Impact of specialized multi-disciplinary approach and an integrated pathway on outcomes in hilar cholangiocarcinoma
Introduction
Biliary malignancies constitute approximately 2% of all cancers found at autopsy, of which hilar or “Klatskin” tumours represent around 50–80% of these cases.1, 2, 3 At present, it is unclear whether there is a true increase in the incidence of hilar cholangiocarcinoma (HC), or additional cases are being identified with more accurate cross-sectional imaging being performed.
The overall 5-year survival rates following hepatic resection of HC varies from 20 to 40%.4, 5, 6, 7 Although surgery remains the only potential curative therapy, it is technically demanding due to the presence of locally advanced disease, proximity of the tumour to hilar vasculature and tumour biology. Various clinico-pathological variables have been shown to influence survival, including margin status, nodal status, tumour differentiation and peri-neural and/or vascular invasion.4, 7, 8, 9 However, the majority of patients with HC are unresectable at either presentation, following staging laparoscopy or during laparotomy. Criteria for unresectable disease include locally advanced tumours involving portal and hepatic vasculature, distant metastases and nodal metastases beyond the hepato-duodenal ligament. In addition, patients must have limited co-morbidities; as most cases require an extended hepatectomy against a background of cholangitis and obstructive jaundice.
The improved treatment of HC over the last decade is not only related to changes in surgical strategy, but also improvement in selection and pre-operative work-up of patients considered for curative resection. With the introduction of specialist multi-disciplinary team (MDT) management, this treatment process may contribute to better outcomes.10 The aim of this study was to assess the outcomes of patients with HC following such a specialist MDT approach.
Section snippets
Patients and methods
Patients with HC referred during an 11-year period from January 2001 to December 2012 were identified from a prospectively maintained hepatobiliary database and specialist multi-disciplinary recording system.
Patients that had potentially resectable and unresectable HC were included. In addition, intra-hepatic cholangiocarcinoma affecting the portal hilum (often termed peri-hilar cholangiocarcinoma) were included, as the treatment is similar and often difficult to differentiate from true HC.
Pre-operative evaluation
Collated data included patient demographics, surgery, histopathology analysis and outcome. Pre-operative assessment included multi-slice triple phase contrast-enhanced computer tomography (CT) scan of the thorax, abdomen and pelvis, and liver-specific contrast enhanced magnetic resonance imaging (MRI) of the liver (from 2008).
Pre-operative biliary drainage was considered in patients with obstructive jaundice. Biliary drainage of the future liver remnant was achieved endoscopically, percutaneous
Multi-disciplinary approach
All patients were discussed in a specialist MDT meeting that consisted of hepatobiliary surgeons, hepatologist, oncologist, radiologist and pathologist prior to surgery. Since 2008, an integrated care pathway was implemented, and jaundiced patients with a proximal biliary stricture were managed by a specialist MDT.
Surgical and post-operative details
Parenchymal transection was performed using the Cavi-Pulse Ultrasonic Surgical Aspirator (CUSA) or Kellyclasia. Intra-operative ultrasound was performed to confirm the findings of pre-operative imaging. The number of hepatic (Couinaud's) segments13 resected was determined by the procedure performed as stated in the Brisbane nomenclature.14 The type of surgical procedure was dependent on the resection of all macroscopic disease and achieving a clear resection margin, while preserving sufficient
Histo-pathological analysis
The Bismuth–Corlette classification11 was used to pre-operatively define tumour extension along the intra-hepatic bile ducts based on cross-sectional imaging. Intra-operatively, tumour extension and margins were examined by histo-pathological evaluation of frozen sections. The histological staging of the disease was determined according to the TNM classification following the criteria of the American Joint Committee on Cancer (AJCC).16 Tumour differentiation was graded as well, moderately and
Follow-up protocol
Patients were followed up in specialist hepatobiliary clinics. Following initial post-operative review at one month after discharge, all patients were seen in the outpatient clinic at 3, 6, 12, 18 and 24 months and annually thereafter. At each clinic review, blood tests were drawn for liver function tests and CA 19.9 levels. Patients underwent 6-monthly surveillance CT scan during the first two post-operative years, followed by annual CT scans thereafter.
Overall and disease-free survival data
Statistical analysis
Categorical data were analysed using the Pearson's chi-squared test. The Kaplan–Meier method was used to assess the actuarial survival and disease-free survival. Uni-variate analysis was performed to assess for a significant difference in clinico-pathological characteristics that influenced survival following resection. Statistical analyses were performed using the SPSS for Windows™ version 16.0 (SPSS Inc, Chicago, Ill, USA), and statistical significance was taken at the 5% level.
Results
During the study period, 345 patients with HC were referred and discussed at the unit's specialist MDT meeting, of which 244 patients were deemed unresectable on initial cross-sectional imaging (Fig. 1). One hundred and one patients considered potentially resectable on imaging underwent staging laparoscopy which subsequently excluded 18 (17.8%) patients due to locally advanced tumour or the presence of liver and/or peritoneal metastasis. Eighty-three patients underwent laparotomy, of which 57
Prognostic factors influencing survival outcome
Fourteen patients that underwent potentially curative surgery developed recurrent disease. The median disease-free survival was 16 (4–101) months. The presence of lymph node metastasis (p = 0.002) was the only predictor of poorer disease-free survival on uni-variate analysis [median survival N1 = 10 (5–87) months versus N0 = 21 (5–101) months, Table 3, Fig. 2].
The 1-, 3-, and 5-year overall survival was 73.5%, 49.6% and 39.5%, respectively in the surgical group. In comparison, the 1- and 3-year
Discussion
Due to both tumour proximity to the hilar vasculature and tumour biology, HC remains a surgical challenge. Nevertheless, surgical resection represents the only potentially curative option for these patients and improves long-term outcome. A radical resection with negative margins is the only factor with a demonstrated impact on outcome that can be influenced by the surgeon, and therefore should be the main aim of treatment.3
Whether there is a true increase in the incidence of HC, these patients
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2019, European Journal of Surgical OncologyCitation Excerpt :Surgery is the only effective curative option for cholangiocarcinoma, yielding 5-year survival rates of approximately 40% [12]. Our current resection rate for hilar cholangiocarcinomas of 19% is a modest, yet important advance on our previous figure of 16.5% published 4 years ago [12]. Most series agree that resection rates for cholangiocarcinoma are low but there is heterogeneity in resectability rates, a range of 10–40% of presenting patients being reported by a recent review [13].