Dataset Information

Impact of metformin use on the recurrence of hepatocellular carcinoma after initial liver resection in diabetic patients.

ABSTRACT:

Background

Metformin is proposed to have chemopreventive effect of various cancer currently. However, the anti-cancer effect of metformin for diabetic patients with hepatocellular carcinoma (HCC) undergoing liver resection remains unclear. The aim of our cohort study was to assess whether metformin influence the recurrence of HCC.

Methods

We retrospectively enrolled 857 HCC patients who received primary resection from April 2001 to June 2016. 222 patients were diagnosed with diabetes mellitus (DM) from medical record. Factors influence the overall survival (OS) and recurrence-free survival (RFS) were analyzed by multivariate analysis.

Results

During the follow-up period (mean, 75 months), 471 (54.9%) patients experienced recurrence, and 158 (18.4%) patients died. Multivariate analysis revealed that DM (p = 0.015), elevated AST (p = 0.006), hypoalbuminemia (p = 0.003), tumor number (p = 0.001), tumor size (p < 0.001), vascular invasion (p <0.001), high Ishak fibrosis score (p <0.001), hepatitis B (p = 0.014), hepatitis C (p = 0.001) were independent predictors for RFS. In diabetic patients, only HbA1c>9% (p = 0.033), hypoalbuminemia (p = 0.030) and vascular invasion (p = 0.001) were independent risk factors for HCC recurrence; but the metformin use revealed no significance on recurrence. DM is a risk factor of HCC recurrence after resection. Adequate DM control can reduce the recurrence of HCC. However, the use of metformin does not reduce the risk of HCC recurrence in diabetic patient after initial resection. Hence, metformin may not have protective influences on HCC recurrence in diabetic patients who undergo initial liver resection.

SUBMITTER: Cho WR

PROVIDER: S-EPMC7932176 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Impact of metformin use on the recurrence of hepatocellular carcinoma after initial liver resection in diabetic patients.

Cho Wei-Ru WR Wang Chih-Chi CC Tsai Meng-Yun MY Chou Chen-Kai CK Liu Yueh-Wei YW Wu Yi-Ju YJ Lin Ming-Tsung MT Chen Kuang-Den KD Chuang Ching-Hui CH Huang Pao-Yuan PY Hu Tsung-Hui TH Tsai Ming-Chao MC

PloS one 20210304 3

<h4>Background</h4>Metformin is proposed to have chemopreventive effect of various cancer currently. However, the anti-cancer effect of metformin for diabetic patients with hepatocellular carcinoma (HCC) undergoing liver resection remains unclear. The aim of our cohort study was to assess whether metformin influence the recurrence of HCC.<h4>Methods</h4>We retrospectively enrolled 857 HCC patients who received primary resection from April 2001 to June 2016. 222 patients were diagnosed with diabe ...[more]

PMID: 33661912

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Project description:BackgroundHepatic resection remains the treatment of choice for patients with early-stage HCC with preserved liver function. Unfortunately, however, the majority of patients develop tumor recurrence. While several clinical factors were found to be associated with tumor recurrence, HCC pathogenesis is a complex process of accumulation of somatic genomic alterations, which leads to a huge molecular heterogeneity that has not been completely understood. The aim of this study is to complement potentially predictive clinical and pathological factors with next-generation sequencing genomic profiling and loss of heterozygosity analysis.Methods124 HCC patients, who underwent a primary hepatic resection from January 2016 to December 2019, were recruited for this study. Next-generation sequencing (NGS) analysis and allelic imbalance assessment in a case-control subgroup analysis were performed. A time-to-recurrence analysis was performed as well by means of Kaplan-Meier estimators.ResultsCumulative number of HCC recurrences were 26 (21%) and 32 (26%), respectively, one and two years after surgery. Kaplan-Meier estimates for the probability of recurrence amounted to 37% (95% C.I.: 24-47) and to 51% (95% C.I.: 35-62), after one and two years, respectively. Multivariable analysis identified as independent predictors of HCC recurrence: hepatitis C virus (HCV) infection (HR: 1.96, 95%C.I.: 0.91-4.24, p = 0.085), serum bilirubin levels (HR: 5.32, 95%C.I.: 2.07-13.69, p = 0.001), number of nodules (HR: 1.63, 95%C.I.: 1.12-2.38, p = 0.011) and size of the larger nodule (HR: 1.11, 95%C.I.: 1.03-1.18, p = 0.004). Time-to-recurrence analysis showed that loss of heterozygosity in the PTEN loci (involved in the PI3K/AKT/mTOR signaling pathway) was significantly associated with a lower risk of HCC recurrence (HR: 0.35, 95%C.I.: 0.13-0.93, p = 0.036).Conclusionsmultiple alterations of cancer genes are associated with HCC progression. In particular, the evidence of a specific AI mutation presented in 20 patients seemed to have a protective effect on the risk of HCC recurrence.

Project description:ImportanceThe remnant liver after hepatectomy may have inadequate blood supply, especially following nonanatomical resection or vascular damage.ObjectiveTo evaluate whether remnant liver ischemia (RLI) may have an adverse effect on long-term survival and morbidity after liver resection in patients with hepatocellular carcinoma.Design, setting, and participantsThis study was a retrospective analysis at Seoul National University Bundang Hospital. Remnant liver ischemia was graded on postoperative computed tomographic scans in 328 patients who underwent hepatectomy for hepatocellular carcinoma between January 1, 2004, and December 31, 2013.Main outcomes and measuresRemnant liver ischemia was defined as reduced or absent contrast enhancement during the venous phase. Remnant liver ischemia was classified as minimal (none or marginal) or severe (partial, segmental, or necrotic).ResultsAmong 328 patients (252 male and 76 female; age range, 26-83 years [mean age, 58.2 years]), radiologic signs of severe RLI were found in 98 patients (29.9%), of whom 63, 16, and 19 had partial, segmental, or necrotic RLI, respectively. These patients experienced more complications and longer hospital stay than patients with minimal RLI. Preoperative history of transarterial embolization (odds ratio [OR], 1.77; 95% CI, 1.02-3.03; P = .04), use of the Pringle maneuver (OR, 1.96; 95% CI, 1.08-3.58; P = .03), and longer operative time (OR, 1.003; 95% CI, 1.002-1.005; P < .001) were independent risk factors for severe RLI. Early recurrence rates within 6 (60.2% vs 9.6%) or 12 (79.6% vs 18.7%) months after hepatectomy were higher in patients with severe RLI than in patients without RLI (P < .001). Severe remnant liver ischemia was an independent risk factor for overall survival (OR, 6.98; 95% CI, 4.27-11.43; P < .001) and disease-free survival (OR, 5.15; 95% CI, 3.62-7.35; P < .001).Conclusions and relevancePreventive management and technical refinements in hepatectomy are important to decrease the risk of RLI and to improve survival of patients with hepatocellular carcinoma.

Dataset Information

Impact of metformin use on the recurrence of hepatocellular carcinoma after initial liver resection in diabetic patients.

Background

Methods

Results

Publications

Impact of metformin use on the recurrence of hepatocellular carcinoma after initial liver resection in diabetic patients.

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