A comparison of prognostic performance of perioperative inflammation markers in surgical resection for hepatocellular carcinoma

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Background: Preclinical studies have shown that local anesthetics may modify the growth and invasion of cancer cells. However, few clinical studies have evaluated their impact on cancer outcomes after tumor resection. Methods: In this single-center cohort study, patients who underwent surgical resection of stage IA through IIIB nonsmall-cell lung cancer and used patient-controlled epidural analgesia from 2005 to 2015 were recruited and followed until May 2017. Data of the epidural bupivacaine dose for each patient were obtained from infusion pump machines. Proportional hazards regression models were used to analyze the associations between bupivacaine dose with postoperative cancer recurrence and all-cause mortality. Results: A total of 464 patients were analyzed. Among these patients, the mean bupivacaine dose was 352 mg (± standard deviation 74 mg). After adjusting for important clinical and pathological covariates, a significant dose-response relationship was observed between epidural bupivacaine dose and all-cause mortality (adjusted hazard ratio: 1.008, 95% confidence interval: 1.001-1.016, p = 0.029). The association between bupivacaine dose and cancer recurrence were not significant (adjusted hazard ratio: 1.000, 95% confidence interval: 0.997-1.002, p = 0.771). Age, sex, body mass index, mean daily maximum pain score, and pathological perineural infiltration were independently associated with bupivacaine dose. Conclusion: A dose-dependent association was found between epidural bupivacaine dose and long-term mortality among patients following surgical resection of nonsmall-cell lung cancer. Our findings do not support the hypothetical anticancer benefits of local anesthetics. More studies are needed to elucidate the role of local anesthetics in cancer treatment.

Section: Discussionmentioning

confidence: 55%

“…Finally, we did not analyze markers of inflammation, and it remains unclear whether inflammatory responses to epidural bupivacaine were responsible for the higher mortality rate among the patients who used more bupivacaine. 41,42…”

Section: Discussionmentioning

confidence: 99%

Dose-response relationship between epidural bupivacaine dose and mortality risk after surgical resection of nonsmall-cell lung cancer

Tai

et al. 2022

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“…41 Over the past two decades, there is accumulating evidence supporting the theory that perioperative NLR can predict long-term survival and recurrence after cancer treatment. [42][43][44] There are some possible mechanisms to explain the association between preoperative NLR and postoperative complications after liver resection. First, neutrophils may facilitate tumor spreading via the production of reactive oxygen species, the release of circulating vascular endothelial growth factor, and overexpression of pro-metastasis protease.…”

Section: Discussionmentioning

confidence: 99%

A predictive model incorporating inflammation markers for high-grade surgical complications following liver resection for hepatocellular carcinoma

Liu

et al. 2022

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Background: Systemic inflammation and immune deficiency predispose surgical patients to infection and adversely affect postoperative recovery. We aimed to evaluate the prognostic ability of inflammation and immune-nutritional markers and to develop a predictive model for high-grade complications after resection of hepatocellular carcinoma (HCC). Methods: This study enrolled 1431 patients undergoing liver resection for primary HCC at a medical center. Preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, prognostic nutritional index, Model for End-Stage Liver Disease score, Albumin-Bilirubin score, Fibrosis-4 score, and Aspartate Aminotransferase to Platelet Ratio Index score were assessed. Stepwise backward variable elimination was conducted to determine the factors associated with Clavien-Dindo grade III to V complications within 30-day postoperative period. The predictive model was internally validated for discrimination performance using area under the receiver operating characteristic curve (AUC). Results: A total of 106 (7.4%) patients developed high-grade complications. Four factors independently predicted a high-grade postoperative complication and were integrated into the predictive model, including NLR (adjusted odds ratio: 1.10, 95% confidence interval [CI], 1.02-1.19), diabetes mellitus, extent of hepatectomy, and intraoperative blood loss. The AUC of the model was 0.755 (95% CI, 0.678-0.832) in the validation dataset. Using the cutoff value based on Youden’s index, the sensitivity and specificity of the risk score were 59.0% and 76.3%, respectively. Conclusion: Preoperative NLR independently predicted a high-grade complication after resection of HCC. The predictive model allows for identification of high-risk patients and appropriate modifications of perioperative care to improve postoperative outcomes.

“…13,65–89 In brief, MAFLD, characterized by the fat accumulation >5% (by histological examination) or >5.6% (by magnetic resonance imaging (MRI)-derived proton density fat fraction [MRI-PDFF]) of hepatocytes (presence of steatosis) without excessive alcohol consumption or secondary causes of hepatic steatosis, presents a biggest health hazard globally, based on its potential continuous progression to advanced liver fibrosis (liver cirrhosis) and finally the development of hepatocellular carcinoma (HCC), contributing to the heavy economic and social burdens worldwide. 65–67,88,90–100…”

Section: Metabolic Dysfunction-associated Fatty Liver Diseases (Also ...mentioning

confidence: 99%

“…13, In brief, MAFLD, characterized by the fat accumulation >5% (by histological examination) or >5.6% (by magnetic resonance imaging (MRI)-derived proton density fat fraction [MRI-PDFF]) of hepatocytes (presence of steatosis) without excessive alcohol consumption or secondary causes of hepatic steatosis, presents a biggest health hazard globally, based on its potential continuous progression to advanced liver fibrosis (liver cirrhosis) and finally the development of hepatocellular carcinoma (HCC), contributing to the heavy economic and social burdens worldwide. [65][66][67]88,[90][91][92][93][94][95][96][97][98][99][100] Pathogenesis of MAFLD, similar to DM, is a result of multiple interactions and/or cross-talks among genetic, epigenetic, environmental and micro-organisms (Fig. 1), including genetic and epigenetic factors (acetyl-CoA carboxylase, adipophilin [adipose differentiation-related protein], apolipoprotein C3, adenosine triphosphate citrate lyase [Acly], calpain 10, carbohydrate response element-binding protein, catalase, ectoenzyme nucleotide pyrophosphate phosphodiesterase 1, Forkhead box protein O1, free fatty acid [FFA] oxidation-related genes such as branched-chain acyl-CoA oxidase, carnitine palmitoyltransferase 1a, cytochrome P450 2E1, cytochrome P4A11, long-chain acyl-CoA dehydrogenase, long-chain L-3-hydroxyacylcoensyme A dehydrogenase alpha, uncoupling protein 2, FFA synthase, glutathione peroxidase [GPX], insulin receptor substrate, patatin like phospholipase domain-containing protein-3, peroxisome proliferator-activated receptor-γ [PPAR-γ], sterol regulatory elementbinding protein, and superoxide dismutase 2 [SOD2]) to result in malfunction of metabolism and dysregulation of immunological system, hormone system and other homeostasis status in human body; gut metabolome and environmental factors, such as drugs, heavy mental, toxins, infection to further augment oxidative stress secondary to unbalance input and output-metabolic dysregulation mediated by production of oxidative stress factors (fibroblast growth factor 21 [FGF 21], thioredoxin, copper-to-zinc SOD2, GPX, Mac-2 binding protein: M2BP, and others) as well as inflammatory factors (CC-chemokine ligand 2, c-Jun-N-terminal kinase, CRP, glycogen synthase kinase 3, interleukin 1-beta, 2, 6 and 8, and tumor necrosis factor-alpha), and formatting reactive oxygen species-reactive oxygen species leading to the increase of superoxide anion radicals to form adducts with cellular nucleophiles, cellular damage, and inflammatory responses as well as the release of a lots of amount of cytokine, adipocytokines (adipokines, adiponectin, apelin, hepcidin leptin, resistin, vaspin, and visfatin), and therefore, IR and MeS develop with subsequently progression to more specific diseases, such as DM, MAFLD, etc.…”

Section: Metabolic Dysfunction-associated Fatty Liver Diseases (Also ...mentioning

confidence: 99%

To Do One and To Get More: Part II. Diabetes and metabolic dysfunction-associated fatty liver diseases

Lee

Wang

Yang

et al. 2022

Type 2 diabetes mellitus (DM) is characterized by inability of faulty pancreatic β-cells to secret a normal amount of insulin to maintain normal body consumption, and/or peripheral tissue has a decreased susceptibility to insulin, resulting in hyperglycemia and insulin resistance. Similar to other chronic systemic inflammatory diseases, DM is a result from dysregulated interactions between ethnic, genetic, epigenetic, immunoregulatory, hormonal, and environmental factors. Therefore, it is rational to suppose the concept as “To do one and to get more”, while using antidiabetic agents (ADA), a main pharmacologic agent for the treatment of DM, can provide an extraglycemia effect on comorbidities or concomittent comorbidities to DM. In this review, based on the much strong correlation between DM and metabolic dysfunction-associated fatty liver diseases (MAFLD) shown by similar pathophysiological mechanisms and a high prevalence of DM in MAFLD and its vice versa (a high prevalence of MAFLD in DM), it is possible to use the strategy to target both diseases simultaneously. We focus on a new classification of ADA, such as glucagon-like peptide-1 receptor (GLP1R) agonist and sodium-glucose cotransporter-2 (SGLT-2) inhibitors to show the potential benefits of extraglycemic effect on MAFLD. We conclude that the management of DM patients, especially for those who need ADA as adjuvant therapy should include healthy lifestyle modification to overcome the metabolic syndrome, contributing to the urgent need of an effective weight-reduction strategy. GLP1R agonist is one of effective body weight-lowering medications, which may be a better choice for DM complicated with MAFLD or its-associated severe form as metabolic associated steatohepatitis (MASH), although the role of SGLT-2 inhibitors is also impressive. The prescription of these two classes of ADA may satisfy the concept “To do one and to get more”, based on successful sugar-lowering effect for controlling DM and extraglycemia benefits of hepatoprotective activity in DM patients.