Indian Journal of Cancer
Home  ICS  Feedback Subscribe Top cited articles Login 
Users Online :1584
Small font sizeDefault font sizeIncrease font size
Navigate here
  Search
 
  
Resource links
 »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
 »  Article in PDF (379 KB)
 »  Citation Manager
 »  Access Statistics
 »  Reader Comments
 »  Email Alert *
 »  Add to My List *
* Registration required (free)  

 
  In this article
 »  Abstract
 » Introduction
 » Patients And Methods
 » Results
 » Discussion
 » Conclusions
 »  References
 »  Article Figures
 »  Article Tables

 Article Access Statistics
    Viewed1347    
    Printed55    
    Emailed0    
    PDF Downloaded120    
    Comments [Add]    

Recommend this journal

 

  Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 54  |  Issue : 1  |  Page : 57-62
 

Metastasectomy for recurrent or metastatic biliary tract cancers: A single center experience


1 Department of Internal Medicine, Division of Hematology-Oncology, Gachon University Gil Medical Center, Incheon, Korea
2 Department of Surgery, Gachon University Gil Medical Center, Incheon, Korea

Date of Web Publication1-Dec-2017

Correspondence Address:
Dr. D B Shin
Department of Internal Medicine, Division of Hematology-Oncology, Gachon University Gil Medical Center, Incheon
Korea
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.219581

Rights and Permissions

 » Abstract 

PURPOSE: To assess efficacy or long-term result of metastasectomy for recurrent or metastatic biliary tract carcinoma (BTC), we conducted a retrospective review of the outcomes of metastasectomy for recurrent or metastatic BTCs, comprising intrahepatic cholangiocellular carcinoma (IHCCC), proximal and distal common bile duct cancer (pCBDC and dCBDC), gallbladder cancer (GBC), and ampulla of Vater cancer (AoVC). PATIENTS AND METHODS: The clinicopathological features and outcomes of BTC patients who underwent surgical resection for the primary and metastatic disease at the Gachon University Gil Medical Centre from 2003 to 2013 were reviewed retrospectively. RESULTS: We found 19 eligible patients. Primary sites were GBC (seven patients, 37%), IHCCC (five patients, 26%), dCBDC (three patients, 16%), pCBDC (two patients, 11%), and AoVC (two patients, 11%). Eight patients (42%) had synchronous metastasis whereas 11 (58%) had metachronous metastasis. The most common metastatic site was liver (nine patients, 47%), lymph node (nine patients, 47%), and peritoneum (three patients, 16%). Nine patients (47%) achieved R0 resection, whereas four (21%) and six (32%) patients had R1 and R2 resection, respectively. With a median follow-up period of 26.7 months, the estimated median overall survival (OS) was 18.2 months (95% confidence interval, 13.6–22.9 months). Lower Eastern Cooperative Oncology Group performance status (P = 0.023), metachronous metastasis (P = 0.04), absence of lymph node metastasis (P = 0.009), lower numbers of metastatic organs (P < 0.001), normal postoperative CA19-9 level (P = 0.034), and time from diagnosis to metastasectomy more than 1 year (P = 0.019) were identified as prognostic factors for a longer OS after metastasectomy. CONCLUSIONS: For recurrent or metastatic BTCs, metastasectomy can be a viable option for selected patients.


Keywords: Biliary tract cancer, metastasectomy, metastasis, prognosis


How to cite this article:
Park I, Kim Y S, Sym S J, Ahn H K, Kim K K, Park Y H, Lee J N, Shin D B. Metastasectomy for recurrent or metastatic biliary tract cancers: A single center experience. Indian J Cancer 2017;54:57-62

How to cite this URL:
Park I, Kim Y S, Sym S J, Ahn H K, Kim K K, Park Y H, Lee J N, Shin D B. Metastasectomy for recurrent or metastatic biliary tract cancers: A single center experience. Indian J Cancer [serial online] 2017 [cited 2020 Mar 31];54:57-62. Available from: http://www.indianjcancer.com/text.asp?2017/54/1/57/219581



 » Introduction Top


Biliary tract carcinomas (BTCs) comprising intrahepatic cholangiocellular carcinoma (IHCCC), proximal and distal common bile duct cancer (pCBDC and dCBDC), gallbladder cancer (GBC), and ampulla of Vater cancer (AoVC) are relatively rare cancers;[1] however, high mortality and incidence rates are still evident in some countries, including Central and Eastern Europe, Japan, Chile, India, and Korea.[2]

Complete surgical resection is the only chance for a cure; however, a limited number of patients present with resectable disease. Unfortunately, even after surgical resection, recurrence is frequently reported. Prognosis for recurrent or metastatic BTC is still poor, with a median overall survival (OS) of around 1 year, even with the best treatment option.[3]

Metastasectomy, resection of distant metastasis, has been increasingly adopted in some types of cancers, and it is associated with prolonged relapse-free survival (RFS) and even cure in prudently selected patients. Some examples of cancers in which metastasectomy is actively performed are colorectal cancer [4],[5] (hepatic metastasis and pulmonary metastasis), soft tissue sarcoma [6] (pulmonary metastasis), and renal cell carcinoma [7] (pulmonary metastasis).

Efficacy or long-term result of metastasectomy for recurrent or metastatic BTC is not well established. Aggressive surgical attempts for advanced GBC have been reported several times;[8],[9],[10],[11],[12],[13],[14],[15] however, most of these reports included patients with locally advanced GBC rather than metastatic GBC. Regarding metastasectomy in BTC, to the best of our knowledge, only a small number of cases involving a very limited number of patients have been reported;[16],[17],[18],[19],[20],[21] therefore, the efficacy of the surgical resection of metastasis in BTC remains unclear.

Against this background, we retrospectively reviewed the outcomes of metastasectomy for recurrent or metastatic BTC in a single tertiary referral center hospital.


 » Patients And Methods Top


Patients

The medical records of consecutive patients with BTCs (IHCCC, pCBDC, dCBDC, GBC, and AoVC) who were treated with surgery, chemotherapy, radiotherapy, or best supportive care at the Gachon University Gil Medical Centre from 2003 to 2013 were reviewed retrospectively. In these patients, the selection criteria for analysis were as follows: Histologically confirmed BTC, synchronous (M1 according to the American Joint Committee on Cancer 7th edition) or metachronous (recurrent) metastatic disease, and surgical resection of primary and metastatic sites. To be eligible for analysis, patients also had to have a proper baseline and follow-up image workup data before and after metastasectomy. Patients treated with metastasectomy for symptom palliation only were not included in the analysis.

Data collection

Clinicopathological data including age, sex, Eastern Cooperative Oncology Group performance status (ECOG PS), date of diagnosis, tumor histology, surgery, pathological stage, completeness of metastasectomy (R0, R1, or R2), metastatic site, prior treatment before metastasectomy, and laboratory data when metastasectomy was employed were collected. R0 is defined as no residual tumor, while R1 and R2 are defined as a microscopic residual tumor and macroscopic residual tumor, respectively. A comprehensive review of the preoperative baseline radiographic images and the follow-up radiographic images were performed. Preoperative images were usually performed within a month prior to metastasectomy, and postoperative disease status was evaluated by chest X-ray or chest computed tomography (CT) and CT of the abdomen and pelvis every 3–6 months. Those who received postoperative chemotherapy and/or radiotherapy, tumor responses were assessed every 2–3 months by CT. The type of subsequent treatment after metastasectomy and survival after metastasectomy were also reviewed. This study was approved by the institutional review board of Gil Medical Center (GBIRB2014-340).

Statistical analyses

Baseline patient characteristics and the outcomes of metastasectomy were evaluated using descriptive statistics. The primary objectives of this study were OS from the date of metastasectomy. Descriptive statistics were used for reporting the baseline patient characteristics. Kaplan–Meier estimates were used in the analysis of time-to-event variables. RFS and OS were defined as the time from the date of metastasectomy to the date of recurrence and death from any cause, respectively. Time-to-metastasectomy (TTM) was defined as the time from the date of surgery for a primary site to the date of the metastasectomy. Univariable analysis with log-rank test was performed for determination of the predictive and prognostic role of clinical factors (including age, sex, primary site, disease status, previous treatment before metastasectomy, resection status of metastasectomy, site of resection, and laboratory values, etc.) associated with OS or RFS. Statistical analyses were performed using the SPSS version 19.0 (SPSS Inc., Chicago, IL, USA) and P < 0.05 (two-sided) was considered statistically significant.


 » Results Top


Patient characteristics

We found 19 eligible patients from 284 consecutive patients who were managed for BTCs from 2003 to 2013. The baseline characteristics of 19 patients meeting the selection criteria are shown in [Table 1]. The median age of patients was 57 (range: 27–68), and 58% of patients were female. Primary sites were GBC (seven patients, 37%), IHCCC (five patients, 26%), dCBDC (three patients, 16%), pCBDC (two patients, 11%), and AoVC (two patients, 11%) in order. Most patients had adenocarcinoma (95%), and eight patients (42%) had synchronous metastasis and 11 patients (58%) had metachronous metastasis. Most patients had good ECOG PS before metastasectomy as more than 70% had ECOG PS 0-1. The most common metastatic site was liver (nine patients, 47%), lymph node (nine patients, 47%), and peritoneum in the form of limited peritoneal implantation without evidence of disseminated peritoneal seeding (three patients, 16%).
Table 1: Patient characteristics (n=19)

Click here to view


Outcomes of metastasectomy

The clinical characteristics and outcome of metastasectomy are shown in [Table 2]. Nine patients (47%) achieved R0 resection, while four (21%) and six (32%) patients had R1 and R2 resection, respectively. Of the six patients with R2 resection, four cases were due to bulky or severely adhesive lymph node metastasis, and two cases were due to metastases in other organs (multiple small lung masses in one case and multiple bone metastases in another). There was no occurrence of metastasectomy-related death within 1 month after surgery. Seventeen patients received postoperative chemotherapy consisting of 5-FU or gemcitabine-based chemotherapy with or without platinum. For the 13 patients with no grossly residual tumor (R0 or R1 resected), 10 patients experienced disease recurrence at the data cutoff, with a median RFS of 9.4 months (95% confidence interval [CI], 7.8–11.0 months). At the time of this analysis, 13 out of 19 patients had died. With a median follow-up period of 26.7 months, the estimated median OS was 18.2 months (95% CI, 13.6–22.9 months) [Figure 1].
Figure 1: The overall survival curve for all patients (n = 19). With a median follow-up duration of 26.7 months, median survival of patients was 18.2 (95% confidence interval, 13.6–22.9 months)

Click here to view
Table 2: Clinical characteristics and outcomes of metastasectomy (n=19)

Click here to view


Prognostic factors and characteristics of patients with longer overall survival

For patients who achieved R0 or R1 resection, predictive factors for RFS were explored using the log-rank test; however, no clinicopathologic factor was proved to be relevant to better PFS. For all patients who underwent metastasectomy, prognostic factors for OS were also explored. Lower ECOG PS (P = 0.023), metachronous metastasis (P = 0.04), absence of lymph node metastasis (P = 0.009), lower numbers of metastatic organs (P< 0.001), normal postoperative CA19-9 level (P = 0.034), and TTM more than 1 year (P = 0.019) were identified as prognostic factors for a longer OS after metastasectomy [Table 3]. Primary tumor location did not show an association with OS (P = 0.717). When categorizing patients according to favorable risk group (four or more prognostic factors) and poor risk group (three or less prognostic factors), OS of the favorable risk group was better with statistical significance, with a median OS of 23.0 months (95% CI, 16.1–30.0) versus 13.5 months (95% CI 8.3–18.6) (P = 0.003, [Figure 2]).
Figure 2: Kaplan–Meier curve according to risk group. The overall survival of the favorable risk group (n = 14) was significantly better than that of the poor risk group (n = 5), with a median overall survival of 23.0 months (95% confidence interval, 16.1–30.0) versus 13.5 months (95% confidence interval 8.3–18.6) (P = 0.003)

Click here to view
Table 3: Log-rank test to determine prognostic factors of overall survival after metastasectomy

Click here to view



 » Discussion Top


In the current study, we found 19 patients with metastatic or recurrent BTC who underwent metastasectomy. Median OS was 18.2 months (95% CI, 13.6–22.9 months), and patients with lower ECOG PS, metachronous metastasis, absence of lymph node metastasis, lower numbers of metastatic organs, normal postoperative CA19-9 level, or TTM more than 1 year had longer OS after metastasectomy.

The previous reports of aggressive surgery in advanced GBC mostly included stage IVA and only a small fraction of stage IVB. It appears that aggressive surgery resulted in long-term survival in a very selected population if curative resection is possible and a number of metastases is limited.[11],[12],[14],[15] Some reports on metastasectomy for BTC include resection of adrenal metastasis from IHCCC,[19] resection of solitary hepatic recurrence of IHCCC,[20] and resection plus radiotherapy for two patients with locoregional failure of main hepatic duct carcinoma.[21] To date, data are insufficient to draw a conclusion regarding whether or not metastasectomy is helpful for patients with recurrent or metastatic BTC.

In a real world practice, clinicians are often faced with a dilemma when patients with BTC present with a single or limited number of metastases. Because the high-level evidence is lacking, recommendation of metastasectomy is not usual. On the other hand, referring to some previous reports on metastasectomy, some selected patients can survive for a lengthy time by the benefit of metastasectomy. For definitive confirmation of the efficacy of metastasectomy, the conduct of a prospective randomized controlled trial comparing metastasectomy with no metastasectomy is needed; however, the rarity of disease and difficulties in patient recruitment have precluded such a trial from being conducted. In fact, even in colorectal cancer, in which metastasectomy is performed very widely, no randomized controlled trial comparing surgery with no surgery has been reported. Despite no prospective randomized trials as evidence supporting metastasectomy from colorectal cancer is mounting,[22] metastasectomy is now a standard of care when feasible, and indication for metastasectomy is expanding with the passage of time.

Recent data on hepatic metastasectomy from colorectal cancer metastasis in the United States and Canada have demonstrated 10-year disease-free survival of 15–25%, which is much better than the survival on even the best systemic chemotherapy during that period.[22] Likewise, pulmonary metastasectomy for soft tissue sarcoma achieved a 3- and 5-year OS rate of approximately 45% and 35%, respectively, which is better than that for patients who did not undergo resection.[6],[23] Lessons from such solid malignancies have shed light on the value of surgical resection in metastatic disease from other malignancies, and metastasectomy strategy could be adopted for advanced BTC with caution.

Because there will be a sparse chance for the conduct of a randomized controlled trial on metastasectomy in BTC, clinicians can make a decision regarding whether or not to perform metastasectomy based on extrapolated criteria from previous reports. In general, metastasectomy is preferred in the following situations: Possibility of complete resection, small number of metastatic lesions (single metastasis or oligometastases rather than multiple metastases), no unresectable metastases in other organs, and good general condition of the patient.

In a previous report on aggressive surgery for BTC, some clinicopathologic features were described as good prognostic factors; low preoperative carcinoembryonic antigen,[11] adjuvant chemotherapy,[11] curative resection,[11],[15] isolated liver metastasis,[14] absence of lymph node metastasis,[15] absence of vascular resection,[15] or absence of hepatoduodenal ligament invasion.[15] In the current study, patients with good ECOG PS, metachronous metastasis, absence of lymph node metastasis, lower numbers of metastatic organs, normal postoperative CA19-9 level, or TTM more than 1 year were depicted as good prognostic factors for longer OS after metastasectomy. Patients in the favorable risk group who had four or more good prognostic factors achieved significantly prolonged OS after metastasectomy. We could not perform multivariable analysis due to a small number of included patients; however, we believe that our results can be helpful in the suggestion of some future criteria for metastasectomy in BTC.

There have been some suggestions that BTC is not a single entity of disease but a heterogeneous group of diseases with different prognoses [24] and biology [25] according to the primary site. Therefore, metastasectomy can have an important role in some diseases while not in others. In addition, after metastasectomy, when visible masses are completely resected, the role of postoperative chemotherapy and/or radiotherapy is not known. In our study, primary site and postmetastasectomy treatment did not affect OS; however, we could not draw a firm conclusion due to the limitation of this study. In the future, if metastasectomy becomes a treatment option for at least some subsets of patients with advanced BTC, outcome differences among primary sites and the role of postoperative treatment should be verified.

There are several limitations in this study. The current study includes only a small number of patients consisting of a heterogeneous group. In addition, this is a retrospective cohort study that included patients over many years so that there could be biases inherent to this type of study. These shortcomings need to be rectified in future studies.


 » Conclusions Top


For recurrent or metastatic BTC, metastasectomy can be a viable option for selected patients, particularly those having good performance status and metachronous disease without recurrence of lymph node metastasis more than 1 year after surgery.

Financial support and sponsorship

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2015R1C1A1A01054452).

Conflicts of interest

There are no conflicts of interest.

 
 » References Top

1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.  Back to cited text no. 1
[PUBMED]    
2.
Randi G, Malvezzi M, Levi F, Ferlay J, Negri E, Franceschi S, et al. Epidemiology of biliary tract cancers: An update. Ann Oncol 2009;20:146-59.  Back to cited text no. 2
[PUBMED]    
3.
Sasaki T, Isayama H, Nakai Y, Koike K. Current status of chemotherapy for the treatment of advanced biliary tract cancer. Korean J Intern Med 2013;28:515-24.  Back to cited text no. 3
[PUBMED]    
4.
Tomlinson JS, Jarnagin WR, DeMatteo RP, Fong Y, Kornprat P, Gonen M, et al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol 2007;25:4575-80.  Back to cited text no. 4
[PUBMED]    
5.
Tampellini M, Ottone A, Bellini E, Alabiso I, Baratelli C, Bitossi R, et al. The role of lung metastasis resection in improving outcome of colorectal cancer patients: Results from a large retrospective study. Oncologist 2012;17:1430-8.  Back to cited text no. 5
[PUBMED]    
6.
Billingsley KG, Burt ME, Jara E, Ginsberg RJ, Woodruff JM, Leung DH, et al. Pulmonary metastases from soft tissue sarcoma: Analysis of patterns of diseases and postmetastasis survival. Ann Surg 1999;229:602-10.  Back to cited text no. 6
[PUBMED]    
7.
Murthy SC, Kim K, Rice TW, Rajeswaran J, Bukowski R, DeCamp MM, et al. Can we predict long-term survival after pulmonary metastasectomy for renal cell carcinoma? Ann Thorac Surg 2005;79:996-1003.  Back to cited text no. 7
[PUBMED]    
8.
Chijiiwa K, Kai M, Nagano M, Hiyoshi M, Ohuchida J, Kondo K. Outcome of radical surgery for stage IV gallbladder carcinoma. J Hepatobiliary Pancreat Surg 2007;14:345-50.  Back to cited text no. 8
[PUBMED]    
9.
Ishikawa T, Horimi T, Shima Y, Okabayashi T, Nishioka Y, Hamada M, et al. Evaluation of aggressive surgical treatment for advanced carcinoma of the gallbladder. J Hepatobiliary Pancreat Surg 2003;10:233-8.  Back to cited text no. 9
[PUBMED]    
10.
Kai M, Chijiiwa K, Ohuchida J, Nagano M, Hiyoshi M, Kondo K. A curative resection improves the postoperative survival rate even in patients with advanced gallbladder carcinoma. J Gastrointest Surg 2007;11:1025-32.  Back to cited text no. 10
[PUBMED]    
11.
Kang MJ, Song Y, Jang JY, Han IW, Kim SW. Role of radical surgery in patients with stage IV gallbladder cancer. HPB (Oxford) 2012;14:805-11.  Back to cited text no. 11
[PUBMED]    
12.
Kondo S, Nimura Y, Kamiya J, Nagino M, Kanai M, Uesaka K, et al. Five-year survivors after aggressive surgery for stage IV gallbladder cancer. J Hepatobiliary Pancreat Surg 2001;8:511-7.  Back to cited text no. 12
[PUBMED]    
13.
Meng H, Wang X, Fong Y, Wang ZH, Wang Y, Zhang ZT. Outcomes of radical surgery for gallbladder cancer patients with lymphatic metastases. Jpn J Clin Oncol 2011;41:992-8.  Back to cited text no. 13
[PUBMED]    
14.
Nishio H, Nagino M, Ebata T, Yokoyama Y, Igami T, Nimura Y. Aggressive surgery for stage IV gallbladder carcinoma; what are the contraindications? J Hepatobiliary Pancreat Surg 2007;14:351-7.  Back to cited text no. 14
[PUBMED]    
15.
Shimizu H, Kimura F, Yoshidome H, Ohtsuka M, Kato A, Yoshitomi H, et al. Aggressive surgical approach for stage IV gallbladder carcinoma based on Japanese Society of Biliary Surgery classification. J Hepatobiliary Pancreat Surg 2007;14:358-65.  Back to cited text no. 15
[PUBMED]    
16.
Moriya T, Kimura W, Hirai I, Mizutani M, Yamamoto T, Toya R, et al. Twelve years survival with repeated hepatectomy and lung resection for metastasis from carcinoma of the papilla of Vater after pancreaticoduodenectomy. Hepatogastroenterology 2007;54:1652-4.  Back to cited text no. 16
[PUBMED]    
17.
Oshikiri T, Morita T, Fujita M, Miyasaka Y, Senmaru N, Yamada H, et al. Resection of lung metastasis from gallbladder carcinoma: Immunohistochemistry of RCAS1 and CD8+T cells in primary and metastatic tumors. Cancer Lett 2006;237:115-22.  Back to cited text no. 17
[PUBMED]    
18.
Oyama K, Kanzaki M, Isaka T, Kikkawa T, Komine H, Wachi N, et al. Surgery for metastatic lung tumor from malignant tumor of liver, biliary duct and pancreas. Kyobu Geka 2013;66:305-10.  Back to cited text no. 18
[PUBMED]    
19.
Pandey D, Tan KC. Surgical resection of adrenal metastasis from primary liver tumors: A report of two cases. Hepatobiliary Pancreat Dis Int 2008;7:440-2.  Back to cited text no. 19
[PUBMED]    
20.
Saiura A, Yamamoto J, Kokudo N, Koga R, Seki M, Hiki N, et al. Intrahepatic cholangiocarcinoma: Analysis of 44 consecutive resected cases including 5 cases with repeat resections. Am J Surg 2011;201:203-8.  Back to cited text no. 20
[PUBMED]    
21.
Todoroki T, Fukuda Y, Kawamoto T, Saida Y, Ohara K, Iwasaki Y, et al. Long-term survivors after salvage surgery combined with radiotherapy for recurrence of stage IV main hepatic duct cancer – Report of two cases. Hepatogastroenterology 1993;40:285-93.  Back to cited text no. 21
[PUBMED]    
22.
Frankel TL, D'Angelica MI. Hepatic resection for colorectal metastases. J Surg Oncol 2014;109:2-7.  Back to cited text no. 22
    
23.
van Geel AN, Pastorino U, Jauch KW, Judson IR, van Coevorden F, Buesa JM, et al. Surgical treatment of lung metastases: The European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group study of 255 patients. Cancer 1996;77:675-82.  Back to cited text no. 23
[PUBMED]    
24.
Park I, Lee JL, Ryu MH, Kim TW, Sook Lee S, Hyun Park D, et al. Prognostic factors and predictive model in patients with advanced biliary tract adenocarcinoma receiving first-line palliative chemotherapy. Cancer 2009;115:4148-55.  Back to cited text no. 24
[PUBMED]    
25.
Hezel AF, Deshpande V, Zhu AX. Genetics of biliary tract cancers and emerging targeted therapies. J Clin Oncol 2010;28:3531-40.  Back to cited text no. 25
[PUBMED]    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
Print this article  Email this article
 

    

  Site Map | What's new | Copyright and Disclaimer
  Online since 1st April '07
  © 2007 - Indian Journal of Cancer | Published by Wolters Kluwer - Medknow