FABP4 deficiency ameliorates alcoholic steatohepatitis in mice via inhibition of p53 signaling pathway.

Fatty acid-binding protein 4 (FABP4) plays an essential role in metabolism and inflammation. However, the role of FABP4 in alcoholic steatohepatitis (ASH) remains unclear. This study aimed to investigate the function and underlying mechanisms of FABP4 in the progression of ASH. We first obtained alcoholic hepatitis (AH) datasets from the National Center for Biotechnology Information-Gene Expression Omnibus database and conducted bioinformatics analysis to identify critical genes in the FABP family. We then established ASH models of the wild-type (WT) and Fabp4-deficient (Fabp4-/-) mice to investigate the role of FABP4 in ASH. Additionally, we performed transcriptional profiling of mouse liver tissue and analyzed the results using integrative bioinformatics. The FABP4-associated signaling pathway was further verified. FABP4 was upregulated in two AH datasets and was thus identified as a critical biomarker for AH. FABP4 expression was higher in the liver tissues of patients with alcoholic liver disease and ASH mice than in the corresponding control samples. Furthermore, the Fabp4-/- ASH mice showed reduced hepatic lipid deposition and inflammation compared with the WT ASH mice. Mechanistically, Fabp4 may be involved in regulating the p53 and sirtuin-1 signaling pathways, subsequently affecting lipid metabolism and macrophage polarization in the liver of ASH mice. Our results demonstrate that Fabp4 is involved in the progression of ASH and that Fabp4 deficiency may ameliorate ASH. Therefore, FABP4 may be a potential therapeutic target for ASH treatment.

Hepatocyte-derived Fetuin-A promotes alcohol-associated liver disease in mice by inhibiting autophagy-lysosome degradation of TLR and M2 macrophage polarization.

BACKGROUND: Alcohol-associated liver disease (ALD) is one of the most common chronic liver diseases worldwide. Fetuin-A (FetA) is a plasma glycoprotein closely related to fat accumulation in the liver. However, the role of FetA in ALD remains unclear. METHODS: Both National Institute on Alcohol Abuse and Alcoholism (NIAAA) model and ethanol (EtOH) treated cell were used in this study. The effect of FetA deficiency on the progression of ALD was analyzed and the underlying mechanism was explored. RESULTS: The expression of FetA was upregulated in the liver tissues of ethanol-fed mice and ALD patients, as well as in AML12 cells treated with ethanol. FetA deletion reduced hepatic steatosis, oxidative stress, and inflammation in ALD mice. Interestingly, the absence of FetA led to a reduction of TLR4 protein level in liver tissue of EtOH-fed mice, without a corresponding change of its mRNA level. Conversely, the administration of recombinant FetA elevated TLR4 protein level in ethanol-treated RAW264.7 cells. FetA knockout significantly impeded the polarization of M1 macrophage in vivo or in vitro. Mechanistically, FetA deficiency drived the autophagy-lysosomal degradation of TLR4, subsequently inhibiting the activation of NF-kB/NLRP3 inflammasome pathway. Furthermore, knockdown of FetA using an adeno-associated virus 8 (AAV8)-shRNA can effectively prevent the progression of ALD in mice. CONCLUSION: Our results indicate that inhibition of FetA reverses the progression of ALD in mice, implying that FetA can serve as a therapeutic target for the treatment of ALD.

Identification and validation of cuproptosis-related genes in acetaminophen-induced liver injury using bioinformatics analysis and machine learning.

Background: Acetaminophen (APAP) is commonly used as an antipyretic analgesic. However, acetaminophen overdose may contribute to liver injury and even liver failure. Acetaminophen-induced liver injury (AILI) is closely related to mitochondrial oxidative stress and dysfunction, which play critical roles in cuproptosis. Here, we explored the potential role of cuproptosis-related genes (CRGs) in AILI. Methods: The gene expression profiles were obtained from the Gene Expression Omnibus database. The differential expression of CRGs was determined between the AILI and control samples. Protein protein interaction, correlation, and functional enrichment analyses were performed. Machine learning was used to identify hub genes. Immune infiltration was evaluated. The AILI mouse model was established by intraperitoneal injection of APAP solution. Quantitative real-time PCR and western blotting were used to validate hub gene expression in the AILI mouse model. The copper content in the mouse liver samples and AML12 cells were quantified using a colorimetric assay kit. Ammonium tetrathiomolybdate (ATTM), was administered to mouse models and AML12 cells in order to investigate the effects of copper chelator on AILI. Results: The analysis identified 7,809 differentially expressed genes, 4,245 of which were downregulated and 3,564 of which were upregulated. Four optimal feature genes (OFGs; SDHB, PDHA1, NDUFB2, and NDUFB6) were identified through the intersection of two machine learning algorithms. Further nomogram, decision curve, and calibration curve analyses confirmed the diagnostic predictive efficacy of the four OFGs. Enrichment analysis indicated that the OFGs were involved in multiple pathways, such as IL-17 pathway and chemokine signaling pathway, that are related to AILI progression. Immune infiltration analysis revealed that macrophages were more abundant in AILI than in control samples, whereas eosinophils and endothelial cells were less abundant. Subsequently, the AILI mouse model was successfully established, and histopathological analysis using hematoxylin-eosin staining along with liver function tests revealed a significant induction of liver injury in the APAP group. Consistent with expectations, both mRNA and protein levels of the four OFGs exhibited a substantial decrease. The administration of ATTAM effectively mitigates copper elevation induced by APAP in both mouse model and AML12 cells. However, systemic administration of ATTM did not significantly alleviate AILI in the mouse model. Conclusion: This study first revealed the potential role of CRGs in the pathological process of AILI and offered novel insights into its underlying pathogenesis.

International consensus guidelines on robotic pancreatic surgery in 2023.

Background: With the rapid development of robotic surgery, especially for the abdominal surgery, robotic pancreatic surgery (RPS) has been applied increasingly around the world. However, evidence-based guidelines regarding its application, safety, and efficacy are still lacking. To harvest robust evidence and comprehensive clinical practice, this study aims to develop international guidelines on the use of RPS. Methods: World Health Organization (WHO) Handbook for Guideline Development, GRADE Grid method, Delphi vote, and the AGREE-II instrument were used to establish the Guideline Steering Group, Guideline Development Group, and Guideline Secretary Group, formulate 19 clinical questions, develop the recommendations, and draft the guidelines. Three online meetings were held on 04/12/2020, 30/11/2021, and 25/01/2022 to vote on the recommendations and get advice and suggestions from all involved experts. All the experts focusing on minimally invasive surgery from America, Europe and Oceania made great contributions to this consensus guideline. Results: After a systematic literature review 176 studies were included, 19 questions were addressed and 14 recommendations were developed through the expert assessment and comprehensive judgment of the quality and credibility of the evidence. Conclusions: The international RPS guidelines can guide current practice for surgeons, patients, medical societies, hospital administrators, and related social communities. Further randomized trials are required to determine the added value of RPS as compared to open and laparoscopic surgery.

Functional genetic variants of the disulfidptosis-related INF2 gene predict survival of hepatitis B virus-related hepatocellular carcinoma.

Disulfidptosis is a novel form of programmed cell death involved in migration and invasion of cancer cells, but few studies investigated the roles of genetic variants in disulfidptosis-related genes in survival of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). We used Cox proportional hazards regression analyses, Kaplan-Meier curves and receiver operating characteristic curves to assess effects of genetic variants in 14 disulfidptosis-related genes on overall survival of 866 HBV-HCC patients. The Bayesian false discovery probability was used for multiple testing corrections. We also investigated biological mechanisms of the significant variants through expression quantitative trait loci analyses using the data from publicly available databases, luciferase reporter assays and differential expression analyses. As a result, we identified two independently functional single nucleotide polymorphisms (SNPs) (INF2 rs4072285 G > A and INF2 rs4444271 A > T) that predicted overall survival of HBV-HCC patients, with adjusted hazard ratios of 1.60 (95% CI = 1.22-2.11, P = 0.001) and 1.50 (95% CI = 1.80-1.90, P < 0.001), respectively, after multiple testing correction. Luciferase reporter assays indicated that both INF2 rs4072285 A and INF2 rs4444271 T alleles increased INF2 mRNA expression levels (P < 0.001) that were also higher in HCC tumor tissues than in adjacent normal tissues (P < 0.001); such elevated INF2 expression levels were associated with a poorer survival of HBV-HCC patients (P < 0.001) in the TCGA database. In summary, this study supported that INF2 rs4072285 and INF2 rs4444271 may be novel biomarkers for survival of HBV-HCC patients.

FBXL19 promotes malignant behaviours by activating MAPK signalling and negatively correlates with prognosis in hepatocellular carcinoma.

FBXL19 is a member of the Skp1-Cullin-F-box family of E3 ubiquitin ligases and is linked to a variety of vital biological processes, such as cell proliferation, migration, and differentiation. Previous studies have identified it as an oncogene in breast cancer and glioma. However, its role in hepatocellular carcinoma (HCC) remains unclear. To comprehensively elucidate its role in tumour biology and its underlying mechanisms, a variety of sophisticated methods, including bioinformatics analysis, RNA-sequencing technique, and in vitro cell biology experiments, were used. Here, we found that FBXL19 was upregulated in patients with HCC and correlated with poor prognosis. In in vitro experiments, the specific targeting of short hairpin RNAs via lentiviruses successfully induced the knockdown of FBXL19, resulting in notable inhibition of the proliferation, migration, and invasion of HCC cells. Furthermore, FBXL19 downregulation resulted in significant induction of G0/G1 phase cell cycle arrest. Importantly, FBXL19 knockdown inhibited tumour malignant behaviour primarily by inactivating extracellular signal-regulated protein kinase 1/2 and p38 mitogen-activated protein kinases. In conclusion, this study revealed that FBXL19 was upregulated in patients with HCC, and that its expression was negatively correlated with prognosis. Thus, FBXL19 displays oncogenic properties in HCC by activating mitogen-activated protein kinase signalling.

Identification and validation of potential diagnostic signature and immune cell infiltration for NAFLD based on cuproptosis-related genes by bioinformatics analysis and machine learning.

Background and aims: Cuproptosis has been identified as a key player in the development of several diseases. In this study, we investigate the potential role of cuproptosis-related genes in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Method: The gene expression profiles of NAFLD were obtained from the Gene Expression Omnibus database. Differential expression of cuproptosis-related genes (CRGs) were determined between NAFLD and normal tissues. Protein-protein interaction, correlation, and function enrichment analyses were performed. Machine learning was used to identify hub genes. Immune infiltration was analyzed in both NAFLD patients and controls. Quantitative real-time PCR was employed to validate the expression of hub genes. Results: Four datasets containing 115 NAFLD and 106 control samples were included for bioinformatics analysis. Three hub CRGs (NFE2L2, DLD, and POLD1) were identified through the intersection of three machine learning algorithms. The receiver operating characteristic curve was plotted based on these three marker genes, and the area under the curve (AUC) value was 0.704. In the external GSE135251 dataset, the AUC value of the three key genes was as high as 0.970. Further nomogram, decision curve, calibration curve analyses also confirmed the diagnostic predictive efficacy. Gene set enrichment analysis and gene set variation analysis showed these three marker genes involved in multiple pathways that are related to the progression of NAFLD. CIBERSORT and single-sample gene set enrichment analysis indicated that their expression levels in macrophages, mast cells, NK cells, Treg cells, resting dendritic cells, and tumor-infiltrating lymphocytes were higher in NAFLD compared with control liver samples. The ceRNA network demonstrated a complex regulatory relationship between the three hub genes. The mRNA level of these hub genes were further confirmed in a mouse NAFLD liver samples. Conclusion: Our study comprehensively demonstrated the relationship between NAFLD and cuproptosis, developed a promising diagnostic model, and provided potential targets for NAFLD treatment and new insights for exploring the mechanism for NAFLD.

Cushing's syndrome presenting as non-atherosclerotic myocardial infarction and heart failure.

Cushing's syndrome is a rare cause of myocardial infarction and heart failure. Herein, we report a female patient who presented acute myocardial infarction and heart failure with reduced ejection fraction. The patient was found to have hypercortisolism secondary to adrenocortical adenoma and responded well to therapy. This case underlines the effects of hypercortisolism on the cardiovascular system. The clinical presentation of this patient is unique because non-atherosclerotic myocardial infarction is rarely reported in Cushing's syndrome patients.

Transcriptome sequencing and metabolome analysis reveal the metabolic reprogramming of partial hepatectomy and extended hepatectomy.

Surgical resection remains a critical treatment option for many patients with primary and secondary hepatic neoplasms. Extended hepatectomy (eHx) may be required for some patients with large tumors, which may cause liver failure and death. Partial hepatectomy (pHx) and eHx mouse models were constructed, liver tissues were sampled at 18, 36, and 72 h posthepatectomy. Transcriptome and metabolome analyses were employed to explore the different potential mechanisms in regeneration and injury between pHx and eHx. The results showed that eHx was associated with more severe liver injury and lower survival rates than pHx. Transcriptomics data showed there were 1842, 2129, and 1277 differentially expressed genes (DEGs) in eHx and 962, 1305, and 732 DEGs in pHx at 18, 36, and 72 h posthepatectomy, respectively, compared with the those in the sham groups. Compared with pHx, the number of DEGs in the eHx group reached a maximum of 230 at 18 h after surgery and decreased sequentially to 87 and 43 at 36 and 72 h. Metabolomics analysis identified a total of 1399 metabolites, and 48 significant differentially produced metabolites (DPMs) were screened between eHx and pHx. Combined analysis of DEGs and DPMs indicated that cholesterol metabolism and insulin resistance may be two important pathways for liver regeneration and mouse survival postextended hepatectomy. Our results showed the global influence of pHx and eHx on the transcriptome and metabolome in mouse liver, and revealed cholesterol metabolism and insulin resistance pathways might be involved in regeneration post-pHx and -eHx.

Blockade of C5aR1 alleviates liver inflammation and fibrosis in a mouse model of NASH by regulating TLR4 signaling and macrophage polarization.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is an advanced form of chronic fatty liver disease, which is a driver of hepatocellular carcinoma. However, the roles of the C5aR1 in the NASH remain poorly understood. Here, we aimed to investigate the functions and mechanisms of the C5aR1 on hepatic inflammation and fibrosis in murine NASH model. METHODS: Mice were fed a normal chow diet with corn oil (ND + Oil), a Western diet with corn oil (WD + Oil) or a Western diet with carbon tetrachloride (WD + CCl4) for 12 weeks. The effects of the C5a-C5aR1 axis on the progression of NASH were analyzed and the underlying mechanisms were explored. RESULTS: Complement factor C5a was elevated in NASH mice. C5 deficiency reduced hepatic lipid droplet accumulation in the NASH mice. The hepatic expression levels of TNFα, IL-1ß and F4/80 were decreased in C5-deficient mice. C5 loss alleviated hepatic fibrosis and downregulated the expression levels of α-SMA and TGFß1. C5aR1 deletion reduced inflammation and fibrosis in NASH mice. Transcriptional profiling of liver tissues and KEGG pathway analysis revealed that several pathways such as Toll-like receptor signaling, NFκB signaling, TNF signaling, and NOD-like receptor signaling pathway were enriched between C5aR1 deficiency and wild-type mice. Mechanistically, C5aR1 deletion decreased the expression of TLR4 and NLRP3, subsequently regulating macrophage polarization. Moreover, C5aR1 antagonist PMX-53 treatment mitigated the progression of NASH in mice. CONCLUSIONS: Blockade of the C5a-C5aR1 axis reduces hepatic steatosis, inflammation, and fibrosis in NASH mice. Our data suggest that C5aR1 may be a potential target for drug development and therapeutic intervention of NASH.

The role of the complosome in health and disease.

The complement system is one of the immune system's oldest defense mechanisms and is historically regarded as a liver-derived and serum-active innate immune system that 'complements' cell-mediated and antibody-mediated immune responses against pathogens. However, the complement system is now recognized as a central component of both innate and adaptive immunity at both the systemic and local tissue levels. More findings have uncovered novel activities of an intracellularly active complement system-the complosome-that have shifted established functional paradigms in the field. The complosome has been shown to play a critical function in regulating T cell responses, cell physiology (such as metabolism), inflammatory disease processes, and cancer, which has amply proved its immense research potential and informed us that there is still much to learn about this system. Here, we summarize current understanding and discuss the emerging roles of the complosome in health and disease.

[Retracted] Downregulation of δ opioid receptor by RNA interference enhances the sensitivity of BEL/FU drug­resistant human hepatocellular carcinoma cells to 5­FU.

Subsequently to the publication of the above article, and a Corrigendum that was published with the intention of showing corrected data for the flow cytometric plots shown in Fig. 3 (DOI: 10.3892/mmr.2018.9415; published online on August 21, 2018), it was drawn to the Editors' attention by a concerned reader that the ß­actin agarose gel electrophoretic blots shown in Fig. 1A were strikingly similar to data appearing in different form in another article by different authors at a different research institute which had already been published elsewhere prior to this paper's submission to Molecular Medicine Reports. Owing to the fact that the contentious data had already been published else prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 13: 59­66, 2016; DOI: 10.3892/mmr.2015.4511].

[Retracted] Isoquercitrin inhibits the progression of liver cancer in vivo and in vitro via the MAPK signalling pathway.

Subsequently to the publication of the above article, a concerned reader drew to our attention that the data panel shown in Fig. 7A for the 400 µM isoquercitrin experiment had previously appeared in Fig. 4A in another article published in the journal International Journal of Oncology [Tang B, Li Y, Yuan S, Tomlinson S and He S: Upregulation of the δ opioid receptor in liver cancer promotes liver cancer progression both in vitro and in vivo. Int J Oncol 43: 1281­1290, 2013], indicating that results that were purported to have been obtained under different experimental conditions had been derived from the same original source. Furthermore, concerns were also raised regarding the originality of some of the other data belonging to this figure. Given the errors that were identified in the compilation of Fig. 7 in this article, the Editor of Oncology Reports has decided that this article should be retracted from the publication owing to a lack of overall confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience that might result from the retraction of this article. [Oncology Reports 31: 2377­2384, 2014; DOI: 10.3892/or.2014.3099].

[Retracted] Upregulation of the δ opioid receptor in liver cancer promotes liver cancer progression both in vitro and in vivo.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the western blotting data shown in Fig. 1C on p. 1284 for the control ß­actin protein bands were strikingly similar to bands appearing in another article written by different authors at different research institutes, which had already been submitted for consideration for publication (Li ZH, Yu Y, Du C, Fu H, Wang J and Tian Y: RNA interference­mediated USP22 gene silencing promotes human brain glioma apoptosis and induces cell cycle arrest. Oncol Lett 5: 1290­1294, 2013). Owing to the fact that the contentious data in the above article had already been submitted for publication elsewhere prior to its submission to International Journal of Oncology, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 43: 1281­1290, 2013; DOI: 10.3892/ijo.2013.2046].

Burden of liver cancer due to hepatitis C from 1990 to 2019 at the global, regional, and national levels.

Background: Liver cancer due to hepatitis C (LCDHC) is one of the leading causes of cancer-related deaths worldwide, and the burden of LCDHC is increasing. We aimed to report the burden of LCDHC at the global, regional, and national levels in 204 countries from 1990 to 2019, stratified by etiology, sex, age, and Sociodemographic Index. Methods: Data on LCDHC were available from the Global Burden of Disease, Injuries, and Risk Factors (GBD) study 2019. Numbers and age-standardized mortality, incidence, and disability-adjusted life year (DALY) rates per 100,000 population were estimated through a systematic analysis of modeled data from the GBD 2019 study. The trends in the LCDHC burden were assessed using the annual percentage change. Results: Globally, in 2019, there were 152,225 new cases, 141,810 deaths, and 2,878,024 DALYs due to LCDHC. From 1990 to 2019, the number of incidences, mortality, and DALY cases increased by 80.68%, 67.50%, and 37.20%, respectively. However, the age-standardized incidence, mortality, and DALY rate had a decreasing trend during this period. In 2019, the highest age-standardized incidence rates (ASIRs) of LCDHC were found in high-income Asia Pacific, North Africa and the Middle East, and Central Asia. At the regional level, Mongolia, Egypt, and Japan had the three highest ASIRs in 2019. The incidence rates of LCDHC were higher in men and increased with age, with a peak incidence in the 95+ age group for women and the 85-89 age group for men in 2019. A nonlinear association was found between the age-standardized rates of LCDHC and sociodemographic index values at the regional and national levels. Conclusions: Although the age-standardized rates of LCDHC have decreased, the absolute numbers of incident cases, deaths, and DALYs have increased, indicating that LCDHC remains a significant global burden. In addition, the burden of LCDHC varies geographically. Male and older adult/s individuals have a higher burden of LCDHC. Our findings provide insight into the global burden trend of LCDHC. Policymakers should establish appropriate methods to achieve the HCV elimination target by 2030 and reducing the burden of LCDHC.

The role of complement in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) has become a leading cause of chronic liver diseases globally. NAFLD includes a range of hepatic manifestations, starting with liver steatosis and potentially evolving towards nonalcoholic steatohepatitis, cirrhosis or even hepatocellular carcinoma. Although the pathogenesis of NAFLD is incompletely understood, insulin resistance and lipid metabolism disorder are implicated. The complement system is an essential part of the immune system, but it is also involved in lipid metabolism. In particular, activation of the alternative complement pathway and the production of complement activation products such as C3a, C3adesArg (acylation stimulating protein or ASP) and C5a, are strongly associated with insulin resistance, lipid metabolism disorder, and hepatic inflammation. In this review, we briefly summarize research on the role of the complement system in NAFLD, aiming to provide a basis for the development of novel therapeutic strategies for NAFLD.

A comparative study of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging and contrast-enhanced ultrasound in the detection of intrahepatic lesion.

We evaluated the diagnostic performance of both gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-MRI) and contrast-enhanced ultrasound (CEUS) for focal liver lesions, especially for the detection of small (<2 cm) intrahepatic lesions. We retrospectively reviewed patients who underwent Gd-EOB-DTPA-MRI and CEUS before liver resection and compared Gd-EOB-DTPA-MRI and CEUS in the detection of focal liver lesions. A total of 216 patients were included, and 309 lesions were found. The sensitivity values of MRI and CEUS for the main lesion were both more than 95%, and the coincidence rates were both more than 80%. Regarding lesions <2 cm, 135 such lesions were detected by MRI, whereas only 85 were detected by CEUS. For lesions <2 cm, the sensitivity, specificity, and coincidence rates of MRI were significantly better than those of CEUS. Among 27 patients, 50 more lesions were detected by MRI than CEUS, 56% (28/50) of which were malignant. For the large lesion, the diagnostic performance is similar between Gd-EOB-DTPA-MRI and CEUS, and the sensitivity and coincidence rates of both methods are high. Gd-EOB-DTPA-MRI is likely to detect small (<2 cm) focal intrahepatic lesions.

Comparison of surgical outcomes among open, laparoscopic, and robotic pancreatoduodenectomy: a single-center retrospective study.

BACKGROUND: There is no general consensus on the feasibility and safety of robotic pancreatoduodenectomy (RPD) and whether it increases surgical risks. The purpose of this study was to assess the safety, feasibility, and rationality of RPD by comparing perioperative data among open pancreatoduodenectomy (OPD), laparoscopic pancreatoduodenectomy (LPD), and RPD performed in our center in recent years. METHODS: Clinical data of patients had undergone RPD (n = 32), LPD (n = 21), and OPD (n = 86) in The First Affiliated Hospital of Guangxi Medical University between January 2016 and June 2020 were retrospectively collected and analyzed. RESULTS: RPD required more time for operation (537.2 min vs. 441.5 min, p < 0.001) than OPD did, but less time to remove abdominal drainage tube (12.5 d vs. 17.3 d, p = 0.001). The differences between the RPD group and LPD group were interesting, as the two groups had similar operation time (537.2 min vs. 592.9 min, p = 1.000) and blood loss (482.8 ml vs. 559.5 ml, p > 0.05), but the RPD group had a higher activity of daily living score on postoperative day 3 (35.8 vs. 25.7, p = 0.0017) and a lower rate of conversion to OPD (6.5% vs. 38.1%, p = 0.011). Regarding complications, such as the postoperative pancreatic fistula, abdominal hemorrhage, intra-abdominal infection, bile leakage, reoperation, and perioperative mortality, there were no significant differences among the three groups. CONCLUSIONS: Not only is RPD feasible and reliable, it also offers significant advantages in that it improves postoperative recovery of skills needed for everyday life, has a low conversion rate to open surgery, and does not increase surgical risks.