation(RFA) represents a procedure that involves the use of a biliary catheter device, via an endoscopic approach. Indications for biliary RFA described in literature are: Palliative treatment of malignant biliary strictures, avoiding stent occlusion, ablating ingrowth of blocked metal stents, prolonging stent patency,ablating residual adenomatous tissue after endoscopic ampullectomy. In this mini-review we addressed focus on technical success defined as deployment of the RF catheter, virtually succeeded in all patients included in the studies. About efficacy, three main outcome measures have been contemplated: Biliary decompression and stent patency, survival. Existing studies suggest a beneficial effect on survival and stent patency with RFA, but current impression is limited because most of studies have been performed using a retrospective design, on diminutive and dissimilar cohorts of patients.     

腔内射频消融治疗胆管恶性狭窄的初步研究

目的 探讨内镜下应用腔内射频消融技术姑息性治疗胆管恶性狭窄的安全性及可行性.方法 前瞻性选取胆管恶性梗阻无法手术切除的12例患者实施ERCP,在胆管插管成功后,循导丝导入专用双极射频电极,于肿瘤部位进行射频烧灼,然后留置胆道支架,观察术后恢复情况并密切随访.结果 所有患者均成功完成射频消融治疗并留置胆道支架(塑料支架6例,金属支架6例,其中3例患者同期放置胰管支架).出现胆管炎1例,胰腺炎1例,均短期保守治疗控制.黄疸迅速缓解率为58.3％ (7/12);平均随访3.4个月(0.5 ～5.5个月),1个月末支架通畅率为100％ (12/12),3个月末通畅率为80％ (8/10);1例患者死于心脑血管意外,其余患者均存活无特殊不适.结论 对于胆管恶性狭窄,经内镜进行腔内射频治疗是安全可行的,初步疗效满意,但远期疗效及最佳治疗方案仍有待进一步探讨.     

Photodynamic therapy of malignant biliary strictures using meso-tetrahydroxyphenylchlorin

OBJECTIVES: The palliation of patients with malignant bile duct obstruction using metal or plastic biliary stents may be limited by stent occlusion. The aim of this study was to determine the safety and efficacy of endoscopically delivered meso-tetrahydroxyphenyl chlorin photodynamic therapy in the treatment of irresectable malignant biliary strictures and recurrent stent occlusion. METHODS: Thirteen patients with malignant biliary obstruction owing to carcinoma of the biliary tract (n=9), pancreas (n=3) or stomach (n=1), were studied. All had been initially palliated with metal (n=10) or polyethylene (n=3) biliary stents, but presented with recurrent obstructive jaundice because of local tumour progression. Patients received meso-tetrahydroxyphenyl chlorin 0.15 mg/kg intravenously 72 h before endoluminal light activation with an endoscopically placed optical fibre, followed by polyethylene stent insertion. RESULTS: Before photodynamic therapy, patients had a median of three (range 0-5) stent occlusions in the preceding 11 (2-22) months, with a median patency of plastic stents placed inside metal bile duct stents for recurrent stent occlusion of 3.5 (0.5-13) months. After photodynamic treatment, tumour necrosis and/or metal stent recanalization was seen in all patients, with a median of 0 (0-3) stent occlusions during 7 (1-43) months follow-up. The median patency of plastic stents placed inside metal stents after photodynamic therapy was 5 (1-43) months. The median survival after diagnosis and photodynamic therapy administration was 21 (10-56) and 8 (1-43) months, respectively. Photodynamic therapy was generally well tolerated but two patients developed cholangitis within the first week, complicated in one by a fatal liver abscess and two developed haemobilia within 4 weeks of treatment, one of whom died with a gall bladder empyema. CONCLUSION: In patients with malignant biliary obstruction, endoscopically delivered meso-tetrahydroxyphenyl chlorin photodynamic therapy causes efficient tumour necrosis and recanalization of blocked metal stents, but there is a significant risk of complications.     

Current status of endoscopic biliary drainage for unresectable malignant hilar biliary strictures

The management of jaundice and cholangitis is important for improving the prognosis and quality of life of patients with unresectable malignant hilar biliary strictures (UMHBS). In addition, effective chemotherapy, such as a combination of gemcitabine and cisplatin, requires the successful control of jaundice and cholangitis. However, endoscopic drainage for UMHBS is technical demanding, and continuing controversies exist in the selection of the most appropriate devices and techniques for stent deployment. Although metallic stents (MS) are superior to the usual plastic stents in terms of patency, an extensive comparison between MS and “inside stents”, which are deployed above the sphincter of Oddi, is necessary. Which techniques are preferred remains as yet unresolved: for instance, whether to use a unilateral or bilateral drainage, or a stent-in-stent or side-by-side method for the deployment of bilateral MS, although a new cell design and thin delivery system for MS allowed us to accomplish successful deployments of bilateral MS. The development of techniques and devices for re-intervention after stent occlusion is also imperative. Further critical investigations of more effective devices and techniques, and increased randomized controlled trials are warranted to resolve these important issues.     

Optimization of biliary drainage in inoperable distal malignant strictures

BACKGROUND Given most patients with distal malignant biliary obstruction present in the nonresectable stage, palliative endoscopic biliary drainage with fully covered metal stent(FCMS) or uncovered metal stent(UCMS) is the only available measure to improve patients' quality of life. Half covered metal stent(HCMS) has been recently introduced commercially. The adverse effects and stent function between FCMS and UCMS have been extensively discussed.AIM To study the duration of stent patency of HCMS and compare it with FCMS and UCMS to optimize biliary drainage in inoperable patients with distal malignant obstruction. Secondary aims in our study included evaluation of patients' survival and the rates of adverse events for each type of stent.METHODS We studied 210 patients and randomized them into three equal groups; HCMS, FCMS and UCMS were inserted endoscopically.RESULTS Stent occlusion occurred in(18.6%, 17.1% and 15.7% in HCMS, FCMS and UCMS groups, respectively, P = 0.9). Stent migration occurred only in patients with FCMS(8.6% of patients). Cholangitis and cholecystitis occurred in 11.4% and 5.7% of patients, respectively, in FCMS. Tumor growth occurred only in 10 cases among patients with UCMS after a median of 140 d, sludge occurred in nine, seven and one patients in HCMS, FCMS and UCMS, respectively(P = 0.04).CONCLUSION Given the prolonged stent functioning time, the use of HCMS is preferred over the use of UCMS and FCMS for optimizing biliary drainage in patients with distal malignant biliary obstruction.     

Prospective study of biliary strictures to determine the predictors of malignancy.

BACKGROUND: There have been few prospective studies regarding the investigation of biliary strictures, principally because of rapid technological change. The present study was designed to determine the sensitivity of various imaging studies for the detection of biliary strictures. Serum biochemistry and imaging studies were evaluated for their role in distinguishing benign from malignant strictures. METHODS: Thirty-one patients with suspected noncalculus biliary obstruction were enrolled consecutively in the study. A complete biochemical profile, ultrasound, Disida scan and cholangiogram (endoscopic retrograde cholangiopancreatography [ERCP] or percutaneous cholangiogram) were obtained at study entry. Stricture etiology was determined based on cytology, biopsy and/or clinical follow-up at one year. RESULTS: Twenty-nine of 31 patients had biliary strictures, of which 15 were malignant. The mean age of the malignant cohort was 73.9 years versus 53.9 years in the benign cohort (P<0.001). Statistically significant differences between the malignant and benign groups, respectively, were as follows: alanine transaminase 235.2 versus 66.9 U/L (P=0.004), aspartate transaminase 189.8 versus 84.5 U/L (P=0.011), alkaline phosphatase 840.2 versus 361.1 U/L (P=0.002), bilirubin 317.8 versus 22.1 micromol/L (P<0. 001) and bile acids 242.5 versus 73.2 micromol/L (P=0.001). Threshold analysis using receiver operative characteristic (ROC) curves demonstrated that a bilirubin level of 75 micromol/L was most predictive of malignant strictures. Intrahepatic duct dilation was present in 93% of malignant strictures versus 36% of benign strictures (P=0.002). Common hepatic duct dilation was less discriminatory (malignant 13.5 versus benign 9.6 mm; P=0.11). Ultrasound was highly sensitive (93%) in the detection of the primary tumour in the bile duct or pancreas, or in the visualization of nodal or liver metastases. In benign disease, ultrasound failed to detect evidence of intrahepatic or extrahepatic biliary dilation in most cases. Disida scans were not able to distinguish between malignant or benign strictures and could not accurately localize the level of obstruction. The sensitivity of Disida scan for the diagnosis of obstruction was 50%. Cholangiographic characterization of strictures revealed an equal distribution of smooth (eight of 13) and irregular (five of 13) strictures in the malignant group. Ten of 13 benign strictures were characterized as smooth. Malignant strictures were significantly longer than benign ones - 30.3 versus 9.2 mm (P=0.001). Threshold analysis using ROC curves showed that strictures greater than or equal to 14 mm were predictive of malignancy (sensitivity 78%, specificity 75%, log odds ratio 11.23). CONCLUSIONS: A serum bilirubin level of 75 micromol/L or higher, or a stricture length of greater than 14 mm was highly predictive of malignancy in patients with a biliary stricture. Ultrasound was useful in predicting malignant strictures by detecting either intrahepatic duct dilation or by visualizing the tumour (primary or metastases). Strictures with a 'benign' cholangiographic appearance are frequently malignant. Disida scan did not add additional information. ERCP is necessary to diagnose benign strictures, which tend to be less extensive at presentation.     

胆管恶性狭窄内镜射频消融术专家共识

内镜引导的胆管射频消融术是近年来新兴的胆管恶性狭窄的治疗手段,联合胆管支架引流和系统化疗等,可有效延缓肿瘤局部进展,改善患者生活质量,延长生存期,主要适用于无法手术的肝外胆管癌和壶腹癌患者。基于现有的临床循证医学依据,中华医学会消化内镜学分会、中国医师协会内镜医师分会消化内镜专业委员会和国家消化系统疾病临床医学研究中心（上海）组织相关专家,对其适应证、禁忌证、技术操作规范及并发症防治等方面进行讨论,并达成共识,旨在为胆管恶性肿瘤的临床规范化治疗提供参考。     

Post-operative biliary strictures

Post-operative biliary stricture is a cumbersome condition, secondary to biliary or vascular damage. Its risk factors include biliary or vascular anatomical variants, local inflammation, and poor surgical expertise. Intra-operative diagnosis is difficult, and in most cases, patients present with obstructive symptoms within a few weeks. Magnetic resonance cholangiography is a pivotal test to confirm the clinical picture, to study the level of the damage, and to guide treatment. Nowadays, endoscopic stenting is the first-line treatment in most centers. Multi-stenting treatment achieves long-term clinical success for more than 90% of patients, however multiple procedures are needed. In order to optimize healthcare provider costs, shorter duration endotherapies with covered metal stents are under evaluation. Radiological and surgical approaches are considered in the event of endoscopy failure.     

Fully covered self-expandable metal stents for treatment of malignant and benign biliary strictures

AIM:To present a series of covered self-expandable metal stents(CSEMS) placed for different indications and to evaluate the effectiveness,complications and extractability of these devices.METHODS:We therefore retrospectively reviewed the courses of patients who received CSEMS due to malignant as well as benign biliary strictures and postsphincterotomy bleeding in our endoscopic unit between January 2010 and October 2011.RESULTS:Twenty-six patients received 28 stents due to different indications(20 stents due to malignant biliary strictures,six stents due to benign biliary strictures and two stents due to post-sphincterotomy bleeding).Biliary obstruction was relieved in all cases,regardless of the underlying cause.Hemostasis could be achieved in the two patients who received the stents for this purpose.Complications occurred in five patients(18%).Two patients(7%) developed cholecystitis,stents dislocated/migrated in other two patients(7%),and in one patient(3.6%) stent occlusion was documented during the study period.Seven stents were extracted endoscopically.Removal of stents was easily possible in all cases in which it was desired using standard forceps.Twelve patients underwent surgery with pylorus preserving duodenopancreatectomy.In all patients stents could be removed during the operation without difficulties.CONCLUSION:Despite the higher costs of these devices,fully covered self-expanding metal stents may be suitable to relief biliary obstruction due to bile duct stenosis,regardless of the underlying cause.CSEMS may also represent an effective treatment strategy of severe post-sphincterotomy bleeding,not controlled by other measures.     

Uncovered Hanaro Versus Luminex metal stents for palliation of malignant biliary strictures

BACKGROUND: Endoscopic stent insertion is the optimum method of palliation for malignant biliary obstruction. Various types of self-expanding metal stents have been introduced in the market. Whether one type of stents is superior to the others in terms of stent patency remains undefined. GOALS: This randomized trial compared 2 uncovered metal stents with similar technical characteristics, but significant cost difference, in the palliation of inoperable malignant biliary strictures. STUDY: Ninety-two patients with inoperable biliary obstruction were randomized to receive either a 10-mm diameter Hanaro or Luminex uncovered metal stent. The duration of stent patency, the overall patient survival, the mechanism of stent occlusion, and the adverse events were analyzed. RESULTS: Eighty-nine patients were included in the analysis; 44 received Hanaro stents and 45 Luminex stents. The overall median patency rates between the 2 stents did not differ (328 d for the Hanaro vs. 289 d for the Luminex stent; P=0.815). Similarly, no difference was found between the overall median survival rates by the 2 stents (347 d for the Hanaro vs. 307 d for the Luminex stent; P=0.654). Two major procedure-related complications occurred, perforation (Hanaro stent) and proximal stent migration (Luminex stent). Stent occlusion requiring reintervention occurred in 25 patients (11 with the Hanaro vs. 14 with the Luminex stent; P=0.521). CONCLUSIONS: The 2 uncovered metal stents are comparable in terms of placement, occlusion rates, overall stent patency, and patient survival; Hanaro stent insertion, however, seems to be a cost-saving strategy at least in Greece.     

Improved endoscopic retrograde cholangiopancreatography brush increases diagnostic yield of malignant biliary strictures

AIM: To determine if a new brush design could im-prove the diagnostic yield of biliary stricture brushings. METHODS: Retrospective chart review was performed of all endoscopic retrograde cholangiopancreatography procedures with malignant biliary stricture brushing between January 2008 and October 2012. A standard wire-guided cytology brush was used prior to proto-col implementation in July 2011, after which, a new 9 French wire-guided cytology brush(Infinity sampling device, US Endoscopy, Mentor, OH) was used for all cases. All specimens were reviewed by blinded pa-thologists who determined whether the sample waspositive or negative for malignancy. Cellular yield was quantified by describing the number of cell clusters seen. RESULTS: Thirty-two new brush cases were compared to 46 historical controls. Twenty-five of 32 (78%) cases in the new brush group showed abnormal cellular find-ings consistent with malignancy as compared to 17 of 46(37%) in the historical control group(P = 0.0003). There was also a significant increase in the average number of cell clusters of all sizes(21.1 vs 9.9 clusters, P = 0.0007) in the new brush group compared to his-torical controls. CONCLUSION: The use of a new brush design for brush cytology of biliary strictures shows increased di-agnostic accuracy, likely due to improved cellular yield, as evidenced by an increase in number of cellular clus-ters obtained.     

Update of cholangioscopy and biliary strictures

Cholangioscopy remains another modality in the investigation of biliary strictures. At cholangioscopy, thetumour vessel sign is considered a specific sign formalignancy. Through its ability to not only visualisemucosa, but to take targeted biopsies, it has a greater accuracy, sensitivity and specificity for malignant strictures than endoscopic retrograde cholangiopancreatography guided cytopathological acquisition. Cholangioscopy however, is time consuming and costly, requires greater technical expertise, a...     

Management of hilar biliary strictures

Biliary strictures at the liver hilum are caused by a heterogeneous group of benign and malignant conditions. In the absence of a clear-cut benign etiology, i.e. bile duct damage during surgery, hilar biliary strictures remain a diagnostic and therapeutic challenge for which a multidisciplinary approach is often necessary. A definitive diagnosis can be achieved in only 40–60% of the patients, while in all the other cases strictures are treated as though they are malignant until surgical pathology determines otherwise. Surgical resection is the only treatment that prolongs survival in patients with malignant strictures. Because these tumors frequently extend longitudinally via the hepatic ducts into the liver parenchyma, partial hepatic resection has been gradually added to biliary resection to ensure tumor-free surgical margins. For unresectable cases, endoscopic stenting of biliary obstruction is considered the preferred palliation modality to relieve pruritus, cholangitis, pain and jaundice, while the percutaneous approach has been reserved for cases of failure. Other modalities of treatment such as radiotherapy, chemotherapy, and photodynamic therapy currently remain investigational. For benign post surgical hilar strictures, surgical repair can be difficult and requires specific skills and experience. As an alternative, a multi-stent technique with endoscopic placement of an increasing number of stents over time until complete resolution of the stricture has been proposed.