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BackgroundThe utility of pre- and post-operative alpha-fetoprotein (AFP) and des-gamma (γ)-carboxy prothrombin (DCP) expression patterns and their dynamic changes as predictors of the outcome of hepatic resection for hepatocellular carcinoma (HCC) has yet to be well elucidated.MethodsFrom a multicenter database, AFP and DCP data during the week prior to surgery and the first post-discharge outpatient visit (within 1-2 months after surgery) were collected from patients with HCC who underwent hepatectomy. AFP-DCP expression patterns were categorized according to the number of positive tumor markers (AFP ≥ 20ng/mL, DCP ≥ 40mAU/mL), including double-negative, single-positive, and double-positive. Changes in the AFP-DCP expression patterns were delineated based on variations in the number of positive tumor markers when comparing pre- and post-operative patterns.ResultsPreoperatively, 53 patients (8.3%), 337 patients (52.8%), and 248 patients (38.9%) exhibited double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Postoperatively, 463 patients (72.6%), 130 patients (20.4%), and 45 patients (7.0%) showed double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Survival analysis showed a progressive decrease in recurrence-free (RFS) and overall survival (OS) as the number of postoperative positive tumor markers increased (both P < 0.001). Multivariate analysis showed that postoperative AFP-DCP expression pattern, but not preoperative AFP-DCP expression pattern, was an independent risk factor for RFS and OS. Further analysis showed that for patients with positive preoperative markers, prognosis gradually improves as positive markers decrease postoperatively. In particular, when all postoperative markers turned negative, the prognosis was consistent with that of preoperative double-negative patients, regardless of the initial number of positive markers.ConclusionsAFP-DCP expression patterns, particularly postoperative patterns, serve as vital sources of information for prognostic evaluation following hepatectomy for HCC. Moreover, changes in AFP-DCP expression patterns from pre- to post-operation enable dynamic prognostic risk stratification postoperatively, aiding the development of individualized follow-up strategies.

Abstract Background Routine clinical staging for hepatocellular carcinoma (HCC) incorporates liver function, general health, and tumor morphology. Further refinement of prognostic assessments and treatment decisions may benefit from the inclusion of tumor biological marker alpha-fetoprotein (AFP) and systemic inflammation indicator C-reactive protein (CRP). Methods Data from a multicenter cohort of 2770 HCC patients undergoing hepatectomy were analyzed. We developed the PACE risk score (Prognostic implications of AFP and CRP Elevation) after initially assessing preoperative AFP and CRP’s prognostic value. Subgroup analyzes were performed in BCLC cohorts A and B using multivariable Cox analysis to evaluate the prognostic stratification ability of the PACE risk score and its complementary utility for BCLC staging. Results Preoperative AFP ≥ 400ng/mL and CRP ≥ 10 mg/L emerged as independent predictors of poorer prognosis in HCC patients who underwent hepatectomy, leading to the creation of the PACE risk score. PACE risk score stratified patients into low, intermediate, and high-risk groups with cumulative 5-year overall (OS) and recurrence-free survival (RFS) rates of 59.6%/44.9%, 43.9%/38.4%, and 20.6%/18.0% respectively (all P

Intramuscular macrophages play key regulatory roles in determining the response of skeletal muscle to injury and disease. Recent investigations showed that the numbers and phenotype of intramuscular macrophages change during aging, suggesting that those changes could influence the aging process. We tested that hypothesis by generating a mouse model that harbors a myeloid cell-specific mutation of Spi1, which is a transcription factor that is essential for myeloid cell development. The mutation reduced the numbers of macrophages biased to the CD163+/CD206+ M2 phenotype in muscles of aging mice without affecting the numbers of CD68-expressing macrophages and reduced the expression of transcripts associated with the M2-biased phenotype. The mutation did not affect the colony-forming ability or the frequency of specific subpopulations of bone marrow hematopoietic cells and did not affect myeloid/lymphoid cell ratios in peripheral blood leukocyte populations. Cellularity of most myeloid lineage cells was not influenced by the mutation. The Spi1 mutation in bone marrow-derived macrophages in vitro also did not affect expression of transcripts that indicate the M2-biased phenotype. Thus, myeloid cell-targeted mutation of Spi1 influences macrophage phenotype in muscle but did not affect earlier stages of differentiation of cells in the macrophage lineage. The mutation reduced age-related muscle fibrosis, which is consistent with the reduction of M2-biased macrophages, and reduced expression of the pro-fibrotic enzyme arginase. Most importantly, the mutation prevented sarcopenia. Together, our observations indicate that intramuscular, M2-biased macrophages play significant roles in promoting detrimental, age-related changes in muscle.

BackgroundThis study evaluates the efficacy of alpha-fetoprotein (AFP) response as a surrogate marker for determining recurrence-free survival (RFS) in patients with unresectable hepatocellular carcinoma (uHCC) who undergo salvage hepatectomy following conversion therapy with tyrosine kinase inhibitor (TKI) and anti-PD-1 antibody-based regimen.MethodsThis multicenter retrospective study included 74 patients with uHCC and positive AFP (>20 ng/mL) at diagnosis, who underwent salvage hepatectomy after treatment with TKIs and anti-PD-1 antibody-based regimens. The association between AFP response—defined as a ≥ 80% decrease in final AFP levels before salvage hepatectomy from diagnosis—and RFS post-hepatectomy was investigated.ResultsAFP responders demonstrated significantly better postoperative RFS compared to non-responders (P