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      Microvascular invasion of single small hepatocellular carcinoma ≤3 cm: Predictors and optimal treatments

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          Abstract

          Background

          Small hepatocellular carcinomas ( HCC ≤3 cm) are generally considered to have low malignant potential; however, some of them display pathological microvascular invasion ( MVI).

          Methods

          Between 1991 and 2013, 414 patients with a single HCC ≤3 cm underwent curative hepatic resection ( HR). Predictors for MVI were identified. Using another cohort (149 patients during 2000‐2014), our predictors for MVI in HCC ≤3 cm were validated. In 428 patients with a single HCC ≤3 cm who had predictors for MVI, survival was compared among anatomical HR (n = 149), partial HR (n = 227), and radiofrequency ablation ( RFA) (n = 52).

          Results

          The positive rate of MVI reached 40.6% (168/414 patients). Independent predictors for MVI were as follows: tumor diameter ≥2 cm (odds ratio 1.84, =  .0052), alpha‐fetoprotein ( AFP) ≥200 ng/mL (odds ratio 1.82, =  .0466), and des‐gamma‐carboxy prothrombin ( DCP) ≥40  mAU/mL (odds ratio 1.79, =  .0126). Matching at least one predictor among these three could predict MVI in HCC ≤3 cm well (sensitivity 82.8%, positive predictive value [PPV] 48.7%). This criterion could also predict MVI in HCC ≤3 cm well in another cohort (sensitivity 82.8%, PPV 30.3%). In patients with single HCC ≤3 cm matching our criterion for predicting MVI, anatomical HR led to significantly better survival in both disease‐free (hazard ratio 0.689, =  .0231) and overall (hazard ratio 0.589, =  .0316) survivals.

          Conclusion

          Matching at least one factor among three (tumor diameter ≥2 cm, AFP ≥200 ng/mL, or DCP ≥40  mAU/mL) can predict MVI in HCC ≤3 cm. In such patients, anatomical HR would be recommended to improve survival.

          Abstract

          Matching at least one factor among three (tumor diameter ≥2 cm, AFP ≥200 ng/mL, or DCP ≥40 mAU/mL) can predict MVI in HCC ≤3 cm. In such patients, anatomical HR should be recommended to improve survival.

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          Most cited references22

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          Performance of PIVKA-II for early hepatocellular carcinoma diagnosis and prediction of microvascular invasion.

          Prothrombin induced by vitamin K absence-II (PIVKA-II) is a diagnostic and surveillance marker for HCC mainly used in Asia, and has also been shown to be a predictor of microvascular invasion (MVI), a major prognostic factor in HCC. However, experience with PIVKA-II in Europe remains limited.
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            Microvascular invasion (MVI) is a poorer prognostic predictor for small hepatocellular carcinoma

            Background Small hepatocellular carcinoma (SHCC) is a special type of hepatocellular carcinoma with the maximum tumor diameter ≤ 3 cm and excellent long-term outcomes. However, the prognostic factors for SHCC remain controversial. The purpose of this study is to clarify the predictive factors of SHCC. Methods The study population consisted of 458 patients underwent hepatectomy for single SHCC between January 2006 and December 2008. Clinical data (included age, gender, virus infection, serum alfa-fetoprotein level, cirrhosis, capsule, border), histopathologic features (included differentiation, morphology subtype, microvascular invasion, tumor infiltrative lymphocytes (TIL), inflammatory injury grade and fibrosis stage of surrounding liver), were evaluated to identify prognostic factors influencing SHCC patients’ survival and microvascular invasion. Results There were 384 males (83.8%) and 74 (16.2%) females with median ages of 52 years. The median progression-free survival (PFS) and overall survival (OS) durations were 53 and 54 months, respectively. About 91.9% (n = 421) SHCC were infected by Hepatitis B. One hundred forty-seven of the 446 (33.0%) patients with pre-operation serum AFP level record had serum alfa-fetoprotein (AFP) level ≥ 200 ug/ml and 178 of the 280 (63.8%) patients with post-operation serum AFP level record had AFP level ≥ 20 ug/ml. Liver cirrhosis was present in 411 cases (89.7%), while 434 (97.3%) tumors had clear border, and 250 (55.6%) tumors were encapsulated. MVI was identified in 83 patients (18.1%). In univariate analysis, a significant association between the presence of MVI and shortened PFS and OS was found (p = 0.012, 0.028, respectively). Histological differentiation had strong relationship with MVI (p = 0.009), in terms of MVI was more easily presented in patients with worse histological differentiation. In patients with MVI, worse survival was correlated with female patients, patients with G2 or G3 histological differentiation, pre-operation serum AFP level ≥ 200 ug/ml or post-operation serum AFP level ≥ 20 ug/ml, and TIL ≥ 50/HPF. Conclusions MVI is an independent poorer prognostic factor for PFS and OS of single SHCC patients. Tumor histological differentiation was closely related with MVI.
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              Predictors for microinvasion of small hepatocellular carcinoma ≤ 2 cm.

              Hepatocellular carcinoma (HCC) ≤ 2 cm in diameter is considered to have a low potential for malignancy.
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                Author and article information

                Contributors
                y-yama@kumamoto-u.ac.jp
                Journal
                Ann Gastroenterol Surg
                Ann Gastroenterol Surg
                10.1002/(ISSN)2475-0328
                AGS3
                Annals of Gastroenterological Surgery
                John Wiley and Sons Inc. (Hoboken )
                2475-0328
                08 January 2018
                May 2018
                : 2
                : 3 ( doiID: 10.1002/ags3.2018.2.issue-3 )
                : 197-203
                Affiliations
                [ 1 ] Department of Gastroenterological Surgery Graduate School of Medical Sciences Kumamoto University Kumamoto Japan
                [ 2 ] Department of Surgery and Science Graduate School of Medical Sciences Kyushu University Fukuoka Japan
                [ 3 ] Department of Pathology & Microbiology Faculty of Medicine Saga University Saga Japan
                Author notes
                [*] [* ] Correspondence

                Yo‐ichi Yamashita, Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

                Email: y-yama@ 123456kumamoto-u.ac.jp

                Author information
                http://orcid.org/0000-0001-8439-6660
                Article
                AGS312057
                10.1002/ags3.12057
                5980603
                29863190
                e1982668-0c0f-4289-8994-ddce63881e77
                © 2018 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 06 October 2017
                : 06 December 2017
                Page count
                Figures: 1, Tables: 8, Pages: 7, Words: 5790
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                ags312057
                May 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.4.0 mode:remove_FC converted:31.05.2018

                alpha‐fetoprotein,anatomical hepatic resection,des‐gamma‐carboxy prothrombin,hepatocellular carcinoma,microvascular invasion

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