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ORIGINAL ARTICLE
Year : 2015  |  Volume : 1  |  Issue : 1  |  Page : 1-5

Prognostic Value of Bismuth Typing and Modified T-stage in Hilar Cholangiocarcinoma


Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, China

Date of Submission24-Dec-2014
Date of Acceptance01-Feb-2015
Date of Web Publication16-Feb-2015

Correspondence Address:
Prof. Xiongying Miao
Department of General Surgery, Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha 410011, Hunan
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2395-3977.151467

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  Abstract 

Aim: Hilar cholangiocarcinoma (HCC) has a very poor prognosis. Surgical resection is a radical treatment option for this disease. However, it is still difficult to cure, and prognostic traits are ambiguous. Evaluation of the tumor typing and staging may elucidate effective prognosis and provide helpful advice for clinical surgeon. This study aimed to analyze the prognostic value of tumor typing and staging in HCC.
Methods: We conducted a retrospective review of 85 patients with HCC undergoing surgical resections procedures at the Second Xiangya Hospital in Hunan Province between 2002 and 2012. The Bismuth type, modified T-stage, postoperative complications, survival time, and other clinical manifestations associated with the surgical treatment were analyzed.
Results: Patients were classified according to Bismuth typing: Subtype I (12 cases), Subtype II (4 cases), Subtype IIIa (3 cases), Subtype IIIb (16 cases), and Subtype IV (50 cases). Patients were classified according to the T staging: Stage T1 (19 cases), Stage T2 (5 cases), and Stage T3 (61 cases). Based on data collected from 67 patients who completed the follow-up survey, both the Bismuth type and modified T-stage were significantly correlated with survival time (each P = 0.01).
Conclusion: The majority of our patients with HCC were characterized as Subtype IV in Bismuth typing and Stage T3 in modified T-stage. Both Bismuth typing and modified T-stage showed prognostic value in HCC. Compared with Bismuth typing, modified T-stage is a better indicator of the resectability of HCC.

Keywords: Bismuth typing, clinical value, Hilar cholangiocarcinoma, modified T-stage


How to cite this article:
Yi S, Cui X, Xiong L, Deng X, Pei D, Wen Y, Miao X. Prognostic Value of Bismuth Typing and Modified T-stage in Hilar Cholangiocarcinoma. Cancer Transl Med 2015;1:1-5

How to cite this URL:
Yi S, Cui X, Xiong L, Deng X, Pei D, Wen Y, Miao X. Prognostic Value of Bismuth Typing and Modified T-stage in Hilar Cholangiocarcinoma. Cancer Transl Med [serial online] 2015 [cited 2019 Nov 19];1:1-5. Available from: http://www.cancertm.com/text.asp?2015/1/1/1/151467


  Introduction Top


Hilar cholangiocarcinoma (HCC), also known as proximal cholangiocarcinoma or high cholangiocarcinoma, is a type of human malignancy occurring in the biliary tract. [1],[2],[3],[4] It is frequently found in the common hepatic duct, left and right hepatic ducts and the hepatic duct confluence. Since 1965, when Klatskin first reported and systematically characterized this disease, it has also been called Klatskin tumor. [5],[6] Bismuth typing has long been used for clinical subtyping of HCC. [7] This system consists of the following four categories: Subtype I-involvement of the common hepatic duct; Subtype II-involvement of the common hepatic duct and confluence; Subtype III-involvement of the common hepatic duct, confluence, and the right hepatic duct (Subtype IIIa) or the left hepatic duct (Subtype IIIb); Subtype IV-involvement of the common hepatic duct, confluence, and both the left and the right hepatic ducts [Figure 1]. However, long-term studies have indicated that the resectability and prognosis of HCC are closely related to portal vein involvement and liver lobe atrophy, largely because of the complex local anatomical structure of HCC and the aggressive nature of the tumor cells. [8],[9] Therefore, Burke et al.[10] and Jarnagin et al.[11] further proposed use of T-stage and modified T-stage, respectively, for clinical subtyping of HCC [Table 1].
Figure 1: Schematic of Bismuth classification of Hilar cholangiocarcinoma: Type I, confined to common hepatic duct; Type II, confined to the bifurcation of common hepatic duct; Type III, affecting the bifurcation of common hepatic duct with spread of tumor to right (IIIa) or left (IIIb) duct; and Type IV, affecting the bifurcation of the common hepatic duct with spread of tumor to both hepatic ducts

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Table 1: Criteria of modified T-stage

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  Methods Top


This retrospective study included 85 patients with HCC who received surgical treatment in the Second Xiangya Hospital in Hunan Province from 2002 to 2012. For all participants, Bismuth typing and modified T-stage were determined based on the results of clinical examinations and information from operative logs. A follow-up survey was conducted for all participants through telephone interview. Patient survival was monitored on a monthly basis. SPSS version 17.0 software (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. The Chi-square test was used to analyze categorical data. The survival curve was plotted according to the Kaplan-Meier method. The log-rank test was used to analyze differences in survival times. In all cases, differences with P < 0.05 were considered as statistically significant.


  Results Top


Clinical subtyping of patients

Among the 85 patients with HCC participating in this study, by Bismuth typing, 12 (14.1%) were characterized as Subtype I, 4 (4.7%) were Subtype II, 3 (3.5%) were Subtype IIIa, 16 (18.8%) were Subtype IIIb, and 50 (58.8%) were Subtype IV.

According to the modified T-stage proposed by the American Memorial Sloan-Kettering Cancer Center in 1998 and revised in 2001 [Table 1], among the 85 patients, 19 (22.3%) were diagnosed as Stage T1, 5 (5.9%) were Stage T2, and 61 (71.8%) were Stage T3.

Bismuth typing, T-stage, and prognosis

Among the 85 patients who received surgical treatment, 67 completed the follow-up survey, with a follow-up rate being 78.8%. The shortest survival time was 3 days postoperatively, whereas the longest was 45 months postoperatively (the patient remained alive and in good health at the end of this study). The median survival time was 6.6 months. The 6-month survival rate, 1-year survival rate, and 2-year survival rate were 58.2%, 32.8%, and 13.4%, respectively.

Bismuth typing

Because there were only four cases of Subtype II among the 85 participants, Subtype I and Subtype II were combined for further analysis. The Kaplan-Meier method was used for single factor analysis. The median survival time of patients of Subtype I and II, Subtype III, and Subtype IV was 15.5 months, 6.3 months, and 6.0 months, respectively (P < 0.05) [Table 2]. These results indicate the prognostic value of Bismuth typing. Further pairwise comparison showed that the survival time of Subtype I and II cases was shorter than that of Subtype III cases and Subtype IV cases, with statistical significance (P = 0.002 and P = 0.015, respectively) [Table 3] and [Figure 2]. There was no significant difference between the survival time of Subtype III and Subtype IV (P > 0.05).
Figure 2: (a) Bismuth Subtype I and II vs. III. In the first 2 months, Bismuth Subtype I and II and Subtype III had similar trend. Then the survival rate of Subtype I and II decreased dramatically, reaching the bottom (0% survival) in the 18th month. In contrast, the survival rate of Subtype III declined more moderately and was higher than that of Subtype I and II at the matching times. The longest survival is 42 months for Subtype III Figure (b) Bismuth Subtype I and II vs. IV. In the second and 3rd month, the survival rate of Bismuth Subtype IV was 3% higher than that of Subtype I and II at the matching times, but declined drastically, reaching 0% in the 28th month. In contrast, the survival rate of Subtype I and II began to exceed that of Subtype IV from the 3rd month, with the longest survival time of 42 months

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Table 2: Analysis of patient survival based on Bismuth typing

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Table 3: Analysis of patient survival based on Bismuth typing using the pairwise comparison


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Among the 67 patients who completed the follow-up survey, 13 were Subtype I and II, of whom 8 received radical resection (61.5%); 16 were Subtype III, of whom 5 received radical resection (31.3%); and 38 were Subtype IV, of whom 9 received radical resection (23.7%). The results showed that the radical resection rate was inversely correlated with the rank of Bismuth typing. According to the Chi-square test, there was no statistically significant difference in the radical resection rate between Subtype I and II cases and Subtype III cases, or between Subtype III cases and Subtype IV cases. However, the radical resection rate was significantly different between Subtype I and II cases and Subtype III cases (χ2 = 6.246, P = 0.006) [Table 4].
Table 4: Chi-square test for the radical resection rate of patients categorized by Bismuth typing using the pairwise comparison

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Modified T-stage

For the 67 patients who completed the follow-up survey, the Kaplan-Meier method was used for single factor analysis. The median survival time of Stage T1, Stage T2, and Stage T3 cases was 15.0 months, 6.7 months, and 5.7 months, respectively (P < 0.05) [Table 5]. These results indicate the prognostic value of modified T-stage. Further pair-wise comparison showed that the survival time of Stage T1 cases were significantly longer than those of Stage T2 and Stage T3 cases (P = 0.005 and P = 0.021, respectively). However, no statistically significant difference in survival time was observed between Stage T2 cases and Stage T3 cases (P > 0.05) [Table 6] and [Figure 3].
Figure 3: (a) Stage T1 vs. T2. Both stages (T1 and T2) survived 100% in the first 3 months. However, the longevity of Stage T2 was quite short. The survival rate declined markedly by 60% in the beginning of the 4th month and further fell to 0% in the following 2 months. In contrast, patients with Stage T2 survived 100% until the 7th month. The survival rate fell dramatically by 30% in the 8th month, and declined gradually afterwards with the longest survival time of 36 months. (b) Stage T1 vs. T3. Both stages (T1 and T3) survived 100% in the first 2 months. For the patients with Stage T3, the survival rate decreased markedly in the following period until the 10th month, then fell moderately, with the longest survival of 42 months. Those with T1 survive 100% in the first 7 months, and then lost 30% of the members in the following 2 months. Afterwards, the survival rate of Stage T1 declined gradually, but higher than that of Stage T3 at the matching times, with the longest survival time of 36 months

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Table 5: Analysis of patient survival based on modified T-stage

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Table 6: Analysis of patient survival based on modified T-stage using the pairwise comparison

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Among the 67 patients who completed the follow-up survey, 14 were diagnosed as Stage T1, of whom 12 received radical resection (85.7%); 5 were Stage T2, of whom 2 received radical resection (40.0%); and 48 were Stage T3, of whom 8 received radical resection (16.7%). The results showed that the radical resection rate was inversely correlated with the rank of modified T-stage. According to the Chi-square test, there was statistically significant difference in the radical resection rate between Stage T1 cases and Stage T2 cases, and between Stage T1 cases and Stage T3 cases (P = 0.046 and P = 0.013, respectively). However, no significant difference in the radical resection rate was observed between Stage T2 and Stage T3 cases [Table 7].
Table 7. Chi-square test for the radical resection rate of patients categorized by modified T-stage using the pairwise comparison

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  Discussion Top


During the past decades, our concepts of HCC have changed significantly. [12] Bismuth typing is performed according to the infiltrative growth pattern of extrahepatic cholangiocarcinoma, which mostly progresses along the bile duct wall from top to bottom. [13] Some surgeons searched for a criterion for HCC resection in order to obtain better survival. [14],[15],[16] Bismuth typing was first proposed in 1975 and was modified in 1992. [17],[18] This system can reflect the anatomical region of the tumor and has been used to guide the selection of surgical approaches in clinical practice. [19],[20],[21] However, it is difficult to accurately determine the substage of HCC by Bismuth typing.

When Jarnagin et al.[11] initially investigated the clinical value of modified T-stage in HCC prognosis, he proposed that modified T-stage was not only correlated with resectability, the negative rate of incisal margin, and the radical resection rate of a tumor, but also associated with the survival time. However, Zervos et al.[22] argued that modified T-stage was not able to provide references for the outcome of radical resection and it was not significantly correlated with postoperative survival time. Later, Chen et al.[23] conducted a retrospective analysis on 99 patients with HCC and found that modified T-stage was negatively correlated with the radical resection rate, but positively correlated with the outcome of combined portal vein resection. They also found that patients of Stage Tl and Stage T2 were all characterized as Subtype I, II and III by Bismuth typing in terms of tumor localization. In addition, several studies showed that patients with HCC who received a radical resection often required combined hepatectomy, or even extended hepatectomy. [6],[7],[24],[25] Generally speaking, patients with HCC of Bismuth Subtype II and above need a combined hepatectomy. [14],[15],[16],[26]

The results of this study demonstrate that Bismuth typing and modified T-stage could serve as postoperative prognostic factors for HCC, particularly in cases of Bismuth Subtype II and above. More specifically, we found that the survival time of Subtype I and II cases was significantly shorter than that of Subtype III and Subtype IV cases. However, no statistically significant difference in the radical resection rate was observed between Subtype I and II and Subtype III, or between Subtype III and Subtype IV. Nevertheless, the radical resection rate of Subtype I and II was significantly different from that of Subtype IV. These results indicate that Bismuth typing is not an ideal indicator of the resectability of HCC.

When the patients were categorized based on modified T-stage, we found that the survival time of Stage T1 cases was significantly longer than that of Stage T2 cases and Stage T3 cases, whereas no significant difference was observed between Stage T2 and Stage T3. This result indicated that the survival time of HCC patients with a higher level of modified T-stage was dramatically shorter than that of Stage T1 patients. Similarly, we also found that the radical resection rate of Stage T1 cases was significantly higher than that of Stage T2 and Stage T3 cases, whereas no statistically significant difference in the radical resection rate was observed between Stage T2 and Stage T3 cases. This result leads us to believe that the radical resectability of HCC patients with a higher modified T-stage declines dramatically compared with that of Stage T1 patients. This probably reflects the fact that the Stage T2 and T3 patients usually suffered from unilateral or contralateral portal vein involvement and homolateral or contralateral hepatic atrophy, as well as vascular involvement, which significantly increased the difficulty of radical resection. Because hepatic atrophy could lead to hepatic failure after radical resection, the radical resection rate was lower in this patient population.

In conclusion, our results indicated that both Bismuth typing and modified T-stage could serve as prognostic factors in HCC, particularly for patient survival. However, compared with Bismuth typing, modified T-stage can better reflect the resectability of HCC, most likely because modified T-stage considers not only the anatomical characteristics of the tumor, but also portal vein involvement, hepatic lobe atrophy, and other factors influencing HCC resectability. Previously, in most cases, pathological T-stage was confirmed by exploring the bile duct during the surgery. Recently, the diagnostic accuracy of CT and MRCP has improved [27] together with an increase in the power of endoscopic retrograde cholangiopancreatography, [28],[29],[30],[31] and T-stage can now be determined before the operation, thereby facilitating preoperative evaluation of tumor resectability. It is noteworthy that there is still room for improvement in the substage system; for example, the involvement of local hepatic artery and lymph nodes, and the degree of local infiltration and metastasis may not be accurately reflected in the current system. [32],[33],[34] Therefore, further investigation on a large scale is warranted to improve this staging system for clinical application in HCC prognosis.

 
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