Skip to main content
Erschienen in: Surgery Today 5/2021

22.09.2020 | Original Article

Enhanced patterns on intraoperative contrast-enhanced ultrasonography predict outcomes after curative liver resection in patients with hepatocellular carcinoma

verfasst von: Ikuo Nakamura, Etsuro Hatano, Masaharu Tada, Yusuke Kawabata, Shinjiro Tamagawa, Ami Kurimoto, Hideaki Iwama, Kan Toriguchi, Hideaki Sueoka, Kenjiro Iida, Masahiro Yoshida, Takashi Nishimura, Hiroko Iijima

Erschienen in: Surgery Today | Ausgabe 5/2021

Einloggen, um Zugang zu erhalten

Abstract

Purpose

This study aimed to clarify what hepatocellular carcinoma (HCC) phenotype, as categorized by intraoperative contrast-enhanced ultrasonography (CEUS), showed a high risk of recurrence after hepatic resection.

Methods

Patients who underwent initial curative hepatectomy with intraoperative CEUS for a single HCC nodule were retrospectively assigned to three patterns of fine (FI), vascular (VA), and irregular (IR) according to the maximum intensity projection pattern based on intraoperative CEUS. Staining was performed for Ki-67, pyruvate kinase type M2 (PKM2), and vascular endothelial growth factor (VEGF) to assess the tumor proliferative activity, tumor glucose metabolism, and angiogenesis, respectively.

Results

Of 116 patients, 18, 50, and 48 were assigned to the FI, VA and IR patterns, respectively. IR patients demonstrated a significantly worse prognosis for both the recurrence-free survival (RFS) and overall survival (OS) (P = 0.0002, 0.0262, respectively) than did patients with other patterns. A multivariate analysis revealed an IR pattern in intraoperative CEUS to be an independent predictive factor for a poor RFS, and major hepatectomy and an IR pattern were independent predictive factors for a poor OS. An IR pattern was closely related to the tumor size (≥ 3.3 cm) and poor histological differentiation and showed a high Ki-67 index, low VEGF expression, and high PKM2 expression.

Conclusion

IR-pattern HCCs as classified by intraoperative CEUS may be associated with a higher risk of recurrence and worse outcomes in HCC patients after hepatic resection than other patterns.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.CrossRef Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.CrossRef
2.
Zurück zum Zitat Teefey SA, Hildeboldt CC, Dehdashti F, Siegel BA, Peters MG, Heiken JP, et al. Detection of primary hepatic malignancy in liver transplant candidates: prospective comparison of CT, MR imaging, US, and PET. Radiology. 2003;226:533–42.CrossRef Teefey SA, Hildeboldt CC, Dehdashti F, Siegel BA, Peters MG, Heiken JP, et al. Detection of primary hepatic malignancy in liver transplant candidates: prospective comparison of CT, MR imaging, US, and PET. Radiology. 2003;226:533–42.CrossRef
3.
Zurück zum Zitat Choi J, Lee JM, Sirlin CB. CT and MR imaging diagnosis and staging of hepatocellular carcinoma: part II. Extracellular agents, hepatobiliary agents, and ancillary imaging features. Radiology. 2014;273:30–50.CrossRef Choi J, Lee JM, Sirlin CB. CT and MR imaging diagnosis and staging of hepatocellular carcinoma: part II. Extracellular agents, hepatobiliary agents, and ancillary imaging features. Radiology. 2014;273:30–50.CrossRef
4.
Zurück zum Zitat Maruyama H, Sekimoto T, Yokosuka O. Role of contrast-enhanced ultrasonography with sonazoid for hepatocellular carcinoma: evidence from a 10-year experience. J Gastroenterol. 2016;51:421–33.CrossRef Maruyama H, Sekimoto T, Yokosuka O. Role of contrast-enhanced ultrasonography with sonazoid for hepatocellular carcinoma: evidence from a 10-year experience. J Gastroenterol. 2016;51:421–33.CrossRef
5.
Zurück zum Zitat Sato K, Tanaka S, Mitsunori Y, Mogushi K, Yasen M, Aihara A, et al. Contrast-enhanced intraoperative ultrasonography for vascular imaging of hepatocellular carcinoma: clinical and biological significance. Hepatology. 2013;57:1436–47.CrossRef Sato K, Tanaka S, Mitsunori Y, Mogushi K, Yasen M, Aihara A, et al. Contrast-enhanced intraoperative ultrasonography for vascular imaging of hepatocellular carcinoma: clinical and biological significance. Hepatology. 2013;57:1436–47.CrossRef
6.
Zurück zum Zitat Postema M, Gilja OH. Contrast-enhanced and targeted ultrasound. World J Gastroenterol. 2011;17:28–41.CrossRef Postema M, Gilja OH. Contrast-enhanced and targeted ultrasound. World J Gastroenterol. 2011;17:28–41.CrossRef
7.
Zurück zum Zitat Wilson SR, Jang HJ, Kim TK, Iijima H, Kamiyama N, Burns PN. Real-time temporal maximum-intensity-projection imaging of hepatic lesions with contrast-enhanced sonography. AJR Am J Roentgenol. 2008;190:691–5.CrossRef Wilson SR, Jang HJ, Kim TK, Iijima H, Kamiyama N, Burns PN. Real-time temporal maximum-intensity-projection imaging of hepatic lesions with contrast-enhanced sonography. AJR Am J Roentgenol. 2008;190:691–5.CrossRef
8.
Zurück zum Zitat Sugimoto K, Moriyasu F, Kamiyama N, Metoki R, Yamada M, Imai Y, et al. Analysis of morphological vascular changes of hepatocellular carcinoma by microflow imaging using contrast-enhanced sonography. Hepatol Res. 2008;38:790–9.CrossRef Sugimoto K, Moriyasu F, Kamiyama N, Metoki R, Yamada M, Imai Y, et al. Analysis of morphological vascular changes of hepatocellular carcinoma by microflow imaging using contrast-enhanced sonography. Hepatol Res. 2008;38:790–9.CrossRef
9.
Zurück zum Zitat Kruskal JB, Kane RA. Intraoperative US of the liver: techniques and clinical applications. Radiographics. 2006;26:1067–84.CrossRef Kruskal JB, Kane RA. Intraoperative US of the liver: techniques and clinical applications. Radiographics. 2006;26:1067–84.CrossRef
10.
Zurück zum Zitat Zhou YT, Cai WW, Li Y, Jiang X, Feng L, Zhu QY, et al. Correlations between quantitative parameters of contrast-enhanced ultrasound and vasculogenic mimicry in murine tumor model: a novel noninvasive technique for assessment? Biol Proc Online. 2019;21:11.CrossRef Zhou YT, Cai WW, Li Y, Jiang X, Feng L, Zhu QY, et al. Correlations between quantitative parameters of contrast-enhanced ultrasound and vasculogenic mimicry in murine tumor model: a novel noninvasive technique for assessment? Biol Proc Online. 2019;21:11.CrossRef
11.
Zurück zum Zitat Cheng LG, He W, Zhang HX, Song Q, Ning B, Li HZ, et al. Intraoperative contrast enhanced ultrasound evaluates the grade of glioma. Biomed Res Int. 2016;2016:2643862.PubMedPubMedCentral Cheng LG, He W, Zhang HX, Song Q, Ning B, Li HZ, et al. Intraoperative contrast enhanced ultrasound evaluates the grade of glioma. Biomed Res Int. 2016;2016:2643862.PubMedPubMedCentral
12.
Zurück zum Zitat Vraka I, Panourgias E, Sifakis E, Koureas A, Galanis P, Dellaportas D, et al. Correlation between contrast-enhanced ultrasound characteristics (qualitative and quantitative) and pathological prognostic factors in breast cancer. In Vivo. 2018;32:945–54.CrossRef Vraka I, Panourgias E, Sifakis E, Koureas A, Galanis P, Dellaportas D, et al. Correlation between contrast-enhanced ultrasound characteristics (qualitative and quantitative) and pathological prognostic factors in breast cancer. In Vivo. 2018;32:945–54.CrossRef
13.
Zurück zum Zitat Kudo M, Kitano M, Sakurai T, Nishida N. General rules for the clinical and pathological study of primary liver cancer, nationwide follow-up survey and clinical practice guidelines: the outstanding achievements of the Liver Cancer Study Group of Japan. Digest Dis. 2015;33:765–70.CrossRef Kudo M, Kitano M, Sakurai T, Nishida N. General rules for the clinical and pathological study of primary liver cancer, nationwide follow-up survey and clinical practice guidelines: the outstanding achievements of the Liver Cancer Study Group of Japan. Digest Dis. 2015;33:765–70.CrossRef
14.
Zurück zum Zitat Tanaka H, Iijima H, Higashiura A, Yoh K, Ishii A, Takashima T, et al. New malignant grading system for hepatocellular carcinoma using the sonazoid contrast agent for ultrasonography. J Gastroenterol. 2014;49:755–63.CrossRef Tanaka H, Iijima H, Higashiura A, Yoh K, Ishii A, Takashima T, et al. New malignant grading system for hepatocellular carcinoma using the sonazoid contrast agent for ultrasonography. J Gastroenterol. 2014;49:755–63.CrossRef
15.
Zurück zum Zitat Lam CM, Fan ST, Lo CM, Wong J. Major hepatectomy for hepatocellular carcinoma in patients with an unsatisfactory indocyanine green clearance test. Br J Surg. 1999;86:1012–7.CrossRef Lam CM, Fan ST, Lo CM, Wong J. Major hepatectomy for hepatocellular carcinoma in patients with an unsatisfactory indocyanine green clearance test. Br J Surg. 1999;86:1012–7.CrossRef
16.
Zurück zum Zitat Couinaud C. Liver lobes and segments: notes on the anatomical architecture and surgery of the liver. Presse Med. 1954;62:709–12.PubMed Couinaud C. Liver lobes and segments: notes on the anatomical architecture and surgery of the liver. Presse Med. 1954;62:709–12.PubMed
17.
Zurück zum Zitat Hasegawa K, Kokudo N, Imamura H, Matsuyama Y, Aoki T, Minagawa M, et al. Prognostic impact of anatomic resection for hepatocellular carcinoma. Ann Surg. 2005;242:252–9.CrossRef Hasegawa K, Kokudo N, Imamura H, Matsuyama Y, Aoki T, Minagawa M, et al. Prognostic impact of anatomic resection for hepatocellular carcinoma. Ann Surg. 2005;242:252–9.CrossRef
18.
Zurück zum Zitat Kitamura K, Hatano E, Higashi T, Narita M, Seo S, Nakamoto Y, et al. Proliferative activity in hepatocellular carcinoma is closely correlated with glucose metabolism but not angiogenesis. J Hepatol. 2011;55:846–57.CrossRef Kitamura K, Hatano E, Higashi T, Narita M, Seo S, Nakamoto Y, et al. Proliferative activity in hepatocellular carcinoma is closely correlated with glucose metabolism but not angiogenesis. J Hepatol. 2011;55:846–57.CrossRef
19.
Zurück zum Zitat Watanabe R, Matsumura M, Chen CJ, Kaneda Y, Ishihara M, Fujimaki M. Gray-scale liver enhancement with sonazoid (NC100100), a novel ultrasound contrast agent; detection of hepatic tumors in a rabbit model. Biol Pharm Bull. 2003;26:1272–7.CrossRef Watanabe R, Matsumura M, Chen CJ, Kaneda Y, Ishihara M, Fujimaki M. Gray-scale liver enhancement with sonazoid (NC100100), a novel ultrasound contrast agent; detection of hepatic tumors in a rabbit model. Biol Pharm Bull. 2003;26:1272–7.CrossRef
20.
Zurück zum Zitat Hagen EK, Forsberg F, Aksnes AK, Merton DA, Liu JB, Tornes A, et al. Enhanced detection of blood flow in the normal canine prostate using an ultrasound contrast agent. Investig Radiol. 2000;35:118–24.CrossRef Hagen EK, Forsberg F, Aksnes AK, Merton DA, Liu JB, Tornes A, et al. Enhanced detection of blood flow in the normal canine prostate using an ultrasound contrast agent. Investig Radiol. 2000;35:118–24.CrossRef
21.
Zurück zum Zitat Takada H, Tsuchiya K, Yasui Y, Nakakuki N, Tamaki N, Suzuki S, et al. Irregular vascular pattern by contrast-enhanced ultrasonography and high serum lens culinaris agglutinin-reactive fraction of alpha-fetoprotein level predict poor outcome after successful radiofrequency ablation in patients with early-stage hepatocellular carcinoma. Cancer Med. 2016;5:3111–200.CrossRef Takada H, Tsuchiya K, Yasui Y, Nakakuki N, Tamaki N, Suzuki S, et al. Irregular vascular pattern by contrast-enhanced ultrasonography and high serum lens culinaris agglutinin-reactive fraction of alpha-fetoprotein level predict poor outcome after successful radiofrequency ablation in patients with early-stage hepatocellular carcinoma. Cancer Med. 2016;5:3111–200.CrossRef
22.
Zurück zum Zitat Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000;182:311–22.CrossRef Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000;182:311–22.CrossRef
23.
Zurück zum Zitat Kitamura K, Hatano E, Higashi T, Seo S, Nakamoto Y, Yamanaka K, et al. Preoperative FDG-PET predicts recurrence patterns in hepatocellular carcinoma. Ann Surg Oncol. 2012;19:156–62.CrossRef Kitamura K, Hatano E, Higashi T, Seo S, Nakamoto Y, Yamanaka K, et al. Preoperative FDG-PET predicts recurrence patterns in hepatocellular carcinoma. Ann Surg Oncol. 2012;19:156–62.CrossRef
24.
Zurück zum Zitat Folkman J. Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov. 2007;6:273–86.CrossRef Folkman J. Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov. 2007;6:273–86.CrossRef
25.
Zurück zum Zitat Kleespies A, Guba M, Jauch KW, Bruns CJ. Vascular endothelial growth factor in esophageal cancer. J Surg Oncol. 2004;87:95–104.CrossRef Kleespies A, Guba M, Jauch KW, Bruns CJ. Vascular endothelial growth factor in esophageal cancer. J Surg Oncol. 2004;87:95–104.CrossRef
26.
Zurück zum Zitat Takahashi Y, Kitadai Y, Bucana CD, Cleary KR, Ellis LM. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res. 1995;55:3964–8.PubMed Takahashi Y, Kitadai Y, Bucana CD, Cleary KR, Ellis LM. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res. 1995;55:3964–8.PubMed
27.
Zurück zum Zitat Yamaguchi R, Yano H, Iemura A, Ogasawara S, Haramaki M, Kojiro M. Expression of vascular endothelial growth factor in human hepatocellular carcinoma. Hepatology. 1998;28:68–77.CrossRef Yamaguchi R, Yano H, Iemura A, Ogasawara S, Haramaki M, Kojiro M. Expression of vascular endothelial growth factor in human hepatocellular carcinoma. Hepatology. 1998;28:68–77.CrossRef
28.
Zurück zum Zitat Zacharoulis D, Hatzitheofilou C, Athanasiou E, Zacharoulis S. Antiangiogenic strategies in hepatocellular carcinoma: current status. Expert Rev Anticancer Ther. 2005;5:645–56.CrossRef Zacharoulis D, Hatzitheofilou C, Athanasiou E, Zacharoulis S. Antiangiogenic strategies in hepatocellular carcinoma: current status. Expert Rev Anticancer Ther. 2005;5:645–56.CrossRef
29.
Zurück zum Zitat Spoden GA, Rostek U, Lechner S, Mitterberger M, Mazurek S, Zwerschke W. Pyruvate kinase isoenzyme M2 is a glycolytic sensor differentially regulating cell proliferation, cell size and apoptotic cell death dependent on glucose supply. Exp Cell Res. 2009;315:2765–74.CrossRef Spoden GA, Rostek U, Lechner S, Mitterberger M, Mazurek S, Zwerschke W. Pyruvate kinase isoenzyme M2 is a glycolytic sensor differentially regulating cell proliferation, cell size and apoptotic cell death dependent on glucose supply. Exp Cell Res. 2009;315:2765–74.CrossRef
30.
Zurück zum Zitat Mazurek S, Boschek CB, Hugo F, Eigenbrodt E. Pyruvate kinase type M2 and its role in tumor growth and spreading. Semin Cancer Biol. 2005;15:300–8.CrossRef Mazurek S, Boschek CB, Hugo F, Eigenbrodt E. Pyruvate kinase type M2 and its role in tumor growth and spreading. Semin Cancer Biol. 2005;15:300–8.CrossRef
Metadaten
Titel
Enhanced patterns on intraoperative contrast-enhanced ultrasonography predict outcomes after curative liver resection in patients with hepatocellular carcinoma
verfasst von
Ikuo Nakamura
Etsuro Hatano
Masaharu Tada
Yusuke Kawabata
Shinjiro Tamagawa
Ami Kurimoto
Hideaki Iwama
Kan Toriguchi
Hideaki Sueoka
Kenjiro Iida
Masahiro Yoshida
Takashi Nishimura
Hiroko Iijima
Publikationsdatum
22.09.2020
Verlag
Springer Singapore
Erschienen in
Surgery Today / Ausgabe 5/2021
Print ISSN: 0941-1291
Elektronische ISSN: 1436-2813
DOI
https://doi.org/10.1007/s00595-020-02145-w

Weitere Artikel der Ausgabe 5/2021

Surgery Today 5/2021 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.