Still elusive: Developments in the accurate diagnosis of indeterminate biliary strictures

Indeterminate biliary strictures pose a significant diagnostic dilemma for gastroenterologists.Despite advances in endoscopic techniques and instruments,it is difficult to differentiate between benign and malignant pathology.A positive histological diagnosis is always preferred prior to high risk hepatobiliary surgery,or to inform other types of therapy.Endoscopic retrograde cholangiopancreato-graphy with brushings has low sensitivity and despite significant improvements in instruments there is still an unacceptably high false negative rate.Other methods such as endoscopic ultrasound and cholangioscopy have improved diagnostic quality.In this review we explore the techniques available to aid accurate diagnosis of indeterminate biliary strictures and obtain accurate histology to facilitate clinical management.

New rabbit model for benign biliary stricture formation with repeatable administration

BACKGROUND The treatment of benign biliary strictures(BBS)is a challenging clinical problem.At present,there is a lack of ideal models for the study of BBS treatment.AIM To develop a novel animal model of BBS to simulate studies on the processes and mechanisms in the human condition.METHODS A rabbit model of benign bile duct stricture was established by surgical injury of the bile duct.After removal of the gallbladder,a drainage tube was placed th-rough the cystic duct at the stump,and a BBS model was induced by surgical injury at the lower end of the common bile duct.RESULTS Compared with the control group,the model rabbits showed gross jaundice,increased serum bilirubin,and decreased liver function.Cholangiography showed segmental bile duct stenosis in the model rabbits.Pathological staining showed inflammatory cell infiltration and fibrosis in the biliary tract of rabbits in the model group.This was consistent with the clinical manifestations of BBS.This model provided serology,imaging,pathology,and other aspects of BBS.CONCLUSION We have successfully established an animal model of benign stricture of the lower bile duct with repeatable administration,which is consistent with the clinical manifestations of BBS.

Diagnosis and Management of Biliary Strictures after Deceased-Donor Liver Transplantation Based on Clinical Practice

Biliary complications are still the main complications for liver transplantation recipients. Biliary strictures comprise the major part of all biliary complications after deceased-donor liver transplantation (LT). Biliary strictures following LT are divided into anastomotic strictures (AS) and non-anastomotic strictures (NAS). A Limitation of current published researches is that most studies aren’t based on clinical practice. The aim of this review is to summarize risk factors, clinical presentation, diagnosis and management in post-LT biliary strictures.

Clinical approach to indeterminate biliary strictures:Clinical presentation,diagnosis,and workup

Despite advances in cross-sectional imaging and endoscopic technology,bile duct strictures remain a challenging clinical entity.It is crucial to make an early determination of benign or malignant nature of biliary strictures.Early diagnosis not only helps with further management but also minimizes mortality and morbidity associated with delayed diagnosis.Conventional imaging and endoscopic techniques,particularly endoscopic retrograde cholangiopancreatography(ERCP)and tissue sampling techniques play a key in establishing a diagnosis.Indeterminate biliary strictures(IDBSs)have no definite mass on imaging or absolute histopathological diagnosis and often warrant utilization of multiple diagnostics to ascertain an etiology.In this review,we discuss possible etiologies,clinical presentation,diagnosis,and management of IDBSs.Based on available data and expert opinion,we depict an evidence based diagnostic algorithm for management of IDBSs.Areas of focus include use of traditional tissue sampling techniques such as ERCP with brush cytology,intraductal biopsies,fluorescence in situ hybridization and flow cytometry.We also describe the role of endoscopic ultrasound(EUS)-guided fine needle aspiration and biopsies,cholangioscopy,confocal laser endomicroscopy,and intraductal EUS in management of IDBSs.

Endoscopic management of benign biliary strictures:Looking for the best stent to place

Benign biliary strictures(BBS)might occur due to different pancreaticobiliary conditions.The etiology and location of biliary strictures are responsible of a wide array of clinical manifestations.The endoscopic approach endoscopic retrograde cholangiopancreatography represents the first-line treatment for BBS,considering interventional radiology and surgery when endoscopic treatment fails or it is not suitable.The purpose of this review is to provide an overview of possible endoscopic treatments for the optimal management of this subset of patients.

Minimally invasive surgery for post cholecystectomy biliary stricture:current evidence and future perspectives

Postcholecystectomy bile duct injury(BDI)remains a devastating iatrogenic complication that adversely impacts the quality of life with high healthcare costs.Despite a decrease in the incidence of laparoscopic cholecystectomy-related BDI,the absolute number remains high as cholecystectomy is a commonly performed surgical procedure.Open Roux-en-Y hepaticojejunostomy with meticulous surgical technique remains the gold standard surgical procedure with excellent longterm results in most patients.As with many hepatobiliary disorders,a minimally invasive approach has been recently explored to minimize access-related complications and improve postoperative recovery.Since patients with gallstone disease are often admitted for a minimally invasive cholecystectomy,laparoscopic and robotic approaches for repairing postcholecystectomy biliary stricture are attractive.While recent series have shown the feasibility and safety of minimally invasive post-cholecystectomy biliary stricture management,most are retrospective analyses with small sample sizes.Also,long-term follow-up is avail-able only in a limited number of studies.The principles and technique of minimally invasive repair resemble open repair except for the extent of adhesiolysis and the suturing technique with continuous sutures commonly used in minimally invasive approaches.The robotic approach overcomes key limitations of laparoscopic surgery and has the potential to become the preferred minimally invasive approach for the repair of postcholecystectomy biliary stricture.Despite increasing use,lack of prospective studies and selection bias with available evidence precludes definitive conclusions regarding minimally invasive surgery for managing postcholecystectomy biliary stricture.High-volume prospective studies are required to confirm the initial promising outcomes with minimally invasive surgery.

Diagnosis of biliary strictures after liver transplantation:Which is the best tool?

AIM: To evaluate the diagnostic value of different indirect methods like biochemical parameters, ultrasound (US) analysis, CT-scan and MRI/MRCP in comparison with endoscopic retrograde cholangiography (ERC), for diagnosis of biliary complications after liver transplantation. METHODS: In 75 patients after liver transplantation, who received ERC due to suspected biliary complications, the result of the cholangiography was compared to the results of indirect imaging methods performed prior to ERC. The cholangiography showed no biliary stenosis (NoST) in 25 patients, AST in 27 and ITBL in 23 patients. RESULTS: Biliary congestion as a result of AST was detected with a sensitivity of 68.4% in US analysis (specificity 91%), of 71% in MRI (specificity 25%) and of 40% in CT (specificity 57.1%). In ITBL, biliary congestion was detected with a sensitivity of 58.8% in the US, 88.9%in MRI and of 83.3% in CT. However, as anastomotic or ischemic stenoses were the underlying cause of biliary congestion, the sensitivity of detection was very low. InMRI detected the dominant stenosis at a correct localization in 22% and CT in 10%, while US failed completely. The biochemical parameters, showed no significant difference in bilirubin (median 5.7; 4,1; 2.5 mg/dL), alkaline phosphatase (median 360; 339; 527 U/L) or gamma glutamyl transferase (median 277; 220; 239 U/L) levels between NoST, AST and ITBL.CONCLUSION: Our data confirm that indirect imaging methods to date cannot replace direct cholangiography for diagnosis of post transplant biliary stenoses. However MRI may have the potential to complement or precede imaging by cholangiography. Optimized MRCP-processing might further improve the diagnostic impact of this method.

Endoscopic therapy of benign biliary strictures

Benign biliary strictures are being increasingly treated with endoscopic techniques. The benign nature of the stricture should be first confirmed in order to ensure appropriate therapy. Surgery has been the traditional treatment, but there is increasing desire for minimally invasive endoscopic therapy. At present, endoscopy has become the first line approach for the therapy of post- liver transplant anastomotic strictures and distal （Bismuth ! and I） post-operative strictures. Strictures related to chronic pancreatitis have proven more difficult to treat, and endoscopic therapy is reserved for patients who are not surgical candidates. The preferred endoscopic approach is aggressive treatment with gradual dilation of the stricture and insertion of multiple plastic stents. The use of uncovered self expandable metal stents should be discouraged due to poor long-term results. Treatment with covered metal stents or bioabsorbable stents warrants further evaluation. This area of therapeutic endoscopy provides an ongoing opportunity for fresh research and innovation.

Role of transforming growth factor-beta signaling pathway in pathogenesis of benign biliary stricture

AIM: To characterize the expression of members of the transforming growth factor-beta (TGF-β)/Smad/ connective tissue growth factor (CTGF) signaling pathway in the tissue of benign biliary stricture, and to investigate the effect of TGF-β signaling pathway in the pathogenesis of benign biliary stricture. METHODS: Paraffin embedded materials from 23 cases of benign biliary stricture were analyzed for members of the TGF-β/Smad/CTGF signaling pathway. TGF-β_1, TβRⅠ, TβRⅡ, Smad4, Smad7 and CTGF protein were detected by immunohistochemical strepto-advidinbiotin complex method, and CTGF mRNA was evaluated by hybridization in situ, while 6 cases of normal bile duct served as controls. The percentages of positive cells were counted. The correlation between TGF-β_1, Smad4 and CTGF was analyzed. RESULTS: The positive expression ratios of TGF-β_1, TβRⅠ , TβRⅡ , Smad4, CTGF and CTGF mRNA in 23 cases with benign biliary stricture were 91.3%, 82.6%, 87.0%, 78.3%, 82.6% and 65.2%, respectively, signifi cantly higher than that in 6 cases of normal bile duct respectively (vs 33.3%, 16.7%, 50.0%, 33.3%, 50.0%, 16.7%, respectively, P < 0.05). The positiveexpression ratio of Smad7 in cases with benign biliary stricture was 70.0%, higher than that in normal bile duct, but this difference is not statistically signifi cant 70.0% vs 50%, P > 0.05). There was a positive correlation between positive expression of TGF-β_1, Smad4 and CTGF in cases with benign biliary stricture. CONCLUSION: The high expression of TGF-β/Smad/ CTGF signaling pathway plays an important role in the pathogenesis of benign biliary stricture.

Mechanism of benign biliary stricture: A morphological and immunohistochemical study

AIM: To explore the mechanism of benign biliary stricture. METHODS: A model of trauma of bile duct was established in 28 dogs. The anastomosed tissues were resected and examined by light and electron microscopes on day 3, in wk 1, 3 and mo 3, 6 after operation. CD68, TGF-β1 and α-SMA were examined by immunohistochemical staining, respectively. RESULTS: The mucosal epithelium of the bile duct was slowly recovered, chronic inflammation lasted for a long time, fibroblasts proliferated actively, extracellular matrix was over-deposited. Myofibroblasts functioned actively and lasted through the whole process. The expression of macrophages in lamina propria under mucosa, TGF-β1 in granulation tissue, fibroblasts and endothelial cells of blood vessels, oc-SMA in myofiroblasts were rather strong from the 1st wk to the 6th mo after operation. CONCLUSION: The type of healing occurring in bile duct belongs to overhealing. Myofibroblasts are the main cause for scar contracture and stricture of bile duct. High expressions of CD68, TGF-β1 and a-SMA are closely related to the active proliferation of fibroblasts, extracellular matrix over-deposition and scar contracture of bile duct.

Management of liver transplantation biliary stricture: Results from a tertiary hospital

AIM: To review results of endoscopic treatment for anastomotic biliary strictures after orthotopic liver transplantation(OLT) during an 8-year period. METHODS: This is a retrospective review of all endoscopic retrograde cholangiopancreatographys(ERCPs) performed between May 2006 and June 2014 in deceased OLT recipients with anastomotic stricture at a tertiary care hospital. Patients were divided into 2 groups, according to the type of stent used(multiple plastic or covered self-expandable metal stents), which was chose on a case-by-case basis and their characteristics. The primary outcome was anastomotic stricture resolution rate determined if there was no more than a minimum waist at cholangiography and a 10 mm balloon could easily pass through the anastomosis with no need for further intervention after final stent removal. Secondary outcomes were technical successrate, number or ERCPs required per patient, number of stents placed, stent indwelling, stricture recurrence rate and therapy for recurrent anastomotic biliary stricture(AS). Stricture recurrence was defined as clinical laboratorial and/or imaging evidence of obstruction at the anastomosis level, after it was considered completely treated, requiring subsequent interventional procedure.RESULTS: A total of 195 post-OLT patients were assessed for eligibility. One hundred and sixty-four(164) patients were diagnosed with anastomotic biliary stricture. ERCP was successfully performed in 157/164(95.7%) patients with AS, that were treated with either multiple plastic(n = 109) or metallic billiary stents(n = 48). Mean treatment duration, number of procedures and stents required were lower in the metal stent group. Acute pancreatitis was the most common procedure related complication, occurring in 17.1% in the covered self-expandable metal stents(c SEMS) and 4.1% in the multiple plastic stent(MPS) group. Migration was the most frequent stent related complication, observed in 4.3% and 5.5%(c SEMS and MPS respectively). Stricture resolution was achieved in 86.8% in the c SEMS group and in 91% in MPS group. Stricture recurrence after a median follow up of 20 mo was observed in 10(30.3%) patients in the c SEMS and 7(7.7%) in the plastic stent group, a statistically significant difference(P = 0.0017). Successful stricture resolution after secondary treatment was achieved in 66.6% and 62.5% of patients respectively in the c SEMS and plastic stents groups. CONCLUSION: Multiple plastic stents are currently the first treatment option for AS in patients with duct-toduct anastomosis. c SEMS was associated with increased pancreatitis risk and higher recurrence rate.

Hepatobiliary scintigraphy for detecting biliary strictures after living donor liver transplantation

AIM:To investigate the diagnostic accuracy of hepatobiliary scintigraphy(HBS) in detecting biliary strictures in living donor liver transplantation(LDLT) patients.METHODS:We retrospectively reviewed 104 adult LDLT recipients of the right hepatic lobe with duct-toduct anastomosis,who underwent HBS and cholangiography.The HBS results were categorized as normal,parenchymal dysfunction,biliary obstruction,or bile leakage without re-interpretation.The presence of biliary strictures was determined by percutaneous cholangiography or endoscopic retrograde cholangiopancreatography(ERCP).RESULTS:In 89 patients with biliary strictures,HBS showed biliary obstruction in 50 and no obstruction in 39,for a sensitivity of 56.2%.Of 15 patients with no biliary strictures,HBS showed no obstruction in 11,for a specificity of 73.3%.The positive predictive value(PPV) was 92.6%(50/54) and the negative predictive value(NPV) was 22%(11/50).We also analyzed the diagnostic accuracy of the change in bile duct size.The sensitivity,NPV,specificity,and PPV were 65.2%,27.9%,80% and 95%,respectively.CONCLUSION:The absence of biliary obstruction on HBS is not reliable.Thus,when post-LDLT biliary strictures are suspected,early ERCP may be considered.

Endoscopic ultrasonography can diagnose distal biliary strictures without a mass on computed tomography

AIM:To assess the diagnostic ability of endoscopic ultrasonography(EUS)for evaluating causes of dista biliary strictures shown on endoscopic retrograde chol angiopancreatography(ERCP)or magnetic resonance cholangiopancreatography(MRCP),even without iden tifiable mass on computed tomography(CT). METHODS:The diagnostic ability of EUS was retro spectively analyzed and compared with that of routine cytology(RC)and tumor markers in 34 patients with distal biliary strictures detected by ERCP or MRCP a Dokkyo Medical School Hospital from December 2005 to December 2008,without any adjacent mass or ec centric thickening of the bile duct on CT that could cause biliary strictures.Findings considered as benign strictures on EUS included preservation of the normasonographic layers of the bile duct wall,irrespective of the presence of a mass lesion.Other strictures were considered malignant.Final diagnosis of underlying diseases was made by pathological examination in 18 cases after surgical removal of the samples,and by clinical follow-up for>10 mo in 16 cases. RESULTS:Seventeen patients(50%)were finally di- agnosed with benign conditions,including 6"normal" subjects,while 17 patients(50%)were diagnosed with malignant disease.In terms of diagnostic ability,EUS showed 94.1%sensitivity,82.3%specificity,84.2% positive predictive value,93.3%negative predictive value(NPV)and 88.2%accuracy for identifying ma- lignant and benign strictures.EUS was more sensi- tive than RC(94.1%vs 62.5%,P=0.039).NPV was also better for EUS than for RC(93.3%vs 57.5%,P= 0.035).In addition,EUS provided significantly higher sensitivity than tumor markers using 100 U/mL as the cutoff level of carbohydrate antigen 19-9(94.1%vs 53%,P=0.017).On EUS,biliary stricture that was fi- nally diagnosed as malignant showed as a hypoechoic, irregular mass,with obstruction of the biliary duct and invasion to surrounding tissues. CONCLUSION:EUS can diagnose biliary strictures caused by malignant tumors that are undetectable on CT.Earlier detection by EUS would provide more therapeutic options for patients with early-stage pancreaticobiliary cancer.

Digital single-operator cholangioscopy for biliary stricture after cadaveric liver transplantation

BACKGROUND Biliary strictures after liver transplantation(LT)remain clinically arduous and challenging situations,and endoscopic retrograde cholangiopancreatography(ERCP)has been considered as the gold standard for the management of biliary strictures after LT.Nevertheless,in the treatment of biliary strictures after LT with ERCP,many studies show that there is a large variation in diagnostic accuracy and therapeutic success rate.Digital single-operator peroral cholangioscopy(DSOC)is considered a valuable diagnostic modality for indeterminate biliary strictures.AIM To evaluate DSOC in addition to ERCP for management of biliary strictures after LT.METHODS Nineteen patients with duct-to-duct biliary reconstruction who underwent ERCP for suspected biliary complications between March 2019 and March 2020 at Beijing Chaoyang Hospital,Capital Medical University,were consecutively enrolled in this observational study.After evaluating bile ducts using fluoroscopy,cholangioscopy using a modern digital single-operator cholangioscopy system(SpyGlass DS^(TM))was performed during the same procedure with patients under conscious sedation.All patients received peri-interventional antibiotic prophylaxis.Biliary strictures after LT were classified according to the manifestations of choledochoscopic strictures and the manifestations of transplanted hepatobiliary ducts.RESULTS Twenty-one biliary strictures were found in a total of 19 patients,among which anastomotic strictures were evident in 18(94.7%)patients,while non-anastomotic strictures in 2(10.5%),and space-occupying lesions in 1(5.3%).Stones were found in 11(57.9%)and loose sutures in 8(42.1%).A benefit of cholangioscopy was seen in 15(78.9%)patients.Cholangioscopy was crucial for selective guidewire placement prior to planned intervention in 4 patients.It was instrumental in identifying biliary stone and/or loose sutures in 9 patients in whom ERCP failed.It also provided a direct vision for laser lithotripsy.A spaceoccupying lesion in the bile duct was diagnosed by cholangioscopy in one patient.Patients with biliary stricture after LT displayed four types:(A)mild inflammatory change(n=9);(B)acute inflammatory change edema,ulceration,and sloughing(n=3);(C)chronic inflammatory change;and(D)acute suppurative change.Complications were seen in three patients with post-interventional cholangitis and another three with hyperamylasemia.CONCLUSION DSOC can provide important diagnostic information,helping plan and perform interventional procedures in LT-related biliary strictures.

Efficacy of multiple biliary stenting for refractory benign biliary strictures due to chronic calcifying pancreatitis

AIMTo investigate endoscopic therapy efficacy for refractory benign biliary strictures (BBS) with multiple biliary stenting and clarify predictors. METHODSTen consecutive patients with stones in the pancreatic head and BBS due to chronic pancreatitis who underwent endoscopic therapy were evaluated. Endoscopic insertion of a single stent failed in all patients. We used plastic stents (7F, 8.5F, and 10F) and increased stents at intervals of 2 or 3 mo. Stents were removed approximately 1 year after initial stenting. BBS and common bile duct (CBD) diameter were evaluated using cholangiography. Patients were followed for &ge; 6 mo after therapy, interviewed for cholestasis symptoms, and underwent liver function testing every visit. Patients with complete and incomplete stricture dilations were compared. RESULTSEndoscopic therapy was completed in 8 (80%) patients, whereas 2 (20%) patients could not continue therapy because of severe acute cholangitis and abdominal abscess, respectively. The mean number of stents was 4.1 &plusmn; 1.2. In two (20%) patients, BBS did not improve; thus, a biliary stent was inserted. BBS improved in six (60%) patients. CBD diameter improved more significantly in the complete group than in the incomplete group (6.1 &plusmn; 1.8 mm vs 13.7 &plusmn; 2.2 mm, respectively, P = 0.010). Stricture length was significantly associated with complete stricture dilation (complete group; 20.5 &plusmn; 3.0 mm, incomplete group; 29.0 &plusmn; 5.1 mm, P = 0.011). Acute cholangitis did not recur during the mean follow-up period of 20.6 &plusmn; 7.3 mo. CONCLUSIONSequential endoscopic insertion of multiple stents is effective for refractory BBS caused by chronic calcifying pancreatitis. BBS length calculation can improve patient selection procedure for therapy.

Management issues in post living donor liver transplant biliary strictures

Biliary complications are common after living donor liver transplant(LDLT) although with advancements in surgical understanding and techniques, the incidence is decreasing. Biliary strictures are more common than leaks. Endoscopic retrograde cholangiopancreatography(ERCP) is the first line modality of treatment of post LDLT biliary strictures with a technical success rate of 75%-80%. Most of ERCP failures are successfully treated by percutaneous transhepatic biliary drainage(PTBD) and rendezvous technique. A minority of patients may require surgical correction. ERCP for these strictures is technically more challenging than routine as well post deceased donor strictures. Biliary strictures may increase the morbidity of a liver transplant recipient, but the mortality is similar to those with or without strictures. Post transplant strictures are short segment and soft, requiring only a few session of ERCP before complete dilatation. Long-term outcome of patients with biliary stricture is similar to those without stricture. With the introduction of new generation cholangioscopes, ERCP success rate may increase, obviating the need for PTBD and surgery in these patients.

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.

Comparative study of rendezvous techniques in post-liver transplant biliary stricture

AIM： To investigate the usefulness of a new rendezvous technique for placing stents using the Kumpe （KMP） catheter in angulated or twisted biliary strictures. METHODS： The rendezvous technique was performed in patients with a biliary stricture after living donor liver transplantation （LDLT） who required the exchange of percutaneous transhepatic biliary drainage catheters for inside stents. The rendezvous technique was performed using a guidewire in 19 patients （guidewire group） and using a KMP catheter in another 19 （KMP catheter group）. We compared the two groups retrospectively. RESULTS： The baseline characteristics did not differ between the groups. The success rate for placing insidestents was 100% in both groups. A KMP catheter was easier to manipulate than a guidewire. The mean pro- cedure time in the KMP catheter group （1012 s, range： 301-2006 s） was shorter than that in the guidewire group （2037 s, range： 251-6758 s, P = 0.022）. The cu- mulative probabilities corresponding to the procedure time of the two groups were significantly different （P = 0.008）. The factors related to procedure time were the rendezvous technique method, the number of inside stents, the operator, and balloon dilation of the stric- ture （P 〈 0.05）. In a multivariate analysis, the rendez- vous technique method was the only significant factor related to procedure time （P = 0.010）. The procedural complications observed included one case of mild acute pancreatitis and one case of acute cholangitis in the guidewire group, and two cases of mild acute pancre- atitis in the KMP catheter group. CONCLUSION： The rendezvous technique involving use of the KIVlp catheter was a fast and safe method for placing inside stents in patients with LDLT biliary stric- ture that represents a viable alternative to the guide- wire rendezvous technique,

Can pigment gallstones be induced by biliary stricture and prevented by medicine in Guinea pigs?

AIM: To determine the relationship between biliary stricture and pigment gallstone formation, and the prevention of pigment gallstones with medicine. METHODS: One hundred and eighteen male guinea pigs were randomly divided into four groups: stricture group (S, n = 30) underwent partial ligation of common bile duct, and fed on regular chow; S plus medicine group (S+M, n = 27) underwent the same operation but fed on medicinal chow (0.3 g chenodeoxycholic acid, 0.5 g glucurolactone, and 0.5 g aspirin were mixed up in 1.2 kg regular chow); medicinal control group (C+M, n = 30) was free of operation, and fed on medicinal chow; and control group (C, n = 31) was free of operation and fed on regular chow. One week later, laparotomy was performed, and the bile of gallbladder was collected, measured, and cultured. RESULTS: Gallstones were identif ied. Pigment gallstones were induced by biliary stricture in 95% (22/23) of S group. In the S+M group, the incidence of gallstone was reduced to 55% (11/20, vs S group, P < 0.01). The changes of indirect bilirubin and ionized calcium in the bile were consistent with gallstone incidences. CONCLUSION: Biliary stricture can cause pigment gallstone formation in guinea pigs, and the medicines used can lower the incidence of gallstones. The bilirubin and ionized calcium play important roles in pigment gallstone formation.

Resolution of tuberculous biliary stricture after medical therapy

Tuberculosis （TB） is a very rare cause of biliary stricture that is difficult to diagnose and usually requires surgical intervention in order to rule out underlying malignant etiology. We report a 56-year-old man presented with jaundice, weight loss and poor appetite. Initial work up showed the dilated biliary system secondary to distal common bile duct stricture. Investigations to define the etiology of this stricture showed inconclusive brush cytology with absent abdominal masses and lymph nodes but enlarged mediastinal lymph nodes. Biopsy from these lymph nodes showed a non-caseating epitheliod granuloma with negative acid fast bacilli （AFB） stain. The patient had a dramatic response to empirical antituberculosis therapy. Six weeks later, culture from lymph nodes was positive for Mycobacteriurn tuberculosis. Three months later, follow-up cholangiogram showed complete resolution of the stricture with normalization of liver enzymes 6 mo after starting anti-tuberculosis therapy. Treatment was continued for 12 mo and the patient had a normal life with normal liver enzymes and regression of the mediastinal lymph nodes at the time when he was reported in this paper. Although 16 cases of tuberculous biliary stricture are available in the English literature, up to our knowledge, this is the second published report of tuberculous biliary stricture, which resolved completely after medical therapy alone and the second reported case from the Middle East. This report emphasizes the importance of keeping TB as a possibility of biliary stricture in this part of the world.