Skip to main content
Erschienen in: Journal of Gastrointestinal Surgery 11/2016

16.06.2016 | Original Article

Multiplication of Tumor Volume by Two Tumor Markers Is a Post-Resection Prognostic Predictor for Solitary Hepatocellular Carcinoma

verfasst von: Shin Hwang, Gi-Won Song, Young-Joo Lee, Ki-Hun Kim, Chul-Soo Ahn, Deok-Bog Moon, Tae-Yong Ha, Dong-Hwan Jung, Gil-Chun Park, Sung-Gyu Lee

Erschienen in: Journal of Gastrointestinal Surgery | Ausgabe 11/2016

Einloggen, um Zugang zu erhalten

Abstract

Background

We hypothesized that microvascular invasion (MVI) and post-resection prognosis in patients with solitary hepatocellular carcinoma (HCC) could be predicted using blood tumor markers and tumor volume (TV). We intended to identify a simple surrogate marker of HCC via a combination of clinical variables.

Methods

This retrospective study used the strictly selected development cohort (n = 1176) and validation cohort (n = 551) containing patients who underwent curative resection of solitary HCC.

Results

In the development cohort study, the median values were 13.7 mL for TV, 24.2 ng/mL for α-fetoprotein (AFP), and 75 mAU/mL for des-γ-carboxy prothrombin (DCP); there was no correlation among these three factors (r 2 ≤ 0.237, p < 0.001). The 1-, 3-, and 5-year rates were 22.4, 41.7, and 46.8 % for tumor recurrence and 93.6, 84.0, and 78.2 % for patient survival, respectively. Independent risk factors for both tumor recurrence and patient survival were tumor diameter >5 cm or TV >50 mL, MVI, satellite nodules, and high DCP. Multiplication of AFP, DCP, and TV (ADV score) resulted in prediction of MVI at a cutoff of 5log with sensitivity of 73.9 % and specificity of 66.7 %. Patient stratifications according to ADV score with cutoffs of 5log alone, 6log and 9log, and its combination with MVI showed significant prognostic differences (all p < 0.001). These prognostic significances were reliably reproduced in the validation cohort study (all p < 0.001).

Conclusions

We suggest that ADV score is an integrated surrogate marker of HCC prognosis. We believe that it can be used to predict MVI and post-resection prognosis for solitary HCC.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
2.
Zurück zum Zitat Pawlik TM, Delman KA, Vauthey JN, Nagorney DM, Ng IO, Ikai I, et al. Tumor size predicts vascular invasion and histologic grade: Implications for selection of surgical treatment for hepatocellular carcinoma. Liver Transpl 2005;11:1086–1092.CrossRefPubMed Pawlik TM, Delman KA, Vauthey JN, Nagorney DM, Ng IO, Ikai I, et al. Tumor size predicts vascular invasion and histologic grade: Implications for selection of surgical treatment for hepatocellular carcinoma. Liver Transpl 2005;11:1086–1092.CrossRefPubMed
3.
Zurück zum Zitat Shirabe K, Itoh S, Yoshizumi T, Soejima Y, Taketomi A, Aishima S, et al. The predictors of microvascular invasion in candidates for liver transplantation with hepatocellular carcinoma-with special reference to the serum levels of des-gamma-carboxy prothrombin. J Surg Oncol 2007;95:235–240.CrossRefPubMed Shirabe K, Itoh S, Yoshizumi T, Soejima Y, Taketomi A, Aishima S, et al. The predictors of microvascular invasion in candidates for liver transplantation with hepatocellular carcinoma-with special reference to the serum levels of des-gamma-carboxy prothrombin. J Surg Oncol 2007;95:235–240.CrossRefPubMed
4.
Zurück zum Zitat Park H, Park JY. Clinical significance of AFP and PIVKA-II responses for monitoring treatment outcomes and predicting prognosis in patients with hepatocellular carcinoma. Biomed Res Int 2013;2013:310427.PubMedPubMedCentral Park H, Park JY. Clinical significance of AFP and PIVKA-II responses for monitoring treatment outcomes and predicting prognosis in patients with hepatocellular carcinoma. Biomed Res Int 2013;2013:310427.PubMedPubMedCentral
5.
Zurück zum Zitat Toso C, Trotter J, Wei A, Bigam DL, Shah S, Lancaster J, et al. Total tumor volume predicts risk of recurrence following liver transplantation in patients with hepatocellular carcinoma. Liver Transpl 2008;14:1107–1115.CrossRefPubMed Toso C, Trotter J, Wei A, Bigam DL, Shah S, Lancaster J, et al. Total tumor volume predicts risk of recurrence following liver transplantation in patients with hepatocellular carcinoma. Liver Transpl 2008;14:1107–1115.CrossRefPubMed
6.
Zurück zum Zitat Hsu CY, Huang YH, Hsia CY, Su CW, Lin HC, Loong CC, et al. A new prognostic model for hepatocellular carcinoma based on total tumor volume: the Taipei Integrated Scoring System. J Hepatol 2010;53:108–117.CrossRefPubMed Hsu CY, Huang YH, Hsia CY, Su CW, Lin HC, Loong CC, et al. A new prognostic model for hepatocellular carcinoma based on total tumor volume: the Taipei Integrated Scoring System. J Hepatol 2010;53:108–117.CrossRefPubMed
7.
Zurück zum Zitat Kashkoush S, El Moghazy W, Kawahara T, Gala-Lopez B, Toso C, Kneteman NM. Three-dimensional tumor volume and serum alpha-fetoprotein are predictors of hepatocellular carcinoma recurrence after liver transplantation: refined selection criteria. Clin Transplant 2014;28:728–736.CrossRefPubMed Kashkoush S, El Moghazy W, Kawahara T, Gala-Lopez B, Toso C, Kneteman NM. Three-dimensional tumor volume and serum alpha-fetoprotein are predictors of hepatocellular carcinoma recurrence after liver transplantation: refined selection criteria. Clin Transplant 2014;28:728–736.CrossRefPubMed
8.
Zurück zum Zitat Hwang S, Ha TY, Song GW, Jung DH, Ahn CS, Moon DB, et al. Quantified risk assessment for major hepatectomy via the indocyanine green clearance rate and liver volumetry combined with standard liver volume. J Gastrointest Surg 2015;19:1305–1314.CrossRefPubMed Hwang S, Ha TY, Song GW, Jung DH, Ahn CS, Moon DB, et al. Quantified risk assessment for major hepatectomy via the indocyanine green clearance rate and liver volumetry combined with standard liver volume. J Gastrointest Surg 2015;19:1305–1314.CrossRefPubMed
9.
Zurück zum Zitat The Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines: management of chronic hepatitis B. Clin Mol Hepatol 2016;22:18–75.CrossRef The Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines: management of chronic hepatitis B. Clin Mol Hepatol 2016;22:18–75.CrossRef
10.
Zurück zum Zitat Hwang S, Lee YJ, Kim KH, Ahn CS, Moon DB, Ha TY, et al. The impact of tumor size on long-term survival outcomes after resection of solitary hepatocellular carcinoma: single-institution experience with 2558 patients. J Gastrointest Surg 2015;19:1281–1290.CrossRefPubMed Hwang S, Lee YJ, Kim KH, Ahn CS, Moon DB, Ha TY, et al. The impact of tumor size on long-term survival outcomes after resection of solitary hepatocellular carcinoma: single-institution experience with 2558 patients. J Gastrointest Surg 2015;19:1281–1290.CrossRefPubMed
11.
Zurück zum Zitat Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, III, eds. AJCC cancer staging manual. 7th ed. New York: Springer; 2010. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, III, eds. AJCC cancer staging manual. 7th ed. New York: Springer; 2010.
13.
Zurück zum Zitat Ha TY, Hwang S, Kim KH, Lee YJ, Ahn CS, Moon DB, et al. Expression pattern analysis of hepatocellular carcinoma tumor markers in viral hepatitis B and C patients undergoing liver transplantation and resection. Transplant Proc 2014;46:888–893.CrossRefPubMed Ha TY, Hwang S, Kim KH, Lee YJ, Ahn CS, Moon DB, et al. Expression pattern analysis of hepatocellular carcinoma tumor markers in viral hepatitis B and C patients undergoing liver transplantation and resection. Transplant Proc 2014;46:888–893.CrossRefPubMed
14.
Zurück zum Zitat Vauthey JN, Lauwers GY, Esnaola NF, Do KA, Belghiti J, Mirza N, et al. Simplified staging for hepatocellular carcinoma. J Clin Oncol 2002;20:1527–1536.CrossRefPubMed Vauthey JN, Lauwers GY, Esnaola NF, Do KA, Belghiti J, Mirza N, et al. Simplified staging for hepatocellular carcinoma. J Clin Oncol 2002;20:1527–1536.CrossRefPubMed
15.
Zurück zum Zitat Zhang H, Yuan SX, Dai SY, Zhang JM, Huang X, Lu CD, et al. Tumor size does not independently affect long-term survival after curative resection of solitary hepatocellular carcinoma without macroscopic vascular invasion. World J Surg 2014;38:947–957.CrossRefPubMed Zhang H, Yuan SX, Dai SY, Zhang JM, Huang X, Lu CD, et al. Tumor size does not independently affect long-term survival after curative resection of solitary hepatocellular carcinoma without macroscopic vascular invasion. World J Surg 2014;38:947–957.CrossRefPubMed
16.
Zurück zum Zitat Yang LY, Fang F, Ou DP, Zhang JM, Huang X, Lu CD, et al. Solitary large hepatocellular carcinoma: a specific subtype of hepatocellular carcinoma with good outcome after hepatic resection. Ann Surg 2009;249:118–123.CrossRefPubMed Yang LY, Fang F, Ou DP, Zhang JM, Huang X, Lu CD, et al. Solitary large hepatocellular carcinoma: a specific subtype of hepatocellular carcinoma with good outcome after hepatic resection. Ann Surg 2009;249:118–123.CrossRefPubMed
17.
18.
Zurück zum Zitat Renzulli M, Brocchi S, Cucchetti A, Mazzotti F, Mosconi C, Sportoletti C, et al. Can current preoperative imaging be used to detect microvascular invasion of hepatocellular carcinoma? Radiology 2016;279:432–442.CrossRefPubMed Renzulli M, Brocchi S, Cucchetti A, Mazzotti F, Mosconi C, Sportoletti C, et al. Can current preoperative imaging be used to detect microvascular invasion of hepatocellular carcinoma? Radiology 2016;279:432–442.CrossRefPubMed
19.
Zurück zum Zitat Ahn SY, Lee JM, Joo I, Lee ES, Lee SJ, Cheon GJ, et al. Prediction of microvascular invasion of hepatocellular carcinoma using gadoxetic acid-enhanced MR and (18)F-FDG PET/CT. Abdom Imaging 2015;40:843–851.CrossRefPubMed Ahn SY, Lee JM, Joo I, Lee ES, Lee SJ, Cheon GJ, et al. Prediction of microvascular invasion of hepatocellular carcinoma using gadoxetic acid-enhanced MR and (18)F-FDG PET/CT. Abdom Imaging 2015;40:843–851.CrossRefPubMed
20.
Zurück zum Zitat Chou CT, Chen RC, Lin WC, Ko CJ, Chen CB, Chen YL. Prediction of microvascular invasion of hepatocellular carcinoma: preoperative CT and histopathologic correlation. AJR Am J Roentgenol 2014;203:W253–259.CrossRefPubMed Chou CT, Chen RC, Lin WC, Ko CJ, Chen CB, Chen YL. Prediction of microvascular invasion of hepatocellular carcinoma: preoperative CT and histopathologic correlation. AJR Am J Roentgenol 2014;203:W253–259.CrossRefPubMed
21.
Zurück zum Zitat Suh YJ, Kim MJ, Choi JY, Park MS, Kim KW. Preoperative prediction of the microvascular invasion of hepatocellular carcinoma with diffusion-weighted imaging. Liver Transpl 2012;18:1171–1178.CrossRefPubMed Suh YJ, Kim MJ, Choi JY, Park MS, Kim KW. Preoperative prediction of the microvascular invasion of hepatocellular carcinoma with diffusion-weighted imaging. Liver Transpl 2012;18:1171–1178.CrossRefPubMed
22.
Zurück zum Zitat Min JH, Kim YK, Lim S, Jeong WK, Choi D, Lee WJ. Prediction of microvascular invasion of hepatocellular carcinomas with gadoxetic acid-enhanced MR imaging: Impact of intra-tumoral fat detected on chemical-shift images. Eur J Radiol 2015;84:1036–1043.CrossRefPubMed Min JH, Kim YK, Lim S, Jeong WK, Choi D, Lee WJ. Prediction of microvascular invasion of hepatocellular carcinomas with gadoxetic acid-enhanced MR imaging: Impact of intra-tumoral fat detected on chemical-shift images. Eur J Radiol 2015;84:1036–1043.CrossRefPubMed
23.
Zurück zum Zitat Shirabe K, Toshima T, Kimura K, Yamashita Y, Ikeda T, Ikegami T, et al. New scoring system for prediction of microvascular invasion in patients with hepatocellular carcinoma. Liver Int 2014;34:937–941.CrossRefPubMed Shirabe K, Toshima T, Kimura K, Yamashita Y, Ikeda T, Ikegami T, et al. New scoring system for prediction of microvascular invasion in patients with hepatocellular carcinoma. Liver Int 2014;34:937–941.CrossRefPubMed
24.
Zurück zum Zitat Poté N, Cauchy F, Albuquerque M, Voitot H, Belghiti J, Castera L, et al. Performance of PIVKA-II for early hepatocellular carcinoma diagnosis and prediction of microvascular invasion. J Hepatol 2015;62:848–854.CrossRefPubMed Poté N, Cauchy F, Albuquerque M, Voitot H, Belghiti J, Castera L, et al. Performance of PIVKA-II for early hepatocellular carcinoma diagnosis and prediction of microvascular invasion. J Hepatol 2015;62:848–854.CrossRefPubMed
25.
Zurück zum Zitat Kurokawa T, Yamazaki S, Mitsuka Y, Moriguchi M, Sugitani M, Takayama T. Prediction of vascular invasion in hepatocellular carcinoma by next-generation des-r-carboxy prothrombin. Br J Cancer 2016;114:53–58.CrossRefPubMed Kurokawa T, Yamazaki S, Mitsuka Y, Moriguchi M, Sugitani M, Takayama T. Prediction of vascular invasion in hepatocellular carcinoma by next-generation des-r-carboxy prothrombin. Br J Cancer 2016;114:53–58.CrossRefPubMed
26.
Zurück zum Zitat Meguro M, Mizuguchi T, Nishidate T, Okita K, Ishii M, Ota S, et al. Prognostic roles of preoperative α-fetoprotein and des-γ-carboxy prothrombin in hepatocellular carcinoma patients. World J Gastroenterol 2015;21:4933–4945.CrossRefPubMedPubMedCentral Meguro M, Mizuguchi T, Nishidate T, Okita K, Ishii M, Ota S, et al. Prognostic roles of preoperative α-fetoprotein and des-γ-carboxy prothrombin in hepatocellular carcinoma patients. World J Gastroenterol 2015;21:4933–4945.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Kiriyama S, Uchiyama K, Ueno M, Ozawa S, Hayami S, Tani M, et al. Triple positive tumor markers for hepatocellular carcinoma are useful predictors of poor survival. Ann Surg 2011;254:984–991.CrossRefPubMed Kiriyama S, Uchiyama K, Ueno M, Ozawa S, Hayami S, Tani M, et al. Triple positive tumor markers for hepatocellular carcinoma are useful predictors of poor survival. Ann Surg 2011;254:984–991.CrossRefPubMed
28.
Zurück zum Zitat Nakagawa S, Beppu T, Okabe H, Sakamoto K, Kuroki H, Mima K, et al. Triple positive tumor markers predict recurrence and survival in early stage hepatocellular carcinoma. Hepatol Res 2014;44:964–974.CrossRefPubMed Nakagawa S, Beppu T, Okabe H, Sakamoto K, Kuroki H, Mima K, et al. Triple positive tumor markers predict recurrence and survival in early stage hepatocellular carcinoma. Hepatol Res 2014;44:964–974.CrossRefPubMed
29.
Zurück zum Zitat Suh SW, Lee KW, Lee JM, You T, Choi Y, Kim H, et al. Prediction of aggressiveness in early-stage hepatocellular carcinoma for selection of surgical resection. J Hepatol 2014;60:1219–1924.CrossRefPubMed Suh SW, Lee KW, Lee JM, You T, Choi Y, Kim H, et al. Prediction of aggressiveness in early-stage hepatocellular carcinoma for selection of surgical resection. J Hepatol 2014;60:1219–1924.CrossRefPubMed
30.
Zurück zum Zitat Kamiyama T, Yokoo H, Kakisaka T, Orimo T, Wakayama K, Kamachi H, et al. Multiplication of alpha-fetoprotein and protein induced by vitamin K absence-II is a powerful predictor of prognosis and recurrence in hepatocellular carcinoma patients after a hepatectomy. Hepatol Res 2015;45:E21–31.CrossRefPubMed Kamiyama T, Yokoo H, Kakisaka T, Orimo T, Wakayama K, Kamachi H, et al. Multiplication of alpha-fetoprotein and protein induced by vitamin K absence-II is a powerful predictor of prognosis and recurrence in hepatocellular carcinoma patients after a hepatectomy. Hepatol Res 2015;45:E21–31.CrossRefPubMed
31.
Zurück zum Zitat An C, Choi YA, Choi D, Paik YH, Ahn SH, Kim MJ, et al. Growth rate of early-stage hepatocellular carcinoma in patients with chronic liver disease. Clin Mol Hepatol 2015;21:279–286.CrossRefPubMedPubMedCentral An C, Choi YA, Choi D, Paik YH, Ahn SH, Kim MJ, et al. Growth rate of early-stage hepatocellular carcinoma in patients with chronic liver disease. Clin Mol Hepatol 2015;21:279–286.CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Galizia MS, Töre HG, Chalian H, Yaghmai V. Evaluation of hepatocellular carcinoma size using two-dimensional and volumetric analysis: effect on liver transplantation eligibility. Acad Radiol 2011;18:1555–1560.CrossRefPubMed Galizia MS, Töre HG, Chalian H, Yaghmai V. Evaluation of hepatocellular carcinoma size using two-dimensional and volumetric analysis: effect on liver transplantation eligibility. Acad Radiol 2011;18:1555–1560.CrossRefPubMed
33.
Zurück zum Zitat Kim HD, Shim JH, Kim GA, Shin YM, Yu E, Lee SG, et al. Optimal methods for measuring eligibility for liver transplant in hepatocellular carcinoma patients undergoing transarterial chemoembolization. J Hepatol 2015;62:1076–1084.CrossRefPubMed Kim HD, Shim JH, Kim GA, Shin YM, Yu E, Lee SG, et al. Optimal methods for measuring eligibility for liver transplant in hepatocellular carcinoma patients undergoing transarterial chemoembolization. J Hepatol 2015;62:1076–1084.CrossRefPubMed
34.
Zurück zum Zitat Xu W, Kwon JH, Moon YH, Kim YB, Yu YS, Lee N, et al. Influence of preoperative transcatheter arterial chemoembolization on gene expression in the HIF-1α pathway in patients with hepatocellular carcinoma. J Cancer Res Clin Oncol 2014;140:1507–1515.CrossRefPubMed Xu W, Kwon JH, Moon YH, Kim YB, Yu YS, Lee N, et al. Influence of preoperative transcatheter arterial chemoembolization on gene expression in the HIF-1α pathway in patients with hepatocellular carcinoma. J Cancer Res Clin Oncol 2014;140:1507–1515.CrossRefPubMed
35.
Zurück zum Zitat Shin HN, Hwang S, Kim KH, Ahn CS, Moon DB, Ha TY, et al. Role of the 1-month protocol transarterial chemoinfusion in detecting intrahepatic metastasis after resection of large hepatocellular carcinoma greater than 10 cm. Korean J Hepatobiliary Pancreat Surg 2013;17:157–161.CrossRefPubMedPubMedCentral Shin HN, Hwang S, Kim KH, Ahn CS, Moon DB, Ha TY, et al. Role of the 1-month protocol transarterial chemoinfusion in detecting intrahepatic metastasis after resection of large hepatocellular carcinoma greater than 10 cm. Korean J Hepatobiliary Pancreat Surg 2013;17:157–161.CrossRefPubMedPubMedCentral
Metadaten
Titel
Multiplication of Tumor Volume by Two Tumor Markers Is a Post-Resection Prognostic Predictor for Solitary Hepatocellular Carcinoma
verfasst von
Shin Hwang
Gi-Won Song
Young-Joo Lee
Ki-Hun Kim
Chul-Soo Ahn
Deok-Bog Moon
Tae-Yong Ha
Dong-Hwan Jung
Gil-Chun Park
Sung-Gyu Lee
Publikationsdatum
16.06.2016
Verlag
Springer US
Erschienen in
Journal of Gastrointestinal Surgery / Ausgabe 11/2016
Print ISSN: 1091-255X
Elektronische ISSN: 1873-4626
DOI
https://doi.org/10.1007/s11605-016-3187-y

Weitere Artikel der Ausgabe 11/2016

Journal of Gastrointestinal Surgery 11/2016 Zur Ausgabe

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare
CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare
CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare
CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.