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Invasion category-oriented lymph node metastases of cholangiocarcinoma and the prognostic impact

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Abstract

Purpose

It was speculated that intrahepatic cholangiocarcinoma (ICC) invasion would influence cancer progression, such as lymph node (LN) metastasis, and the efficacy of LN dissection (LND). The purpose of this study is to evaluate the LN metastatic pattern of intrahepatic cholangiocarcinoma, including the invasion category and prognosis after surgical resection, in order to explore effective LND.

Methods

We analyzed a prospectively collected cohort for ICC with a previously reported invasion category: hilar type, showing invasion to the main or first branch of Glisson; peripheral type, showing no invasion to less than the third branch; and intermediate type, for all others.

Results

Data from a total of 180 patients who underwent surgical resection were analyzed (LN dissection in 142 (79%)). In single ICC, hilar type had a higher LN metastatic rate than the others (hilar; 23/45 (51%), intermediate; 7/25 (28%), peripheral; 1/34 (3%)). Although the survival with LN metastasis (LN+) was worse, single and hilar/intermediate ICC LN+ had a better survival than peripheral type LN+ (3-year OS: hilar/intermediate 30–37%, peripheral 0%). The most frequent LN metastatic region was the hepatico-duodenal ligament for all invasion categories, and the LN metastatic region was not related to the survival. In peripheral ICC, LND did not affect the survival. By contrast, hilar/intermediate ICC LN+ had a better survival than did peripheral ICC LN+, and the 3-year OS was ≥ 20%.

Conclusion

LN metastasis depended on the ICC invasion category in addition to the tumor number, which affected patients’ survival and the need for LND. In hilar-type disease, LN dissection may contribute to the survival.

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Data availability

The datasets analyzed during the current study available from the corresponding author on reasonable request.

Abbreviations

BTC:

Biliary tract cancer

CA19-9:

Carbohydrate antigen 19-9

CEA:

Carcinoembryonic antigen

CT:

Computed tomography

FNA:

Fine-needle aspiration

FNB:

Fine-needle biopsy

ICC:

Intrahepatic cholangiocarcinoma

OS:

Overall survival

LN:

Lymph node

LND:

Lymph node dissection

LNR:

Lymph node metastatic ratio

MST:

Median survival time

References

  1. Endo I, Gonen M, Yopp AC, Dalal KM, Zhou Q, Klimstra D, D'Angelica M, DeMatteo RP, Fong Y, Schwartz L, Kemeny N, O'Reilly E, Abou-Alfa GK, Shimada H, Blumgart LH, Jarnagin WR (2008) Intrahepatic cholangiocarcinoma: rising frequency, improved survival, and determinants of outcome after resection. Ann Surg 248(1):84–96

    Article  Google Scholar 

  2. Saha SK, Zhu AX, Fuchs CS, Brooks GA (2016) Forty-year trends in cholangiocarcinoma incidence in the U.S.: intrahepatic disease on the rise. Oncologist 21(5):594–599

    Article  Google Scholar 

  3. Colvin H, Mizushima T, Eguchi H, Takiguchi S, Doki Y, Mori M (2017) Gastroenterological surgery in Japan: the past, the present and the future. Ann Gastorenterol Surg 1:5–10

    Article  Google Scholar 

  4. Uchiyama K, Yamamoto M, Yamaue H, Ariizumi S, Aoki T, Kokudo N, Ebata T, Nagino M, Ohtsuka M, Miyazaki M, Tanaka E, Kondo S, Uenishi T, Kubo S, Yoshida H, Unno M, Imura S, Shimada M, Ueno M, Takada T (2011) Impact of nodal involvement on surgical outcomes of intrahepatic cholangiocarcinoma: a multicenter analysis by the Study Group for Hepatic Surgery of the Japanese Society of Hepato-Biliary-Pancreatic Surgery. J Hepatobiliary Pancreat Sci 18(3):443–452

    Article  Google Scholar 

  5. Kobayashi S, Nagano H, Tomokuni A, Gotoh K, Sakai D, Hatano E, Seo S, Terajima H, Uchida Y, Ajiki T, Satake H, Kamei K, Tohyama T, Hirose T, Ikai I, Morita S, Ioka T (2019) A prospective, randomized phase II study of adjuvant gemcitabine versus s-1 after major hepatectomy for biliary tract cancer (KHBO 1208). Ann Surg 270(2):230–237

    Article  Google Scholar 

  6. Kobayashi S, Tomokuni A, Gotoh K, Takahashi H, Akita H, Marubashi S, Yamada T, Teshima T, Fukui K, Fujiwara Y, Sakon M (2017) A retrospective analysis of the clinical effects of neoadjuvant combination therapy with full-dose gemcitabine and radiation therapy in patients with biliary tract cancer. Eur J Surg Oncol 43(4):763–771

    Article  CAS  Google Scholar 

  7. Okuda K, Kubo Y, Okazaki N, Arishima T, Hashimoto M (1977) Clinical aspects of intrahepatic bile duct carcinoma including hilar carcinoma: a study of 57 autopsy-proven cases. Cancer 29(1):232–246

    Article  Google Scholar 

  8. Makino H, Sonoyama T, Yamagishi H, Oka T, Naito K, Ohmori Y, Hironaka T (1995) Clinicopathological studies of central type of cholangiocarcinoma compared with hilar bile duct cancer. Jpn J Gastroenterol Surg 28:1049–1054

    Article  Google Scholar 

  9. Nakanuma Y, Hoso M, Sanzen T, Sasaki M (1997) Microstructure and development of the normal and pathologic biliary tract in humans, including blood supply. Microsc Res Tech 38:552–570

    Article  CAS  Google Scholar 

  10. Nakanuma Y, Sato Y, Harada K, Sasaki M, Xu J, Ikeda H (2010) Pathological classification of intrahepatic cholangiocarcinoma based on a new concept. World J Hepatol 2(12):419–427

    Article  Google Scholar 

  11. Miyazaki M, Ohtsuka M, Miyakawa S, Nagino M, Yamamoto M, Kokudo N, Sano K, Endo I, Unno M, Chijiiwa K, Horiguchi A, Kinoshita H, Oka M, Kubota K, Sugiyama M, Uemoto S, Shimada M, Suzuki Y, Inui K, Tazuma S, Furuse J, Yanagisawa A, Nakanuma Y, Kijima H, Takada T (2015) Classification of biliary tract cancers established by the Japanese Society of Hepato-Biliary-Pancreatic Surgery: 3(rd) English edition. J Hepatobiliary Pancreat Sci 22(3):181–196

    Article  Google Scholar 

  12. Orimo T, Kamiyama T, Mitsuhashi T, Kamachi H, Yokoo H, Wakayama K, Shimada S, Nagatsu A, Taketomi A (2018) Impact of tumor localization on the outcomes of surgery for an intrahepatic cholangiocarcinoma. J Gastroenterol 53(11):1206–1215

    Article  Google Scholar 

  13. Yamamoto M, Takasaki K, Yoshikawa T (1999) Lymph node metastasis in intrahepatic cholangiocarcinoma. Jpn J Clin Oncol 29(3):147–150

    Article  CAS  Google Scholar 

  14. Zhou R, Lu D, Li W, Tan W, Zhu S, Chen X, Min J, Shang C, Chen Y (2019) Is lymph node dissection necessary for resectable intrahepatic cholangiocarcinoma? A systematic review and meta-analysis. HPB (Oxford) 21(7):784–792

    Article  Google Scholar 

  15. Okami J, Dono K, Sakon M, Tsujie M, Hayashi N, Fujiwara Y, Nagano H, Umeshita K, Nakamori S, Monden M (2003) Patterns of regional lymph node involvement in intrahepatic cholangiocarcinoma of the left lobe. J Gastrointest Surg 7(7):850–856

    Article  Google Scholar 

  16. Marubashi S, Gotoh K, Takahashi H, Ohigashi H, Yano M, Ishikawa O, Sakon M (2014) Prediction of the postoperative prognosis of intrahepatic cholangiocarcinoma (ICC): importance of preoperatively- determined anatomic invasion level and number of tumors. Dig Dis Sci 59(1):201–213

    Article  Google Scholar 

  17. Sobin L, Gospodarowicz M, Wittekind C (2009). TNM classification of maligngnt tumours, 7th edn. UICC International Union Against Cancer. Wiley-blackwell

  18. Kobayashi S, Nagano H, Marubashi S, Kawamoto K, Wada H, Eguchi H, Tanemura M, Umeshita K, Doki Y, Mori M (2013) Clinicopathological features of long-term survivors for advanced biliary tract cancer and impact of the number of lymph nodes involved. Int J Surg 11(2):145–151

    Article  Google Scholar 

  19. Tamandl D, Kaczirek K, Gruenberger B, Koelblinger C, Maresch J, Jakesz R, Gruenberger T (2009) Lymph node ratio after curative surgery for intrahepatic cholangiocarcinoma. Br J Surg 96(8):919–925

    Article  CAS  Google Scholar 

  20. Ruzzenente A, Conci S, Viganò L, Ercolani G, Manfreda S, Bagante F, Ciangherotti A, Pedrazzani C, Pinna AD, Iacono C, Torzilli G, Guglielmi A (2019) Role of lymph node dissection in small (≤3 cm) intrahepatic cholangiocarcinoma. J Gastrointest Surg 23(6):1122–1129

    Article  Google Scholar 

  21. Kobayashi S, Nagano H, Hoshino H, Wada H, Marubashi S, Eguchi H, Takeda Y, Tanemura M, Kim T, Shimosegawa E, Hatazawa J, Doki Y, Mori M (2011) Diagnostic value of FDG-PET for lymph node metastasis and outcome of surgery for biliary cancer. J Surg Oncol 103(3):223–229

    Article  Google Scholar 

  22. Kobayashi S, Tomokuni A, Takahashi H, Akita H, Marubashi S, Gotoh K, Yanagimoto Y, Takahashi Y, Sugimura K, Miyoshi N, Moon JH, Yasui M, Omori T, Miyata H, Ohue M, Fujiwara Y, Yano M, Sakon M (2018) Laparoscopic hilar lymph node sampling in patients with biliary tract cancers that are rarely associated with nodal metastasis. Surg Laparosc Endosc Percutan Tech 28(2):90–95

    PubMed  Google Scholar 

  23. Kobayashi S, Nagano H, Sakai D, Eguchi H, Hatano E, Kanai M, Seo S, Taura K, Fujiwara Y, Ajiki T, Takemura S, Kubo S, Yanagimoto H, Toyokawa H, Tsuji A, Terajima H, Morita S, Ioka T (2014) Phase I study of adjuvant gemcitabine or S-1 in patients with biliary tract cancers undergoing major hepatectomy: KHBO1003 study. Cancer Chemother Pharmacol 74(4):699–709

    Article  CAS  Google Scholar 

  24. Toyoda M, Ajiki T, Fujiwara Y, Nagano H, Kobayashi S, Sakai D, Hatano E, Kanai M, Nakamori S, Miyamoto A, Tsuji A, Kaihara S, Ikoma H, Takemura S, Toyokawa H, Terajima H, Morita S, Ioka T (2014) Phase I study of adjuvant chemotherapy with gemcitabine plus cisplatin in patients with biliary tract cancer undergoing curative resection without major hepatectomy (KHBO1004). Cancer Chemother Pharmacol 73(6):1295–1301

    Article  CAS  Google Scholar 

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Funding

The present study was supported by a Grant-in-Aid for Scientific Research (C) 15K10202 and 18K08703 of Japan Society for the Promotion of Science.

Author information

Authors and Affiliations

  1. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 (E2) Yamadaoka, Suita city, Osaka, 537-8511, Japan

    Shogo Kobayashi, Kunihito Gotoh, Masaki Mori, Yuichiro Doki & Hidetoshi Eguchi

  2. Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan

    Shogo Kobayashi, Hiroshi Wada, Akira Tomokuni, Hidenori Takahashi & Masato Sakon

  3. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Masaki Mori

Authors
  1. Shogo Kobayashi
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  2. Hiroshi Wada
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  3. Akira Tomokuni
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  4. Hidenori Takahashi
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  5. Kunihito Gotoh
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  6. Masato Sakon
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  7. Masaki Mori
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  8. Yuichiro Doki
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  9. Hidetoshi Eguchi
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Contributions

The individual contributions were as follows:

Study conception and design: All authors

Surgery: SK, HW, HE, AT, HT, KG

Statistical analysis: SK, HW, HE, AT, HT, KG

Data acquisition: All authors

Data analysis and interpretation: All authors

Drafting of the manuscript: All authors

Critical revision of the manuscript: All authors

Corresponding author

Correspondence to Shogo Kobayashi.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

This study was approved by the institutional review board (approve number: 1511209163).

Consent to participate

All patients signed an informed consent form in accordance with the Declaration of Helsinki.

Consent for publication

All patients signed an informed consent form.

Code availability

The statistical software program used was StatView J-5.0 (SAS, Cary, NC, USA).

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Kobayashi, S., Wada, H., Tomokuni, A. et al. Invasion category-oriented lymph node metastases of cholangiocarcinoma and the prognostic impact. Langenbecks Arch Surg 405, 989–998 (2020). https://doi.org/10.1007/s00423-020-01955-3

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  • DOI: https://doi.org/10.1007/s00423-020-01955-3

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