Type Of Cholangiocarcinoma Research Articles

Diagnostic criteria for IgG4-related sclerosing cholangitis based on cholangiographic classification

IgG4-related sclerosing cholangitis (IgG4-SC) needs to be differentiated from pancreatic cancer (PCa), primary sclerosing cholangitis (PSC), and cholangiocarcinoma (CC). We attempted to establish diagnostic criteria for IgG4-SC based on cholangiographic classification by comparison with several diagnostic modalities. We classified 62 IgG4-SC patients into three groups on the basis of cholangiographic findings to allow differentiation from PCa, PSC, and CC: Group A IgG4-SC showed features similar to PCa (Type 1, n=32), Group B showed similarity to PSC (Type 2, n=15), and Group C showed similarity to CC (Type 3, 4, n=15). Thirty-five patients with PCa, 40 with PSC, and 32 CC were enrolled as controls. We retrospectively compared the clinical, imaging, serological, and histopathological features and involvement of other organs between Group A and PCa, Group B and PSC, and Group C and CC. Association with autoimmune pancreatitis (AIP) (P<0.001) and involvements with other organs (specificity 100%) were common useful diagnostic parameters in all three IgG4-SC groups. A high serum IgG4 level was a useful parameter in Groups A and B (P<0.001). Discriminant analysis of cholangiograms (P<0.001), liver biopsy (specificity 100%), and exclusion of inflammatory bowel disease (specificity 100%) were useful parameters in Group B. Intraductal ultrasonography findings (P<0.001) and exclusion of malignancy by bile duct biopsy (specificity 100%) were useful parameters in Group C. We established diagnostic criteria for IgG4-SC (sensitivity 100%, specificity 96.3%) by incorporating parameters that showed P<0.001 or 100% specificity. Diagnostic criteria for IgG4-SC based on cholangiographic classification are useful for distinguishing it from PCa, PSC, and CC.

Clinical diagnosis and staging of cholangiocarcinoma

Cholangiocarcinoma is the most frequent biliary malignancy. It is difficult to diagnose owing to its anatomic location, growth patterns and lack of definite diagnostic criteria. Currently, cholangiocarcinoma is classified into the following types according to its anatomic location along the biliary tree: intrahepatic, perihilar or distal extrahepatic cholangiocarcinoma. These cholangiocarcinoma types differ in their biological behavior and management. The appropriate stratification of patients with regard to the anatomic location and stage of cholangiocarcinoma is a key determinate in their management. Staging systems can guide this stratification and provide prognostic information. In addition, staging systems are essential in order to compare and contrast the outcomes of different therapeutic approaches. A number of staging systems exist for cholangiocarcinoma-several early ones have been updated, and new ones are being developed. We discuss the emerging diagnostic criteria as well as the different staging systems for cholangiocarcinoma, and provide a critical appraisal regarding these advances in biliary tract malignancies.

Cholangiocarcinoma—controversies and challenges

Cholangiocarcinomas are a diverse group of tumors that are presumed to originate from the biliary tract epithelium either within the liver or the biliary tract. These cancers are often difficult to diagnose, their pathogenesis is poorly understood, and their dismal prognosis has resulted in a nihilistic approach to their management. The two major clinical phenotypes are intrahepatic, mass-forming tumors and large ductal tumors. Among the ductal cancers, lesions at the liver hilum are most prevalent. The risk factors, clinical presentation, natural history and management of these two types of cholangiocarcinoma are distinct. Efforts to improve outcomes for patients with these diseases are affected by several challenges to effective management. For example, designations based on anatomical characteristics have been inconsistently applied, which has confounded analysis of epidemiological trends and assessment of risk factors. The evaluation of therapeutic options, particularly systemic therapies, has been limited by a lack of appreciation of the different phenotypes. Controversies exist regarding the appropriate workup and choice of management approach. However, new and emerging tools for improved diagnosis, expanded indications for surgical approaches, an emerging role for locoregional and intrabiliary therapies and improved systemic therapies provide optimism and hope for improved outcomes in the future.

Intraductal papillary neoplasm of the bile duct (IPNB): A biliary equivalent to IPMN of the pancreas?

201 Background: Intraductal papillary neoplasm of the bile duct (IPNB) is a type of cholangiocarcinoma characterized by intraductal growth, mucin production and a better outcome compared to the more common nodular-sclerosing type. IPNB may be analogous to IPMN of the pancreas and may be a precursor of invasive cholangiocarcinoma, but its pathogenesis and natural history are ill-defined. This study examines the incidence, clinicopathologic features and outcome of IPNB in a single center. Methods: A consecutive cohort of patients with bile duct cancer (hilar, intrahepatic or distal) was reviewed and those with papillary features identified. Histopathologic morphology and immunohistochemical staining for cytokeratin and mucin proteins were utilized to classify IPNB into subtypes. Survival data were analyzed and correlated with clinicopathological parameters. Results: Between 1993 and 2008, 40 IPNBs were identified in hilar (24/144), intrahepatic (4/86) and distal (12/113) bile duct cancer specimens (11.7%). Histopathologic examination revealed 27 pancreatobiliary, 4 gastric, 3 intestinal, and 6 oncocytic subtypes; cytokeratin and mucin staining was similar to that of IPMNs of the pancreas. Invasive carcinoma was seen in 29/40 (72%) IPNBs. Overall median survival was 59 months and was not different between IPNB locations or subtypes. Factors associated with a worse median survival included depth of invasion (39 months for &gt; 5mm, 128 months for &lt; 5mm, and 144 months for none, p &lt;0.05), R1 vs R0 resection (36 months vs 82 months, p &lt;0.05), MUC1 expression (53 months for positive vs 144 months for negative, p &lt;0.006), and CEA expression (42 months for positive vs 128 for negative, p&lt;0.02). Expression of MUC2, MUC5A, MUC6, CDX2, mesothelin, p53, Ki67, HepPar1, and B72.3 were not predictive of outcome. Conclusions: IPNBs are an uncommon variant of bile duct cancer, representing approximately 10% of all cases, occur throughout the biliary tract and share histologic and clinical features with IPMNs of the pancreas. These lesions may represent an alternative carcinogenesis pathway. Given their significant malignant potential, they should be treated aggressively with margin-negative resection. No significant financial relationships to disclose.

Differentiation of Intraductal Growing–type Cholangiocarcinomas from Nodular-type Cholangiocarcinomas at Biliary MR Imaging with MR Cholangiography

To describe the magnetic resonance (MR) findings of intraductal growing (IDG)-type cholangiocarcinoma (CC) and to identify the features that differentiate it from nodular-type CC. The institutional review board approved this retrospective study and waived the informed consent requirement. Thirty-nine patients with pathologically proved IDG-type (n = 19) or nodular-type (n = 20) CCs who had undergone preoperative gadolinium-enhanced MR imaging with MR cholangiography were included in this study. Analysis of MR findings included determination of the (a) shape, enhancement degree, and pattern of the tumor; (b) outer caliber of the tumor-bearing segment; and (c) presence of tumor multiplicity, upstream and downstream bile duct dilatation, bile duct wall thickening adjacent to the tumor, and adjacent organ invasion. The significance of these findings was determined with the χ² test. Significant features in the differentiation of IDG-type CCs from nodular-type CCs included papillary or irregular polypoid shape, lack of constriction of the tumor-bearing segment, hypoenhancement of the tumor to the liver during the equilibrium phase, tumor multiplicity, upstream and downstream bile duct dilatation, and no bile duct wall thickening adjacent to the tumor (P < .05). When at least two of these six imaging features were used in combination, sensitivity and specificity in the diagnosis of IDG-type CCs were 95% and 70%, respectively. By using characteristic MR features, one can differentiate IDG-type CC from nodular-type CC with a high degree of accuracy at biliary MR imaging with MR cholangiography.

Multimodal Oncological Therapy Comprising Stents, Brachytherapy, and Regional Chemotherapy for Cholangiocarcinoma

To prospectively evaluate our palliative management of unresectable cholangiocarcinoma (CC) treated with tailored multimodal oncological therapy. Between January 2005 and January 2010, 50 consecutive patients with unresectable CC and jaundice were palliated with percutaneous drainage. Forty-three patients underwent metallic-stent implantation followed by brachytherapy. Patients were divided into two arms: the intra-arterial chemotherapy arm (IA arm, n=17) consisted of patients treated with locoregional treatment (IA admission of Cisplatin and 5-fluorouracil, or chemoembolization with Lipiodol) and/or systemic chemotherapy, while the systemic chemotherapy arm (IV arm, n=23) included all the other patients, who were treated only with systemic chemotherapy. In total, 78 metal self-expandable stents were placed. Hilar involvement with mass-forming and periductal infiltrating types of CC (84%) was predominant. The average number of percutaneous interventional procedures was 11.61 per patient (range, 4-35). The median overall survival from diagnosis of disease for all patients was 13.5 months (range, 11.0-18.8 months). The median overall survival times were 25.2 months (range, 15.2-31.3 months) and 11.5 months (range, 8.5-12.6 months) in the IA and IV arms, respectively (p<0.05). The 1-, 2-, and 3-year survival rates in the IA and IV arms were 88.2%, 52.9%, and 10.1% and 43.5%, 25.4, and 0%, respectively. There were no major complications (WHO III/IV) due to interventional procedures. We could reach acceptable prognosis in patients with unresectable CC using complex tailored oncological therapy. However, the main limitations of prolonging survival are performance status, patient compliance and the maintaining of biliary tract patency.

Role of Preoperative Optimization of the Liver for Resection in Patients with Hilar Cholangiocarcinoma Type III

Long-term survival after complete resection of hilar cholangiocarcinoma remains disappointing. The aim of this retrospective study was to assess the impact of liver optimization on postoperative outcome of hilar cholangiocarcinoma type III. In a retrospective, single-center analysis, outcomes in patients with hilar cholangiocarcinoma type III who underwent resection after preoperative liver optimization (preoperative transhepatic biliary drainage [PTBD], bile replacement, and/or portal vein embolization [PVE]) were compared with nonoptimized controls. Of 41 patients undergoing surgery, 38 patients undergoing curative intent procedures were identified, of whom 15 underwent preoperative optimization. After PTBD, direct bilirubin decreased from 218.0 ± 184.2 to 75.9 ± 42.7 μmol/L (P = 0.03), and there was a trend toward decreased AST and ALT levels. Overall, 3- and 5-year survival rates were 47.9 ± 9.1 and 41.9 ± 9.8%. The primary endpoint, 5-year survival after surgery, was not significantly different between groups. Preoperative jaundice was identified as an independent prognostic factor for poor outcome (hazard ratio [HR] 2.12, P = 0.02). Four patients (10.5%) without preoperative optimization died of liver failure within the first 30 days postsurgery, preceded in three cases by intra-abdominal abscesses. PTBD was associated with a lower rate of postoperative intra-abdominal abscesses; however this factor was not independently predictive of higher survival. Preoperative optimization of the liver in hilar cholangiocarcinoma Type III reduced the incidence of intra-abdominal abscesses, but its impact on postoperative survival remains unclear.

CD10+ fibroblasts are more involved in the progression of hilar/extrahepatic cholangiocarcinoma than of peripheral intrahepatic cholangiocarcinoma

To identify the role of CD10 expression of tumour-associated fibroblastic cells in the progression of cholangiocarcinoma (CC). The CD10 expression of fibroblastic cells was investigated immunohistochemically in 167 cases of intrahepatic and extrahepatic CC and 29 cases of biliary dysplasia, comparing the clinicopathological parameters. CD10 expression of fibroblastic cells was observed in 5.7% (4/70) of peripheral intrahepatic CC, 29.2% (14/48) of hilar intrahepatic CC, and 57.1% (28/49) of extrahepatic CC. As for biliary dysplasia, CD10 expression of fibroblastic cells was observed in 4.3% (1/23) in the hepatic hilum and 20% (3/15) in the extrahepatic bile duct. CD10 expression had a strong relationship with the anatomical location of CC, and was more frequently detected in the periductal infiltrating type of hilar intrahepatic CC (P < 0.0001) and in less differentiated cases in extrahepatic CC (P = 0.0151). CD10 expression was observed more frequently in CC than in biliary dysplasia of hepatic hilum (P = 0.0365) and extrahepatic bile duct (P = 0.0262). CD10 expression was not a prognostic indicator in CC. We suggest that CD10+ fibroblasts are more involved in the progression of hilar and extrahepatic CC than of peripheral intrahepatic CC.

Biliary Intraductal Papillary-Mucinous Neoplasm Manifesting Only as Dilatation of the Hepatic Lobar or Segmental Bile Ducts: Imaging Features in Six Patients

The purpose of this study was to evaluate the imaging features of intrahepatic biliary intraductal papillary-mucinous neoplasm manifesting only as dilatation of the lobar or segmental bile ducts without a visible mass to determine whether this type of cholangiocarcinoma can be recognized on the basis of distinct imaging features. Intrahepatic biliary intraductal papillary-mucinous neoplasm can spread along the mucosa without forming a mass and can produce a large amount of mucin. Severe dilatation of the lobar or segmental intrahepatic bile ducts with crowding and severe atrophy of the hepatic parenchyma are helpful imaging findings.

Capecitabine plus oxaliplatin as first-line treatment in patients with advanced biliary system adenocarcinoma: a prospective multicentre phase II trial

This prospective multicentre phase II study characterises the toxicity and activity of first-line capecitabine and oxaliplatin combination therapy (CAPOX) in advanced biliary system adenocarcinomas. Patients received oxaliplatin (130 mg m−2, day 1) plus capecitabine (1000 mg m−2 b.i.d., days 1–14) every 3 weeks. Patients were stratified prospectively into two groups based on location of the primary (gallbladder carcinoma (GBC) or extrahepatic cholangiocarcinoma (ECC) versus intrahepatic mass-forming type cholangiocarcinoma (ICC)). Sixty-five patients were evaluable. The response rate in 47 patients with GBC/ECC was 27% (4% complete responses), and in 23 patients (49%) stable disease (SD) was encountered. In 18 patients with ICC, we observed no objective responses, but 6 patients (33%) had SD. Median survival was 12.8 months (95% CI, 10.0–15.6) for patients with GBC or ECC (GBC: 8.2 months; 95% CI, 4.3–11.7; ECC: 16.8 months; 95% CI, 12.7–20.5), and 5.2 months (95% CI, 0.6–9.8) for ICC patients. In both cohorts, therapy was well tolerated. The most common grade 3–4 toxicity was peripheral sensory neuropathy (11 patients). Our data suggest that the CAPOX regimen is a well-tolerated and active treatment option for advanced ECC and GBC but might produce poorer results for ICC.

Major Hepatectomy for Hilar Cholangiocarcinoma Type 3 and 4: Prognostic Factors and Longterm Outcomes

Major Hepatectomy for Hilar Cholangiocarcinoma Type 3 and 4: Prognostic Factors and Longterm Outcomes

Intrahepatic Cholangiocarcinoma with Old Infestation of Schistosoma japonicum: Report of a Case

We report a rare case of intrahepatic cholangiocarcinoma associated with old infestation of Schistosoma japonicum. The patient was a 76-year-old Japanese man who had lived his childhood in an endemic area of this parasite. He presented with jaundice and computed tomography showed a 4-cm, hypodense tumor in segment VIII of the liver. Microscopically, the resected mass was composed of well-differentiated adenocarcinoma cells. Fibrosis and inflammation were seen around the dilated peripheral portal veins embolized with dead S. japonicum eggs. Our search of the literature found only one other case of cholangiocarcinoma coincident with S. japonicum, suggesting that it is not a risk factor for cholangiocarcinoma, although the inflammation and fibrosis caused by the S. japonicum eggshells may predispose to carcinogenesis. However, there is no evidence supporting this hypothesis. More data are necessary to evaluate the differences in clinicopathological findings between cholangiocarcinoma concomitant with S. japonicum and the usual type of cholangiocarcinoma.

F-18]Fluorodeoxyglucose Positron Emission Tomography and Positron Emission Tomography

We retrospectively assessed the diagnostic utility of dedicated positron emission tomography (PET) and hybrid PET-computed tomography (CT) scans with [F-18]fluorodeoxyglucose (FDG) in the imaging evaluation of patients with known or suspected recurrent and metastatic cholangiocarcinoma. The study group included 24 patients (13 males and 11 females; age range, 34-75 years) with known or suspected recurrent and metastatic cholangiocarcinoma. We performed 8 dedicated PET scans (Siemens 953/A, Knoxville, Tenn) in 8 patients and 24 hybrid PET-CT scans (Siemens Biograph, Knoxville, Tenn) in 16 patients. Four patients underwent both pretreatment and posttreatment scans. Nonenhanced CT transmission scans were obtained for attenuation correction after administration of oral contrast material. PET images were obtained 60 minutes after the intravenous administration of 15 mCi (555 MBq) FDG. Prior treatments included surgery alone in 12 patients, surgery and chemotherapy in 6 patients, and surgery and combined chemoradiation therapy in 6 patients. Diagnostic validation was conducted through clinical and radiologic follow-up (2 months to 8 years). PET and CT were concordant in 18 patients. PET-CT correctly localized a hypermetabolic metastatic lesion in the anterior subdiaphragmatic fat instead of within the liver and was falsely negative in intrahepatic infiltrating type cholangiocarcinoma. PET was discordant with CT in 6 patients. PET was negative in an enlarged right cardiophrenic lymph node on CT, which remained stable for 1 year. In 1 patient, PET-CT scan showed hypermetabolic peritoneal disease in the right paracolic gutter without definite corresponding structural abnormalities, which was subsequently confirmed on a follow-up PET-CT scan performed 6 months after the initial study, at which time peritoneal nodular thickening was evident on concurrent CT. PET-CT documented the progression of locally recurrent and metastatic disease in another patient based on interval appearance of several new hypermetabolic lesions and significant increase in the standardized uptake values of the known lesions despite little interval change in the size and morphologic character of lesions on concurrent CT. It was also helpful in excluding metabolically active disease in patients with contrast enhancement at either surgical margin of hepatic resection site or focally within hepatic parenchyma and in an osseous lesion. Overall, based on the clinically relevant patient basis for detection of recurrent and metastatic cholangiocarcinoma, the sensitivity and specificity of PET (alone and combined with CT) were 94% and 100% and, for CT alone, were 82% and 43%, respectively. FDG PET and PET-CT are useful in the imaging evaluation of patients with cholangiocarcinoma (except for infiltrating type) for detection of recurrent and metastatic disease and for assessment of treatment response. In particular, the combined structural and metabolic information of PET-CT enhances the diagnostic confidence in lesion characterization.

Pathology of cholangiocarcinoma

Cholangiocarcinoma, which is endemic in certain geographic regions, shows a strong association with liver fluke infection and hepatolithiasis, with recurrent inflammation and the high consumption of nitrates, nitrites, dimethylnitrosamines and N -nitropyrolidines as probable mutagenic cofactors. K-ras , p53 and bcl-2 have been implicated in cholangiocarcinogenesis and several immunohistological markers have been studied, although none is a reliable predictor of outcome. Three macroscopic types of cholangiocarcinoma have been characterized and implicated to be of prognostic relevance, but their behaviour might be a function of their anatomical location rather than a biological characteristic. Periductal-infiltrating tumours present at an advanced stage with infiltration of the portal pedicle. They arise closer to the hepatic hilum than mass-forming tumours, which tend to be peripherally located and show portal invasion and intrahepatic recurrence. The intraductal tumour shows the best prognosis, and long-term survival has been reported. Poor prognostic factors include large tumour size, multifocality, lymphovascular, perineural and serosal invasion, lymph node metastases and involvement of resection margins. Survival following surgical resection, the mainstay of treatment, is generally very poor.

Major Hepatectomy for Hilar Cholangiocarcinoma Type 3 and 4: Prognostic Factors and Longterm Outcomes

Radical operation for hilar cholangiocarcinoma, including major hepatectomy with vascular resection, seems to improve longterm survival. This study retrospectively evaluates several prognostic risk factors that can influence survival after resection of types 3 to 4 Klatskin tumors. Between 1984 and 2003, 59 patients (36 men and 23 women) with types 3 to 4 hilar cholangiocarcinoma underwent liver resection with curative intent. Medical records and pathologic findings were reviewed to assess prognostic risk factors and survival. Disease-free and overall survival were analyzed using Kaplan-Meier and Cox proportional hazards models. Survival rates at 1, 3, and 5 years were 82%, 45%, and 20% respectively. In-hospital mortality was 5% and morbidity was 42%. In multivariable analysis, male gender (relative risk [RR] = 5.4; 95% CI, 2.2 to 13.5), absence of preoperative chemotherapy (RR = 4; 95% CI, 1.5 to 10.7), R1 biliary tract margin (RR = 2.6; 95% CI, 1.1 to 4.4), and metastatic celiac lymph nodes (RR = 19.9; 95% CI, 4 to 71.4) were found to be independent factors for overall survival. Pedicular metastatic lymph nodes were not associated with poorer overall survival. If biliary positive-margin is the only risk factor, the 5-year estimated overall survival is 70%. Major hepatectomy can improve outcomes of hilar cholangiocarcinoma. Compared with nonoperative treatment or R0 hepatectomy, R1 resection in patients with no other risk factor can offer longterm survival.

TWO CASES OF MUCIN‐PRODUCING CHOLANGIOCARCINOMA DIAGNOSED BY PERORAL CHOLANGIOSCOPY

Mucin‐producing cholangiocarcinoma, which excretes excessive amounts of mucin into the biliary tract and causes obstructive jaundice and cholangitis due to the mucin retention, is rare. In this paper, we report two cases of this disease, which were demonstrated by peroral cholangioscopy (POCS). The radiologic features of these tumors show the diffuse dilatation of the bile ducts demonstrated by computed tomography (CT) and ultrasonography (US), the amorphous filling defects in the dilated bile ducts revealed by cholangiography. Their endoscopic features are mucin flowing out from the papilla of Vater during endoscopic retrograde cholangiography (ERC), and the papillary tumor with contiguous superficial spread in the bile ducts observed by cholangioscopy, although removal of mucin in the biliary tract is sometimes necessary before cholangioscopy in order to examine the lesion sufficiently. According to the previous reports, prognosis after curative resection of these tumors is better than that of ordinary type of cholangiocarcinoma. Therefore, it is important to examine the tumor extension in the bile ducts by cholangioscopy, although a selection of route inserting cholangioscope is controversial.

Phenotypic diversity of intrahepatic and extrahepatic cholangiocarcinoma on aspiration cytology and core needle biopsy

Cholangiocarcinoma (CC) represents approximately 10% of primary liver malignancies and can mimic metastatic adenocarcinoma. The authors retrospectively reviewed the cytopathology files at the University of Texas Medical Branch to identify patients who were diagnosed with intrahepatic or extrahepatic CC by aspiration cytology between 1995 and 2004. Brush cytology specimens of extrahepatic CC were excluded. All diagnoses were confirmed as CC by clinical, imaging, and histopathologic findings and by chart review. Cytopathology files from 13 patients with CC diagnosed by FNA were retrieved. The male:female ratio was 5:8, and the patients ranged in age from 29 years to 74 years (mean age, 59 years). In 12 of 13 patients, aspirates were obtained by ultrasound guidance; and, in 1 patient, computed tomography guidance was used. Three patients had aspirates only, 10 patients also had core biopsies, and 1 patient had cell block preparations. The phenotypic distribution of CC according to the World Health Organization (WHO) histologic classification was 9 adenocarcinoma (intrahepatic), not otherwise specified (NOS) (69%); 2 gastric foveolar type (extrahepatic) CCs (15%); 1 intestinal type (extrahepatic) CC (8%); and 1 sarcomatous/spindle cell type (intrahepatic) CC (8%). One adenocarcinoma, NOS was well differentiated CC with bland tubular architecture, and one was pleomorphic. Ancillary histochemical and immunochemical stains were performed on 5 of 13 specimens, which included 4 core biopsies and 1 aspirate with Mucicarmine positivity (3 specimens), carcinoembryonic antigen positivity (3 specimens), and a cytokeratin 7 (CK7)-positive/CK20-negative pattern (2 specimens). The 1 sarcomatous/spindle cell type CC was chromogranin-negative and low molecular weight keratin (cell adhesion molecule 5.2)-positive, which excluded metastatic carcinoid. Classification of intrahepatic and extrahepatic CC in aspiration cytology specimens was achieved in a reliable manner concordant with the WHO histologic classification. Special types of CC with bland nuclear features posed a diagnostic challenge on cytologic evaluation, particularly the well differentiated CC with tubular architecture and the gastric foveolar type CC with mucin-producing tumor cells. The addition of core biopsy and/or ancillary studies, such as histochemical and immunochemical stains, were helpful in reaching the correct diagnosis.

Spanish experience in liver transplantation for hilar and peripheral cholangiocarcinoma.

To assess the real utility of orthotopic liver transplantation (OLT) in patients with cholangiocarcinoma, we need series with large numbers of cases and long follow-ups. The aim of this paper is to review the Spanish experience in OLT for hilar and peripheral cholangiocarcinoma and to try to identify the prognostic factors that could influence survival. Palliative treatment of nondisseminated irresectable cholangiocarcinoma carries a zero 5-year survival rate. The role of OLT in these patients is controversial, due to the fact that the survival rate is lower than with other indications for transplantation and due to the lack of organs. We retrospectively reviewed 59 patients undergoing OLT in Spain for cholangiocarcinoma (36 hilar and 23 peripheral) over a period of 13 years. We present the results and prognostic factors that influence survival. The actuarial survival rate for hilar cholangiocarcinoma at 1, 3, and 5 years was 82%, 53%, and 30%, and for peripheral cholangiocarcinoma 77%, 65%, and 42%. The main cause of death, with both types of cholangiocarcinoma, was tumor recurrence (present in 53% and 35% of patients, respectively). Poor prognosis factors were vascular invasion (P < 0.01) and IUAC classification stages III-IVA (P < 0.01) for hilar cholangiocarcinoma and perineural invasion (P < 0.05) and stages III-IVA (P < 0.05) for peripheral cholangiocarcinoma. OLT for nondisseminated irresectable cholangiocarcinoma has higher survival rates at 3 and 5 years than palliative treatments, especially with tumors in their initial stages, which means that more information is needed to help better select cholangiocarcinoma patients for transplantation.

Expression of matrix metalloproteinase-2 and -9 and tissue inhibitor of metalloproteinase-1 and -2 in intraductal and nonintraductal growth type of cholangiocarcinoma.

The intraductal growth (IG) type of cholangiocarcinoma has a better prognosis than the mass forming (MF) and periductal infiltrating (PI) types. Matrix metalloproteinase (MMP)-2 and MMP-9, regulated by tissue inhibitor of metalloproteinases (TIMP)-2 and TIMP-1, respectively, play important roles in the degradation of the basement membrane during tumor invasion. Alteration in MMPs and TIMPs may regulate the gross morphology of cholangiocarcinoma. MMP-2 and MMP-9 were analyzed in 35 cholangiocarcinomas and 4 normal livers with fresh tissue using zymography and real-time reverse transcription-polymerase chain reaction (RT-PCR), and expressions of MMP-2, MMP-9, TIMP-1, and TIMP-2 were evaluated in 76 cholangiocarcinomas by immunohistochemistry. Activity of MMP-2 and its active form were detected in 80% and 57% of cholangiocarcinomas respectively. The total MMP-2, active 62 kDa MMP-2, and MMP-2 mRNA increased 5.4 and 8.2 times, 4.4 and 10.9 times, and 2.9 and 5.8 times in the MF and PI types, respectively, compared to the IG type. The majority of MMP-9 was in the proform and active 82 kDa MMP-9 was detected in 9% of cholangiocarcinomas. MMP-9 revealed no significant difference in relation to the gross types. The balanced expressions of MMP-2/TIMP-2 and MMP-9/TIMP-1 were significantly decreased in the MF and PI types, compared to the IG type. In the normal and nonneoplastic livers, the expressions of MMP-2 and MMP-9 were very low without active forms. The activities of MMP-2 and loss of balanced expressions of MMP-2/TIMP-2 and MMP-9/TIMP-1 are suggested as playing important roles in invasive growth related to the gross type of cholangiocarcinoma.

Fluorodeoxyglucose PET imaging in the evaluation of gallbladder carcinoma and cholangiocarcinoma.

Our goal was to evaluate fluorodeoxyglucose (FDG) positron emission tomography (PET) in staging patients with biliary tract cancers. Fifty consecutive patients who underwent FDG-PET for suspected cholangiocarcinoma (n=36) or gallbladder carcinoma (n=14) were reviewed. Patients with cholangiocarcinoma were divided into two groups: group 1 had nodular type (mass=1 cm) (n=22) and group 2 had infiltrating type (n=14) cholangiocarcinoma. Thirty-one of 36 patients evaluated for cholangiocarcinoma had cholangiocarcinoma and five did not. Sensitivity was 85% for nodular morphology but only 18% for infiltrating morphology. Sensitivity for metastases was 65% but false negative for carcinomatosis in three of three patients. One false positive result occurred in a patient with primary sclerosing cholangitis who had acute cholangitis. Seven (58%) of 12 patients had FDG uptake along the tract of a biliary stent. FDG-PET led to a change in surgical management in 30% (11 of 36) of patients evaluated for cholangiocarcinoma because of detection of unsuspected metastases. Eleven of 14 patients with gallbladder carcinoma were newly diagnosed by cholecystectomy or another type of exploratory procedure, whereas three patients were undergoing follow-up. Nine had residual gallbladder carcinoma at the time of PET. Sensitivity for gallbladder carcinoma was 78%. Sensitivity for extrahepatic metastases was 50% in eight patients; six of them had carcinomatosis. These data suggest that PET is accurate in predicting the presence of nodular cholangiocarcinoma (mass>1cm) but was not helpful for the infiltrating type. PET was also helpful for detecting residual gallbladder carcinoma following cholecystectomy, but was not helpful in patients with carcinomatosis. Although FDG-PET led to a change in management in 30% of patients with cholangiocarcinoma, it must be interpreted with caution in patients with primary sclerosing cholangitis and with stents in place, as well as in those with known granulomatous disease.