Introduction
Hepatocellular carcinoma (HCC), the most typical main liver most cancers and the third main reason behind most cancers dying worldwide, represents a serious well being problem (1). Persistent liver illness—cirrhosis—which may be associated to alcohol, NASH, HBV or HCV an infection, or much less steadily main biliary cholangitis, hemochromatosis, or α1-antitrypsin deficiency, is the strongest threat issue of HCC growth, regarding greater than 90% of the circumstances. The therapy technique is at the moment primarily pushed by the Barcelona Clinic Liver Most cancers staging system (BCLC), a five-stage classification scale integrating the traits of the first tumor (measurement, variety of nodules), the illness extent (portal invasion, N+ and M+ standing), the liver perform (Baby-Pugh), and the efficiency standing (ECOG). Very early and early-stage HCC sufferers might profit from numerous healing choices (resection, ablation or liver transplantation), whereas extra superior levels are candidate to chemoembolization, systemic therapies together with immunotherapy, or greatest supportive care. In early-stage HCC, post-operative recurrence stays the strongest survival prognostic issue (2) making the correct choice of sufferers with curable HCC a vital difficulty. Tumor differentiation is a serious predictive issue of post-operative recurrence in HCC (3, 4). Nevertheless, the histological evaluation of tumor differentiation, which stays the gold commonplace, is at the moment carried out solely in atypical circumstances. Typical imaging is crucial for the administration of HCC sufferers (5–8), however its restricted worth in such atypical circumstances and the necessity for non-invasive biomarkers of tumor differentiation have progressively motivated the usage of PET imaging on this subject (9), whereas this practical imaging remains to be not consensually beneficial. As a result of 18F-fluorodeoxyglose (18F-FDG) exhibits mitigated efficiency to detect HCC (10, 11) however wonderful specificity for HCC metastases (9), PET radiotracers of fatty acid synthase (FAS) have been proposed as enhances, such radiolabeled choline, probably the most broadly used FAS-targeted radiotracer in medical apply (12, 13). Though 18F-FDG and FAS PET radiotracers have proven their complementarity for the preliminary staging and therapy administration of HCC sufferers (14–17) their mixed use remains to be not consensual, making devoted suggestions difficult (18).
The very first twin 18F-FDG/18F-Choline PET research recommended 18F-FDG/FAS PET conduct be linked to the diploma of differentiation of HCC tumors (19, 20). Though this key idea might impression the rational for utilizing dual-tracer PET in HCC, its stage of proof stays largely unexplored. On this research, we performed a scientific assessment of the out there evidence-based information, to make clear whether or not 18F-FDG/18F-Choline dual-tracer PET conduct is a related imaging biomarker of tumor differentiation in HCC.
Strategies
This methodological research was performed in accordance with the PRISMA 2020 assertion for systematic assessment stories (21).
Search Technique
Two authors (JG and FLB) independently carried out a complete search of PubMed/Medline and Embase databases to seek out research utilizing 18F-FDG and 18F-Choline twin PET tracers for HCC functions. The search technique mixed the next key phrases: “HCC + PET” or “HCC + FDG” AND “HCC + Choline.” No beginning date was used, and the search process was up to date till 10 November 2021. Furthermore, references of the retrieved articles have been additionally screened for added research. The inclusion standards have been as follows: (i) articles solely in English; (ii) the mixed use of 18F-FDG and 18F/11C-Choline twin PET tracers for every HCC tumor, so as to assess the dual-tracer PET conduct with no priori; (iii) histology-confirmed HCC analysis; and (iv) out there description of HCC differentiation for every affected person. All of the articles not fulfilling the inclusion standards talked about above, along with assessment articles, editorials, letters, feedback, or case stories, have been excluded from the evaluation. For every eligible research, the next data was independently extracted: research date; design; affected person cohort traits, together with pattern measurement, variety of sufferers with HCC, and variety of HCC lesions per affected person confirmed by histology (both by surgical procedure or biopsy); delay time between the 18F-FDG and 18F-Choline PET acquisitions; histological differentiation of HCC; and twin PET radiotracer conduct of HCC sufferers per histological subtype. For all included research, the identical predefined definition of PET positivity was thought of: any focal uptake superior to the locoregional background was thought of optimistic, whereas iso or hypometabolic lesions have been thought of damaging for the radiotracer of curiosity.
High quality Evaluation of the Research
The general high quality of every included research was critically assessed by two authors (JG and FLB) based mostly on the “STROBE tips” (22). As a result of the twin PET tracer conduct in accordance with the extent of differentiation of HCC was by no means thought of the first final result, a common standardized guidelines of twenty-two gadgets masking the general high quality statements of non-interventional research (22) was independently utilized by the 2 readers as follows: every merchandise was quoted “sure” if current, “no” if absent, or “unclear” if the assertion was equivocal. All disagreements between the 2 readers have been resolved by consensus.
Ethics and Knowledge
The necessity for moral approval was waived as a result of nature of the research (assessment article).
Outcomes
Literature Search
The PRISMA move diagram of the literature search is supplied in Determine 1. The great literature search from PubMed/MEDLINE and Embase recognized the next data: 440 data utilizing the “HCC + PET CT” key phrases; 353 data utilizing the “HCC + FDG” key phrases; 192 data utilizing the “HCC + Choline” key phrases; and 19 data utilizing the “HCC + FDG + Choline” key phrases. Among the many 19 articles, 12 have been discarded as a result of research kind (critiques n = 4), evaluation of metastatic illness (n = 1), cholangiocarcinoma research (n = 1), use of Choline solely in 18F-FDG-negative sufferers (n = 1), and preclinical research (n = 2). On the finish of the screening course of, 7 full-text articles have been retrieved. Amongst them, one article was discarded as a result of no specific HCC differentiation standing per affected person was supplied (23), and two research offered affected person information overlap (20, 24). Of the 2 research with affected person information overlap, we discarded the second research (24). Lastly, 6 full-text articles over the past 15 years (2006–2021) have been included within the systematic assessment (14, 16, 19, 20, 25, 26).
Methodological High quality of the Included Research
The general high quality evaluation of the 6 included research is proven in Determine 2. The research have been of restricted high quality with 12 gadgets (55%) thought of current (vary = 9–16), 3 gadgets (14%) thought of absent (vary = 0–6) and 6 gadgets (27%) thought of unclear after a double blinded studying (vary = 5–11). Specifically, solely two research supplied a majority of unequivocal merchandise statements for the outcomes part (19, 26), and one research supplied unclear or no data for almost all of the STROBE statements of the dialogue part (25). Contemplating these statements, the extent of proof for the devoted use of twin 18F-FDG/18F-Choline PET tracer for the characterization of HCC differentiation was thought of a stage 4–5 (grade C-D of advice) in accordance with the Oxford Centre for Proof-Based mostly Medication.
Determine 2. STROBE high quality evaluation.
Qualitative Evaluation (Systematic Overview)
The primary traits of the 6 included research are supplied in Desk 1. The first outcomes have been as follows: the detection fee of 18F-FDG and 18F-Choline PET tracers for HCC tumors (16, 19); the diagnostic efficiency of 18F-FDG and 18F-Choline PET tracers for detecting and staging HCC in sufferers with persistent liver illness (14, 20); and the evaluation of twin 18F-FDG and 18F-Choline PET with perfusion CT behaviors of HCC tumors (25). The twin radiotracer PET information of 99 biopsy-proven HCC sufferers have been reanalyzed. The research samples have been primarily restricted with solely two potential research reaching greater than 20 histologically confirmed HCC samples (14, 20). Talbot et al. (20) included a case mixture of 34 HCC sufferers (27 biopsy confirmed), 2 hepato-cholangiocarcinoma sufferers, 10 sufferers with different malignancies, and eight sufferers with benign circumstances. Castilla-Lièvre et al. (14) included 38 HCC sufferers (22 biopsy confirmed) with 4 cholangiocarcinoma sufferers and one adenoma affected person. The opposite 4 research solely centered on HCC sufferers. Among the many pooled 99 HCC tumors, 43 have been thought of well-differentiated tumors, and 56 have been thought of reasonable to poorly differentiated tumors. The classification used for tumor differentiation (Edmonson Steiner or WHO) was talked about for less than 57% of the HCC tumors as follows: biopsy for 14 HCC tumors (14, 16) surgical procedure for 37 HCC tumors (14, 19), and a case mixture of biopsy/surgical procedure for the remainder of the dataset with none data regarding the ratio. Moreover, 50 HCC sufferers have been explicitly certified as having unifocal HCC tumors (14, 16, 19), and 25 HCC sufferers have been explicitly certified as having multifocal HCC tumors (14, 16, 19, 25). In all research, PET positivity was outlined visually as non-physiological focal liver radiotracer uptake in 4 research (14, 16, 19, 25), whereas one research additionally proposed a “photopenic” sample for Choline PET positivity (20).
Desk 1. Traits of the included research with twin PET tracer.
The 18F-FDG and 18F-Choline PET tumor behaviors in accordance with the differentiation of the tumors are proven in Desk 2. Within the well-differentiated subgroup, 51% have been solely optimistic for 18F-Choline, 39% have been optimistic for each 18F-FDG and 18F-Choline, and solely 5% have been solely optimistic for FDG. Two sufferers have been damaging for the 2 PET radiotracers (20, 26). Within the poorly differentiated subgroup, 37% of HCC sufferers have been solely optimistic for 18F-FDG, 36% have been optimistic for each 18F-FDG and 18F-Choline, and 25% have been solely optimistic for Choline. One affected person was thought of damaging for each radiotracers (20).
Desk 2. Twin PET radiotracer behaviors perform of HCC stage of differentiation.
5 research additionally carried out SUV-based semiquantitative analyses (14, 16, 19, 25, 26) with discrepant outcomes. In a single research, no vital distinction was noticed between the 18F-FDG or 18F-Choline signal-to-noise ratio no matter the HCC stage of differentiation (16). Yamamoto et al. discovered no vital distinction in radiotracer uptake between the histological subgroups (19). Tulin et al. reported a big distinction in radiotracer uptake in accordance with the liver areas (well-differentiated HCC, poorly differentiated HCC, or regular parenchyma) (25). Chotipanich et al. discovered a big distinction between well- and poorly differentiated HCC just for 18F-FDG (26). The final research didn’t carry out any comparative analyses (14).
Dialogue
Based mostly on our evaluation of the literature information, well-differentiated HCC sufferers have been optimistic for 18F-FDG in roughly 44% of the reported circumstances and optimistic for 18F-Choline in 90% of the reported circumstances. For the less-differentiated HCC tumors (reasonable to poorly differentiated HCC), 73% of reported HCC circumstances have been 18F-FDG-positive, and 61% of reported HCC circumstances have been 18F-Choline-positive. Among the many 56 much less differentiated tumors thought of within the current research, 16 have been explicitly talked about as poorly differentiated HCC, of which 100% have been 18F-FDG-positive and 31% have been 18F-Choline-positive. Nevertheless, the 8 poorly differentiated tumors all thought of 18F-FDG-positive and 18F-Choline-negative in a single research had no data concerning the motivation of their inclusion standards (25). Specializing in the 8 remaining poorly differentiated HCC sufferers (16, 19, 26), 100% have been reported to be optimistic for 18F-FDG, of whom 63% have been additionally optimistic for 18F-Choline. Furthermore, greater than one-third of sufferers confirmed twin PET tracer positivity whatever the diploma of HCC differentiation.
A pattern towards an inverse gradient of dual-PET HCC tumor conduct has been beforehand recommended (16, 20), however our systematic assessment confirmed {that a} robust mirrored dual-PET tumor conduct in accordance with HCC differentiation ought to be thought of with warning. First, the dearth of standardized histological grading of HCC stays a serious difficulty. Though Edmonson Steiner and WHO classifications share similarities (4-level grades and structural/mobile options), the respective definitions for well- and fewer differentiated grades usually are not totally concordant with a associated impression on subgroup outcomes (27). In our systematic assessment, solely two of the six included research explicitly talked about both Edmonson Steiner (19) or WHO (14) classifications (39% of the included HCC). As 61% of the biopsy-proven reported HCC circumstances have been probably a blinded case mixture of ES/WHO definitions, any generalizability of 18F-FDG/18F-Choline twin PET tracer conduct in accordance with HCC grading can be ambiguous. Second, a big affiliation between glucose metabolism assessed by FDG PET and microvascular invasion (MVI), one other robust prognostic consider HCC (28, 29), has been broadly reported (23, 30–32). Surprisingly, Kornberg et al. reported that 14 of the 16 HCC sufferers who have been optimistic for 18F-FDG PET had MVI (87.5%), of whom just one/3 have been poorly differentiated (5 sufferers) (30). Though an in depth assessment by Gouw et al. confirmed that high-grade tumors but in addition tumor measurement and variety of nodules to be predictive of MVI (33), MVI has additionally been reported in 29% of HCCs with a measurement starting from 2 to five cm (34). Sabaté-Llobera et al. reported that the ratios of well- to much less differentiated tumors ranged from 1.3 within the 18F-FDG-positive group to five.7 within the 18F-FDG-negative group (31). Nevertheless, almost 50% of 18F-FDG-positive circumstances within the current research have been well-differentiated HCC. Consequently, 18F-FDG PET positivity might mirror each MVI and tumor differentiation, that are two prognostic components that aren’t extremely interlinked. Third, research by Okazumi, Torizuka, and Trojan (35–37) have recommended {that a} lack of FDG 6-phosphatase exercise in undifferentiated tumor cells explains the upper 18F-FDG avidity of poorly differentiated HCC. Importantly, the research by Okazumi and Torizuka have been primarily dynamic PET research (35, 36). The tissue conduct of superior PET kinetic parameters, particularly k3 or k4 microparameters, can’t be straight extrapolated to static PET metrics, resembling SUV, a surrogate of the glucose retention index in cells. Trojan et al. reported that the 18F-FDG uptake (SUV) was extra environment friendly not solely in poorly differentiated tumors but in addition in giant tumors and elevated AFP (37). Specifically, the overwhelming majority of the reported FDG-positive tumors additionally confirmed a number of nodules, all being predictive components of MVI (38).
Proof-based evaluation of the literature over the previous 20 years suggests advanced interlinks between tumor grade and MVI, and the associated FDG PET behaviors in HCC sufferers. In distinction, 18F-Choline seems not as informative as 18F-FDG to characterize tumor aggressiveness in HCC sufferers. In 29 HCC sufferers, Mulé et al. confirmed a better 18F-FDG uptake for MVI-positive HCC circumstances in comparison with MVI-negative HCC circumstances (SUVr 2.65 vs. 1, p = 0.003) with none vital distinction in 18F-Choline uptake (39). This lack of prognostic significance of 18F-Choline was additionally reported by Castilla-Lièvre et al. (14). Notably, a mixed photopenic 18F-Choline with a optimistic 18F-FDG-PET sample has been recommended to be a pejorative prognostic issue of HCC recurrence (24). In gentle of this methodological assessment, the query of the main prognostic worth of 18F-FDG PET arises. The organic significance of glucose- and Choline-based PET tracer behaviors in HCC sufferers stays poorly understood.
Not too long ago, a greater understanding of organic pathways of HCC tumors has led to the emergence of a brand new molecular-based classification of HCC, dichotomizing the tumors into proliferation and non-proliferation lessons based mostly on their multidimensional molecular sample (40–45). Whereas the proliferative class is characterised by poorly differentiated tumors, excessive vascular invasion, and elevated AFP, the non-proliferative class corresponds to nicely to reasonably differentiated tumors, much less vascular invasion, and decrease stage of AFP. In each teams, the traits of T-cell infiltrates additional outline 4 immune-related subclasses (46). As a result of the characterization of tumor heterogeneity on the molecular stage is rising in HCC (47, 48), the highly effective capabilities of vectorized PET molecular imaging on this subject would achieve in relevance. Though a number of 18F-FDG/FAS research emphasize the medical usefulness of PET to handle HCC sufferers (17, 49), future multitracer PET research are obligatory to raised perceive the deep organic that means of multitracer PET conduct on this subject.
Our systematic assessment had a number of limitations. The restricted variety of twin 18F-FDG/18F-Choline PET articles with out there per patient-based HCC tumor differentiation hampered any quantitative evaluation. Nevertheless, our pooled semiquantitative evaluation revealed the excessive overlap of 18F-FDG/18F-Choline PET conduct between well- and fewer differentiated HCC. Moreover, we didn’t embody acetate PET research on this systematic assessment (11, 50–52). Initially, evaluated in cardiac (53) and urological oncology settings (54, 55), acetate exhibits a biodistribution fairly just like that of Choline. Though each substrates are fed into fatty acid synthesis, also referred to as the Kennedy pathway (56–58), Choline and acetate have numerous different organic features (59, 60), making them not strictly comparable. Moreover, 18F-Choline is at the moment probably the most broadly used FAS-targeted PET tracer of HCC in medical apply, which is why we centered on this PET radiotracer on this research.
Conclusion
The 18F-FDG/18F-Choline dual-tracer PET conduct of uptake exhibits excessive overlap between well- and fewer differentiated HCC, making the characterization of tumors difficult based mostly on such PET mixture alone. Given our rising information of the molecular complexity of HCC, additional research are essential to refine our understanding of radiotracers’ conduct on this subject and enhance the usefulness of PET imaging within the medical choice means of HCC.
Creator Contributions
All authors: design, acquisition evaluation, revising for mental content material, last approval, and settlement to be accountable for all features of this work (accuracy and integrity of any a part of the work).
Battle of Curiosity
The authors declare that the analysis was performed within the absence of any business or monetary relationships that could possibly be construed as a possible battle of curiosity.
Writer’s Notice
All claims expressed on this article are solely these of the authors and don’t essentially symbolize these of their affiliated organizations, or these of the writer, the editors and the reviewers. Any product that could be evaluated on this article, or declare that could be made by its producer, isn’t assured or endorsed by the writer.
Abbreviations
PET, Positron emission tomography; HCC, Hepatocellular carcinoma; 18F-FDG, 18F-Fluorodeoxyglucose; FAS, Fatty acid synthase; BCLC, Barcelona Clinic Liver Most cancers staging system; NASH, Non-Alcoholic SteatoHepatitis; HBV, Hepatitis B Virus; HBC, Hepatitis C Virus; SUV, Commonplace Uptake Worth.
References
1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. World most cancers statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 international locations. CA Most cancers J Clin. (2021) 71:209–49. doi: 10.3322/caac.21660
PubMed Summary | CrossRef Full Textual content | Google Scholar
2. Colecchia A. Prognostic components for hepatocellular carcinoma recurrence. World J Gastroenterol. (2014) 20:5935.
3. Imamura H, Matsuyama Y, Tanaka E, Ohkubo T, Hasegawa Ok, Miyagawa S, et al. Danger components contributing to early and late part intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol. (2003) 38:200–7. doi: 10.1016/s0168-8278(02)00360-4
PubMed Summary | CrossRef Full Textual content | Google Scholar
4. Cucchetti A, Piscaglia F, Caturelli E, Benvegnù L, Vivarelli M, Ercolani G, et al. Comparability of recurrence of hepatocellular carcinoma after resection in sufferers with cirrhosis to its incidence in a surveilled cirrhotic inhabitants. Ann Surg Oncol. (2009) 16:413–22. doi: 10.1245/s10434-008-0232-4
PubMed Summary | CrossRef Full Textual content | Google Scholar
5. Chernyak V, Fowler KJ, Kamaya A, Kielar AZ, Elsayes KM, Bashir MR, et al. Liver imaging reporting and information system (LI-RADS) model 2018: imaging of hepatocellular carcinoma in at-risk sufferers. Radiology. (2018) 289:816–30. doi: 10.1148/radiol.2018181494
PubMed Summary | CrossRef Full Textual content | Google Scholar
6. van der Pol CB, Lim CS, Sirlin CB, McGrath TA, Salameh JP, Bashir MR, et al. Accuracy of the liver imaging reporting and information system in computed tomography and magnetic resonance picture evaluation of hepatocellular carcinoma or total malignancy-a systematic assessment. Gastroenterology. (2019) 156:976–86. doi: 10.1053/j.gastro.2018.11.020
PubMed Summary | CrossRef Full Textual content | Google Scholar
8. Llovet JM, Villanueva A, Marrero JA, Schwartz M, Meyer T, Galle PR, et al. Trial design and endpoints in hepatocellular carcinoma: AASLD consensus convention. Hepatology. (2021) 73:158–91. doi: 10.1002/hep.31327
PubMed Summary | CrossRef Full Textual content | Google Scholar
9. Sharma B, Martin A, Zerizer I. Positron emission tomography-computed tomography in liver imaging. Semin Ultrasound CT MR. (2013) 34:66–80.
10. Khan MA, Combs CS, Brunt EM, Lowe VJ, Wolverson MK, Solomon H, et al. Positron emission tomography scanning within the analysis of hepatocellular carcinoma. J Hepatol. (2000) 32:792–7. doi: 10.1016/s0168-8278(00)80248-2
PubMed Summary | CrossRef Full Textual content | Google Scholar
11. Park JW, Kim JH, Kim SK, Kang KW, Park KW, Choi JI, et al. A potential analysis of 18F-FDG and 11C-acetate PET/CT for detection of main and metastatic hepatocellular carcinoma. J Nucl Med. (2008) 49:1912–21. doi: 10.2967/jnumed.108.055087
PubMed Summary | CrossRef Full Textual content | Google Scholar
12. Bertagna F, Bertoli M, Bosio G, Biasiotto G, Sadeghi R, Giubbini R, et al. Diagnostic function of radiolabelled choline PET or PET/CT in hepatocellular carcinoma: a scientific assessment and meta-analysis. Hepatol Int. (2014) 8:493–500. doi: 10.1007/s12072-014-9566-0
PubMed Summary | CrossRef Full Textual content | Google Scholar
13. Signore G, Nicod-Lalonde M, Prior JO, Bertagna F, Muoio B, Giovanella L, et al. Detection fee of radiolabelled choline PET or PET/CT in hepatocellular carcinoma: an up to date systematic assessment and meta-analysis. Clin Transl Imaging. (2019) 7:237–53.
14. Castilla-Lièvre MA, Franco D, Gervais P, Kuhnast B, Agostini H, Marthey L, et al. Diagnostic worth of mixing 11C-choline and 18F-FDG PET/CT in hepatocellular carcinoma. Eur J Nucl Med Mol Imaging. (2016) 43:852–9. doi: 10.1007/s00259-015-3241-0
PubMed Summary | CrossRef Full Textual content | Google Scholar
15. Wu HB, Wang QS, Li BY, Li HS, Zhou WL, Wang QY. F-18 FDG along with 11C-choline PET/CT within the analysis of hepatocellular carcinoma. Clin Nucl Med. (2011) 36:1092–7. doi: 10.1097/RLU.0b013e3182335df4
PubMed Summary | CrossRef Full Textual content | Google Scholar
16. Talbot JN, Gutman F, Fartoux L, Grange JD, Ganne N, Kerrou Ok, et al. PET/CT in sufferers with hepatocellular carcinoma utilizing [(18)F]fluorocholine: preliminary comparability with [(18)F]FDG PET/CT. Eur J Nucl Med Mol Imaging. (2006) 33:1285–9. doi: 10.1007/s00259-006-0164-9
PubMed Summary | CrossRef Full Textual content | Google Scholar
17. Chalaye J, Costentin CE, Luciani A, Amaddeo G, Ganne-Carrié N, Baranes L, et al. Positron emission tomography/computed tomography with 18F-fluorocholine enhance tumor staging and therapy allocation in sufferers with hepatocellular carcinoma. J Hepatol. (2018) 69:336–44. doi: 10.1016/j.jhep.2018.02.018
PubMed Summary | CrossRef Full Textual content | Google Scholar
18. European Affiliation for the Research of the Liver. EASL medical apply tips: administration of hepatocellular carcinoma. J Hepatol. (2018) 69:182–236.
19. Yamamoto Y, Nishiyama Y, Kameyama R, Okano Ok, Kashiwagi H, Deguchi A, et al. Detection of hepatocellular carcinoma utilizing 11C-choline PET: comparability with 18F-FDG PET. J Nucl Med. (2008) 49:1245–8. doi: 10.2967/jnumed.108.052639
PubMed Summary | CrossRef Full Textual content | Google Scholar
20. Talbot JN, Fartoux L, Balogova S, Nataf V, Kerrou Ok, Gutman F, et al. Detection of hepatocellular carcinoma with PET/CT: a potential comparability of 18F-fluorocholine and 18F-FDG in sufferers with cirrhosis or persistent liver illness. J Nucl Med. (2010) 51:1699–706. doi: 10.2967/jnumed.110.075507
PubMed Summary | CrossRef Full Textual content | Google Scholar
21. Web page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 assertion: an up to date guideline for reporting systematic critiques. BMJ. (2021) 372:n71. doi: 10.1136/bmj.n71
PubMed Summary | CrossRef Full Textual content | Google Scholar
22. Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, Pocock SJ, et al. Strengthening the reporting of observational research in epidemiology (STROBE): clarification and elaboration. Ann Intern Med. (2007) 147:W163–94.
23. Mulé S, Chalaye J, Legou F, Tenenhaus A, Calderaro J, Galletto Pregliasco A, et al. Hepatobiliary MR distinction agent uptake as a predictive biomarker of aggressive options on pathology and decreased recurrence-free survival in resectable hepatocellular carcinoma: comparability with dual-tracer 18F-FDG and 18F-FCH PET/CT. Eur Radiol. (2020) 30:5348–57. doi: 10.1007/s00330-020-06923-5
PubMed Summary | CrossRef Full Textual content | Google Scholar
24. Fartoux L, Balogova S, Nataf V, Kerrou Ok, Huchet V, Rosmorduc O, et al. A pilot comparability of 18F-fluorodeoxyglucose and 18F-fluorocholine PET/CT to foretell early recurrence of unifocal hepatocellular carcinoma after surgical resection. Nucl Med Commun. (2012) 33:757–65. doi: 10.1097/MNM.0b013e328350fb9f
PubMed Summary | CrossRef Full Textual content | Google Scholar
25. Tulin PE, Dolgushin MB, Odzharova AA, Mikhaylov AI, Medvedeva BM, Shiryaev SV, et al. Perfusion CT and PET with 18F-FDG and 18F-FCh within the advanced analysis of hepatocellular carcinoma. Eur J Hybrid Imaging. (2017) 1:13. doi: 10.1186/s41824-017-0018-7
PubMed Summary | CrossRef Full Textual content | Google Scholar
26. Chotipanich C, Kunawudhi A, Promteangtrong C, Tungsuppawattanakit P, Sricharunrat T, Wongsa P. Prognosis of hepatocellular carcinoma utilizing C11 choline PET/CT: comparability with F18 FDG, contrastenhanced MRI and MDCT. Asian Pac J Most cancers Prev. (2016) 17:3569–73.
27. Martins-Filho SN, Paiva C, Azevedo RS, Alves VAF. Histological grading of hepatocellular carcinoma-a systematic assessment of literature. Entrance Med. (2017) 4:193. doi: 10.3389/fmed.2017.00193
PubMed Summary | CrossRef Full Textual content | Google Scholar
28. Rodríguez-Perálvarez M, Luong TV, Andreana L, Meyer T, Dhillon AP, Burroughs AK. A scientific assessment of microvascular invasion in hepatocellular carcinoma: diagnostic and prognostic variability. Ann Surg Oncol. (2013) 20:325–39. doi: 10.1245/s10434-012-2513-1
PubMed Summary | CrossRef Full Textual content | Google Scholar
29. Sumie S, Nakashima O, Okuda Ok, Kuromatsu R, Kawaguchi A, Nakano M, et al. The importance of classifying microvascular invasion in sufferers with hepatocellular carcinoma. Ann Surg Oncol. (2014) 21:1002–9. doi: 10.1245/s10434-013-3376-9
PubMed Summary | CrossRef Full Textual content | Google Scholar
30. Kornberg A, Freesmeyer M, Bärthel E, Jandt Ok, Katenkamp Ok, Steenbeck J, et al. 18F-FDG-uptake of hepatocellular carcinoma on PET predicts microvascular tumor invasion in liver transplant sufferers. Am J Transplant. (2009) 9:592–600. doi: 10.1111/j.1600-6143.2008.02516.x
PubMed Summary | CrossRef Full Textual content | Google Scholar
31. Sabaté-Llobera A, Mestres-Martí J, Reynés-Llompart G, Lladó L, Mils Ok, Serrano T, et al. 2-[18F]FDG PET/CT as a predictor of microvascular invasion and excessive histological grade in sufferers with hepatocellular carcinoma. Cancers. (2021) 13:2554. doi: 10.3390/cancers13112554
PubMed Summary | CrossRef Full Textual content | Google Scholar
32. Cuccurullo V, Di Stasio GD, Mazzarella G, Cascini GL. Microvascular invasion in HCC: the molecular imaging perspective. Distinction Media Mol Imaging. (2018) 2018:9487938. doi: 10.1155/2018/9487938
PubMed Summary | CrossRef Full Textual content | Google Scholar
33. Gouw ASH, Balabaud C, Kusano H, Todo S, Ichida T, Kojiro M. Markers for microvascular invasion in hepatocellular carcinoma: the place will we stand? Liver Transplant. (2011) 17(Suppl. 2):S72–80. doi: 10.1002/lt.22368
PubMed Summary | CrossRef Full Textual content | Google Scholar
34. Yamashita Y, Tsuijita E, Takeishi Ok, Fujiwara M, Kira S, Mori M, et al. Predictors for microinvasion of small hepatocellular carcinoma ≤ 2 cm. Ann Surg Oncol. (2012) 19:2027–34. doi: 10.1245/s10434-011-2195-0
PubMed Summary | CrossRef Full Textual content | Google Scholar
35. Okazumi S, Isono Ok, Enomoto Ok, Kikuchi T, Ozaki M, Yamamoto H, et al. Analysis of liver tumors utilizing fluorine-18-fluorodeoxyglucose PET: characterization of tumor and evaluation of impact of therapy. J Nucl Med. (1992) 33:333–9.
36. Torizuka T, Tamaki N, Inokuma T, Magata Y, Sasayama S, Yonekura Y, et al. In vivo evaluation of glucose metabolism in hepatocellular carcinoma with FDG-PET. J Nucl Med. (1995) 36:1811–7.
37. Trojan J, Schroeder O, Raedle J, Baum RP, Herrmann G, Jacobi V, et al. Fluorine-18 FDG positron emission tomography for imaging of hepatocellular carcinoma. Am J Gastroenterol. (1999) 94:3314–9.
38. Zhao WC, Fan LF, Yang N, Zhang HB, Chen BD, Yang GS. Preoperative predictors of microvascular invasion in multinodular hepatocellular carcinoma. Eur J Surg Oncol. (2013) 39:858–64. doi: 10.1016/j.ejso.2013.04.003
PubMed Summary | CrossRef Full Textual content | Google Scholar
39. Mulé S, Pigneur F, Quelever R, Tenenhaus A, Baranes L, Richard P, et al. Can dual-energy CT exchange perfusion CT for the practical analysis of superior hepatocellular carcinoma? Eur Radiol. (2018) 28:1977–85. doi: 10.1007/s00330-017-5151-y
PubMed Summary | CrossRef Full Textual content | Google Scholar
40. Lee JS, Heo J, Libbrecht L, Chu IS, Kaposi-Novak P, Calvisi DF, et al. A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nat Med. (2006) 12:410–6. doi: 10.1038/nm1377
PubMed Summary | CrossRef Full Textual content | Google Scholar
41. Boyault S, Rickman DS, de Reyniès A, Balabaud C, Rebouissou S, Jeannot E, et al. Transcriptome classification of HCC is said to gene alterations and to new therapeutic targets. Hepatology. (2007) 45:42–52. doi: 10.1002/hep.21467
PubMed Summary | CrossRef Full Textual content | Google Scholar
42. Chiang DY, Villanueva A, Hoshida Y, Peix J, Newell P, Minguez B, et al. Focal features of VEGFA and molecular classification of hepatocellular carcinoma. Most cancers Res. (2008) 68:6779–88. doi: 10.1158/0008-5472.CAN-08-0742
PubMed Summary | CrossRef Full Textual content | Google Scholar
43. Hoshida Y, Nijman SMB, Kobayashi M, Chan JA, Brunet JP, Chiang DY, et al. Integrative transcriptome evaluation reveals frequent molecular subclasses of human hepatocellular carcinoma. Most cancers Res. (2009) 69:7385–92. doi: 10.1158/0008-5472.CAN-09-1089
PubMed Summary | CrossRef Full Textual content | Google Scholar
44. Most cancers Genome Atlas Analysis Community. Complete and integrative genomic characterization of hepatocellular carcinoma. Cell. (2017) 169:1327–41.e23. doi: 10.1016/j.cell.2017.05.046
PubMed Summary | CrossRef Full Textual content | Google Scholar
45. Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, et al. Hepatocellular carcinoma. Nat Rev Dis Primer. (2021) 7:6.
46. Sia D, Jiao Y, Martinez-Quetglas I, Kuchuk O, Villacorta-Martin C, Castro de Moura M, et al. Identification of an immune-specific class of hepatocellular carcinoma, based mostly on molecular options. Gastroenterology. (2017) 153:812–26. doi: 10.1053/j.gastro.2017.06.007
PubMed Summary | CrossRef Full Textual content | Google Scholar
47. Ding X, He M, Chan AWH, Music QX, Sze SC, Chen H, et al. Genomic and epigenomic options of main and recurrent hepatocellular carcinomas. Gastroenterology. (2019) 157:1630–45.e6.
48. Zhang Q, Lou Y, Bai XL, Liang TB. Intratumoral heterogeneity of hepatocellular carcinoma: from single-cell to population-based research. World J Gastroenterol. (2020) 26:3720–36. doi: 10.3748/wjg.v26.i26.3720
PubMed Summary | CrossRef Full Textual content | Google Scholar
49. Cheung TT, Ho CL, Chen S, Chan SC, Poon RTP, Fan ST, et al. Reply: underestimated function of 18F-FDG PET for HCC analysis and promise of 18F-FDG PET/MR imaging on this setting. J Nucl Med. (2013) 54:1511–2. doi: 10.2967/jnumed.113.126185
PubMed Summary | CrossRef Full Textual content | Google Scholar
50. Ho CL, Yu SCH, Yeung DWC. 11C-acetate PET imaging in hepatocellular carcinoma and different liver lots. J Nucl Med. (2003) 44:213–21.
51. Hwang KH, Choi DJ, Lee SY, Lee MK, Choe W. Analysis of sufferers with hepatocellular carcinomas utilizing [(11)C]acetate and [(18)F]FDG PET/CT: a preliminary research. Appl Radiat Isot. (2009) 67:1195–8. doi: 10.1016/j.apradiso.2009.02.011
PubMed Summary | CrossRef Full Textual content | Google Scholar
52. Au KP, Dai WC, Chi-Yan Chan A, Cheung TT, Lo CM, Chok KSH. Efficiency of dual-tracer PET-CT for staging post-liver transplant hepatocellular carcinoma recurrence. Transplant Direct. (2021) 7:e769. doi: 10.1097/TXD.0000000000001213
PubMed Summary | CrossRef Full Textual content | Google Scholar
53. Brown M, Marshall DR, Sobel BE, Bergmann SR. Delineation of myocardial oxygen utilization with carbon-11-labeled acetate. Circulation. (1987) 76:687–96. doi: 10.1161/01.cir.76.3.687
PubMed Summary | CrossRef Full Textual content | Google Scholar
54. Shreve P, Chiao PC, Humes HD, Schwaiger M, Gross MD. Carbon-11-acetate PET imaging in renal illness. J Nucl Med. (1995) 36:1595–601.
55. Oyama N, Akino H, Kanamaru H, Suzuki Y, Muramoto S, Yonekura Y, et al. 11C-acetate PET imaging of prostate most cancers. J Nucl Med. (2002) 43:181–6.
58. Deford-Watts LM, Mintz A, Kridel SJ. The potential of 11C-acetate PET for monitoring the fatty acid synthesis pathway in tumors. Curr Pharm Biotechnol. (2013) 14:300–12. doi: 10.2174/1389201011314030006
PubMed Summary | CrossRef Full Textual content | Google Scholar
59. Wellen KE, Hatzivassiliou G, Sachdeva UM, Bui TV, Cross JR, Thompson CB. ATP-citrate lyase hyperlinks mobile metabolism to histone acetylation. Science. (2009) 324:1076–80. doi: 10.1126/science.1164097
PubMed Summary | CrossRef Full Textual content | Google Scholar
60. Moffett JR, Puthillathu N, Vengilote R, Jaworski DM, Namboodiri AM. Acetate revisited: a key biomolecule on the nexus of metabolism, epigenetics and oncogenesis-part 1: acetyl-CoA, acetogenesis and acyl-CoA short-chain synthetases. Entrance Physiol. (2020) 11:580167. doi: 10.3389/fphys.2020.580167
PubMed Summary | CrossRef Full Textual content | Google Scholar
