Indexed in MEDLINE, SCI & KoreaMed
pISSN 1011-8934   eISSN 1598-6357
Open Access, Peer-reviewed, Weekly
    J Korean Med Sci. 2014 Oct;29(10):1333-1340. English.
    Published online Oct 08, 2014.
    https://doi.org/10.3346/jkms.2014.29.10.1333
    © 2014 The Korean Academy of Medical Sciences.
    Review

    Practical Guidelines for the Surgical Treatment of Gallbladder Cancer

    Seung Eun Lee,1,* Kyung Sik Kim,2,* Wan Bae Kim,3 In-Gyu Kim,4 Yang Won Nah,5 Dong Hee Ryu,6 Joon Seong Park,2 Myung Hee Yoon,7 Jai Young Cho,8 Tae Ho Hong,9 Dae Wook Hwang,5 Dong Wook Choi,10 and Korean Association of Hepato-Biliary and Pancreas Surgery
      • 1Department of Surgery, Chung-Ang University College of Medicine, Seoul, Korea.
      • 2Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
      • 3Department of Surgery, Korea University College of Medicine, Seoul, Korea.
      • 4Department of Surgery, Hallym University College of Medicine, Chuncheon, Korea.
      • 5Department of Surgery, University of Ulsan College of Medicine, Ulsan, Korea.
      • 6Department of Surgery, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Korea.
      • 7Department of Surgery, Kosin University College of Medicine, Busan, Korea.
      • 8Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
      • 9Department of Surgery, Catholic University College of Medicine, Seoul, Korea.
      • 10Department of Surgery, Sungkyunkwan University College of Medicine, Seoul, Korea.
    • Address for Correspondence: Dong Wook Choi, MD. Department of Surgery, Sungkyunkwan University College of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Korea. Tel: +82.2-3410-0200, Fax: +82.2-745-2282, Email: dwchoi@skku.edu

      *Seung Eun Lee and Kyung Sik Kim contributed equally to this work.
    Received June 10, 2014; Accepted July 24, 2014.

    This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Abstract

    At present, surgical treatment is the only curative option for gallbladder (GB) cancer. Many efforts therefore have been made to improve resectability and the survival rate. However, GB cancer has a low incidence, and no randomized, controlled trials have been conducted to establish the optimal treatment modalities. The present guidelines include recent recommendations based on current understanding and highlight controversial issues that require further research. For T1a GB cancer, the optimal treatment modality is simple cholecystectomy, which can be carried out as either a laparotomy or a laparoscopic surgery. For T1b GB cancer, either simple or an extended cholecystectomy is appropriate. An extended cholecystectomy is generally recommended for patients with GB cancer at stage T2 or above. In extended cholecystectomy, a wedge resection of the GB bed or a segmentectomy IVb/V can be performed and the optimal extent of lymph node dissection should include the cystic duct lymph node, the common bile duct lymph node, the lymph nodes around the hepatoduodenal ligament (the hepatic artery and portal vein lymph nodes), and the posterior superior pancreaticoduodenal lymph node. Depending on patient status and disease severity, surgeons may decide to perform palliative surgeries.

    Graphical Abstract

    Keywords
    Gallbladder; Neoplasm; General Surgery; Guideline

    INTRODUCTION

    According to the Korea Central Cancer Registry's annual report of 2011, as published by the Korean Ministry of Health and Welfare, gallbladder (GB) cancer accounts for 1.1% of all cancers in Korea, making it the 11th most prevalent cancer in the country (1). In patients aged 65 yr or older, it is the fifth most prevalent cancer. Its incidence continually increased between 1999 and 2002 and given that Korea is an aging society, this trend is expected to continue. It is therefore imperative to establish practical guidelines for the diagnosis and appropriate treatment of GB cancer.

    GB cancer can be cured with radical surgery, and many efforts have been made in the attempt to improve resectability and the survival rate. However, GB cancer has a low incidence, and no randomized, controlled trials have been conducted to establish the optimal treatment modalities. Although a few retrospective studies have been conducted in large series of patients with GB cancer, these have been limited in scope. Treatment guidelines for GB cancer have been published in peer-reviewed journals in countries outside of Korea, but these have been limited in their provision of established, evidence-based rationales for the most optimum surgical treatment of GB cancer (2, 3, 4). The Korean Association of Hepato-Biliary and Pancreas Surgery conducted a systematic review of the Korean and English literature to establish standard treatment guidelines for GB cancer and to improve treatment outcomes. The treatment guidelines described herein present evidence-based rationales to assist our colleagues in establishing optimal treatment strategies for GB cancer patients in clinical settings. Recommendations for treatment are noted (the grades of these recommendations are defined in Table 1) and the levels of evidence are also given (in parentheses) in the reference citations (see the definitions of levels in Table 2).

    Table 1
    Definitions of evidence by level

    Table 2
    Recommendation levels

    SURGICAL APPROACHES FOR PATIENTS WITH SUSPECTED GB CANCER

    According to published treatment guidelines, it is recommended that patients undergo laparotomy if they are suspected of having GB cancer based on the preoperative work-up (2, 3). This is based on the rationale that GB cancer should be treated by surgical modalities, such as laparotomic cholecystectomy, hepatectomy for GB fossa, and lymph node dissection. However, several recent studies have recommended that a simple cholecystectomy should be the standard treatment modality for T1 GB cancer (5, 6, 7, 8, 9, 10, 11). Laparoscopic cholecystectomy has shown equivalent or better treatment outcomes compared to those for laparotomy (5, 6, 7). This has led to the sugggestion that patients should undergo laparoscopic cholecystectomy unless there is evidence of invasion to the GB fossa (Level of evidence 4, Level of recommendation B). Otherwise, a laparotomy would be advised (Level of evidence 3, Level of recommendation B). Table 3 summarizes the recommendation for suspected GB cancer.

    Table 3
    Summary of recommendations for patients with suspicious GB cancer

    SURGICAL TREATMENT FOR EARLY GB CANCER

    T1a GB cancer

    Based on a literature review, simple cholecystectomy is the optimal treatment for patients with T1a GB cancer confined to mucosa. Laparoscopic cholecystectomy is also an appropriate modality (5, 6, 7, 8, 12, 13). The five-year survival rate for simple cholecystectomy is as high as 95%-100%. An extended cholecystectomy is not effective in prolonging long-term survival unless there are tumor invasions into the resection margin of the cystic duct (9). According to a systematic review of the T1a GB cancer literature, the recurrence rate is 1.1% in such cases. The most frequent site of recurrence was the common bile duct (6) (more than 50% of the total cases). Therefore, histopathologic examination should be performed to determine whether there are tumor invasions into the resection margin of the cystic duct. If this is the case, extrahepatic bile duct (EHBD) resection should be considered (6, 7) (Level of evidence 3, level of recommendation A). Lymph node metastasis has been reported in less than 2.5% of total cases; therefore, lymph node dissection is not recommended for patients with T1a GB cancer (6, 10). The five-year survival rate is estimated at 100% for T1a GB patients who undergo laparoscopic cholecystectomy (6, 7), but there are some reports that bile juice leakage during laparoscopic cholecystectomy is associated with peritoneal metastasis and tumor recurrence at trocar sites. As such the surgical procedure should be carefully performed so as to prevent intraoperative GB perforation, and the resected GB should be removed using a vinyl bag (6, 12) (Level of evidence 3, level of recommendation A). Table 4 summarizes the recommendations for T1a GB cancer.

    Table 4
    Summary of recommendations for patients with T1a GB cancer

    T1b GB cancer

    There is no clear evidence that extended cholecystectomy increases survival compared to the results for simple cholecystectomy in patients with T1b GB cancer (5, 6, 12). Moreover, several studies have shown that there is no significant difference in five-year survival between patients who undergo laparoscopic cholecystectomy and those who undergo laparotomy. It can therefore be inferred that laparoscopic cholecystectomy is not associated with poor prognosis (8, 11, 12). According to a systematic review of the T1 GB cancer literature, lymph node metastasis is present in approximately 11% of all cases, and the recurrence rate is 9.3% (6). However, this rate is higher in patients with T1b GB cancer who have undergone simple cholecystectomy (5, 6). Although there is a lack of clear evidence demonstrating that extended cholecystectomy increases patient's survival as compared with a simple cholecystectomy, the former may nevertheless be recommended for patients who are not at increased risk of developing postoperative complications in that simple cholecystectomy has a relatively higher recurrence rate (6, 7, 9, 14) (Level of evidence 3, level of recommendation B). Table 5 summarizes the recommendations for T1b GB cancer.

    Table 5
    Summary of recommendations for patients with T1b GB cancer

    SURGICAL TREATMENTS FOR OTHER GB CANCER STAGES

    An extended cholecystectomy is generally recommended for patients with GB cancer at stage T2 or above (15, 16, 17, 18, 19, 20) (Level of evidence 3, Level of recommendation B). In patients who are indicated for radical cholecystectomy, a combined approach can also be considered.

    Extent of hepatic resection in extended cholecystectomy

    A wedge resection of the GB bed or segmentectomy IVb/V can be performed (Level of evidence 3, Level of recommendation B). In a wedge resection, it is recommended that the hepatic resection margin width should be proposed to be approximately 2-3 cm; however, there is by no means universal consensus on this point. Table 6 summarizes the recommendations for the ideal extent of hepatic resection in extended cholecystectomy.

    Table 6
    Summary of recommendations for extent of hepatic resection or lymph node dissection in extended cholecystectomy

    Extent of lymph node dissection in extended cholecystectomy

    Lymph node metastasis is a well-known prognostic indicator, and its incidence varies depending on the depth of mural invasion as follows: pT1a, 0%-2.5%; pT1b, 5%-16%; pT2, 9%-30%; T3, 39%-72%; and T4, 67%-80% (6, 9, 21, 22). There is no consensus on the optimum extent of lymph node dissection in extended cholecystectomy for GB cancer patients. The seventh edition of the AJCC Cancer Staging Manual (23), defines, regional lymph node group 1 (N1) as comprising the cystic duct lymph node, common bile duct lymph node, and the lymph nodes around the hepatoduodenal ligament (i.e., the hepatic artery lymph node and portal vein lymph node). The posterior pancreaticoduodenal lymph node, celiac artery lymph node, superior mesenteric artery lymph node, para-aortic lymph node, and pericaval lymph node are classified as belonging to regional lymph node group 2 (N2). N2 metastasis would be interpreted as remote metastasis, and such patients would be classified as TNM IVB. In most cases, the long-term survival cannot be predicted for patients with N2 metastasis, and radical lymph node dissection is not routinely performed (17, 24, 25, 26). Regional lymph node dissection is recommended for the cystic duct lymph node, common bile duct lymph node, the lymph nodes around the hepatoduodenal ligament (hepatic artery and portal vein lymph nodes), and the posterior superior pancreaticoduodenal lymph node (Level of evidence 3, Level of recommendation C). There is no consensus on the minimum or optimal number of resected lymph nodes required to accurately determine the TNM stage. The sixth edition of the AJCC Staging Manual stated that more than three lymph nodes are required to accurately determine the N-stage. However, this point was deleted in the manual's seventh edition. Some surgeons are of the opinion that only 3-4 lymph nodes can be collected despite N1 regional lymph node dissection although 1-2 lymph nodes can be collected using a simple cholecystectomy. Based on this, we propose that more than three lymph nodes should be collected for histopathologic examinations (Level of evidence 4, Level of recommendation C). Table 7 summarizes the recommendations for extent of the optimal lymph node dissection in extended cholecystectomy.

    Table 7
    Summary of recommendations for extrahepatic bile duct (EHBD) resection in radical surgery, surgery in GB cancer patients with para-aortic lymph node metastasis, surgical treatments in patients with invasion of the hepatic artery, portal vein, and adjacent organs, and palliative surgery in patients who are not indicated for radical surgery

    Clinical significance of extrahepatic bile duct resection in radical surgery

    Since the early 1990s, it has been maintained that EHBD resection should be performed for GB cancer irrespective of the TNM stage (27). This is based on the rationale that this procedure achieves complete lymph nodes resection around the hepatoduodenal ligament in early GB cancer and also helps achieve radical tumor mass resection with perineural invasion in advanced GB cancer. However, it has been subsequently found that EHBD resection is not associated with increased survival (28, 29, 30, 31, 32). There are also contradictory reports that the incidence of early and late-stage complications is increased by this procedure (28, 33). Therefore, EHBD resection should not be seen as mandatory in the radical resection of GB cancer but rather as an option to be selectively performed in specific types of cases, such as GB cancer with extrahepatic bile duct invasion (Level of evidence 3, Level of recommendation C). Table 7 summarizes the recommendations for EHBD resection in radical surgery.

    Clinical significance of surgery in GB cancer patients with para-aortic lymph node metastasis

    It is generally known that patients with advanced GB cancer with para-aortic lymph node metastasis are contraindicated in surgery. However, it has been reported that survival is significantly prolonged following radical resection that includes para-aortic lymph node dissection in patients with GB cancer with para-aortic lymph node metastasis, compared to results for patients with distant metastasis or advanced, unresectable GB cancer (34). Conversely, another study reported that patients with TNM stage III or IV GB cancer should undergo extended lymph node dissection involving the para-aortic lymph node (35). Currently, surgical treatment efficacy cannot be predicted in GB cancer patients with para-aortic lymph node metastasis. The decision to perform radical surgery should thus be based on the surgeon's judgment (Level of evidence 3, Level of recommendation C). Table 7 summarizes the recommendations for surgery in GB cancer patients with para-aortic lymph node metastasis.

    Clinical significance of surgical treatments in patients with invasion of the hepatic artery, portal vein, and adjacent organs

    Very poor prognoses are expected in advanced GB cancer cases, and most patients refuse to undergo surgery when invasion of the hepatic artery and portal vein are suspected. Kobayashi et al. (36) performed analysis in 71 patients with GB cancer and found that the prognosis was poorer if surgeons performed a combined resection of the hepatic artery and portal vein for patients with invasion of both vessels as compared with results for those patients who had no invasion. Moreover, the authors reported that invasion of the hepatic artery and portal vein is a key prognostic indicator (36, 37). There are no effective treatment modalities other than surgery for patients with GB cancer. Surgical treatments are recommended for GB cancer patients if complete tumor removal (R0 resection) can be achieved through a combined resection of the hepatic artery and portal vein (Level of evidence 3, Level of recommendation C).

    Combined resection is routinely recommended for advanced GB cancer cases in which there is invasion of adjacent organs (colon and duodenum). As this requires both a combined resection and R0 resection, favorable prognoses are not guaranteed. The selection of appropriate patients is essential (38) (Level of evidence 3, Level of recommendation C). Table 7 summarizes the recommendations for surgical treatment in patients with invasion of the hepatic artery, portal vein, and adjacent organs.

    Clinical significance of palliative surgery in patients who are not indicated for radical surgery

    The median and one-year survival rates in patients with unresectable GB cancer are reported to be approximately 2-4 months and less than 5%, respectively. It is also known that cytoreductive surgery is not useful in patients with GB cancer (39, 40, 41, 42). However, palliative surgery will most likely be able to prolong the short-term survival period and improve the quality of life of patients with unresectable GB cancer. Palliative surgery options here include non-radical, simple cholecystectomy. If biliary atresia or gastric outlet obstruction are concurrently present, bypass surgery would also improve patient quality of life. Surgeons should therefore decide the optimal treatment modality in view of the patient status involved (43, 44) (Level of evidence 3, Level of recommendation C). Table 7 summarizes the recommendations for palliative surgery in patients who are not indicated for radical surgery.

    TREATMENT OF INCIDENTALLY FOUND GB CANCER AFTER CHOLECYSTECTOMY

    GB cancer incidentally found on postoperative histopathology

    The core principles for the surgical treatment of GB cancer incidentally found on postoperative histopathology are identical to those described earlier. That is, no additional surgeries should be considered for histologically-proven T1a GB cancer if the GB was completely resected during surgery (5, 6, 7, 8, 12, 13) (Level of evidence 3, Level of recommendation A). However, in cases of histologically-proven T1b GB cancer, there is still controversy regarding whether extended cholecystectomy or follow-up without additional surgeries should be performed (5, 6, 8, 11, 12) (Level of evidence 3, Level of recommendation B). In cases of GB cancer at T2 or above, the additional use of extended cholecystectomy is recommended (Level of evidence 3, Level of recommendation B). There are no established reports regarding the timing of additional surgeries; however, some studies have been performed immediately after GB cancer diagnosis (45, 46) (Level of evidence 3, Level of recommendation C). Table 8 summarizes the recommendations for GB cancer incidentally found on postoperative histopathology.

    Table 8
    Summary of recommendations for GB cancer found incidentally on postoperative histopathology

    GB cancer incidentally found during surgery

    The surgical treatment principles for histologically-proven GB cancer found during surgery are identical to those for GB cancer incidentally found on postoperative histopathology. However, in patients who are suspected of having T1 GB cancer during surgery, it is difficult to differentiate between T1a and T1b GB cancers. Therefore, cholecystectomy should be the first-choice treatment. It is recommended that additional surgeries should be determined based on the postoperative histopathology (Level of evidence 4, Level of recommendation C). In GB cancer at T2 or above, extended cholecystectomy should be performed based on a tentative or revised diagnosis (Level of evidence 4, Level of recommendation C). Table 9 summarizes the recommendations for GB cancer incidentally found during surgery.

    Table 9
    Summary of recommendations for GB cancer found incidentally during surgery

    SURGICAL TREATMENT OF GB CANCER ACCOMPANIED BY ACUTE CHOLECYSTITIS

    GB cancer is often accompanied by bile stones, leading to acute cholecystitis symptoms in many cases. There are no accurate reports on the incidence of acute cholecystitis, although it has been reported to range from 8.8% to 20% (47, 48, 49). A preoperative differential diagnosis of acute cholecystitis accompanied by GB cancer is essential for determining surgical plans, but there are some situations in which such a differential diagnosis is difficult. Indeed, surgery should possibly be delayed in patients with GB cancer who have concurrent acute cholecystitis. In addition, the appropriate extent of surgery cannot be intraoperatively determined, leading to poor prognoses (50). Surgeons are recommended to consider the possibility of GB cancer in patients who are suspected of having acute cholecystitis if they are older and exhibit focal GB wall thickening, a mass within the internal GB lumen, overall GB wall thickening with decreased GB size, or lymphadenopathy around the GB (51) (Level of evidence 4, Level of recommendation C).

    POSTOPERATIVE ADJUVANT THERAPY

    Complete surgical excision of GB cancer is the only radical treatment modality at present, but the rate of resection is at most 25%-30%. Nearly half of patients are at increased risk for recurrent GB cancer despite having undergone complete resection (52, 53). Recurrent GB cancer may be the result of distant metastasis, but it may also be characterized by local recurrence (54, 55, 56). Patients with recurrent GB cancer are therefore required to undergo local treatment modalities, such as postoperative adjuvant chemotherapy or concurrent chemoradiation therapy (CCRT). For postoperative adjuvant chemotherapy, fluoropyrimidine drugs such as 5-fluorouracil or capecitabine are the preferred choice. CCRT is also recommended to be carried out in conjunction with these drugs. Depending on patient status or surgeon preference, monotherapy or combination treatment regimens using gemcitabine or fluoropyrimidine may also be considered (6). However, postoperative adjuvant chemotherapy or CCRT are not recommended in patients with T1 GB cancer who have undergone radical resection (58, 59, 60) (Level of evidence 3, Level of recommendation C). Table 10 summarizes the recommendations for the optimum postoperative adjuvant therapy for GB cancer.

    Table 10
    Summary of recommendations for postoperative adjuvant therapy for GB cancer

    CONCLUSIONS

    There are no randomized, prospective studies assessing the surgical treatments for GB cancer. Moreover, there are only a few systematic reviews of the GB cancer surgical literature. There are many retrospective studies in this series, but when taken as a whole, these have the following limitations: 1) small numbers of enrolled patients; 2) heterogeneity of patient populations across studies, and 3) inconsistent surgical procedures across studies. Therefore, we experienced considerable difficulty in drawing conclusions and developing recommendations based on the existing clinical evidence. Nevertheless, the current report is based on a systematic review of the literature and in-depth discussion among board members. We believe that these treatment guidelines are of value for selecting the optimal surgical modalities in GB cancer patients.

    Notes

    The authors have no conflicts of interest to disclose.

    References

      1. Ministry of Health and Welfare, Korea Central Cancer Registry, National Cancer Center. Annual report of cancer statistics in Korea in 2009. [accessed on 1 September 2014].
        Available at http://ncc.re.kr/manage/manage03_033_view.jsp?bbsnum=229&hSelSearch=&hTxtKeyword=¤t_page=1&cd=null.
      1. Ettinger DS, Agulnik M, Cates JM, Cristea M, Denlinger CS, Eaton KD, Fidias PM, Gierada D, Gockerman JP, Handorf CR, et al. Occult primary. J Natl Compr Canc Netw 2011;9:1358–1395.
      1. Kondo S, Takada T, Miyazaki M, Miyakawa S, Tsukada K, Nagino M, Furuse J, Saito H, Tsuyuguchi T, Yamamoto M, et al. Guidelines for the management of biliary tract and ampullary carcinomas: surgical treatment. J Hepatobiliary Pancreat Surg 2008;15:41–54.
      1. Eckel F, Brunner T, Jelic S. ESMO Guidelines Working Group. Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2011;22:vi40–vi44.
      1. Lee SE, Jang JY, Kim SW. The surgical strategy for treating T1 gallbladder cancer. Korean J Hepatobiliary Pancreat Surg 2009;13:69–75.
      1. Lee SE, Jang JY, Lim CS, Kang MJ, Kim SW. Systematic review on the surgical treatment for T1 gallbladder cancer. World J Gastroenterol 2011;17:174–180.
      1. Hardiman KM, Sheppard BC. What to do when the pathology from last week's laparoscopic cholecystectomy is malignant and T1 or T2. J Gastrointest Surg 2009;13:2037–2039.
      1. Lee HS, Kim KS, Choi JS, Lee SH, Lee WJ, Kim BR. Gallbladder carcinoma diagnosed after laparoscopic cholecystectomy. Korean J Hepatobiliary Pancreat Surg 2002;6:73–79.
      1. Isambert M, Leux C, Métairie S, Paineau J. Incidentally-discovered gallbladder cancer: When, why and which reoperation? J Visc Surg 2011;148:e77–e84.
      1. Pilgrim C, Usatoff V, Evans PM. A review of the surgical strategies for the management of gallbladder carcinoma based on T stage and growth type of the tumour. Eur J Surg Oncol 2009;35:903–907.
      1. Choi ST, Hwang S, Lee SG, Lee YJ, Park KM, Kim KH, Ahn CS, Moon DB. Prognosis of patients with the gallbladder carcinoma undergone laparoscopic cholecystectomy as an initial operation. J Korean Surg Soc 2003;65:140–144.
      1. Ouchi K, Mikuni J, Kakugawa Y. Laparoscopic cholecystectomy for gallbladder carcinoma: results of a Japanese survey of 498 patients. J Hepatobiliary Pancreat Surg 2002;9:256–260.
      1. Choi SB, Han HJ, Kim CY, Kim WB, Song TJ, Suh SO, Kim YC, Choi SY. Incidental gallbladder cancer diagnosed following laparoscopic cholecystectomy. World J Surg 2009;33:2657–2663.
      1. Varshney S, Butturini G, Gupta R. Incidental carcinoma of the gallbladder. Eur J Surg Oncol 2002;28:4–10.
      1. Chijiiwa K, Nakano K, Ueda J, Noshiro H, Nagai E, Yamaguchi K, Tanaka M. Surgical treatment of patients with T2 gallbladder carcinoma invading the subserosal layer. J Am Coll Surg 2001;192:600–607.
      1. Wise PE, Shi YY, Washington MK, Chapman WC, Wright JK, Sharp KW, Pinson CW. Radical resection improves survival for patients with pT2 gallbladder carcinoma. Am Surg 2001;67:1041–1047.
      1. 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;11:1025–1032.
      1. Shih SP, Schulick RD, Cameron JL, Lillemoe KD, Pitt HA, Choti MA, Campbell KA, Yeo CJ, Talamini MA. Gallbladder cancer: the role of laparoscopy and radical resection. Ann Surg 2007;245:893–901.
      1. Kohya N, Miyazaki K. Hepatectomy of segment 4a and 5 combined with extra-hepatic bile duct resection for T2 and T3 gallbladder carcinoma. J Surg Oncol 2008;97:498–502.
      1. Dai M, Fong Y, Lowy A. Treatment of T3 gallbladder cancer. J Gastrointest Surg 2009;13:2040–2042.
      1. Miyakawa S, Ishihara S, Horiguchi A, Takada T, Miyazaki M, Nagakawa T. Biliary tract cancer treatment: 5,584 results from the Biliary Tract Cancer Statistics Registry from 1998 to 2004 in Japan. J Hepatobiliary Pancreat Surg 2009;16:1–7.
      1. Kiran RP, Pokala N, Dudrick SJ. Incidence pattern and survival for gallbladder cancer over three decades--an analysis of 10301 patients. Ann Surg Oncol 2007;14:827–832.
      1. Edge SB. American Joint Committee on Cancer, American Cancer Society. In: AJCC cancer staging manual. 7th ed. New York: Springer; 2010.
      1. Shimada H, Endo I, Fujii Y, Kamiya N, Masunari H, Kunihiro O, Tanaka K, Misuta K, Togo S. Appraisal of surgical resection of gallbladder cancer with special reference to lymph node dissection. Langenbecks Arch Surg 2000;385:509–514.
      1. Kondo S, Nimura Y, Hayakawa N, Kamiya J, Nagino M, Uesaka K. Regional and para-aortic lymphadenectomy in radical surgery for advanced gallbladder carcinoma. Br J Surg 2000;87:418–422.
      1. Sasaki R, Itabashi H, Fujita T, Takeda Y, Hoshikawa K, Takahashi M, Funato O, Nitta H, Kanno S, Saito K. Significance of extensive surgery including resection of the pancreas head for the treatment of gallbladder cancer--from the perspective of mode of lymph node involvement and surgical outcome. World J Surg 2006;30:36–42.
      1. Nakamura S, Sakaguchi S, Suzuki S, Muro H. Aggressive surgery for carcinoma of the gallbladder. Surgery 1989;106:467–473.
      1. Shimada H, Endo I, Togo S, Nakano A, Izumi T, Nakagawara G. The role of lymph node dissection in the treatment of gallbladder carcinoma. Cancer 1997;79:892–899.
      1. Wakai T, Shirai Y, Yokoyama N, Nagakura S, Watanabe H, Hatakeyama K. Early gallbladder carcinoma does not warrant radical resection. Br J Surg 2001;88:675–678.
      1. Reid KM, Ramos-De la Medina A, Donohue JH. Diagnosis and surgical management of gallbladder cancer: a review. J Gastrointest Surg 2007;11:671–681.
      1. Suzuki S, Yokoi Y, Kurachi K, Inaba K, Ota S, Azuma M, Konno H, Baba S, Nakamura S. Appraisal of surgical treatment for pT2 gallbladder carcinomas. World J Surg 2004;28:160–165.
      1. Shukla PJ, Barreto SG. Systematic review: should routine resection of the extra-hepatic bile duct be performed in gallbladder cancer? Saudi J Gastroenterol 2010;16:161–167.
      1. Kosuge T, Sano K, Shimada K, Yamamoto J, Yamasaki S, Makuuchi M. Should the bile duct be preserved or removed in radical surgery for gallbladder cancer? Hepatogastroenterology 1999;46:2133–2137.
      1. 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;14:351–357.
      1. Coburn NG, Cleary SP, Tan JC, Law CH. Surgery for gallbladder cancer: a population-based analysis. J Am Coll Surg 2008;207:371–382.
      1. Kobayashi A, Oda T, Fukunaga K, Sasaki R, Ohkohchi N. Invasion of the hepatic artery is a crucial predictor of poor outcomes in gallbladder carcinoma. World J Surg 2012;36:645–650.
      1. Murakami Y, Uemura K, Sudo T, Hashimoto Y, Nakashima A, Kondo N, Sakabe R, Kobayashi H, Sueda T. Prognostic factors of patients with advanced gallbladder carcinoma following aggressive surgical resection. J Gastrointest Surg 2011;15:1007–1016.
      1. Lim CS, Jang JY, Lee SE, Kang MJ, Kim SW. Reappraisal of hepatopancreatoduodenectomy as a treatment modality for bile duct and gallbladder cancer. J Gastrointest Surg 2012;16:1012–1018.
      1. Oertli D, Herzog U, Tondelli P. Primary carcinoma of the gallbladder: operative experience during a 16 year period. Eur J Surg 1993;159:415–420.
      1. Wanebo HJ, Castle WN, Fechner RE. Is carcinoma of the gallbladder a curable lesion? Ann Surg 1982;195:624–631.
      1. Ito H, Matros E, Brooks DC, Osteen RT, Zinner MJ, Swanson RS, Ashley SW, Whang EE. Treatment outcomes associated with surgery for gallbladder cancer: a 20-year experience. J Gastrointest Surg 2004;8:183–190.
      1. Batra Y, Pal S, Dutta U, Desai P, Garg PK, Makharia G, Ahuja V, Pande GK, Sahni P, Chattopadhyay TK, et al. Gallbladder cancer in India: a dismal picture. J Gastroenterol Hepatol 2005;20:309–314.
      1. Pradeep R, Kaushik SP, Sikora SS, Bhattacharya BN, Pandey CM, Kapoor VK. Predictors of survival in patients with carcinoma of the gallbladder. Cancer 1995;76:1145–1149.
      1. Xiao WD, Peng CH, Zhou GW, Wu WD, Shen BY, Yan JQ, Yang WP, Li HW. Surgical treatment for Nevin stage IV and V gallbladder carcinoma: report of 70 cases. Hepatobiliary Pancreat Dis Int 2005;4:589–592.
      1. Goetze TO, Paolucci V. Immediate re-resection of T1 incidental gallbladder carcinomas: a survival analysis of the German Registry. Surg Endosc 2008;22:2462–2465.
      1. Goetze TO, Paolucci V. Adequate extent in radical re-resection of incidental gallbladder carcinoma: analysis of the German Registry. Surg Endosc 2010;24:2156–2164.
      1. Chao TC, Jeng LB, Jan YY, Hwang TL, Wang CS, Chen MF. Concurrent primary carcinoma of the gallbladder and acute cholecystitis. Hepatogastroenterology 1998;45:921–926.
      1. Lam CM, Yuen AW, Wai AC, Leung RM, Lee AY, Ng KK, Fan ST. Gallbladder cancer presenting with acute cholecystitis: a population-based study. Surg Endosc 2005;19:697–701.
      1. Liu KJ, Richter HM, Cho MJ, Jarad J, Nadimpalli V, Donahue PE. Carcinoma involving the gallbladder in elderly patients presenting with acute cholecystitis. Surgery 1997;122:748–754.
        discussion 54-6.
      1. Han HS, Cho JY, Yoon YS, Ahn KS, Kim H. Preoperative inflammation is a prognostic factor for gallbladder carcinoma. Br J Surg 2011;98:111–116.
      1. Liang JL, Chen MC, Huang HY, Ng SH, Sheen-Chen SM, Liu PP, Kung CT, Ko SF. Gallbladder carcinoma manifesting as acute cholecystitis: clinical and computed tomographic features. Surgery 2009;146:861–868.
      1. Macdonald OK, Crane CH. Palliative and postoperative radiotherapy in biliary tract cancer. Surg Oncol Clin N Am 2002;11:941–954.
      1. Kim WS, Choi DW, You DD, Ho CY, Heo JS, Choi SH. Risk factors influencing recurrence, patterns of recurrence, and the efficacy of adjuvant therapy after radical resection for gallbladder carcinoma. J Gastrointest Surg 2010;14:679–687.
      1. Kopelson G, Galdabini J, Warshaw AL, Gunderson LL. Patterns of failure after curative surgery for extra-hepatic biliary tract carcinoma: implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 1981;7:413–417.
      1. Jarnagin WR, Ruo L, Little SA, Klimstra D, D'Angelica M, DeMatteo RP, Wagman R, Blumgart LH, Fong Y. Patterns of initial disease recurrence after resection of gallbladder carcinoma and hilar cholangiocarcinoma: implications for adjuvant therapeutic strategies. Cancer 2003;98:1689–1700.
      1. Jung SJ, Woo SM, Park HK, Lee WJ, Han MA, Han SS, Kim SH, Park SJ, Kim TH, Koh YH, et al. Patterns of initial disease recurrence after resection of biliary tract cancer. Oncology 2012;83:83–90.
      1. Hezel AF, Zhu AX. Systemic therapy for biliary tract cancers. Oncologist 2008;13:415–423.
      1. Park HS, Lim JY, Yoon DS, Park JS, Lee DK, Lee SJ, Choi HJ, Song SY, Lee WJ, Cho JY. Outcome of adjuvant therapy for gallbladder cancer. Oncology 2010;79:168–173.
      1. Cho SY, Kim SH, Park SJ, Han SS, Kim YK, Lee KW, Lee WJ, Woo SM, Kim TH. Adjuvant chemoradiation therapy in gallbladder cancer. J Surg Oncol 2010;102:87–93.
      1. Gold DG, Miller RC, Haddock MG, Gunderson LL, Quevedo F, Donohue JH, Bhatia S, Nagorney DM. Adjuvant therapy for gallbladder carcinoma: the Mayo Clinic Experience. Int J Radiat Oncol Biol Phys 2009;75:150–155.
    Cited by
    Crossref 61
    Google Scholar 
    PubMed Central 32
    Scopus 65
    Web of Science 59
    MeSH Terms
    Cholecystectomy, Laparoscopic/methods*
    Gallbladder Neoplasms/epidemiology
    Gallbladder Neoplasms/mortality
    Gallbladder Neoplasms/surgery*
    Humans
    Incidental Findings
    Laparotomy
    Liver Neoplasms/secondary
    Liver Neoplasms/surgery*
    Lymph Node Excision/methods*
    Lymph Nodes/pathology
    Lymph Nodes/surgery
    Lymphatic Metastasis/pathology*
    Survival Rate
    Metrics
    Share
    Links to
    Figures
    slide

    1 / 1

    Tables
    slide
    slide
    slide
    slide
    slide
    slide
    slide
    slide
    slide
    slide

    1 / 10

    ORCID IDs
    PERMALINK