Oncology
Resected biliary tract cancers: A novel clinical–pathological score correlates with global outcome

https://doi.org/10.1016/j.dld.2012.08.012Get rights and content

Abstract

Background

Biliary tract cancer presents a poor prognosis.

Aims

The objective of this study is to find clinical-laboratory parameters like prognostic factors to select patients who can benefit from surgery and post-operative treatments.

Methods

Between 2005 and 2010, 41 patients underwent radical surgery at our Institution.

A novel score was retrospectively calculated assigning a grade to the clinical-laboratory findings at diagnosis. 0 and 1 point were respectively assigned to the normal or abnormal parameter. Two groups were identified: SCORE 0 and SCORE 1.

Results

Patients with cholangiocarcinoma or Klatskin tumours or asymptomatic at diagnosis presented a significantly better overall survival (OS) than patients with different primary sites or who presented pain, jaundice or cholangitis. At univariate analysis, high levels of aspartate aminotransferase, alanine aminotransferase and CA19-9 before surgery, hyperbilirubinemia before and after surgery had a negative correlation with OS. A worse OS was observed in patients with a higher score (median OS in the “score 0” group = 30.79 months vs. median OS in the “score 1” = 17.98 months).

Conclusion

Our results suggest that pre and post-surgery clinical-laboratory parameters and the novel score, could be useful, especially for intrahepatic tumours, in predicting the outcome in patients undergoing surgery and in selecting patients to receive adjuvant therapy.

Introduction

Cancers of the biliary tract include cholangiocarcinoma, Klatskin tumour and gallbladder cancer. Patients with intrahepatic cholangiocarcinoma (cholangiocellular carcinoma) develop early metastasis and present a poor prognosis. Bile duct cancer differs from gallbladder cancer since it presents a similar incidence in males and females and a better survival. All cholangiocarcinomas show a slow growth, causing locally infiltration rather than metastasis. Gallbladder cancer is more frequent, with a poor survival due to the late diagnosis. Estimated new cases and deaths from gallbladder (and other biliary) cancer in the United States in 2011 are 9250 and 3300, respectively. In Italy, biliary tract cancer incidence accounts approximately 3000 new cases every year. It represents 0.8% of all tumours in males and 1.6% of all tumours in females [1].

Patients with tumours of the biliary tract can be asymptomatic or may present jaundice due to the obstruction of the biliary tree caused by the tumour, palpable mass in the right upper abdomen, abdominal lymphadenopathy, left supraclavicular adenopathy or fever.

Tumour marker CA19-9 can be significantly high both in cholangiocarcinoma and in gallbladder cancer. Serum carcinoembryonic antigen (CEA) alone has a low predictive value, while CA19-9 >100 U/ml has a sensitivity of 89% and a specificity of 86%. In a recent prospective study, serum CA19-9 was of clinical usefulness in the diagnosis of cholangiocarcinoma, as well as after radical resection and in monitoring the efficacy of the treatment. After curative resection, serum levels decrease from a preoperative level [2], [3]. It is important to notice that obstructive jaundice is frequently associated with false CA19-9 elevation. Therefore a cut-off value of 90–100 U/ml could be considered in order to increase sensibility of this marker in presence of jaundice [4].

Liver function tests are relevant as well. High levels of alkaline phosphatase and bilirubin are often related to cholestasis. In complete biliary ducts obstruction, serum bilirubin is markedly elevated. Serum alkaline phosphatase and gamma glutamyl transferase are also high, since they are markers of bile duct injury. Serum aspartate aminotransferase and alanine aminotransferase are usually only moderately elevated. Anaemia is usually present, while CEA and alpha fetoprotein (AFP) are usually normal.

Although radical surgical resection represents the only curative option, the 5-year survival rate, even in radically resected cases, approaches only as few as the 40% of all cases [5], [6], [7]. This may be due to the fact that adequate surgical margins may be difficult to achieve. Nevertheless significant increases in survival rates have been reported after curative surgery is attempted and only microscopic residual disease remains by a multimodal approach including radiotherapy. Thus survival in these patients ranges from 6 to 7 months after surgery alone and can be prolonged to longer than 12 months by a combined approach [8].

Negative prognostic factors after resection include positive surgical margins, lymph node metastasis, perineural invasion and portal vein and/or hepatic artery invasion. Prognostic factors after resection for gallbladder cancer also include the depth of mural invasion and extra-parietal invasion [9], [10], [11], [12].

The objective of this study is to find clinical and laboratory parameters that can be considered prognostic factors in order to select patients who can benefit from post-operative treatments.

Section snippets

Patients selection

The study includes all the consecutive patients who underwent radical surgery at Polytechnic University of Marche Region from January 2005 to December 2010 and who were then followed on a regular basis in a specific follow-up programme. Neither chemotherapy nor radiotherapy were administered before surgery in this series [13].

Methods

Recorded patient characteristics and clinical-laboratory features included: age, sex, symptoms at the diagnosis, site of tumour, type of surgery and laboratory exams

Results

Forty-one patients were included into the study. All the patients underwent radical surgery for cancer of the biliary tract, with negative margins after surgical resection.

No patients received adjuvant therapy.

Table 2 shows patients’ characteristics and Table 3 reports the results of laboratory exams.

Patients with cholangiocarcinoma or Klatskin tumours presented a significantly better OS (median OS = 30.8 months and 24.2 months, respectively) if compared with patients with gallbladder cancer or

Discussion

Our results suggest that a novel score, calculated from pre-operative clinical and laboratory findings at diagnosis, could represent an important parameter able to predict the outcome in patients undergoing surgery for biliary tract cancer. In particular in our experience, a worse OS was observed in patients with a higher score (SCORE 0 = ≤1 vs. SCORE 1 = >1).

In literature, other prognostic scores based on clinical–pathological features, have been investigated in different gastro-intestinal tumours

Conflict of interest statement

None of the authors have any financial disclosures.

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    These authors equally contributed to the manuscript.

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