Surgical management of cholangiocarcinoma

Biliary tract cancer affects approximately 7500 Americans each year. Tumors arising from the gallbladder are the most common; those of bile duct origin, or cholangiocarcinoma, are less frequently encountered, constituting approximately 2% of all reported cancers. Although cholangiocarcinoma can arise anywhere within the biliary tree, tumors involving the biliary confluence (i.e., hilar cholangiocarcinoma) represent the majority, accounting for 40 to 60% of all cases. Twenty to 30% of cholangiocarcinomas originate in the lower bile duct, and approximately 10% arise within the intrahepatic biliary tree and will present as an intrahepatic mass. Complete resection remains the most effective and only potentially curative therapy for cholangiocarcinoma. For all patients with intrahepatic cholangiocarcinoma and nearly all patients with hilar tumors, complete resection requires a major partial hepatectomy. Distal cholangiocarcinomas, on the other hand, are treated like all periampullary malignancies and typically require pancreaticoduodenectomy. Most patients with cholangiocarcinoma present with advanced disease that is not amenable to surgical treatment, and even with a complete resection, recurrence rates are high. Adjuvant therapy (chemotherapy and radiation therapy) has not been shown clearly to reduce recurrence risk.     

Mucin-producing cholangiocarcinoma: clinical experience of 24 cases in 16 years

OBJECTIVE: Mucin-producing cholangiocarcinoma (MPCC) is an uncommon biliary tract malignancy. This retrospective study was designed to investigate the clinical presentations, associated diseases, the value of tumor markers, and treatment and prognosis of MPCC. MATERIAL AND METHODS: The study included 24 MPCC cases (7 M, 17 F) from 132 histopathology-proven cholangiocarcinoma patients seen between 1988 and 2003. MPCC and non-mucin-producing cholangiocarcinoma (non-MPCC) were compared. RESULTS: Common clinical symptoms and signs included epigastric or right upper quadrant pain, fever and chills, jaundice, and anemia. Seventeen patients had mucobilia in surgical, cholangiographic, or CT findings. Biliary stones were found in 71% of MPCC patients. In detecting MPCC, a serum CA-19-9 level > 120 U/ml had 73% sensitivity, 41% specificity, 25% positive predictive value, 85% negative predictive value, and 48% accuracy in the 132 cholangiocarcinoma patients. The 1-, 2-, 3-, 4-, and 5-year survival rates were 44.3%, 33.8%, 28.1%, 21.1%, and 21.1%, respectively. Univariate analysis showed that tumor type (MPCC) was the only significant factor predicting survival when compared with non-MPCC patients in 5-year cumulative survival rates (21.1% versus 5.4%). MPCC patients receiving surgical resection had a prolonged median survival time (13 months versus 6 months) than those without resection. CONCLUSIONS: MPCC clinical presentations were similar to non-MPCC in Taiwan except for more jaundice, fever and chills. The major factor predisposing to MPCC was biliary stones. Using serum CA19-9 levels greater than 120 U/ml was a diagnostic aid to detecting MPCC patients. MPCC patients had a better prognosis than non-MPCC patients. The recommended treatment for MPCC is surgical resection.     

Cholangiocarcinoma

Cholangiocarcinoma is an uncommon adenocarcinoma with poor prognosis. Although the 1-year survival has increased over time, the 5-year survival has not shown any significant change (less than 5%). Cure can only be expected from surgical resection of early stage tumours but most patients initially present with advanced disease. Cancer cachexia, liver failure, and recurrent sepsis due to biliary obstruction are among the main causes of mortality.Patients’ prognosis is strongly related to radical surgery and complete resection is the most effective therapy; the location within the biliary tree (proximal versus distal) has no impact on survival when a complete resection is achieved despite the fact the rate of resectability is up to 70% in case of distal cancer and 15–20% for high bile ducts tumours. Prognosis of cholangiocarcinoma remains poor even with aggressive surgical therapy because of the high incidence of local or regional recurrence and distant metastasis.Based on these data many questions need an answer: is there a role for adjuvant chemotherapy or radiotherapy? Neoadjuvant treatments provide best results? There is a standard therapy in unresectable or metastatic cholangiocarcinoma?This report tries to answer to frequently asked questions that the readers are faced with their patients every day (from diagnostic procedures to palliative treatment) and tries to suggest useful information for their professional practice.     

Mucin-producing cholangiocarcinoma: Clinical experience of 24 cases in 16 years

Objective Mucin-producing cholangiocarcinoma (MPCC) is an uncommon biliary tract malignancy. This retrospective study was designed to investigate the clinical presentations, associated diseases, the value of tumor markers, and treatment and prognosis of MPCC. Material and methods The study included 24 MPCC cases (7 M, 17 F) from 132 histopathology-proven cholangiocarcinoma patients seen between 1988 and 2003. MPCC and non-mucin-producing cholangiocarcinoma (non-MPCC) were compared. Results Common clinical symptoms and signs included epigastric or right upper quadrant pain, fever and chills, jaundice, and anemia. Seventeen patients had mucobilia in surgical, cholangiographic, or CT findings. Biliary stones were found in 71% of MPCC patients. In detecting MPCC, a serum CA-19-9 level >120 U/ml had 73% sensitivity, 41% specificity, 25% positive predictive value, 85% negative predictive value, and 48% accuracy in the 132 cholangiocarcinoma patients. The 1-, 2-, 3-, 4-, and 5-year survival rates were 44.3%, 33.8%, 28.1%, 21.1%, and 21.1%, respectively. Univariate analysis showed that tumor type (MPCC) was the only significant factor predicting survival when compared with non-MPCC patients in 5-year cumulative survival rates (21.1% versus 5.4%). MPCC patients receiving surgical resection had a prolonged median survival time (13 months versus 6 months) than those without resection. Conclusions MPCC clinical presentations were similar to non-MPCC in Taiwan except for more jaundice, fever and chills. The major factor predisposing to MPCC was biliary stones. Using serum CA19-9 levels greater than 120 U/ml was a diagnostic aid to detecting MPCC patients. MPCC patients had a better prognosis than non-MPCC patients. The recommended treatment for MPCC is surgical resection.     

Role of fluorescence in situ hybridization in diagnosing cholangiocarcinoma in indeterminate biliary strictures

Background and Aim

Brush cytology, the conventional method to diagnose cholangiocarcinoma, has been plagued by low diagnostic sensitivity and false‐negative results. This paper aims to study the clinical utility of fluorescence in situ hybridization (FISH) in enhancing identification of malignant biliary strictures.

Methods

Brush cytologic specimens collected from endoscopic retrograde cholangiopancreatography for biliary strictures in a tertiary hospital in Singapore from March 2013 to July 2015 were examined by FISH technique using UroVysion probe set in this study.

Results

Thirty patients were chosen with five patients having multiple FISH performed due to indeterminate results. The diagnoses for biliary strictures were 13 (43.3%) cholangiocarcinomas, seven (23.3%) pancreatic cancers, seven (23.3%) benign biliary strictures, and three (10%) primary sclerosing cholangitis. Conventional brush cytology had sensitivity of 53.8% with specificity of 82.4%. FISH had sensitivity of 30.8% with specificity of 100%. When FISH results were interpreted in cases with negative or atypical brush cytology, two patients had positive FISH results and cholangiocarcinomas. Based on this pilot study, FISH increased sensitivity of brush cytology in detection of cholangiocarcinoma from 53.8% to 69.2% while preserving specificity of 82.4%.

Conclusion

Compared with conventional cytology with low sensitivity, FISH may help to increase sensitivity on top of brush cytology while maintaining high specificity.     

Liver transplantation for primary sclerosing cholangitis

Although the development of interventional radiology and biliary surgical techniques has prolonged the survival time of patients with primary sclerosing cholangitis, liver transplantation remains the only effective treatment for patients with primary sclerosing cholangitis with liver cirrhosis. Several prognostic survival models have been establised for this disease, and the efficacy of actual liver transplantations has been reported in comparison with these survival models. One- and 5-year actuarial patient survivals after liver transplantation for primary sclerosing cholangitis were shown to be greater than and approximately equal to 90%, respectively. An association with cholangiocarcinoma is the most adverse factor affecting survival after liver transplantation for primary sclerosing cholangitis, while the association of inflammatory bowel disease or previous bili-ary surgery does not adversely affect the outcome of the liver transplantation. Recurrent sclerosing cholangitis is an important issue for posttransplant patients with primary sclerosing cholangitis, and occurs in 10%—20% of such patients. Although our understanding of recurrent sclerosing cholangitis is still in the early stages, its potential occurrence indicates the need for a longer follow-up period after liver transplantation.     

Cholangiocarcinoma： A 7-year experience at a single center in Greece

AIM： To evaluate survival rate and clinical outcome of cholangiocarcinoma. METHODS： The medical records of 34 patients with cholangiocarcinoma, seen at a single hospital between the years 1999-2006, were retrospectively reviewed. RESULTS： Thirty-four patients with a median age of 75 years were included. Seventeen （50%） had painless jaundice at presentation. Sixteen （47.1%） were perihilar, 15 （44.1%） extrahepatic and three （8.8%） intrahepatic. Endoscopic retrograde cholangiography （ERCP） and/or magnetic resonance cholangiography （MRCP） were used for the diagnosis. Pathologic confirmation was obtained in seven and positive cytological examination in three. Thirteen patients had co-morbidities （38.2%）. Four cases were managed with complete surgical resection. All the rest of the cases （30） were characterized as non-resectable due to advanced stage of the disease. Palliative biliary drainage was performed in 26/30 （86.6%）. The mean follow-up was 32 mo （95% CI, 20-43 too）. Overall median survival was 8.7 mo （95% CI, 2-16 mo）. The probability of 1-year, 2-year and 3-year survival was 46%, 20% and 7%, respectively. The survival was slightly longer in patients who underwent resection compared to those who did not, but this difference failed to reach statistical significance. Patients who underwent biliary drainage had an advantage in survival compared to those who did not （probability of survival 53% vs 0% at 1 year, respectively, P = 0.038）. CONCLUSION： Patients with cholangiocarcinoma were usually elderly with co-morbidities and/oradvanced disease at presentation. Even though a slight amelioration in survival with palliative biliary drainage was observed, patients had dismal outcome without resection of the tumor.     

Altered Mucin Gene Expression in Stone-Containing Intrahepatic Bile Ducts and Cholangiocarcinomas

Neoplastic transformation of epithelial cells is commonly associated with alterations in the synthesis and structures of mucin. Mucin protein epitopes and mRNA levels were frequently altered in adenocarcinomas compared to corresponding normal tissues. Clinically, hepatolithiasis has been regarded as a risk factor for cholangiocarcinoma. The aims of this study were to determine the possible alteration of mucin gene expression in stone-containing intrahepatic bile ducts and cholangiocarcinomas and to try to predict whether or not hepatolithiasis has a predisposition to development of cholangiocarcinoma. In situ hybridization with DIG-tailed oligonucleotides was performed on sections of paraffin-embedded tissues of stone-containing intrahepatic bile ducts, cholangiocarcinomas, and normal controls to identify the expression of MUC2, MUC3, MUC4, MUC5B, and MUC5AC in nonneoplastic and neoplastic biliary epithelium. The findings showed that (1) while multiple diverse mucin genes were expressed in the biliary epithelium, MUC3 and MUC5B mRNA were the main mucin genes expressed in the biliary epithelium of stone-containing intrahepatic bile ducts and normal controls; (2) absent or decreased expression of MUC2, MUC3, and MUC5B of mRNA was found in cholangiocarcinomas in contrast to nonneoplastic biliary epithelium; and (3) increased expression of MUC4 and MU5AC of mRNA was found in cholangiocarcinomas and the biliary epithelium, especially for dysplastic cells of stone-containing intrahepatic bile ducts compared with normal controls. In this study, using in situ hybridization we demonstrated that neoplastic transformation of the biliary epithelium is accompained by alterations in mucin gene expression, the altered mucin gene expression in dysplastic cells of stone-containing intrahepatic bile ducts may reflect a higher potential for malignant transformation in these cells, and it could be a precursor of cholangiocarcinoma in the presence of hepatolithiasis.     

Bile duct carcinoid tumors: an uncommon disease but with a good prognosis?

Carcinoid tumors of the biliary tract are exceedingly uncommon. We report 3 cases of primary carcinoid tumors of the biliary tract, which are compared to the reported patients in the literature and to the patients' data with other types of biliary malignancies in our experience. SETTING: Retrospective analysis in a single academic institution. From a consecutive series of 79 resected tumors of the biliary tract between 1979 and 2002, 3 patients were found to suffer from primary carcinoid tumors (3.8%). There were 2 males and one female patient, with a mean age of 56 years old (range: 46-73), younger than other malignant biliary cancer cases. Clinical presentation included obstructive jaundice in 2 patients. There were no signs of diarrhea or carcinoid syndrome. Location of the tumor included the extrahepatic bile duct in all patients. Two of these patients had a polypoid tumor obstructing the bile duct. The disease was localized in 2 patients, but with liver metastases in the remaining patient. Final diagnosis was achieved on final pathological examination in 2 patients, but preoperative endoscopic biopsies allowed correct diagnosis of nature and tumor staging by octreotide scintigraphy in one patient. Radical resection was achieved in 2 patients with long-term cure at 8.5 and 9.5 years, respectively. A high-risk patient with a small residual liver metastasis after resection is still alive and disease-free under LAR Octreotide SC administration at 17 months postoperatively. The median survival time for patients suffering from carcinoid tumors was 102 months while it was 33 months for patients suffering from cholangiocarcinomas in our experience. Carcinoid tumors of the biliary tract are exceedingly rare. Preoperative diagnosis is uncommon but possible by endoscopic biopsies. Radical resection seems to be associated with a longer survival than classical cholangiocarcinoma.     

Liver transplantation for cholestatic liver disease

Opinion statement Liver transplantation is an effective form of therapy for patients with end-stage cholestatic disease that improves both survival and quality of life. Liver transplantation is very effective for the treatment of intractable pruritus but less effective for the treatment of lethargy. Survival rates are good (more than 70% at 5 years); these patients are at greater risk of developing acute and chronic rejection and are more likely to require long-term immunosuppression. Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) recur in the graft. Recurrent PSC may be difficult to differentiate from secondary sclerosing cholangitis, but it recurs in up to 60% of patients at 5 years and may reduce graft survival. PBC recurrence, noted in up to 40% of patients at 10 years, has little effect on graft survival with respect to cancers. Patients with PSC are at greater risk of both colonic cancer (which may be reduced by ursodeoxycholic acid) and cholangiocarcinoma. Diagnosis of cholangiocarcinoma before transplantation usually contraindicates transplantation. The main challenges facing liver transplantation are the need to expand the donor pool and the need to find immunosuppressive regimens with fewer long-term toxicities.     

Liver transplantation for primary sclerosing cholangitis: timing, outcome, impact of inflammatory bowel disease and recurrence of disease

Over the past decade, the outcome of liver transplantation in primary sclerosing cholangitis (PSC) patients with end-stage liver disease has improved significantly with many centres reporting 1-year patient and graft survival of 90-97% and 85-88%, respectively. Based on these results, liver transplantation has emerged as the treatment of choice for PSC patients. Specific complications related to PSC remain problematical. Inflammatory bowel disease (IBD) occurs in 70% of patients, and there is a distinctly increased risk of colorectal neoplasia both pre- and post-transplantation. Furthermore, symptoms related to IBD post-transplantation can become severe and lead to the need for proctocolectomy. Cholangiocarcinoma remains a major risk facing the PSC patient and develops in 15-30% of patients. Markers to detect the early neoplastic changes of cholangiocarcinoma are not available. To date, outcome following liver transplantation in PSC patients who have associated cholangiocarcinoma has been dismal. However, those patients who are found to have an incidental cholangiocarcinoma have an acceptable low incidence of recurrence of disease. To assess optimal timing of liver transplantation, natural history risk scores have been developed and utilized. Utilizing such risk scores, estimated survival for the individual PSC patient can be obtained. Finally, there is an increased incidence of both acute and chronic rejection, hepatic artery thrombosis and biliary stricturing in PSC patients undergoing liver transplantation. A late rise in serum alkaline phosphatase level is almost always indicative of biliary stricturing and recurrence of disease. Approximately 20% of patients followed for 5 years or more will have recurrence of PSC documented both on cholangiography and histology.     

Photodynamic therapy in patients with non-resectable hilar cholangiocarcinoma: 5-year follow-up of a prospective phase II study

BACKGROUND: Median survival of patients with non-resectable hilar cholangiocarcinoma is 3 to 6 months, even after biliary drainage. Therefore, a single-arm phase II study was conducted (July 1996 to October 1998) to investigate the effect of local photodynamic therapy; a significant improvement in survival (74%) was noted at 6 months. The present study is an analysis of the long-term follow-up for patients enrolled in that phase II study. METHODS: Five-year follow-up data for the 23 patients enrolled in the original prospective study were analyzed by using Kaplan-Meier log-rank analysis. RESULTS: Median survival after treatment was 11.2 months for patients without distant metastases (M0) and 9.3 months for all patients (M0+M1). The 1-year, 2-year, 3-year, and 4-year survival rates were estimated to be 47%, 21%, 11% and 5%, respectively, for patients with stage M0 cholangiocarcinoma, and 39%, 17%, 9%, and 4%, respectively, for patients with stages M0 and M1. Of the patients who died, 73.9% (n=17) were because of tumor progression; 26.1% (n=6) died as a result of cholangitis (n=4), septic shock (n=1), or appendicitis/peritonitis (n=1). For all patients, except one with diffuse liver metastases, there was improvement in cholestasis, performance, and quality of life, which was maintained for an extended period. CONCLUSIONS: This 5-year follow-up study confirms that photodynamic therapy is safe and effective for non-resectable hilar cholangiocarcinoma, although it does not prevent progression of the disease.     

Photodynamic therapy and Klatskin tumour: an overview

The prognosis of patients with an unresectable bile duct cancer is poor. In 60-70% of patients, cholangiocarcinoma is located in the hepatic duct bifurcation and known as Klatskin tumour. Surgical resection offers the only chance for 5-year survival, but less than 20% are surgical candidates. Patients with unresectable cholangiocarcinoma are treated with biliary drains, but commonly die of liver failure or cholangitis due to biliary obstruction within 6 to 12 months. Chemotherapy and/or radiotherapy have not been evaluated in randomized, controlled trials. Photodynamic therapy (PDT) is a new and promising locoregional treatment, the aim of which is to destroy tumour cells selectively. PDT involves the injection of a photosensitizer followed by percutaneous or endoscopic direct illumination of the tumour with light of a specific wavelength. In recent non-randomized studies of small numbers of patients with unresectable cholangiocarcinoma, PDT induced a decrease in serum bilirubin levels, improved quality of life and a slightly better survival. Other non-randomized trials failed to show clinical benefits. Recently, the first prospective, randomized controlled study with PDT in a selected group of non-resectable cholangiocarcinoma patients was stopped prematurely. The improvement in survival in the PDT-randomized patients was so impressive that it was considered to be unethical to continue randomization. However, further studies are awaited in unselected patients with unresectable cholangiocarcinoma before PDT can be considered as the standard adjuvant therapy.     

Surgical treatment of hilar cholangiocarcinoma in the “new era”: the Nagoya University experience

Objective

To review our surgical experience with hilar cholangiocarcinoma in the “new era.”

Methods

The medical records of 428 patients with hilar cholangiocarcinoma who underwent treatment between 2001 and 2008 at the First Department of Surgery, the Nagoya University Hospital, were retrospectively reviewed.

Results

Of the 428 patients, 298 (70%) underwent surgical resection (R0, n = 220; R1, n = 70; R2, n = 8). Portal vein resection was performed in 111 (37%) patients, and hepatic artery resection was performed in 53 (18%) patients. Several different types of postoperative complications occurred in a total of 129 (43%) patients and led to 6 (2%) deaths. Of the 298 resected tumors, 206 (69%) were extrahepatic type tumors, and the remaining 92 (31%) were intrahepatic type tumors. Using the Bismuth classification criteria, we identified 15 (5%) type I, 21 (7%) type II, 120 (40%) type III, and 142 (48%) type IV tumors. The overall 1-, 3-, and 5-year survival rates for all 298 patients were 77, 49, and 42%, respectively. The survival rates were highest among the 197 patients with pM0 disease who underwent R0 resection. Patients in this subgroup had a 5-year survival rate of 52%. The 5-year overall survival rate for the 55 patients with pM0 disease who underwent R1 resection was 32%. The survival rate for patients who had pM1 disease and/or underwent R2 resection was the worst of all the subgroups, but was nonetheless significantly better than that of patients with unresectable tumors. The survival rate for patients who underwent vascular resection and reconstruction was unexpectedly better, with 5-year survival of >20%.

Conclusions

The surgical approach to hilar cholangiocarcinoma has become more challenging in the new era. Nevertheless, surgical outcomes have been improved, with decreased morbidity and mortality rates being observed. Long-term survival has also steadily improved. These findings indicate that biliary surgeons should use an aggressive surgical strategy to treat this intractable disease.     

Magnetic resonance imaging of cholangiocarcinoma

Cholangiocarcinoma arises from the bile ducts and is the most common primary malignancy of the biliary tree. Cholangiocarcinoma is classified according to its growth pattern: mass-forming, periductal-infiltrating, or intraductal-growing type. The majority of cholangiocarcinomas occur at the common hepatic duct (CHD) and its bifurcation, also referred to as Klatskin's tumor, but they also can occur in more peripheral branches within the hepatic parenchyma. Microscopically, cholangiocarcinoma represents an adenocarcinoma with a glandular appearance arising from the epithelium of the bile ducts. On magnetic resonance (MR) images, cholangiocarcinomas appear hypointense on T1-weighted images, and hyperintense on T2-weighted images. Central hypointensity can be seen on T2-weighted images and correspond to fibrosis. On dynamic MR images, cholangiocarcinomas show moderate peripheral enhancement followed by progressive and concentric filling in the tumor with contrast material. Pooling of contrast within the tumor on delayed MR images is suggestive of peripheral cholangiocarcinoma. The role of MR imaging in hilar cholangiocarcinoma is to confirm/reach a diagnosis and to assess resectability. Hilar cholangiocarcinoma shows the same signal intensity pattern of peripheral tumors both on T1- and T2-weighted images. On magnetic resonance cholangiopancreatography (MRCP) images, hilar cholangiocarcinoma appears as a moderately irregular thickening of the bile duct wall (>/=5 mm) with symmetric upstream dilation of the intrahepatic bile ducts. The aim of preoperative investigation in Klatskin tumors typically requires the evaluation of the level of biliary obstruction, the intrahepatic tumor spread, and the vascular involvement; it also needs to show any atrophy-hypertrophy complex. Because of its intrinsic high tissue contrast and multiplanar capability, MR imaging and MRCP are able to detect and preoperatively assess patients with cholangiocarcinoma, investigating all involved structures such as bile ducts, vessels and hepatic parenchyma. The main reason for surgical/imaging discrepancy is represented by the microscopic diffusion along the mucosa and in the perineural space.     

Surgical management of perihilar cholangiocarcinoma: a Khon Kaen experience

Cholangiocarcinoma is the most common cancer in the northeast of Thailand. Most of the patients present when the disease is in an advanced stage. Improvement of preoperative diagnoses and surgical techniques provide more satisfactory results. Herein we reviewed our 30‐year experience in management of perihilar cholangiocarcinoma in Khon Kaen northeast Thailand. Between 1982 and 2012 we reviewed four specific studies of perihilar cholangiocarcinoma in Srinagarind Hospital, Khon Kaen, Thailand. The first study focused on advanced surgical pathology and palliative surgery, which were used to treat obstructive jaundice cholangiocarcinoma patients. Long‐term survival in this study was rare with a one‐year survival of just 15%. The second study was conducted on 30 consecutive cases of perihilar cholangiocarcinoma who presented with obstructive jaundice without preoperative biliary drainage. All the patients underwent major liver resection with bilio‐enteric reconstruction. Perioperative mortality was 6.7% without a 5‐year survival. The third study aimed to analyze the survival rates and factors affecting survival in extrahepatic CCA patients following surgical treatment at Srinagarind Hospital and concluded that resection margins are an important prognostic factor. The last study objective was the analysis of curative surgical attempt in 99 consecutive perihilar cholangiocarcinoma and results showed that R0 resection could improve long‐term survival. We evaluated four studies of perihilar cholangiocarcinoma in Srinagarind Hospital, Khon Kaen, Thailand from 1982–2012. Viewed chronologically there has been a progressive improvement of diagnosis and surgical treatment during the past 30 years. Despite these advances the 5‐year survival rate remains unsatisfactorily low. Future improvement of patient selection and surgical techniques can lead to a greater survival rate for patients.     

Primary sclerosing cholangitis and cholangiocarcinoma

Primary sclerosing cholangitis (PSC), a cholestatic liver disease characterized by fibrosing inflammatory damage of the biliary tree, is a risk factor for cholangiocarcinoma (CCA). Indeed, the prevalence of CCA in patients with PSC ranges from 7 to 13%. The major challenges of CCA in PSC patients relate to lack of methods for early diagnosis and the absence of effective treatment. Early diagnosis of CCA in PSC is delayed because its clinical presentation can mimic benign dominant biliary strictures. Moreover, biliary and serum tests to diagnose development of CCA in PSC are limiting, although the use of advanced cytologic techniques for aneuploidy and chromosomal aberrations are promising in this regard. As a result, current therapies do not extend survival with the exception of protocol liver transplantation available to a selected group of patients. Future studies should emphasize deciphering the sequence of events that transform the inflammatory changes of the biliary tree to cancer. Only then will chemoprevention, early diagnosis, and therapy of CCA in patients with PSC improve.     

Detection of ras gene mutations of primary hepatic malignant tumors by polymerase chain reaction and direct sequencing method

Ras genes are converted to active oncogenes by point mutations occurring in either codon 12, 13 or 61. We used polymerase chain reaction and direct sequence method for the analysis of these mutations. We examined 13 hepatocellular carcinomas, 8 cholangiocarcinomas, 2 hepatoblastomas and 1 biliary cystadenocarcinoma. Of these tumors, ras gene mutations were detected solely in cholangiocarcinomas. Cholangiocarcinoma showed a high incidence of K-ras gene mutation. Among 8 patients with cholangiocarcinoma, the mutation was detected at codon 12 in 4 and at codon 61 in 1. The incidence of K-ras gene mutation was especially high in the hilar type of cholangiocarcinoma as compared with the peripheral type.     

Preoperative evaluation with T-staging system for hilar cholangiocarcinoma

AIM： To investigate the clinical value of T-staging system in the preoperative assessment of hilar cholangiocarcinoma. METHODS： From March 1993 to January 2006, 85 patients who had cholangiocarcinoma diagnosed by operative tissue-biopsy were placed into one of three stages based on the new T-staging system, and it was evaluated the resectability and survival correlated with T-staging. RESULTS： The likelihood of resection and achieving tumor-free margin decreased progressively with increasing T stage （P 〈 0.05）. The cumulative 1-year survival rates of T1, T2 and T3 patients were 71.8%, 50.8% and 12.9% respectively, and the cumulative 3-year survival rate was 34.4%, 18.2% and 0% respectively; the survival of different stage patients differed markedly （P 〈 0.001）. Median survival in the hepatic resection group was greater than in the group that did not undergo hepatic resection （28 mo vs 18 mo; P 〈 0.05）. The overall accuracy for combined MRCP and color Doppler Ultrasonagraphy detecting disease was higher than that of combined using CT and color Doppler Ultrasonagraphy （91.4% vs 68%; P 〈 0.05 ）. And it was also higher in detecting port vein involvement （90% vs 54.5%; P 〈 0.05）.CONCLUSION： The proposed staging system for hilar cholangiocarcinoma can accurately predict resectability, the likelihood of metastatic disease, and survival. A concomitant partial hepatectomy would help to attain curative resection and the possibility of longterm survival. MRCP/MRA coupled with color Doppler UItrasonagraphy was necessary for preoperative evaluation of hilar cholangiocarcinoma.（OR = 2.46, 95% CI = 0.98-6.14）, and a significantly elevated risk of developing esophageal cancer among alcohol drinkers among alcohol drinkers （OR = 9.86, 95% CI = 3.10-31.38）. CONCLUSION： ADH2 and ALDH2 genotypes areassociated with esophageal cancer risk. ADH2＊1 allele and ALDH2＊2 allele carriers have a much higher risk of developing esophageal cancer, especially among alcohol drinkers.     

Indication for Postoperative Adjuvant Therapy in Biliary Carcinoma Based on Analysis of Recurrence and Survival After Surgical Resection

Postoperative adjuvant therapy is mandatory for biliary carcinoma because of its unfavorable prognosis. The aim of this study was to evaluate the indication for postoperative adjuvant therapy in biliary carcinoma. The charts of 139 consecutive patients with biliary carcinoma (37 ampullary carcinomas, 36 distal carcinomas, 38 carcinomas of the gallbladder, and 28 hilar cholangiocarcinomas) who underwent surgical resection were retrospectively reviewed. Recurrence rates and survival rates after surgery were analyzed. Of the 139 carcinomas, the recurrence rates of International Union Against Cancer (UICC) stages IA, IB, IIA, IIB, and III cancers were 9%, 20%, 60%, 83%, and 100%, respectively. The recurrence rates of UICC stages II and III cancers were significantly higher than that of UICC stage I cancer (82% vs 13%, P < 0.001). The 5-year survival rates for patients with UICC stages IA, IB, IIA, IIB, and III cancers were 85%, 75%, 36%, 20%, and 0%, respectively. The 5-year survival rates for UICC stages II and III cancers were significantly lower than that for UICC stage I cancer (21% vs 82%, P < 0.001). Postoperative adjuvant therapy should be given to patients with UICC stages II and III biliary carcinomas because of their high rate of recurrence and the poor prognosis.