Development of novel biological resection criteria for safe and oncologically satisfying resection of hepatocellular carcinoma

Schoenberg, Markus Bo; Anger, H; Hao, Jihua; Vater, Adrian; Bucher, Julian Nikolaus; Thomas, Michael; Lauseker, Michael; Rentsch, Markus; Schiergens, Tobias S.; Angele, Martin K.; Bazhin, Alexandr V.; Werner, Jens; Guba, Markus

doi:10.1016/j.suronc.2018.08.007

Cited by 8 publications

(4 citation statements)

References 28 publications

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“…When considering these differences, it is clear that accurate prediction of tumor specific survival after resection is needed. Until now mostly retrospective studies offered clinical prediction, which could not be confirmed in independent test cohorts [ 4 , 7 ]. Besides novel statistical techniques, some groups of variables show great promise for preoperative prediction of disease-free survival after resection [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Highly differential count of circulating and tumor infiltrating immune cells in patients with non-HCV/non-HBV hepatocellular carcinoma

Schoenberg

Zhu

Hao

et al. 2021

Cancer Immunol Immunother

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Background Liver transplantation and liver resection are curative options for early hepatocellular carcinoma (HCC). The outcome is in part depended on the immunological response to the malignancy. In this study, we aimed to identify immunological profiles of non-HCV/non-HBV HCC patients. Methods Thirty-nine immune cell subsets were measured with multicolor flow cytometry. This immunophenotyping was performed in peripheral blood (PB) and tumor specimens of 10 HCC resection patients and 10 healthy donors. The signatures of the highly differential leukocyte count (hDIF) were analyzed using multidimensional techniques. Functional capability was measured using intracellular IFN-γ staining (Trial Registration DRKS00013567). Results The hDIF showed activation (subsets of T-, B-, NK- and dendritic cells) and suppression (subsets of myeloid-derived suppressor cells and T- and B-regulatory cells) of the antitumor response. Principal component analysis of PB and tumor infiltrating leukocytes (TIL) illustrated an antitumor activating gradient. TILs showed functional capability by secreting IFN-γ but did not kill HCC cells. Conclusions In conclusion, the measurement of the hDIF shows distinct differences in immune reactions against non-HBV/non-HCV HCC and illustrates an immunosuppressive gradient toward peripheral blood. Trial Registration DRKS00013567

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Section: Introductionmentioning

confidence: 99%

Highly differential count of circulating and tumor infiltrating immune cells in patients with non-HCV/non-HBV hepatocellular carcinoma

Schoenberg

Zhu

Hao

et al. 2021

Cancer Immunol Immunother

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“…The determination of FDG-PET behavior is in the same direction, whereby PET-positive tumors are characterized by poor differentiation and thus a higher recurrence rate [29]. Furthermore, the degree of inflammation seems to influence the recurrence rate of HCCs, which is expressed in the neutrophil/lymphocyte ratio, tumor-infiltrating leukocytes, or CRP value [30, 31]. These measures, however, are all static and are applied only at one time point prior to or, in case of tumor-infiltrating leukocytes, even after transplantation.…”

Section: Discussionmentioning

confidence: 99%

Liver Transplantation for Extended Criteria Hepatocellular Carcinoma Using Stable Response to Locoregional Therapy and Alpha-Fetoprotein as Selection Criteria

et al. 2020

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Introduction: Current practice to only prioritize hepatocellular carcinoma (HCC) that fulfill the Milan criteria (IN MC) is changing, since it causes the exclusion of patients who could benefit from liver transplantation. To select patients outside MC (OUT MC) for transplantation, we implemented extended selection criteria without up-front morphometric restrictions containing surrogate parameters of tumor biology. Methods: OUT MC patients were considered without restrictions of morphometrics and received locoregional treatment after interdisciplinary consultation. Our dynamic selection criteria for OUT MC patients required (IN MUC): (1) treatment response over (2) at least 6 months and (3) alpha-fetoprotein ≤400 ng/mL over the entire evaluation period. Patients with IN MC tumors served as control and internal validation cohort. Results: 31 of 170 liver transplant candidates were OUT MC. Of these, 8 dropped out. The remaining 23 patients met the selection criteria and underwent transplantation. Recurrence-free survival was higher in patients transplanted IN MC compared to those OUT MC IN MUC (92.2% vs. 70.8%; p = 0.026) after 5 years of follow-up. Overall survival showed no significant difference (p = 0.552). With dynamic selection of transplant candidates, recurrence could also be predicted for the IN MC patients as internal validation cohort (c-index: 0.896; CI 0.588-0.981, p = 0.005). Conclusion: Dynamic selection criteria for the stratification of patients with OUT MC HCCs is feasible and allows for excellent long-term results and acceptable tumor recurrence rates comparable to IN MC patients.

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“…Furthermore, from an oncologic perspective, liver resection and alternative local ablative procedures are burdened with high recurrence rates, primarily due to de novo tumors arising in the precancerous liver. Overall, about 70% of resected patients will present with tumor recurrence within 5 years [ 2 ]. In contrast, tumor recurrence rates after transplantation are comparatively low at 15–20% after 5 years, depending on patient selection [ 3 ].…”

Section: Transplantation For Cancermentioning

confidence: 99%

Liver Transplant Oncology: Towards Dynamic Tumor-Biology-Oriented Patient Selection

Ilmer

Guba

2022

Cancers

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While liver transplantation was initially considered as a curative treatment modality only for hepatocellular carcinoma, the indication has been increasingly extended to other tumor entities over recent years, most recently to the treatment of non-resectable colorectal liver metastases. Although oncologic outcomes after liver transplantation (LT) are consistently good, organ shortage forces stringent selection of suitable candidates. Dynamic criteria based on tumor biology fulfill the prerequisite of an individual oncological prediction better than traditional morphometric criteria based on tumor burden. The availability of specific (neo-)adjuvant therapies and customized modern immunosuppression may further contribute to favorable post-transplantation outcomes on the one hand and simultaneously open the path to LT as a curative option for advanced stages of tumor patients. Herein, we provide an overview of the oncological LT indications, the selection process, and expected oncological outcome after LT.

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Development of novel biological resection criteria for safe and oncologically satisfying resection of hepatocellular carcinoma

Cited by 8 publications

References 28 publications

Highly differential count of circulating and tumor infiltrating immune cells in patients with non-HCV/non-HBV hepatocellular carcinoma

Highly differential count of circulating and tumor infiltrating immune cells in patients with non-HCV/non-HBV hepatocellular carcinoma

Liver Transplantation for Extended Criteria Hepatocellular Carcinoma Using Stable Response to Locoregional Therapy and Alpha-Fetoprotein as Selection Criteria

Liver Transplant Oncology: Towards Dynamic Tumor-Biology-Oriented Patient Selection

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