Skip Navigation

This Article
Right arrow Abstract Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (35)
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Sakamoto, M
Right arrow Articles by Hirohashi, S
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sakamoto, M
Right arrow Articles by Hirohashi, S
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Japanese Journal of Clinical Oncology Pages 604-608

Natural History and Prognosis of Adenomatous Hyperplasia and Early Hepatocellular Carcinoma: Multi-institutional Analysis of 53 Nodules Followed Up for More Than 6 Months and 141 Patients with Single Early Hepatocellular Carcinoma Treated by Surgical Resection or Percutaneous Ethanol Injection
Introduction
Materials and Methods
   Criteria for Classification of Small Nodular Lesions
   Cases and Follow-up
Results
   Natural History of Adenomatous Hyperplasia and Early HCC
   Prognosis of Early HCC
Discussion
Acknowledgments
References
Natural History and Prognosis of Adenomatous Hyperplasia and Early Hepatocellular Carcinoma: Multi-institutional Analysis of 53 Nodules Followed Up for More Than 6 Months and 141 Patients with Single Early Hepatocellular Carcinoma Treated by Surgical Resection or Percutaneous Ethanol Injection

Natural History and Prognosis of Adenomatous Hyperplasia and Early Hepatocellular Carcinoma: Multi-institutional Analysis of 53 Nodules Followed Up for More Than 6 Months and 141 Patients with Single Early Hepatocellular Carcinoma Treated by Surgical Resection or Percutaneous Ethanol Injection

Michiie Sakamoto and Setsuo Hirohashi

Pathology Division, National Cancer Center Research Institute, Tokyo, Japan

Background: The natural history and posttherapeutic outcome of adenomatous hyperplasia and early hepatocellular carcinoma have rarely been analyzed.
Methods: Fifty-three hepatic tumors diagnosed as adenomatous hyperplasia or early hepatocellular carcinoma and followed up for more than 6 months and 141 patients with single early hepatocellular carcinoma treated by surgical resection or ethanol injection were collected retrospectively and analyzed.
Results: Some of the adenomatous hyperplasias developed to early and to advanced hepatocellular carcinoma. Tumors tended to grow faster in the order adenomatous hyperplasia, early hepatocellular carcinoma and advanced hepatocellular carcinoma, with respective mean (SD) tumor volume doubling times of 21.2 (10.7), 13.9 (11.7) and 6.0 (5.2) months. Overall survival rates at 5 years in 53 patients treated by surgery and 88 patients treated by ethanol injection were 89.6 and 71.9%, respectively.
Conclusion: Progression of adenomatous hyperplasia and early HCC was confirmed pathologically. Early HCC was shown to have a good prognosis.

Key words: hepatocellular carcinoma - adenomatous hyperplasia - tumor progression - prognosis

INTRODUCTION

Hepatocellular carcinoma (HCC) in countries where it is endemic is strongly associated with chronic infection with hepatitis viruses. Close follow-up of high-risk patients and advances in imaging techniques have made it possible to find HCC at an early stage or equivocal nodular lesions without the features of classical HCC. Histopathological and molecular biological analyses of these lesions have revealed a type of hypercellular lesion known as adenomatous hyperplasia (AH), which lacks structural atypia and cannot be identified as malignant morphologically and is thought to be a precancerous lesion. Early HCC in which the pre-existing liver structure is fairly well preserved within the nodule is considered to correspond to in situ or microinvasive HCC and nodule-in-nodule type HCC composed of progressed HCC within an early HCC is considered to be a transitional form between early and advanced HCC (1-6).

Clinicopathological studies have also indicated malignant transformation of AH (7) and progression of early HCC through a nodule-in-nodule lesion shown by the appearance of a hypervascular nodule within an early HCC (8,9). Based on this understanding of early hepatocarcinogenesis, an increased number of small HCCs have been detected and treated clinically. At present percutaneous ethanol injection and surgical resection are the main treatments for small HCCs (10,11). However, it is still unclear what type of lesion should be treated and when treatment should be started, owing to the lack of extensive analysis of the natural history and prognosis of AH and early HCC.

In this study we retrospectively collected cases of AH or early HCC followed up for more than 6 months to clarify their natural history and treated cases of single early HCC to clarify their prognosis.

MATERIALS AND METHODS

Criteria for Classification of Small Nodular Lesions

Pathological diagnosis was made according to the criteria described previously (1,4). Both early HCC and AH show preservation of pre-existing liver structure within the nodule and do not form definite cancerous nodules macroscopically (Fig. 1). Microscopically early HCC contains Glisson's components including the bile duct and portal vein, corresponding to its macroscopic features and is thought to correspond in situ or microinvasive carcinoma. It is a hypercellular lesion (usually with more than twice the cellularity of the non-tumorous liver) with structural atypia such as abnormal cord structures or formation of acini and mostly with little cell atypia (Edmondson grade I) (Fig. 1). AH is also a hypercellular lesion but lacks structural atypia and cannot be identified as malignant morphologically (Fig. 1). Advanced HCC appears as a definite cancerous nodule with expansive or invasive growth. The terminology of the International Working Party (12) states that some small and well differentiated HCCs have features of early HCC preserving Glisson's sheath, but recommends that the term `early HCC' be avoided. However, we prefer our own classification because it matches the angiographic features fairly well, i.e. early HCC usually has a portal supply without tumor staining, whereas advanced HCC including small and well differentiated HCC shows tumor staining without portal flow (13). AH is considered to be almost equivalent to the dysplastic nodule defined by the International Working Party. In the case of biopsy specimens, especially from well differentiated HCC, histological information is insufficient for differentiating early from advanced HCC. Therefore, in this study we combined angiographic data with histological information and defined early HCC as well differentiated HCC (Edmondson's grade I or grade I with a minor component of grade II) negative for tumor staining and advanced HCC as that with tumor staining in angiographic examination.

   a

   b

   c

Figure 1. Examples of early HCC and AH. (a) Macroscopic view of early HCC. Interpseudolobular connective tissue can be identified within the nodule. (b) Microscopically early HCC shows increased cellularity with an acinar and thin trabecular structure. (c) Microscopic view of AH. It is a hypercellular lesion with no distinct structural atypia. The boundary consists of interpseudolobular connective tissue.

Cases and Follow-up

Fifty-three hepatic tumors diagnosed clinically as AH or early HCC and followed up for more than 6 months in 45 patients were collected from nine institutions and analyzed. The mean age of the patients at initial diagnosis was 63 years and the male:female ratio was 3.9:1.0. All the tumors were examined histologically by needle biopsy or surgical resection at least once during follow-up. Tumors were examined clinically by ultrasonography (US), computed tomography or other modalities. In order to monitor tumor size, maximum tumor diameter determined by US was analyzed. The tumor volume doubling time (TVDT) was calculated as t divided by 10(logd - logd0), where the nodular diameter increased from d0 to d in t days (14).

Next, 141 patients with single early HCC treated by surgical resection or ethanol injection were studied. Fifty-three patients (group A) underwent hepatectomy and were diagnosed to have a single early HCC both clinically and pathologically. The other 88 (group B) were clinically diagnosed as having a single tumor which was revealed to be early HCC by needle biopsy based on the criteria described above and underwent percutaneous ethanol injection. The mean age of the patients at initial treatment and the male:female ratio were 59 and 1.8 in group A and 64 and 1.7 in group B, respectively. All the patients were followed up and recurrence of HCC was diagnosed either by histological examination or typical CT and/or angiographic findings, or was based on a markedly elevated serum [alpha]-fetoprotein level along with a space-occupying lesion demonstrated by various imaging techniques. The overall survival rate and recurrence-free survival rate were calculated by the Kaplan-Meier method (15).

RESULTS

Natural History of Adenomatous Hyperplasia and Early HCC

Changes in tumor size and pathological diagnosis of 53 tumors followed up more than 6 months are summarized in Fig. 2. Most of the tumors grew larger during their follow-up and their growth rate accelerated in some cases, suggesting tumor progression. In some cases tumor progression was confirmed by histological examination. Eighteen tumors were diagnosed as adenomatous hyperplasia by needle biopsy during follow-up, among which 13 tumors and one tumor were shown to progress to early and advanced HCC, respectively, by histological examination. Diagnosis of early HCC by biopsy was made for 12 tumors during follow-up and four tumors were shown to progress to advanced HCC by histological examination.


Figure 2. Natural history of 53 nodules followed up for more than 6 months. Each circle indicates maximum tumor diameter monitored by ultrasonography at the indicated time during follow-up. Histological diagnoses obtained by biopsy or resection are indicated as follows: dotted circles, adenomatous hyperplasia; striped circles, early hepatocellular carcinoma; solid circles, advanced hepatocellular carcinoma.

TVDT of each type of tumor was analyzed by comparing tumor at the time of histological diagnosis and 6 months or as near to 6 months as possible, prior to histological diagnosis. Therefore, TVDT of 15 and six tumors histologically diagnosed as AH and eHCC, respectively, at the start of observation were not evaluated in this study. TVDT of AH was analyzed for five tumors (in the case of repeated histological diagnosis of AH, only the last one diagnosed was analyzed). TVDT of early HCC and advanced HCC was analyzed for 29 and 10 tumors, respectively, in the same manner as AH.

The TVDT ranges for AH, early HCC and advanced HCC were 8.0-37.4, 1.8-49.6 and 1.2-18.4 months, with mean (SD ) periods of 21.2 (10.7), 13.9 (11.7) and 6.0 (5.2) months, respectively.

Prognosis of Early HCC

The overall survival and recurrence-free survival curves for patients with single early HCC treated by surgical resection (group A) or ethanol injection (group B) are shown in Fig. 3. The overall survival rate in group A was 100% at 1 year, 97.8% at 3 years, 89.6% at 5 years and 60.6% at 7 years. In contrast, the corresponding recurrence-free survival rates were 92.2, 72.6, 48.3 and 26.9%, respectively. In group B, the respective overall survival rates were 98.8, 87.7, 71.9 and 17.1% and the recurrence-free survival rates were 84.5, 41.1, 27.9 and 20.9%, respectively.


Figure 3. Overall survival and recurrence-free survival of patients with single early hepatocellular carcinoma who underwent (a) surgical resection or (b) ethanol injection.

At the time of analysis, eight out of 53 patients in group A and 19 out of 88 patients in group B had died. The causes of death were liver failure in one and seven patients, tumor progression in no and eight patients, other causes in two and one patients and unidentified in five and three patients in groups A and B, respectively.

Tumor recurrence was identified in 22 of the 51 patients in group A and in 44 of the 84 patients in group B. Based on the number of tumors at the first recurrence after treatment, we classified the pattern of recurrence as single, multiple (two to five) and diffuse (more than five), as described previously (16). Of the patients in groups A and B, 15, six and one patients and 31, 14 and no patients showed single, multiple and diffuse patterns of recurrence, respectively.

DISCUSSION

The clinical outcome of early HCC and precancerous lesions (AH) has rarely been analyzed in comparison with their histopathological and radiological features (17). In the present study, the natural behavior of AH and early HCC and the post-therapeutic outcome of early HCC were analyzed retrospectively. To our knowledge, no other study has analyzed such a large number of cases followed up with histological confirmation or treated against single early HCC. It was confirmed histologically that AH develops to early and to advanced HCC in some cases. This is in agreement with the previous follow-up study reporting malignant transformation of AH (7) and molecular biological evidence of subclonal progression of high-grade nodules within early HCC (5,6,8). The incidence of tumor progression was not assessed, because histological examination was not always done systematically in the present cases and many tumors could not be evaluated as to whether they had progressed or not by biopsy or surgical resection. It is not easy to differentiate AH from eHCC or eHCC from advanced HCC by imaging diagnosis alone, so we focused on histologically confirmed tumors. The difficulty in performing histological examination by repeated biopsies caused some limitations as described above.

TVDT analysis indicated that tumors tended to grow faster in the order AH, early HCC and advanced HCC. Immunohistochemical analysis using the PCNA labeling index has shown a higher proliferative activity in advanced than in early HCC (18), which is also consistent with the present data. However, TVDT of each type of tumor showed wide deviations, indicating the existence of unusual cases such as early HCC showing very slow growth, AH without progression during the observation period or early HCC showing rapid growth and progression to advanced HCC. In the present analysis of TVDT, the type of tumor at the time of histological diagnosis and 6 months prior to it might not be same and we might be underestimating the TVDT of early or advanced HCC, which also might cause a wide deviation of the TVDT of those tumors. It would be very useful for making decisions about treatment and the follow-up schedule if some prediction could be made about whether AH or early HCC nodules would progress rapidly or remain at an early stage. It has been reported that the diameter and cellularity of AH can predict the time until transformation (7), that AH with reduced portal flow has more potential for transformation (19) and that tumor cells with fatty change in early HCC show less proliferative activity than those without fatty change (20). Further study is needed to evaluate whether these factors are also useful in the present cases and to find other molecular biological, histological and radiological markers for predicting the biological behavior of AH and early HCC.

In HCC patients, multicentric tumor development is not rare (21) and this makes it difficult to assess the prognostic value of each nodule. Therefore, we selected cases of single early HCC at the time of initial treatment for evaluation of prognosis after treatment. The over-all survival rate at 5 years for patients treated by surgical resection (group A) was 89.6% and for those treated by ethanol injection (group B) it was 71.9%; these rates were higher than those for patients with single advanced HCC <2 cm in diameter who underwent hepatectomy at the National Cancer Center Hospital, where the rate was 65% (T. Takayama, et al., unpublished observation). The concept of early HCC is that the lesion corresponds to a relatively early stage of hepatocarcinogenesis (1,13,22-24) and in this study we were able to show that it is a lesion with a better clinical prognosis than advanced HCC.

In the present study we did not intend to determine which treatment, i.e. ethanol injection or surgical resection, is better for early HCC because the modalities used for tumor staging differed between the two groups (in group A the tumor was single, even after intraoperative US and pathological analysis of the resected specimen). The accuracy of tumor unicentricity is considered to be higher in group A than in group B. The criteria for diagnosis of early HCC were also different; tumors in group B might involve minor components of high-grade HCC which could not be detected by needle biopsy or angiography. Finally, the preserved function of the background liver was not matched in this study.

Even in group A patients who underwent hepatectomy, the recurrence-free survival rate was relatively low. About 70% of recurrences involved a single recurrent tumor and the recurrence rate was almost constant during the observation period. We consider that most of the recurrent tumors were new tumors that developed in a multicentric manner. Hence evaluation of the risk of multicentric hepatocarcinogenesis in the non-tumorous liver will also be important.

Acknowledgments

This work was supported by Grants-in-Aid for Cancer Research (2-2, 5-1 and 8-3) from the Ministry of Health and Welfare, Japan. The authors are grateful to the following for offering their important cases and for valuable discussions: Drs Kojiro Masamichi, Yasuo Majima and Kyuichi Tanikawa (Kurume University), Dr Kenji Jinno (Shikoku National Cancer Center Hospital), Dr Masatoshi Kudo (Kobe City General Hospital), Dr Yo Sasaki (Osaka Medical Center for Cancer and Cardiovascular Diseases), Dr Hiroaki Kinoshita (Osaka City University), Drs Masashi Unoura and Shuichi Kaneko (Kanazawa University), Dr Masatoshi Makuuchi (Shinshu University), Dr Kazuki Ito (Shizuoka General Hospital), Dr Ken Takasaki (Tokyo Women's Medical College), Dr Masahiro Yoshino (National Cancer Center Hospital East), Dr Masaaki Ebara (Chiba University) and Drs Kenichi Takayasu, Shuichi Okada and Tadatoshi Takayama (National Cancer Center Hospital).

References

1. Sakamoto M, Hirohashi S, Shimosato S. Early stages of multistep hepatocarcinogenesis: adenomatous hyperplasia and early hepatocellular carcinoma. Hum Pathol 1991;22:172-8. MEDLINE Abstract

2. Arakawa M, Kage M, Sugihara S, Nakashima T, Suenaga M, Okuda K. Emergence of malignant lesions within an adenomatous hyperplastic nodule in a cirrhotic liver. Observations in five cases. Gastroenterology 1986;91:198-208. MEDLINE Abstract

3. Kondo Y, Niwa Y, Akikusa B, Takazawa K, Okabayashi A. A histopathologic study of early hepatocellular carcinoma. Cancer 1983;52:687-92. MEDLINE Abstract

4. Kanai T, Hirohashi S, Upton MP, Noguchi M, Kishi K, Makuuchi M, Yamasaki S, et al. Pathology of small hepatocellular carcinoma. A proposal for a new gross classification. Cancer 1987;60:810-9. MEDLINE Abstract

5. Tsuda H, Hirohashi S, Shimosato Y, Terada M, Hasegawa H. Clonal origin of atypical adenomatous hyperplasia of the liver and clonal identity with hepatocellular carcinoma. Gastroenterology 1988;95:1664-6. MEDLINE Abstract

6. Rim KS, Sakamoto M, Watanabe H, Matsuno Y, Nakanishi Y, Mukai K, Hirohashi S. Pathology and DNA cytophotometry of small hepatocellular carcinoma with a nodule-in-nodule appearance-Evidence for stepwise progression of hepatocellular carcinoma. Jpn J Clin Oncol 1993;23: 26-33. MEDLINE Abstract

7. Takayama T, Makuuchi M, Hirohashi S, Sakamoto M, Okazaki N, Takayasu K, Kosuge T, et al. Malignant transformation of adenomatous hyperplasia to hepatocellular carcinoma. Lancet 1990;336:1150-3. MEDLINE Abstract

8. Oda T, Tsuda H, Sakamoto M, Hirohashi S. Different mutations of the p53 gene in nodule-in-nodule hepatocellular carcinoma as evidence for multistage progression. Cancer Lett 1994;83:197-200. MEDLINE Abstract

9. Winter TC III, Takayasu K, Muramatsu Y, Furukawa H, Wakao F, Koga H, Sakamoto M, et al. Early advanced hepatocellular carcinoma: evaluation of CT and MR appearance with pathologic correlation. Radiology 1994;192:379-87.

10. Sugiura N, Takara K, Ohto M, Okuda K, Hirooka N. Treatment of small hepatocellular carcinoma by percutaneous injection of ethanol into tumor with real-time ultrasound monitoring. Acta Hepatol Jpn 1983;24:920.

11. Castells A, Bruix J, Bru C, Fuster J, Vilana R, Navasa M, et al. Treatment of small hepatocellular carcinoma in cirrhotic patients: a cohort study comparing surgical resection and percutaneous ethanol injection. Hepatology 1993;18:1121-6. MEDLINE Abstract

12. International Working Party. Terminology of nodular hepatocellular lesions. Hepatology 1995;22:983-93.

13. Takayasu K, Muramatsu Y, Furukawa H, Wakao F, Moriyama N, Takayama T, Yamasaki S, et al. Early hepatocellular carcinoma: appearance at CT during arterial portography and CT arteriography with pathologic correlation. Radiology 1995;194:101-5. MEDLINE Abstract

14. Schwartz MA. Biomathematical approach to clinical tumor growth. Cancer 1961;14:1272-94.

15. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;63:457-81.

16. Okada S, Shimada K, Yamamoto J, Takayama T, Kosuge T, Yamasaki S, et al. Predictive factors for postoperative recurrence of hepatocellular carcinoma. Gastroenterology 1994;106:1618-24. MEDLINE Abstract

17. Kaneko S, Unoura M, Kobayashi K. Early detection of hepatocellular carcinoma. In: Okuda K, Tabor E, editors. Liver Cancer. New York: Churchill Livingstone, 1997;393-406.

18. Matsuno Y, Hirohashi S, Furuya S, Sakamoto M, Mukai K, Shimosato Y. Heterogeneity of proliferative activity in nodule-in-nodule lesions of small hepatocellular carcinoma. Jpn J Cancer Res 1990;81:1137-40. MEDLINE Abstract

19. Tochio H, Tomita S, Kudo M, OkabeY, Kashida H, Hamada M, et al. Clinical tracing of small hypovascular hepatic nodules associated with chronic liver disease. Kanzo 1994;35:333-46 (in Japanese).

20. Aoki K, Sakamoto M, Hirohashi S. Nucleolar organizer regions in small nodular lesions representing early stages of human hepatocarcinogenesis. Cancer 1994;73:289-93. MEDLINE Abstract

21. Tsuda H, Oda T, Sakamoto M, Hirohashi S. Different pattern of chromosomal allele loss in multiple hepatocellular carcinomas as evidence of their multifocal origin. Cancer Res 1992;52:1504-9. MEDLINE Abstract

22. Sakamoto M, Ino Y, Fujii T, Hirohashi S. Phenotype changes in tumor vessels associated with the progression of hepatocellular carcinoma. Jpn J Clin Oncol 1993;23:98-104. MEDLINE Abstract

23. Ohsawa N, Sakamoto M, Saito T, Kobayashi M, Hirohashi S. Numerical chromosome aberrations in hepatocellular carcinoma detected by fluorescence in situ hybridization. J Hepatol 1996;25:655-62. MEDLINE Abstract

24. Hui AM, Sakamoto M, Kanai Y, Ino Y, Gotoh M, Yokota J, Hirohashi S. Inactivation of p16INK4 in hepatocellular carcinomas. Hepatology 1996;24:575-9. MEDLINE Abstract

Received April 24, 1998; accepted July 24, 1998
For reprints and all correspondence: Setsuo Hirohashi, Pathology Division, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. E-mail: shirohas{at}ganz.ncc.go.jp Abbreviations: HCC, hepatocellular carcinoma; AH, adenomatous hyperplasia; US, ultrasonography; TVDT, tumor volume doubling time

This page is run by Oxford University Press, Great Clarendon Street, Oxford OX2 6DP, as part of the OUP Journals
Comments and feedback: www-admin{at}oup.co.uk
Last modification: 16 Oct 1998
Copyright©Japanese Journal of Clinical Oncology, 1998.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 JCOHome page
C. M. Pacella, G. Francica, F. M. L. Di Lascio, V. Arienti, E. Antico, B. Caspani, F. Magnolfi, A. S. Megna, S. Pretolani, R. Regine, et al.
Long-Term Outcome of Cirrhotic Patients With Early Hepatocellular Carcinoma Treated With Ultrasound-Guided Percutaneous Laser Ablation: A Retrospective Analysis
J. Clin. Oncol., June 1, 2009; 27(16): 2615 - 2621.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Roentgenol.Home page
J.-J. Chung, J. S. Yu, J. H. Kim, M.-J. Kim, and K. W. Kim
Nonhypervascular Hypoattenuating Nodules Depicted on Either Portal or Equilibrium Phase Multiphasic CT Images in the Cirrhotic Liver
Am. J. Roentgenol., July 1, 2008; 191(1): 207 - 214.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Roentgenol.Home page
K. Takayasu, Y. Muramatsu, Y. Mizuguchi, T. Okusaka, K. Shimada, T. Takayama, and M. Sakamoto
CT Evaluation of the progression of hypoattenuating nodular lesions in virus-related chronic liver disease.
Am. J. Roentgenol., August 1, 2006; 187(2): 454 - 463.
[Abstract] [Full Text] [PDF]

Home page
 RadiologyHome page
E. M. Hecht, A. E. Holland, G. M. Israel, W. Y. Hahn, D. C. Kim, A. B. West, J. S. Babb, B. Taouli, V. S. Lee, and G. A. Krinsky
Hepatocellular Carcinoma in the Cirrhotic Liver: Gadolinium-enhanced 3D T1-weighted MR Imaging as a Stand-alone Sequence for Diagnosis.
Radiology, May 1, 2006; 239(2): 438 - 447.
[Abstract] [Full Text] [PDF]

Home page
 RadiologyHome page
H. K. Hussain, I. Syed, H. V. Nghiem, T. D. Johnson, R. C. Carlos, W. J. Weadock, and I. R. Francis
T2-weighted MR Imaging in the Assessment of Cirrhotic Liver
Radiology, March 1, 2004; 230(3): 637 - 644.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (35)
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Sakamoto, M
Right arrow Articles by Hirohashi, S
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sakamoto, M
Right arrow Articles by Hirohashi, S
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?