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.     

Current management of biliary complications after liver transplantation: Emphasis on endoscopic therapy

Biliary complications occur in 5-25% of patients after liver transplantation and represent a major source of morbidity in this group of individuals. The major risk factor for most of these complications is ischemia of the bile tree usually due to obstruction or vascular insufficiency of the hepatic artery. The most common complications include biliary strictures (anastomostic and nonanastomotic), bile leaks, and biliary filling defects. The initial diagnostic approach starts with a high index of suspicion along with an abdominal ultrasound and Doppler exam. Magnetic resonance imaging is highly sensitive and is usually reserved for confirmation. The vast majority of these complications can be successfully treated with endoscopic retrograde cholangiography, however if this procedure cannot be performed a percutaneous approach or surgery is recommended. Nonanastomotic strictures and living donor recipients present a less favorable response to endoscopic management. This review focuses on the current diagnostic and therapeutic approaches for the management of biliary complications after liver transplantation.     

Tips and tricks for the diagnosis and management of biliary stenosis-state of the art review

Biliary stenosis may represent a diagnostic and therapeutic challenge resulting in a delay in diagnosis and initiation of therapy due to the frequent difficulty in distinguishing a benign from a malignant stricture. In such cases, the diagnostic flowchart includes the sequential execution of imaging techniques, such as magnetic resonance, magnetic resonance cholangiopancreatography, and endoscopic ultrasound, while endoscopic retrograde cholangiopancreatography is performed to collect tissue for histopathological/cytological diagnosis or to treat the stenosis by insertion of stent. The execution of percutaneous transhepatic drainage with subsequent biopsy has been shown to increase the possibility of tissue diagnosis after failure of the above techniques. Although the diagnostic yield of histopathology and imaging has increased with improvements in endoscopic ultrasound and peroral cholangioscopy, differential diagnosis between malignant and benign stenosis may not be easy in some patients, and strictures are classified as indeterminate. In these cases, a multidisciplinary workup including biochemical marker assays and advanced technologies available may speed up a diagnosis of malignancy or avoid unnecessary surgery in the event of a benign stricture. Here, we review recent advancements in the diagnosis and management of biliary strictures and describe tips and tricks to increase diagnostic yields in clinical routine.     

Current endoscopic approach to indeterminate biliary strictures

Biliary strictures are considered indeterminate when basic work-up, including transabdominal imaging and endoscopic retrograde cholangiopancreatography with routine cytologic brushing, are non-diagnostic. Indeterminate biliary strictures can easily be mischaracterized which may dramatically affect patient’s outcome. Early and accurate diagnosis of malignancy impacts not only a patient’s candidacy for surgery, but also potential timely targeted chemotherapies. A significant portion of patients with indeterminate biliary strictures have benign disease and accurate diagnosis is, thus, paramount to avoid unnecessary surgery. Current sampling strategies have suboptimal accuracy for the diagnosis of malignancy. Emerging data on other diagnostic modalities, such as ancillary cytology techniques, single operator cholangioscopy, and endoscopic ultrasonography-guided fine needle aspiration, revealed promising results with much improved sensitivity.     

Weitere Abklärung unklarer Gallengangsstenosen

The differentiation between malignant and benign biliary strictures remains challenging. New peroral cholangioscopes have been introduced to obtain a visual image of the strictures. Other interesting innovations are the combination of peroral cholangioscopy with narrow band imaging (NBI), confocal laser microscopy, endoscopic ultrasound, and intraductal optical coherence tomography. The clinical benefit of these new diagnostic approaches was investigated in pilot studies. But in the future, the clinical benefit of these technical innovations for the accurate diagnosis of suspicious bile duct strictures has to be shown in multicenter studies.     

Endobiliary biopsy

The differential diagnosis between benign and malignant biliary strictures is challenging and requires a multidisciplinary approach with the use of serum biomarkers, imaging techniques, and several modalities of endoscopic or percutaneous tissue sampling. The diagnosis of biliary strictures consists of laboratory markers, and invasive and non-invasive imaging examinations such as computed tomography (CT), contrast-enhanced magnetic resonance cholangiopancreatography, and endoscopic ultrasonography (EUS). Nevertheless, invasive imaging modalities combined with tissue sampling are usually required to confirm the diagnosis of suspected malignant biliary strictures, while pathological diagnosis is mandatory to decide the optimal therapeutic strategy. Although EUS-guided fine-needle aspiration biopsy is currently the standard procedure for tissue sampling of solid pancreatic mass lesions, its diagnostic value in intraductal infiltrating type of cholangiocarcinoma remains limited. Moreover, the “endobiliary approach” using novel slim biopsy forceps, transpapillary and percutaneous cholangioscopy, and intraductal ultrasound-guided biopsy, is gaining ground on traditional endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography endobiliary forceps biopsy. This review focuses on the available endobiliary techniques currently used to perform biliary strictures biopsy, comparing the diagnostic performance of endoscopic and percutaneous approaches.     

The role of endoscopic ultrasound in biliary strictures

The role of endoscopic ultrasound (EUS) in the diagnosis of biliary strictures is well established, and emerging evidence suggests it may also play a therapeutic role. Differentiating between benign and malignant causes of biliary strictures can be challenging, but EUS can aid in their diagnosis and may predict resectability. The diagnostic yield of EUS combined with fine-needle aspiration (FNA) is excellent, especially in distal bile duct strictures, and far surpasses endoscopic retrograde cholangiopancreatography (ERCP) with brushings. Intraductal ultrasound may add to the diagnostic sensitivity of ERCP with brushings when no mass is seen on cross-sectional imaging or EUS, or when EUS with FNA is negative and suspicion of cancer persists. EUS-guided cholangiography is an emerging technique that may aid biliary decompression when ERCP has failed or is not possible; however, new therapeutic echoendoscopes or accessories are needed before the use of this technique can become more widespread.     

Biliary complications in liver transplant recipients

Despite numerous advancements in the management of patients who have undergone cadaveric liver transplantation, biliary complications continue to challenge clinicians. Biliary leaks in the early postoperative period and strictures in the late postoperative period represent the two major posttransplant biliary complications. Intrahepatic and hilar strictures are particularly difficult to manage and frequently require retransplantation, which should not be delayed. Choledocholithiasis and the biliary cast syndrome are frequently associated with underlying biliary strictures, and endoscopic attempts at removal should precede surgical interventions. Sphincter of Oddi dysfunction is increasingly recognized despite unclear pathophysiology. Hemobilia is most commonly iatrogenic and requires a high suspicion and prompt intervention. Although the number of diagnostic and therapeutic options have increased, there is no consensus as to which is superior. In recent years there has been a trend toward nonsurgical interventions, in particular endoscopic approaches.     

Biliary tract candidiasis: diagnostic and therapeutic approaches in a case series

BACKGROUND: Biliary obstruction with its wide range of potential causes is a common disorder in gastroenterology. Infections of the biliary tract with Candida and other fungal species leading to obstructive jaundice have increasingly been recognized in the last few years. Besides a few case reports, there are few data in the literature giving us an idea how to diagnose and treat these patients. METHODS: We report on a series of seven patients suffering from biliary tract candidiasis who were diagnosed and treated at our institution. Predisposition factors, reliability of various diagnostic modalities, and treatment options based on our own experience are presented and discussed. RESULTS: Besides the general diagnostic modalities such as laboratory findings or ultrasonography, we often observed mycelia in the bile duct system endoscopically. Typical morphological changes in peripheral bile ducts could be detected during endoscopic retrograde cholangiopancreatography (ERCP). Aspiration of bile and subsequent microbiological analysis in combination with ERCP findings revealed diagnosis of bile duct candidiasis in all cases. Treatment included both antiinfectious drugs and endoscopic therapy such as bile duct drainage, lavage, or débridement. With respect to fungal eradication, therapy was successful in 71% of cases as proven by microbiological analysis of bile aspirates. Since many of these patients suffer not only from biliary mycosis but also from disease necessitating immunosuppression, the prognosis was poor in some cases. CONCLUSION: Biliary tract candidiasis because of immunosuppression is an increasingly recognized disease and remains a major clinical challenge. Besides laboratory analysis and ultrasonography, diagnostic modalities should include aspiration of bile during ERCP and microbiological analysis. Antiinfectious drug treatment as the main therapeutic column for biliary candidiasis should be complemented by endoscopic intervention.     

Biliary Tract Obstruction Secondary to Malignant Lymphoma: Experience at a Referral Center

Lymphoma is a rare cause of biliary obstruction and, on cholangiography, may mimic other causes of obstructive jaundice. The optimum treatment for these patients is unclear. The aim of this study is to evaluate the incidence, clinical and imaging findings, management, and outcome of biliary obstruction caused by lymphoma. Our database was searched retrospectively for patients with biliary obstruction due to lymphoma between 1999 and 2005. Biliary obstruction secondary to lymphoma was found in 7 (0.6%) of 1123 patients with malignant biliary obstruction. One patient had benign biliary obstruction related to lymphoma. Of the eight patients (five male, three female; mean age, 34.50 ± 17.93 years), four had Hodgkin’s disease and four had non-Hodgkin’s lymphoma. Biliary obstruction occurred as part of the initial or early presentation of lymphoma in two patients. The most common cause of obstruction was compression of the biliary tract by enlarged lymph nodes (six patients). Cholangiographic appearances were diverse: narrowing of the common bile duct (six patients), splayed and narrowed common bile duct (one patient), and multiple strictures and dilatations of the intrahepatic bile ducts (one patient). Biliary drainage was performed in all patients including endoscopic stent placement in six patients, nasobiliary drainage in one, and choledochoduodenostomy in one. Hyperbilirubinemia resolved in all but one of the patients with a stent; however, none could be maintained in a stent-free condition. Five patients died within 1 year after onset of jaundice. One of the surviving patients developed a late benign stricture at the site of the earlier lymphoma. We conclude that lymphoma should be considered in the differential diagnosis of obstructive jaundice, particularly in younger patients. We suggest that biliary drainage by the endoscopic or percutaneous route is necessary for the treatment of these patients. Late benign strictures may develop. Biliary obstruction is a sign of poor prognosis in lymphoma.     

Endoscopic management of biliary complications after liver transplantation

Biliary complications are common in liver transplant recipients and may develop in up to one-third of all patients. Bile leaks generally occur within the first 3 months and are frequently related to T-tube removal. The recent trend to avoid of T-tubes has probably resulted in a reduced incidence of such bile leaks. The other major biliary complications in liver transplant recipients include biliary strictures, choledocholithiasis, biliary casts and sphincter of Oddi dysfunction. Biliary strictures can be classified into anastomotic and non-anastomotic strictures. Anastomotic strictures are generally related to technical complications of choledochocholedochostomy, while non-anastomotic strictures are frequently related to hepatic artery thrombosis. The overwhelming majority of biliary complications choledochocholedochostomy can be managed by endoscopic means, ranging from use of plastic stents, balloon dilation or endoscopic sphincteromoty. Surgical revision may be required in rare instances such as recurrent biliary casts or large caliber leaks associated with anastomotic strictures. The purpose of this review is to review the incidence, risk factors for and pathogenesis of biliary complications after liver transplantation. The results of endoscopic management of these strictures is also described in detail and should be of interest to therapeutic endoscopists, liver transplant physicians, transplant surgeons and therapeutic endoscopists.     

Endoscopic interventions in the biliary tract

Opinion statement In patients with common bile duct stones, the endoscopic removal of such stones has become the standard therapy. The surgical approach is indicated only for stones that cannot be extracted endoscopically. In biliary obstruction due to pancreaticobiliary malignancy, endoscopic interventions represent the first-line therapy in the palliative situation. If endoscopic access is not possible, the percutanous approach often represents an alternative, followed by palliative surgical options. Biliary strictures or bile leaks after liver transplantation very often may be treated effectively by endoscopic dilatation or temporary stenting. In most cases, endoscopic therapy of such problems represents the first option before the percutaneous or surgical approach is indicated. In primary sclerosing cholangitis, dominant biliary strictures develop frequently and endoscopic treatment allows their opening in most cases. There is no real alternative to endoscopy in this situation. The situation is more complex in postoperative biliary strictures and chronic pancreatitis. In these conditions, advantages and disadvantages of the endoscopic versus the surgical approach have to be evaluated to find the most effective form of treatment in the individual situation. The surgical intervention often represents the better alternative.     

Progress in the endoscopic management of benign biliary strictures

Benign biliary strictures can now be effectively treated with endoscopic therapy in a variety of clinical situations. Despite recent developments in imaging techniques (endoscopic ultrasound and magnetic resonance imaging), it is often difficult to differentiate benign from malignant biliary strictures. The sensitivity of tissue diagnosis (cytology and needle biopsy) at endoscopic retrograde cholangiopancreatography (ERCP) remains poor (40-50%), and further diagnostic methods are required. Endoscopic therapy offers a definitive treatment in 70-90% of patients following post-operative biliary stricture, including anastomotic strictures following liver transplant. Endoscopic therapy successfully achieves symptomatic, biochemical, and cholangiographic response, and may improve survival in patients with primary sclerosing cholangitis. Strictures secondary to chronic pancreatitis are resistant to standard endoscopic therapy and metallic endoprotheses have been trialed with varying success. Endoscopic therapy is technically difficult and should be performed in specialized centres using a multidisciplinary approach.     

Common controversies in management of biliary strictures

Biliary strictures are caused by a heterogeneous group of benign and malignant conditions, each requiring a specific treatment approach. Management of biliary strictures often involves endoscopy either for definite treatment, as a bridge to surgery or for palliative purposes. Endoscopic treatment of various types of biliary strictures is not standardized and there are multiple areas of controversy regarding the best treatment options. These controversies are mainly due to lack of well-designed comparative studies to support a specific therapy. This paper reviews three common areas of controversy in the endoscopic management of biliary strictures. The areas discussed in this editorial include the role of biliary drainage in resectable malignant strictures and whether such drainage should be performed routinely prior to surgery, the best endoscopic palliation for unresectable hilar strictures and whether unilateral or bilateral stenting should be attempted, and the optimal endoscopic management for dominant strictures in patients with primary sclerosing cholangitis. The goal of this editorial is twofold. The first is to review the current literature on management of the aforementioned strictures and offer recommendations based on available evidence. The second goal is to highlight the gaps in our knowledge which in turn can encourage future research on these topics.     

Differentiating pancreatic cancer from pseudotumorous chronic pancreatitis

The differentiation between pancreatic carcinoma and pseudotumorous pancreatitis continues to be a challenge. Several diagnostic imaging and endoscopic modalities can assist in making the differentiation, but the accuracy of each method varies. Radiologic imaging techniques include transabdominal ultrasound, computed tomography, magnetic resonance imaging, magnetic resonance cholangiopancreatography, and positron emission tomography. Endoscopic techniques include endoscopic ultrasonography, intraductal ultrasonography, and endoscopic retrograde cholangiopancreatography with brush cytology of pancreatobiliary strictures, endoscopic forceps biopsy, and analysis of pancreatic juices for malignant cells. Tumor markers appear to be promising, but further studies are needed to define the role of these markers.     

Endoscopic ultrasound guided therapy of benign and malignant biliary obstruction: a case series

OBJECTIVES: Endoscopic retrograde cholangiography is an established method for treatment of common bile duct stones as well as for palliation of patients with malignant pancreaticobiliary strictures. It may be unsuccessful in the presence of a complex peripapillary diverticulum, prior surgery, obstructing tumor, papillary stenosis, or impacted stones. Percutaneous transhepatic biliary drainage and surgery are alternative methods with a higher morbidity and mortality in these cases. Recently, endoscopic ultrasound (EUS) guided biliary stent placement has been described in patients with malignant biliary obstruction. We describe our experience with this method that was also used for the treatment of cholangiolithiasis for the first time. METHODS: The EUS guided transduodenal puncture of the common bile duct with stent placement was performed in 5 patients. In 2 of these patients, the stents were removed after several weeks and common bile duct stones were extracted. In another patient with gastrectomy, the left intrahepatic bile duct was punctured transjejunally and a metal stent was introduced transhepatically to bridge a distal common bile duct stenosis. RESULTS: Biliary decompression was successful in all 6 patients. No immediate complications occurred. One patient developed a subacute phlegmonous cholecystitis. CONCLUSIONS: Interventional EUS guided biliary drainage is a new technique that allows drainage of the biliary system in benign and malignant diseases when the bile duct is inaccessible by conventional ERCP.     

Management of biliary complications after orthotopic liver transplantation： The role of endoscopy

Biliary complications are significant causes of morbidity and mortality after orthotopic liver transplantation （OLT）. The estimated incidence of biliary complications after OLT ranges between 10%-25%, however, these numbers continue to decline due to improvement in surgical techniques. The most common biliary complications are strictures （both anastomotic and non-anastomotic） and bile leaks. Most of these problems can be appropriately managed with endoscopic retrograde colangiography （ERC）. Other complications such as bile duct stones, bile casts, sphincter of Oddi dysfunction, and hemobilia, are less frequent and also can be managed with ERC. This article will review the risk factors, diagnosis, and endoscopic management of the most common biliary complications after OLT.     

Malignant pancreaticobiliary strictures: Techniques for diagnosis and management

Malignant pancreaticobiliary strictures create both a diagnostic and therapeutic challenge for the interventional endoscopist. Traditionally, malignant strictures have been managed with surgical intervention; however, the development of endoscopic retrograde cholangiopancreatoscopy, specialized endoscopic accessories, and pancreaticobiliary endoprostheses have largely replaced surgical techniques for patients with unresectable or inoperative tumors. Pancreaticobiliary malignancies include pancreatic ductal adenocarcinomas, ampullary neoplasms, gallbladder tumors, and cholangiocarcinomas. Most of these patients present with locally advanced disease precluding curative surgical resection secondary to either local vascular invasion or metastatic disease. Discerning between benign and malignant disease is a crucial first-step in the appropriate management of pancreaticobiliary strictures. Tissue sampling techniques, cholangiopancreatoscopy, confocal laser endomicroscopy, and intraductal ultrasound can assist in differentiating between benign and malignant disease. Occasionally, conventional endoscopic management of malignant pancreaticobiliary strictures may be hampered by altered surgical anatomy or invasive tumors precluding retrograde access with endoscopic retrograde cholangiopancreatoscopy. Traditionally, these patients were managed with either percutaneous or surgical drainage. The development of linear array endosonography and evolution of interventional endoscopic ultrasound have provided alternative means for both biliary and pancreatic decompression. Novel endoscopic devices and techniques are emerging for both the diagnosis and management of malignant pancreatobiliary strictures.     

The combination of stricture dilation, endoscopic needle aspiration, and biliary brushings significantly improves diagnostic yield from malignant bile duct strictures.

BACKGROUND: Brush cytology, routinely performed at ERCP to assess malignant-appearing biliary strictures, is limited by relatively low sensitivity and negative predictive value. This study assessed whether the combination of stricture dilation, endoscopic needle aspiration, and biliary brushing improves diagnostic yield. METHODS: In a prospective nonrandomized study, 46 consecutive patients were evaluated with malignant-appearing biliary strictures at ERCP. Twenty-four patients (Group A) underwent standard brush cytology alone and 22 patients (Group B) underwent stricture dilatation to 10F, endoscopic needle aspiration, and subsequent biliary brushing by using the Howell biliary system. The diagnostic yields for both techniques were compared. RESULTS: Of the 46 patients, 34 had proven malignant strictures (14 Group A, 20 Group B). Compared with brushing alone, the combination of stricture dilatation, endoscopic needle aspiration, and subsequent biliary brushing significantly increased both the sensitivity (57% vs. 85%, p < 0.02) and specificity (80% vs. 100%, p < 0.02) of cytology with positive brushings in all patients with pancreatic or gallbladder carcinoma. CONCLUSIONS: The combination of stricture dilation, endoscopic needle aspiration, and biliary brushing significantly improves diagnostic yield for malignant bile duct strictures and may particularly be of benefit for extrinsic strictures caused by pancreatic or gallbladder carcinoma.     

Use of fully covered self-expanding metal stents in benign biliary diseases

Biliary fully covered self-expanding metal stents (FCSEMS) are now being used to treat several benign biliary conditions. Advantages include small predeployment and large postexpansion diameters in addition to an easy insertion technique. Lack of imbedding of the metal into the bile duct wall enables removability. In benign biliary strictures that usually require multiple procedures, despite the substantially higher cost of FCSEMS compared with plastic stents, the use of FCSEMS is offset by the reduced number of endoscopic retrograde cholangiopancreatography interventions required to achieve stricture resolution. In the same way, FCSEMS have also been employed to treat complex bile leaks, perforation and bleeding after endoscopic biliary sphincterotomy and as an aid to maintain permanent drainage tracts obtained by means of Endoscopic Ultrasound-guided biliary drainage. Good success rates have been achieved in all these conditions with an acceptable number of complications. FCSEMS were successfully removed in all patients. Comparative studies of FCSEMS and plastic stents are needed to demonstrate effi cacy and cost-effectiveness