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Klatskin Tumors and the Accuracy of the Bismuth-Corlette Classification [American Surgeon, The]
(American Surgeon, The Via Acquire Media NewsEdge) The Bismuth-Corlette (BC) classification is the current preoperative standard to assess hilar cholangiocarcinomas (HC). The aim of this study is to evaluate the accuracy, sensitivity, and prognostic value of the BC classification. Data of patients undergoing resection for HC were analyzed. Endoscopic retrograde cholangiography and standard computed tomography were undertaken in all cases. Additional 3D-CT-reconstructions, magnetic resonance imaging, and percutaneous transhepatic cholangiography were obtained in selected patients. A systematic review and meta-analysis of the literature was performed. Ninety patients underwent resection of the hilar bile duct confluence, with right or left hemihepatectomy in 68 instances. The overall accuracy of the BC classification was 48 per cent. Rates of BC under- and over-estimation were 29 per cent and 23 per cent, respectively. The addition of MRI, SD-CT-reconstructions, or percutaneous transhepatic cholangiography improved the accuracy to 49 per cent (P = 1.0), 53 per cent (P = 0.074), and 64 per cent (P < 0.001), respectively. Lowest sensitivity rates were for BC Type IIIA/IIIB tumors. Meta-analysis of published BC data corresponding to 540 patients did not reach significance. The BC classification has low accuracy and no prognostic value in cases of HC undergoing resection.
MORE THAN 50 YEARS after the first reported resections1' 2 and over 40 years after Klatskin' s description,3 the treatment of hilar cholangiocarcinoma remains a major challenge. Lesions tend to be slow growing with low metastatic propensity, but diagnosis is usually coincident with obstructive jaundice.4 Surgical resection remains the only curative approach, with optimal results achieved in cases of tumor free margins (RO resections).5"15 The "no-touch" right trisectionectomy with en bloc portal vein and bile duct resection is reported as an independent prognostic factor for survival after curative resection.16 Extended resections however, entail physiologically viable remnant parenchyma to avoid postoperative liver failure. Furthermore, because cholestasis negatively impacts liver regeneration, preoperative drainage by endoscopie retrograde cholangiography (ERC) or percutaneous transhepatic cholangiography (PTC) is the "standard" approach.
The Bismuth-Corlette (BC) classification17· 18 provides preoperative assessment of local spread, and classifies Klatskin tumors as Type I (below the confluence of the left and right hepatic ducts), Type ? (reaching the confluence), Types G?? and IÏB (occluding the common hepatic duct and the right or left hepatic ducts, respectively), and Type IV (involving the confluence and both the right and left hepatic ducts). Despite its worldwide application however, little information on its predictive accuracy is available.
The purpose of our study was to evaluate: 1) the overall accuracy of the BC classification, 2) the impact of various imaging/endoscopic methods on the accuracy of the BC classification, 3) the sensitivity of the BC classification according to tumor types, and 4) the prognostic accuracy of the BC classification according to a meta-analysis of the literature.
Patients and Methods
Data of 90 patients who underwent surgical resection for Klatskin tumor at the Department of General, Visceral, and Transplantation Surgery, University Hospital Essen, Germany within a 9-year period were prospectively collected and retrospectively analyzed for the purposes of this study.
All patients underwent preoperative ERC drainage of the biliary system, and contrast enhanced spiral computer tomography (CT) for tumor staging. PTC, thin-slice (1 mm) CT, and/or MRI/magnetic resonance cholangiography were also performed in selected instances on special request of the leading surgeon. Cases were grouped and registered in our database according to the BC classification. Patients with extrahepatic métastases or severe parenchymal damage (cirrhosis, fibrosis, or >50% steatohepatitis/steatosis) were excluded from the study. Because mini-laparoseopy or exploratory laparoscopy were only sporadically performed in our center for hilar cholangiocarcinomas (in n = 4 and n = 2 cases, respectively), patients undergoing laparoscopy were excluded from this analysis.
Resected specimens were evaluated by pathology and classified according to Bismuth-Corlette. The accuracy of the BC classification was determined by comparing preoperative clinical (endoscopic/imaging) and pathological findings. The best diagnostic tool was picked out. The accuracy of the clinical classification was further determined by addressing the individual BC Types.
Search Strategy and Selection Criteria
In December 2009, PubMed, the Cochrane Library, Embase, Scopus, and Mediine were accessed and searched to estimate the outcome of patients with hilar cholangiocarcinoma undergoing resection. Searched terms included the Mesh terms "Klatskin's Tumor," "cholangiocarcinoma," "bile duct neoplasms," "hepatectomy," "survival analysis," and "outcome assessment," as well as the following free text search: "hilar cholangiocarcinoma," "Klatskin tumor," "extrahepatic cholangiocarcinoma," "cholangiocarcinoma," "bile duct cancer," "liver resection," "hepatectomy," "tumor recurrence," "patient outcome," "survival," and "prognostic factors," both independently and in multiple combinations. English and German language papers published between 1985 and 2008 were considered.
Only original works reporting data on the prognostic value of the BC classification according to survival analysis for patients with Klatskin tumors were included. Reviews, editorials, case reports, technical reports, as well as studies reporting mixed data on hilar cholangiocarcinomas, intrahepatic cholangiocarcinomas, gallbladder carcinomas, or combination therapies such as liver resection and transplantation were excluded from the review. In cases of reports originating from the same center, only the most recent or most informative one was included in this study.
Statistical Analysis
Mean values with standard deviation and median values with range were used for numerical data. The significance of differences was assessed with ?2 test and Kruskal-Wallis one way analysis of variance on ranks. For the discriminant analysis among "standard" evaluation with CT/ERC and additional modality (MRT (magnetic resonance imaging), 1 mm CT, or PTC) the nonparametric McNemar's test was applied. Differences of P < 0.05 were considered to be statistically significant. Statistical analyses were performed using StatXact (Cytel Software Corp., Cambridge, MA).
For combined P values, the truncated product method19· 20 was used with truncation point at 0.05. This allowed for the inclusion in the meta-analysis of non significant results reported without specific P values.
Results
A total of 90 patients (36 women and 54 men) with a mean age of 60.83 ±11.75 years underwent resection of the hilar bile duct confluence at our center. In 68 instances, it was combined with a right or left hemihepatectomy.
The BC classification had an overall accuracy of 48 per cent (43/90 cases). Its under- and over-estimation rates were 29 per cent (26/90) and 23 per cent (21/90), respectively.
When diagnosis was optimized with MRI, thin slice CT (1 mm), or PTC, the overall rates increased to 49 per cent (P = 1.000), 53 per cent (P = 0.074), and 64 per cent (P < 0.001), respectively (Table 1). Although PTC was additionally applied to only a small group of patients in our series (n = 11), a fact representing a limitation to the interpretation of these results, it seems to offer the best accuracy, as the BC classification concerns.
Preoperative sensitivity was 50 per cent for BC Type I, 100 per cent for Type ?, and 57 per cent for Type IV tumors (Table 2). The worst sensitivity rates were for BC Type IUA and Type IIIB tumors (33% and 35%, respectively) (P = 0.082 by Kruskal-Wallis one way analysis of variance on ranks).
Literature Review
There were 427 clinical studies screened (Fig. 1). Three hundred and thirty two were excluded for mixed data or lack of original results. Of the remaining 95 studies, 66 with no univariate analysis of prognostic factors were also excluded. P values corresponding to eight of the 29 remaining studies9· 21~27 were analyzed, for an overall cohort of 540 patients (Table 3). These P values represented univariate statistical results for patient survival according to the parameter "Bismuth-Corlette classification" . Because none of the separate P values was significant, no multivariate analysis was performed. The univariate analysis of P values by truncated product method (TPM) for the Bismuth-Corlette classification did not reach significance (P = 1), implying that this classification has no prognostic relevance when assessing patients with hilar cholangiocarcinomas.
Discussion
Although surgical resection remains the treatment of choice for hilar cholangiocarcinoma,9' 21~29 its transmural invasion of bile ducts and extension into adjacent structures limits the ability to achieve free margins (RO resection). Furthermore, classification of Klatskin tumors according to the tumor node metastasis (TNM) staging system of the Union International Contre le Cancer (commonly used to stage most malignant tumors) is almost impossible. The BC classification provides a preoperative assessment of the magnitude of the resection that will be necessary to encompass the longitudinal intraductal extension of Klatskin tumors. Patients with Type ? or larger tumors are usually referred to tertiary centers for further evaluation and treatment.
The cross sectional imaging study routinely used in patients with obstructive jaundice is computed tomography. Several other modalities have been tried to improve the information obtained preoperatively. Thinslice (1 mm) CT with 3-dimentional reconstruction and virtual resections has proven very useful with other malignancies.30 However, its impact in the assessment of Klatskin tumors remains up to now unexplored. ERC allows for diagnostic and drainage interventions, and can be performed in nonspecialized centers. Magnetic resonance cholangiography is the current imaging technique of choice for bile duct cancer. It is noninvasive, allows for visualization of both obstructed and nonobstructed ducts, and provides information on the extent of intra and extra ductal involvement.31 PTC is becoming increasingly popular as a drainage procedure.24 It also allows clear visualization of the biliary tree without the risk of ascending infections. An imaging modality that is lacking hi this report is ultrasound evaluation. In experienced hands, ultrasound examination with duplex scanning may provide reliable information concerning segmental involvement of Klatskin tumors.
Resectability and curative resection rates range from 28 per cent to 95 per cent and from 14 per cent to 95 per cent, respectively.28 Such variability can be attributed at least in part, to a heterogeneous patient selection, multiple preoperative imaging techniques, and a broad range of study dates. Apart from proximal and distal extent of tumor into the intrahepatic biliary tree, resectability of Klatskin tumors is determined by intra and extrahepatic métastases, involvement of portal vein and/or hepatic artery, volume of the future remnant liver, and the possibility of portal vein embolization and complete preoperative biliary drainage of at least the part of the liver to be preserved; all these factors, which are reported to play an important prognostic role in tumor recurrence and patient survival, are not incorporated into the BC classification.
The goal of this study was to examine the accuracy of the BC classification and its impact on the management of patients with Klatskin tumors. According to our observations, the BC classification had an accuracy rate <50 per cent, with a sensitivity for Type ???/??? tumors in the 30 per cent range. The accuracy may be significantly better with the addition of PTC. The meta-analysis of data corresponding to 540 patients (shown hi Table 3) confirmed that the BC classification had no prognostic value. Although the BC classification provides the first preoperative assessment of the possibility and extent of surgical resection, decision for laparotomy cannot be based on it, and further preoperative workup has to be made.
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ANDREAS PAUL, M.D.,* GERNOT M. KAISER, M.D.,* ERNESTO P. MOLMENTI, M.D., M.B.A./1
TOBIAS SCHROEDER, M.D.,t SPIRIDON VERNADAKIS, M.D.,* ARZU OEZCELIK, M.D.,*
HIDEO A. BABA, M.D. VITO R. CICINNATI, M.D.,§ GEORGIOS C. SOTIROPOULOS, M.D.*
From the Departments of *General, Visceral, and Transplantation Surgery and +Diagnostic and Interventional
Radiology and Neuroradiology, the ^Institute of Pathology and Neuropathology, and the ^Department of
Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany, and the ^Department of
Surgery, North Shore University Hospital, Manhasset, New York
Address correspondence and reprint requests to Georgios C. Sotiropoulos, M.D., Department of General, Visceral, and Transplantation Surgery, University Hospital Essen, Hufelandstraße 55, 45122 Essen, Germany. E-mail: georgios.sotiropoulos@uni-due.de or gsotirop@yahoo.com.
(c) 2011 Southeastern Surgical Congress
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