Malignant Biliary Tumors Research Articles

Monocentric study of bile aspiration associated with biliary brushing performed during endoscopic retrograde cholangiopancreatography in 239 patients with symptomatic biliary stricture.

The cytologic diagnosis obtained by brushing or biopsy in malignant biliary strictures is considered to be highly specific but poorly sensitive. The diagnostic association of biliary brushing and bile exfoliate cytology has been suggested but is rarely performed in clinical practice. The objective of this study was to assess the diagnostic performance of bile aspiration associated with biliary brushing during therapeutic endoscopic retrograde cholangiopancreatography (ERCP). From 2004 to 2009, 239 consecutive patients who underwent ERCP were included in the study. The biliary strictures were considered clinically benign in 26% of patients, uncertain in 25%, and malignant in 49%. The 298 cytologic samples collected were divided in 3 groups: bile aspiration alone (26%), biliary brushing alone (20%), and bile aspiration combined with brushing (54%). The definitive diagnosis of malignancy was obtained by biopsy, surgery, and fine-needle aspiration or was determined by an unfavorable disease course. The cytologic diagnoses were as follows: 149 samples were benign (50%), 114 were malignant (38%), 34 had atypia (12%), and 1 had no diagnostic value. The procedure output values were as follows: for bile aspiration alone, sensitivity was 56.4%, specificity was 93.9%, the positive predictive value (PPV) was 91.7%, and the negative predictive value (NPV) was 64.6%; for brushing alone, sensitivity was 62.5%, both specificity and the PPV were 100%, and the NPV was 73%; and, for bile aspiration and brushing combined, sensitivity was 81%, both specificity and the PPV were 100%, and the NPV was 75%. For patients who have symptomatic biliary stricture, bile aspiration during ERCP is a simple and safe procedure. Bile aspiration combined with brushing significantly increases the yield of cytology for malignant biliary tumors (sensitivity, 81%), particularly in cholangiocarcinomas. Cancer Cytopathol 2016;124:330-9. © 2015 American Cancer Society.

The risk of carcinogenesis in congenital choledochal cyst patients: an analysis of 214 cases

Background. Choledochal cysts are most common in Asian populations. In addition, the incidence of biliary tract malignancies from choledochal cysts is increasing, but the risk of carcinogenesis is still unclear.Material and methods. Clinical data from 214 congenital choledochal cyst cases from 1968 to 2013 were retrospectively analyzed.Results. Todani type I was more common (139, 65.0%) than type IVa (53, 24.8%) or type V (17, 7.9%) in these choledochal cyst patients. Biliary tract malignant tumors occurred in the gallbladder (2, 13.3%), common bile duct (10, 66.7%), and intrahepatic bile duct (3, 20%) in 15 patients (7.0%), including one patient in whom malignant transformation occurred in the intrahepatic bile duct in a type IVa patient 15 years after extrahepatic cyst resection. An age at symptom onset ≥ 60 years was a risk factor (p < 0.001), while an initial complete surgery was a protective factor for carcinogenesis (p = 0.001).Conclusions. Choledochal cysts should be removed once diagnosed because of an increased risk of malignant transformation with increasing age. Complete cyst removal is necessary for the first surgical treatment. Additional hepatectomy should be considered for type IVa choledochal cysts because cholangiocarcinoma can arise from the intrahepatic bile duct years after the extrahepatic cyst excision.

Diagnosis and treatment of obstructive jaundice following transcatheter hepatic arterial chemoembolization for hepatic cavernous hemangioma

Hepatic cavernous hemangioma is the most common benign tumor of liver.Hepatic artery embolism chemotherapy is one of the commonly used treatment methods,but more and more related complications and sequelae have been reported recently,including obstructive jaundice caused by damaged biliary tract.Because the symptoms are not typical,obstructive jaundice might be misdiagnosed as malignant biliary tumor,which brought troubles to subsequent treatment.In this article,the clinical data of 2 patients with obstructive jaundice following transcatheter hepatic arterial chemoembolization for hepatic cavernous hemangioma were retrospectively analyzed,and the experience in the diagnosis and treatment of this disease was summarized. Key words: Obstructive jaundice; Cavernous hemangioma; Transcatheter hepatic arterial chemoembolization

SpyGlass by single-operator in ERCP-guided cholangiopancreatoscopy system for bile-duct disorders

Objective To evaluate the clinical utility of SpyGlass single-operator ERCP-guided cholangiopancreatoscopy system for the diagnosis and treatment of bile duct disorders. Methods A total of 9 patients with biliary diseases were treated with SpyGlass single-operator ERCP-guided cholangiopancreato-scopy system. Four patients with large bile duct stones accepted laser hthotripsy, and stones were removed by ERCP. Five patients with indeterminate bile duct stricture accepted cholangioscopy-guided sampling. All patients underwent ENBD, routine blood test, blood amylase test, oral food and water restriction, acid sup- pression and prophylactic antibiotics. Results SpyGlass was successful in all patients with a manipulating time of 21.2min and total procedure time of 46. 2min. Complete stone clearance was achieved in all 4 pa-tients with large biliary stones. Sample quality was adequate in all patients with bile duct stricture with 2 pa-tients diagnosed as having malignant biliary tumor and 3 as inflammatory bile duct stenosis. Post-ERCP com plications including mild pancreatitis in 2 patients, and the patients recovered gradually after corresponding treatment. Conclusion ERCP-guided cholangiopancreatoscopy with the SpyGlass system is technically fea-sible and can be successfully and safely performed in patients with biliary disorders. Key words: Biliary tract diseases ; Duodenoscope ; Cholangiopancreatography, endoscopic retro-grade

A case of xanthogranulomatous cholecystitis which could be differentiated preoperatively from malignant biliary tumor by MDCT

Xanthogranulomatous cholecystitis (XGC) is difficult to differentiate from malignant tumors, such as gallbladder and bile duct carcinoma. We report a case of XGC which was diagnosed preoperatively by recognizing the continuity of the mucosal layer in the gallbladder wall on multi-detector computed tomography (MDCT) . A 63-year-old man was admitted to the hospital because of jaundice. Abdominal ultrasound showed intrahepatic bile duct dilatation and stones in the gallbladder. MDCT showed diffuse thickening of the gallbladder wall and stenosis of the upper biliary tract. ERC showed bile duct stricture extending from the common bile duct to both hepatic ducts. Positron emission tomography (PET) showed abnormal accumulation in the bile duct stricture, with a standardized uptake value (SUV) of 5.0. The serum levels of the tumor markers CA19-9, DUPAN2 and SUPAN1 were also elevated. Based on these findings, the diagnosis of gallbladder carcinoma infiltrating the bile duct was suspected. On the other hand, ERCP brush cytology and EUSFNA did not reveal any evidence of malignancy. Furthermore, we recognized continuity of the mucosal layer in the gallbladder wall on MDCT. Although XGC was strongly suspected based on the imaging findings, we performed resection of the gallbladder bed. Intraoperative pathological examination confirmed the diagnosis of XGC and ruled out malignancy. The findings on MDCT allowed us to avoid unnecessary extended operation.

CD24 induces the invasion of cholangiocarcinoma cells by upregulating CXCR4 and increasing the phosphorylation of ERK1/2

Cholangiocarcinoma is a malignant biliary tract tumor with an extremely poor prognosis. CD24 expression has been linked to the aggressiveness of cholangiocarcinoma cells and the adverse prognosis of cholangiocarcinoma patients. In the present study, the underlying mechanism of aggressive CD24+ cholangiocarcinoma cell behavior was elucidated. The magnetic-activated cell sorting system was used to isolate CD24+ and CD24− cell populations from RMCCA1 cholangiocarcinoma cells. Using a human tumor metastasis PCR array, it was observed that numerous tumor-associated genes were upregulated in the CD24+ cells, including CXC chemokine receptor type 4 (CXCR4). In addition, an intracellular signaling array demonstrated the activation of extracellular signal-regulated kinase (ERK)1/2, which is downstream of the CXCR4 signaling cascade, in the CD24+ cells. Inhibition of CXCR4 or ERK1/2 significantly inhibited the motility and invasiveness of the CD24+ cells. The present study indicates that CXCR4 and ERK1/2 are induced by CD24 and that these proteins are associated with cholangiocarcinoma cell invasion.

Clinical manifestations of pyogenic liver abscesses of cryptogenic origin

Total 118 patients with pyogenic liver abscess admitted to Zhongshan Hospital were classified into pypgenic liver abscesses of cryptogenic origin (PLAC, n=54), pyogenic liver abscesses of biliary origin (PLAB, n=48) and pyogenic liver abscesses of hemagenous origin (PLAH, n=16) according to the causes. The clinical features of three groups were compared and analyzed. The results showed that no statistically significant difference existed among three groups in clinical manifestation and signs. Compared to PLAB, the abscesses in right lobe of liver were more common in PLAC, diabetes mellitus was more prevalent in PLAC, but the co-existing diseases including chronic liver disease, non biliary malignant tumor and ALP elevation were less in PLAC. Klebsiella pneumoniae was frequently detected in PLAC, but there was no significant difference comparing to other two groups. No significant difference was found among three groups in the choice of therapeutic methods, the course of antibiotics, length of hospital stay and the days from admission to diagnosis. Key words: Liver abscess, pyogenic; Clinical features

Mo2032 Small Cell Carcinoma of the Ampulla of Vater

[Background/Aim] An extensive hepatic resection is required in cases of malignant hepatic and biliary tract tumor. The prognosis is influenced by a shortage of functional capacity of the remnant liver. Since preoperative portal vein embolization (PVE) was first reported, this technique has become widely used in such cases. However, the indication for PVE and its outcome are unclear. In the present study, we retrospectively analyzed preoperative PVE patients. [Patients] From January 2002 to December 2011, 58 patients underwent preoperative PVE at our institute. In this study, we analyzed 46 patients (29 cases of hilar bile duct cancer [no liver damage group] and 17 colorectal liver metastatic tumor cases after chemotherapy [liver damage group]). In cases of hilar bile duct cancer or colorectal hepatic metastasis, we compared the resection rate and prognosis of these patients before and after PVE introduction. [Results] Two of 46 patients had complications caused by preoperative PVE (minimal bleeding into the biliary tract). Four cases in the group without liver damage (13.8%) could not undergo hepatectomy (3 cases, progressive disease; 1 case, no hypertrophy of the remnant liver). Five cases in the liver damage group (29.4%) could not undergo hepatectomy (1 case, severe steatohepatitis; 4 cases, no hypertrophy of the remnant liver). The median rates of hypertrophy of the remnant liver in the group without liver damage and the liver damage group were 9.4% and 7.5%, respectively (no statistical difference). The median maximum total bilirubin levels after hepatectomy in the group without liver damage and the liver damage group were 4.3 and 1.9 mg/dL, respectively (no statistical difference). In cases of hilar bile duct cancer and colorectal hepatic metastasis, the resection rate and the prognosis improved significantly after PVE introduction (resection rate: 56.7% vs. 90.2% and 30.0% vs. 58.2%, respectively; 3-year survival rate: 35.2% vs. 70.2% and 35.2% vs. 45.2%, respectively). [Conclusion] In the present study, no statistical difference was noted between the liver damage group and the group without liver damage in the rate of hypertrophy of the remnant liver after PVE and postoperative complications. However, the incidence of unresectability because of lack of hypertrophy of the remnant liver was higher in the liver damage group than in the group without liver damage. Thus, we believe that PVE has potential benefits for hilar bile duct cancer patients and colorectal liver metastasis patients because of the associated improved resection rate and prognosis.

Simultaneous Occurrence of Gallbladder Cancer in a Laundry Couple: Association between Gallbladder Cancer and Benzene

Gallbladder (GB) cancer occurs predominately as a biliary tract malignant tumor. It generally has a very poor prognosis, and early detection is often difficult. A variety of carcinogens have been implicated as an important cause for GB cancer. Benzene is a well-known carcinogen for hematologic malignancy, and its casual relationship with GB cancer has been suggested. We report a case of two patients who had operated a laundry cleaning facility together and later simultaneously got GB cancer after prolonged benzene exposure.

Reappraisal of Hepatopancreatoduodenectomy as a Treatment Modality for Bile Duct and Gallbladder Cancer

BackgroundHepatopancreatoduodenectomy has been performed to achieve radical resection in malignant biliary tumors. We reviewed clinical outcomes to evaluate the clinical feasibility of hepatopancreatoduodenectomy for the treatment of gallbladder and bile duct cancer. MethodsTwenty-three patients underwent hepatopancreatoduodenectomy from 1995 to 2007; 10 gallbladder cancer and 13 bile duct cancer. Median follow-up periods were 15.0 months. ResultsR0 resection was performed in 17 of 23 patients (73.9%). Morbidity and mortality rates were 91.3% and 13.0%, respectively. Five-year survival rates were 10.0% for gallbladder cancer and 32.3% for bile duct cancer. Survival more than 3 years was possible for most patients with stage IIA or less, whereas all gallbladder cancer patients with stage III and all bile duct cancer with stage IIB or more died within 2 years. Bile duct cancer patients with pN0 survived longer than those with pN1 (p < 0.001). ConclusionsTo obtain negative proximal and distal ductal resection margins in the biliary tract cancer, R0 resection and long-term survival can be achieved by hepatopancreatoduodenectomy. However, its adoption in patients with lymph node metastasis or adjacent organ invasion cannot be recommended.

Gemcitabine release behavior of polyurethane matrixes designed for local anti-cancer drug delivery via stent

Gemcitabine is a potent anti-cancer drug, but it has a very short half-life in vivo, necessitating systematic infusion at high doses. We prepared gemcitabine-incorporated polyurethane (GIPU) films with various drug loading levels that can be used as stent coverings for local drug delivery and tumor control around the stent. The release behavior of the film depended on the drug loading level. An initial burst at 4 hours increased from 10 % to 55 % to 75 % of the loading when the Gemzar concentration in the PU film increased from 10 % to 15 % to 20 %, respectively. The amount of the drug released per day reversed the trend, however, at 2 days, and the GIPU film with a lower drug loading released a larger amount of the drug for up to 16 days. GIPU films could be used as stent coverings for the control of unresectable pancreatic or biliary malignant tumors.

Choledochal Cyst and Associated Malignant Tumors in Adults

To determine the clinical features and clinical outcomes of Korean adults treated surgically for choledochal cyst. Retrospective nationwide multicenter study. Fifteen university hospitals (tertiary care referral centers) located in all 7 Korean provinces. A total of 808 patients aged 18 years or older who underwent surgery for choledochal cyst from January 1, 1990, through December 31, 2007. Demographic information, surgical data, associated biliary malignant tumors, and factors predicting malignant tumors. Type I was most common (499 [68.2%]) followed by type IVa (208 [28.4%]). Of 654 patients, anomalous pancreaticobiliary ductal union was identified in 467 patients (71.4%), 291 with the choledochal type (62.3%), 96 with the pancreatic type (20.6%), and 80 with the complex type (17.1%). Biliary tract malignant tumor was associated in 80 patients (9.9%); 40 had bile duct cancer (50.0%), 35 had gallbladder cancer (43.8%), 3 had periampullary cancer, and 2 had synchronous gallbladder and bile duct cancer. Twenty-two patients (26.3%) had a recurrence, with a median follow-up duration of 51.8 months. Factors predicting malignant tumor by univariate analysis were age more than 40 years, the absence of a gallstone, elevated carcinoembryonic antigen or cancer antigen 19-9 serum level, and the presence of anomalous pancreaticobiliary ductal union, and by multivariate analysis, an elevated cancer antigen 19-9 level. Associated biliary malignant tumor should always be considered in patients with choledochal cyst, especially in aged patients or patients with anomalous pancreaticobiliary ductal union or an elevated tumor marker level. Lifelong follow-up is needed even after complete cyst excision because of the risk of the development of a metachronous biliary malignant tumor.

Clinical and pathological features of primary carcinoma of the cystic duct

According to Farrar's criteria, a tumor restricted to the cystic duct is defined as cystic duct carcinoma, but this definition excludes advanced carcinoma originating from the cystic duct. For the purpose of this study, primary cystic duct carcinoma was defined as a tumor originating from the cystic duct. We investigated the clinicopathological features of 15 cystic duct carcinomas, including 13 that did not fit Farrar's criteria, and compared them with those of 52 cases of gallbladder carcinoma and 161 cases of extrahepatic bile duct carcinoma. The incidence of primary cystic duct carcinoma was 6.6% among all malignant biliary tumors. The main symptom was jaundice in 67% of cases. The operative procedures employed ranged from cholecystectomy to hepatopancreatoduodenectomy. The cases of cystic duct carcinoma and bile duct carcinoma showed a high frequency of perineural infiltration. The overall 5-year survival rate of the 15 patients was 40%. Patients with advanced cystic duct carcinoma show a high frequency of jaundice and perineural infiltration. Our data suggest that cystic duct carcinoma may be considered a distinct subgroup of gallbladder carcinoma. Radical surgery is necessary for potentially curative resection in patients with advanced cystic duct carcinoma.

Feasibility evaluation of chitosan coatings on polyethylene tubing for biliary stent applications

AbstractEndoscopic palliation for the obstructive jaundice caused by biliary or pancreatic malignant tumors is a commonly used medical treatment. However, plastic biliary stents are occluded by sludge deposition caused by bacterial adhesion in 3–5 months. Chitosan, which has both good biocompatibility and antimicrobial capability, was used to modify the inner surface of polyethylene (PE) tubing in this study. Chitosan was deposited onto the inner surface of oxidized PE tubing with the methanol precipitation technique. Attenuated total reflection/Fourier transform infrared and electron spectroscopy for chemical analysis indicated that the chitosan coating was feasible. Contact‐angle measurements revealed that the surface hydrophilicity of the PE tubing increased with the chitosan coating. Morphological analysis with scanning electron microscopy showed that the PE surface became rougher and exhibited micropores after the chitosan coating. The adhesion of living Escherichia coli to chitosan‐coated PE stents, characterized by the spreading plate method and scanning electron microscopy analysis, was more significant than that to unmodified stents after a 24‐h phosphate‐buffered saline or bile perfusion test. This finding may be attributed to the rougher and slightly positively charged surface of chitosan‐coated PE tubing and to the CH3 hydrophobic functional groups in the chitosan structure. Because of its good biocompatibility, chitosan coated on the surface of PE can still be used for biliary stent applications with further chemical modification, such as sulfonation and quaternization, to increase its antimicrobial ability. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 97: 893–902, 2005

Efficacy of the Za Self-Expandable Metal Stent for Palliation of Malignant Biliary Obstruction

The efficacy and safety of the uncoated self-expandable Za metal stent for palliation of malignant distal biliary obstruction was prospectively analyzed. Twenty-one patients with unresectable malignant tumors involving mid to distal common bile duct who presented with obstructive jaundice underwent endoscopic implantation of an uncoated self-expandable metal stent. Technical success with stent placement, adverse events, patient survival, duration of stent patency, and device performance were analyzed. Endoscopic biliary stenting was successful in all patients. No adverse events were encountered. The mean follow-up period of the 21 patients was 128 days (range, 3-263): 14 died of progressive disease at mean of 81 days (range, 3-210), 3 remain alive (at days 239, 250, and 263), and 4 were lost to follow-up (at days 90, 91, 92, and 116). The mean duration of stent patency was 249 days. Tumor ingrowth was observed in one patient (5%). Minor technical problems were encountered in 3 patients: 1 proximal deployment, 1 distal deployment, and difficulty associated with the delivery system in 1. The Za-metal stent provided effective palliation for patients with inoperable malignant biliary tumors. Although minor technical problems were encountered with stent deployment, the overall stent patency, efficacy, and safety profile appear satisfactory.

ERCP in patients with long-limb Roux-en-Y gastrojejunostomy and intact papilla

Background: ERCP by means of long-limb Roux-en-Y surgical anastomoses has been reported primarily in patients with biliary or pancreatic anastamoses, but rarely in patients with an intact papilla. Methods: All ERCP procedures attempted over a 6-year interval in patients with Roux-en-Y gastrojejunostomies and an intact papilla were reviewed. Patients with a prior Billroth II operation or alteration of the major papilla were excluded. Cannulation and therapy were primarily performed with a duodenoscope after exploration and placement of a guidewire in the afferent limb with a forward-viewing colonoscope. In some cases the duodenoscope was pulled into the afferent limb with a wire-guided balloon passed retrograde into the afferent limb. A follow-up of 30 days was obtained for all patients as part of a prospective ERCP outcome study. Results: Of 15 patients in whom ERCP was attempted, the papilla was reached in 10 patients (67%), the bile duct being accessed in all 10. Needle-knife precut papillotomy after placement of a pancreatic duct stent was performed in 3 patients. Biliary sphincterotomy with a variety of techniques was successful in all 9 patients in whom it was attempted. Other maneuvers included stone extraction, sphincter of Oddi manometry, and biliary stent placement. Final diagnoses were sphincter of Oddi dysfunction (6), malignant biliary stricture (2), choledocholithiasis plus tumor (1), and choledocholithiasis (1). Complications occurred after 3 (12%) of 25 ERCP procedures including pancreatitis (1 mild, 1 moderate) and bleeding (1 mild), all in patients with sphincter of Oddi dysfunction. Conclusions: Diagnostic and therapeutic ERCP was ultimately successful in two thirds of patients with long-limb gastrojejunostomies and an intact papilla. The success of the ERCP is determined primarily by ability to advance a duodenoscope through the afferent limb. Once the major papilla was accessed with a duodenoscope, advanced biliary and pancreatic therapeutic techniques were feasible. (Gastrointest Endosc 2002;56:225-32.)

Spontaneous regression of an inflammatory pseudotumor of the liver presenting as an obstructing malignant biliary tumor

Inflammatory pseudotumors (IPT) of the liver are uncommon benign lesions of unclear etiology and behavior.1 Although uncommon, IPT of the liver have been increasingly recognized in recent years, mainly in Asian countries.1 IPT are often treated by hepatic resection because they are usually mistaken for malignant lesions.

Spontaneous regression of an inflammatory pseudotumor of the liver presenting as an obstructing malignant biliary tumor

Spontaneous regression of an inflammatory pseudotumor of the liver presenting as an obstructing malignant biliary tumor