Integrated Multiomics Reveals Silencing of has_circ_0006646 Promotes TRIM21-Mediated NCL Ubiquitination to Inhibit Hepatocellular Carcinoma Metastasis.

Recent studies suggest that circular RNA (circRNA)-mediated post-translational modification of RNA-binding proteins (RBP) plays a pivotal role in metastasis of hepatocellular carcinoma (HCC). However, the specific mechanism and potential clinical therapeutic significance remain vague. This study attempts to profile the regulatory networks of circRNA and RBP using a multi-omics approach. Has_circ_0006646 (circ0006646) is an unreported circRNA in HCC and is associated with a poor prognosis. Silencing of circ0006646 significantly hinders metastasis in vivo. Mechanistically, circ0006646 prevents the interaction between nucleolin (NCL) and the E3 ligase tripartite motif-containing 21 to reduce the proteasome-mediated degradation of NCL via K48-linked polyubiquitylation. Furthermore, the change of NCL expression is proven to affect the phosphorylation levels of multiple proteins and inhibit p53 translation. Moreover, patient-derived tumor xenograft and lentivirus injection, which is conducted to simulate clinical treatment confirmed the potential therapeutic value. Overall, this study describes the integrated multi-omics landscape of circRNA-mediated NCL ubiquitination degradation in HCC metastasis and provides a novel therapeutic target.

Gp78 deficiency in hepatocytes alleviates hepatic ischemia-reperfusion injury via suppressing ACSL4-mediated ferroptosis.

Ferroptosis, which is driven by iron-dependent lipid peroxidation, plays an essential role in liver ischemia-reperfusion injury (IRI) during liver transplantation (LT). Gp78, an E3 ligase, has been implicated in lipid metabolism and inflammation. However, its role in liver IRI and ferroptosis remains unknown. Here, hepatocyte-specific gp78 knockout (HKO) or overexpressed (OE) mice were generated to examine the effect of gp78 on liver IRI, and a multi-omics approach (transcriptomics, proteomics, and metabolomics) was performed to explore the potential mechanism. Gp78 expression decreased after reperfusion in LT patients and mice with IRI, and gp78 expression was positively correlated with liver damage. Gp78 absence from hepatocytes alleviated liver damage in mice with IRI, ameliorating inflammation. However, mice with hepatic gp78 overexpression showed the opposite phenotype. Mechanistically, gp78 overexpression disturbed lipid homeostasis, remodeling polyunsaturated fatty acid (PUFA) metabolism, causing oxidized lipids accumulation and ferroptosis, partly by promoting ACSL4 expression. Chemical inhibition of ferroptosis or ACSL4 abrogated the effects of gp78 on ferroptosis and liver IRI. Our findings reveal a role of gp78 in liver IRI pathogenesis and uncover a mechanism by which gp78 promotes hepatocyte ferroptosis by ACSL4, suggesting the gp78-ACSL4 axis as a feasible target for the treatment of IRI-associated liver damage.

Role of the immune system in liver transplantation and its implications for therapeutic interventions.

Liver transplantation (LT) stands as the gold standard for treating end-stage liver disease and hepatocellular carcinoma, yet postoperative complications continue to impact survival rates. The liver's unique immune system, governed by a microenvironment of diverse immune cells, is disrupted during processes like ischemia-reperfusion injury posttransplantation, leading to immune imbalance, inflammation, and subsequent complications. In the posttransplantation period, immune cells within the liver collaboratively foster a tolerant environment, crucial for immune tolerance and liver regeneration. While clinical trials exploring cell therapy for LT complications exist, a comprehensive summary is lacking. This review provides an insight into the intricacies of the liver's immune microenvironment, with a specific focus on macrophages and T cells as primary immune players. Delving into the immunological dynamics at different stages of LT, we explore the disruptions after LT and subsequent immune responses. Focusing on immune cell targeting for treating liver transplant complications, we provide a comprehensive summary of ongoing clinical trials in this domain, especially cell therapies. Furthermore, we offer innovative treatment strategies that leverage the opportunities and prospects identified in the therapeutic landscape. This review seeks to advance our understanding of LT immunology and steer the development of precise therapies for postoperative complications.

Establishment and validation of a cholesterol metabolism-related prognostic signature for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) represents the most important type of liver cancer, the 5-year survival rate for advanced HCC is 2%. The heterogeneity of HCC makes previous models fail to achieve satisfactory results. The role of Cholesterol-based metabolic reprogramming in cancer has attracted more and more attention. In this study, we screened cholesterol metabolism-related genes (CMRGs) based on a systematical analysis from TCGA and GEO database. Then, we constructed a prognostic signature based on the screened 5 CMRGs: FDPS, FABP5, ANXA2, ACADL and HMGCS2. The clinical value of the five CMRGs was validated by TCGA database and HPA database. HCC patients were assigned to the high-risk and low-risk groups on the basis of median risk score calculated by the five CMRGs. We evaluated the signature in TCGA database and validated in ICGC database. The results revealed that the prognostic signature had good prognostic performance, even among different clinicopathological subgroups. The function analysis linked CMRGs with KEGG pathway, such as cell adhesion molecules, drug metabolism-cytochrome P450 and other related pathways. In addition, patients in the high-risk group exhibited characteristics of high TP53 mutation, high immune checkpoints expression and high immune cell infiltration. Furthermore, based on the prognostic signature, we identified 25 most significant small molecule drugs as potential drugs for HCC patients. Finally, a nomogram combined risk score and TNM stage was constructed. These results indicated our prognostic signature has an excellent prediction performance. This study is expected to provide a potential diagnostic and therapeutic strategies for HCC.

The Landscape Of Alpha Fetoprotein In Hepatocellular Carcinoma: Where Are We?

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has been acknowledged as a leading cause of death among cirrhosis patients. Difficulties in early diagnosis and heterogeneity are obstacles to effective treatment, especially for advanced HCC. Liver transplantation (LT) is considered the best therapy for HCC. Although many biomarkers are being proposed, alpha-fetoprotein (AFP), which was identified over 60 years ago, remains the most utilized. Recently, much hope has been placed in the immunogenicity of AFP to develop novel therapies, such as AFP vaccines and AFP-specific adoptive T-cell transfer (ACT). This review summarizes the performance of AFP as a biomarker for HCC diagnosis and prognosis, as well as its correlation with molecular classes. In addition, the role of AFP in LT is also described. Finally, we highlight the mechanism and application prospects of two immune therapies (AFP vaccine and ACT) for HCC. In general, our review points out the prevalence of AFP in HCC, accompanied by some controversies and novel directions for future research.

C-Reactive Protein Is an Independent Predictor of 30-Day Bacterial Infection Post-Liver Transplantation.

The relationship between aseptic systemic inflammation and postoperative bacterial infection is unclear. We investigated the correlation of systemic inflammation biomarkers with 30-day clinically significant bacterial infections (CSI) after liver transplantation (LT). This retrospective study enrolled 940 patients who received LT and were followed for 30 days. The primary end point was 30-day CSI events. The cohort was divided into exploratory (n = 508) and validation (n = 432) sets according to different centers. Area under the receiver operated characteristic (AUROC) and Cox regression models were fitted to study the association between baseline systemic inflammation levels and CSI after LT. A total of 255 bacterial infectious events in 209 recipients occurred. Among systemic inflammation parameters, baseline C-reactive protein (CRP) was independently associated with 30-day CSI in the exploratory group. The combination of CRP and organ failure number showed a good discrimination for 30-day CSI (AUROC = 0.80, 95% CI, 0.76-0.84) and the results were confirmed in an external verification group. Additionally, CRP levels were correlated with bacterial product lipopolysaccharide. In conclusion, our study suggests that pre-transplantation CRP is independent of other prognostic factors for 30-day CSI post-LT, and can be integrated into tools for assessing the risk of bacterial infection post-LT or as a component of prognostic models.

Low Growth Hormone Levels Predict Poor Outcome of Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.

Background and Aims: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) remains a serious entity with high mortality. Growth hormone (GH) is related to the liver metabolism and regeneration. The present study aimed to explore the changes and prognostic efficacy of GH on the outcome of HBV-ACLF. Methods: A prospective cohort of 124 patients and a cross-sectional cohort of 142 subjects were enrolled. GH and insulin-like growth factor-1(IGF-1) were detected by ELISA. Thirty-day survival was collected and the association between GH and the 30-day mortality of HBV-ACLF was analyzed. Results: The mean age of the whole prospective cohort was 46.61 ± 12.71 years, and 19 (15.3%) patients were female. The median (IQR) of GH levels in non-survivors were 1106.55 (674.25, 1922.4) pg/ml, which were significantly lower than in survivors (p < 0.001). In the cross-sectional cohort, GH level was significantly higher in liver cirrhosis - acute decompensation (LC-AD) group than liver cirrhosis (LC) group (p < 0.001) while IGF-1 decreased significantly in LC, LC-AD, ACLF groups than health control (HC) and chronic Hepatitis B (CHB) groups (p < 0.001). The area under the receiver operating characteristic curve (AUROC) of GH for predicting 30-day mortality was 0.793. We built a new prognostic model, namely MELD-GH, which showed better predictive efficacy than Child-Pugh, MELD, CLIF-SOFA, and CLIF-C ACLF scores. Conclusions: Low GH predicted the poor outcome of HBV-ACLF patients. GH and IGF-1 levels were differently distributed among HC, CHB, LC, LC-AD, and ACLF patients. MELD-GH had better predictive accuracy when compared to Child-Pugh, MELD, CLIF-SOFA, and CLIF-C ACLF scores.

Endoplasmic reticulum stress triggers delanzomib-induced apoptosis in HCC cells through the PERK/eIF2α/ATF4/CHOP pathway.

For limited clinical benefits and acquired resistance by sorafenib, new therapeutic strategies and molecular targets for the treatment of advanced hepatocellular carcinoma (HCC) are urgently needed. This study aimed to evaluate the potential antitumor effects of the second-generation proteasome inhibitor delanzomib on HCC. The results demonstrated that delanzomib displayed excellent antitumor activity on HCC cells with sensitivity or resistance to sorafenib in a time- and dose-response manner, by inducing G2/M cell cycle arrest and apoptosis in vitro. Cell cycle arrest was associated with the activation of p21/Cdc2/cyclin B1 pathway, and cell apoptosis was confirmed by PARP and caspase-3 cleavage. In addition, delanzomib induced endoplasmic reticulum stress (ERS) in HCC cells by activating the PERK and ERS-associated proteins including p-eIF2α, ATF4 and CHOP. Selective inhibition of eIF2α dephosphorylation by salubrinal could significantly reduce delanzomib-induced apoptosis in HCC cells. In vivo, delanzomib could also exhibit effective antitumor properties on patient-derived xenograft mouse model of HCC with relative low drug-associated cytotoxicity. Compared to control group, 3 and 10 mg/kg of delanzomib significantly reduced the tumor volume by 33.1% and 87.2% respectively after 3 weeks treatment, with no significant change on the body weight and the level of serum biochemical indexes including ALT, AST and BUN. In conclusion, delanzomib could exhibit good pre-clinical antitumor effects against HCC cells by inducing ERS and activating the PERK/eIF2α/ATF4/CHOP pathway, as potential drug candidate on treatment of advanced HCC patients.

Y-320, a novel immune-modulator, sensitizes multidrug-resistant tumors to chemotherapy.

Y-320, a novel immune-modulator, inhibits IL-17 production by CD4+ T cells stimulated with IL-15. Its use in autoimmune diseases such as rheumatoid arthritis has been documented. However, no studies have be conducted to evaluate its application in cancer treatment either as mono or combined therapy. This study demonstrated that while Y-320 had little effect on multidrug resistance (MDR) cell lines, it induced remarkable injury to MDR tumor cells when concurrently administered with other chemotherapeutic agents. Concomitant use of Y-320 with a low dose of paclitaxel significantly sensitized MDR tumors by inducing G2/M phase arrest and apoptosis. Further analyses indicated that Y-320 was a substrate of P-glycoprotein (P-gp). It could inhibit P-gp efflux function without altering P-gp expression, and subsequently reverse P-gp mediated drug resistance in MDR cells. The co-administration of Y-320 and paclitaxel suppressed tumor growth remarkably with an inhibition rate of 77.1% compared to 6.5% in the paclitaxel monotherapy group in vivo. This co-treatment did not increase extra complications in MDR tumor xenograft models. Particularly, no significant changes in body weight and hepatorenal serology were observed with the co-treatment. In conclusion, our results confirm that Y-320 is a promising chemotherapy sensitizer for the first time. The co-administration of Y-320 and chemotherapeutic agents might be an effective and low-toxicity chemotherapeutic regime for the MDR tumor patients.

Synthetic lethality: A promising therapeutic strategy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), the main cause of liver cancer-related death, is one of the main cancers in terms of incidence and mortality. However, HCC is difficult to target and develops strong drug resistance. Therefore, a new treatment strategy is urgently needed. The clinical application of the concept of synthetic lethality in recent years provides a new therapeutic direction for the accurate treatment of HCC. Here, we introduce the concept of synthetic lethality, the screening used to study synthetic lethality, and the identified and potential genetic interactions that induce synthetic lethality in HCC. In addition, we propose opportunities and challenges for translating synthetic lethal interactions to the clinical treatment of HCC.

NKILA, a prognostic indicator, inhibits tumor metastasis by suppressing NF-κB/Slug mediated epithelial-mesenchymal transition in hepatocellular carcinoma.

The metastasis of hepatocellular carcinoma (HCC) is one of the major obstacles hindering its therapeutic efficacy, leading to low surgical resection rate, high mortality and poor prognosis. Accumulating evidence has shown that both long noncoding RNA (lncRNA) and NF-κB play vital roles in the regulation of cancer metastasis. However, the clinical significance and biological function of NKILA (NF-κB interacting lncRNA) and its interaction with NF-κB in HCC remain unknown. In this study, we demonstrated that NKILA was down-regulated in HCC tissues and cell lines, and decreased NKILA expression was significantly associated with larger tumor size and positive vascular invasion in HCC patients. NKILA reduction was an independent risk factor of HCC patients' poor prognosis, and the 5-year overall survival (OS) rates of patients with low and high NKILA expression were 15.6% and 60.0%, respectively. Moreover, NKILA inhibits migration and invasion of HCC cells both in vitro and in vivo. Mechanistically, NKILA prevents Slug/epithelial to mesenchymal transition (EMT) pathway via suppressing phosphorylation of IκBα, p65 nuclear translocation and NF-κB activation. In conclusion, these results indicate that NKILA might serve as an effective prognostic biomarker and a promising therapeutic target against HCC metastasis.

LY2228820 induces synergistic anti-cancer effects with anti-microtubule chemotherapeutic agents independent of P-glycoprotein in multidrug resistant cancer cells.

Side-effects and resistance substantially limit the efficacy of chemotherapy. One possible solution to this persistent problem would be co-administration of targeted therapy and chemotherapy to achieve synergistic anti-cancer effects without extra toxicity. Here, we reported that LY2228820, a selective inhibitor of p38-MAPK signaling pathway, could induce synergistic anti-cancer effects with anti-microtubule (AMT) chemotherapy both in vitro and in vivo. In drug-resistant cancer cells, treatment with either LY2228820 or AMT drug alone was compatible with viability, while co-administration of both led to dramatic cytotoxicity, G2/M arrest and apoptosis. Moreover, co-treatment with LY2228820 notably improved the effectiveness of paclitaxel without exhibiting adverse effects in vivo. Mechanistic studies showed that LY2228820 sensitized cancer cells to AMT agents independent of P-gp. LY2228820 did not influence either the expression or the function of P-gp. Instead, it could inhibit p38-HSP27 signaling axis by down-regulating p-HSP27. Furthermore, LY2228820 blocked the p-HSP27 mediated protective response against AMT drugs in tumor cells, resulting in mitochondrial instability and the activation of mitochondrial death pathways. This P-gp-independent regime containing LY2228820 and AMT agents could produce synergistic anti-cancer effects without extra systematic toxicity. Our study offers a novel strategy for improving the therapeutic efficacy of AMT drugs by achieving a better balance between efficacy and toxicity. This new combination regime could be advantageous in patients who show little response to the maximal dosage of AMT chemotherapy, as well as those unable to tolerate the systematic toxicity of these agents in clinic.

COL6A1 promotes metastasis and predicts poor prognosis in patients with pancreatic cancer.

Pancreatic cancer is one of the most aggressive cancers worldwide with a high mortality rate. Prognosis remains poor even in this era of advanced medicine mainly due to early metastasis and invasion. The present study aimed to explore and validate predictors of distant metastasis and prognosis in pancreatic cancer. In our preliminary experiment, we established a novel metastatic pancreatic cancer cell line BxPC­M8 from parent BxPC­3 cells. Via whole genome sequencing, RT­qPCR, western blotting, migration and invasion assays, we initially found that BxPC­M8 shared similar biological characteristics to BxPC­3, but only differed in enhanced metastatic and invasive capabilities with a significant increase in collagen type VI α1 chain (COL6A1) expression. Knockdown of COL6A1 via small interfering RNA led to a significant decrease in migration and invasion of BxPC­M8 cells, suggesting suppressed epithelial­mesenchymal transition. Furthermore, a significant increase in COL6A1 expression was observed in cancerous tissue compared with paracancerous tissue (40.7 vs 3.7, P=0.001). Additionally, its expression was observed to be significantly associated with distant metastasis and vascular invasion at the time of surgery. Multivariate analysis revealed that COL6A1 expression (hazard ratio 1.90, 95% confidence interval 1.04­3.47, P=0.037) is an independent predictor of overall survival (OS). The median OS observed for COL6A1+ and COL6A1­ patients was found to be 8±4 and 14±7 months (P=0.021), respectively. Of note, we identified that COL6A1 expression in tissue samples was associated with significantly reduced OS (P=0.001), demonstrating that COL6A1 may serve an important role in the metastatic process and could be considered as a predictor of poor outcomes in patients with pancreatic cancer. In addition, our findings suggest that COL6A1 could be an indicator of distant metastasis and a valid prognostic predictor in such patients; however, further investigation is required.

Cabazitaxel, a novel chemotherapeutic alternative for drug-resistant hepatocellular carcinoma.

The prognosis of advanced hepatocellular carcinoma (HCC) patients remains extremely poor, partially due to the development of acquired resistance to sorafenib and chemotherapy. Cabazitaxel, a semisynthetic taxane, has been approved for the therapy of docetaxel-resistant prostate cancer. However, no studies have been performed on the effect of cabazitaxel on HCC, and whether cabazitaxel remains sensitive in chemotherapy-resistant and sorafenib-resistant HCC cells is not clear. Our results demonstrate that cabazitaxel is highly toxic to HCC cell lines in a time- and dose-dependent manner by inducing G2/M phase arrest and apoptosis in vitro. Cabazitaxel also significantly suppresses HCC tumor growth in vivo. In chemotherapy-resistant HCC cell Huh-TS-48 with P-gp-overexpression, cabazitaxel shows less cross-resistant to other chemotherapeutic agents. The resistance fold of cabazitaxel, doxorubicin, paclitaxel, docetaxel and vinorelbine is 1.53, 8.60, 38.58, 15.53 and 18.06 respectively. Furthermore, sorafenib-resistant HCC cell SK-sora-5 is still sensitive to cabazitaxel. The IC50 values of cabazitaxel after 72 h exposure for parental cell SK-hep-1 and resistant cell SK-sora-5 are 0.84 and 0.73 nM. The results indicate that cabazitaxel is a potential agent to treat HCC after developing chemotherapy resistance caused by overexpression of P-gp and acquired resistance to sorafenib, and might improve prognosis in advanced HCC patients.

Risk factors for postoperative pancreatic fistula after laparoscopic distal pancreatectomy using stapler closure technique from one single surgeon.

Laparoscopic distal pancreatectomy (LDP) is a safe and reliable treatment for tumors in the body and tail of the pancreas. Postoperative pancreatic fistula (POPF) is a common complication of pancreatic surgery. Despite improvement in mortality, the rate of POPF still remains high and unsolved. To identify risk factors for POPF after laparoscopic distal pancreatectomy, clinicopathological variables on 120 patients who underwent LDP with stapler closure were retrospectively analyzed. Univariate and multivariate analyses were performed to identify risk factors for POPF. The rate of overall and clinically significant POPF was 30.8% and13.3%, respectively. Higher BMI (≥25kg/m2) (p-value = 0.025) and longer operative time (p-value = 0.021) were associated with overall POPF but not clinically significant POPF. Soft parenchymal texture was significantly associated with both overall (p-value = 0.012) and clinically significant POPF (p-value = 0.000). In multivariable analyses, parenchymal texture (OR, 2.933, P-value = 0.011) and operative time (OR, 1.008, P-value = 0.022) were risk factors for overall POPF. Parenchymal texture was an independent predictive factor for clinically significant POPF (OR, 7.400, P-value = 0.001).

Laparoscopic ligation of celiac trunk and splenic artery aneurysms with function preservation.

Celiac trunk aneurysms (CTAs) are rare and usually asymptomatic. Although most of these aneurysms can be treated with percutaneous embolization, some uncommon locations of the aneurysm may make this approach impossible. We report a patient with a celiac trunk aneurysm (CTA) and a proximal splenic artery aneurysm (SAA). Due to the size and location of these two aneurysms, after multidisciplinary discussion, endovascular management was considered inappropriate and they were treated by laparoscopic ligation of the two aneurysms and revascularization. This procedure offers good postoperative recovery with good preservation of the visceral function. Some collateral vessels in the viscera were obvious on postoperative day 7.

Laparoscopic duodenum-preserving pancreatic head resection: A case report.

BACKGROUND: Solid pseudopapillary neoplasms (SPNs) of the pancreas are uncommon neoplasms and are potentially malignant. Complete resection is advised due to rare recurrence and metastasis. Duodenum-preserving pancreatic head resection (DPPHR) is indicated for SPNs located in the pancreatic head and is only performed using the open approach. To the best of our knowledge, there are no reports describing laparoscopic DPPHR (LDPPHR) for SPNs. METHODS: Herein, we report a case of 41-year-old female presented with a 1-week history of epigastric abdominal discomfort, and founded an SPN of the pancreatic head by abdominal computed tomography/magnetic resonance, who was treated by radical LDPPHR without complications, such as pancreatic fistula and bile leakage. Histological examination of the resected specimen confirmed the diagnosis of SPN. RESULTS: The patient was discharged 1 week after surgery following an uneventful postoperative period. She was followed up 3 months without readmission and local recurrence according to abdominal ultrasound. CONCLUSION: LDPPHR is a safe, feasible, and effective surgical procedure for SPNs.

Intracorporeal esophagojejunostomy after totally laparoscopic total gastrectomy: A single-center 7-year experience.

AIM: To assess the efficacy and safety of intracorporeal esophagojejunostomy in patients undergoing laparoscopic total gastrectomy (LTG) for gastric cancer. METHODS: A retrospective review of 81 consecutive patients who underwent LTG with the same surgical team between November 2007 and July 2014 was performed. Four types of intracorporeal esophagojejunostomy using staplers or hand-sewn suturing were performed after LTG. Data on clinicopatholgoical characteristics, occurrence of complications, postoperative recovery, anastomotic time, and operation time among the surgical groups were obtained through medical records. RESULTS: The average operation time was 288.7 min, the average anastomotic time was 54.3 min, and the average estimated blood loss was 82.7 mL. There were no cases of conversion to open surgery. The first flatus was observed around 3.7 d, while the liquid diet was started, on average, from 4.9 d. The average postoperative hospital stay was 10.1 d. Postoperative complications occurred in 14 patients, nearly 17.3%. However, there were no cases of postoperative death. CONCLUSION: LTG performed with intracorporeal esophagojejunostomy using laparoscopic staplers or hand-sewn suturing is feasible and safe. The surgical results were acceptable from the perspective of minimal invasiveness.

Robotic versus Laparoscopic Distal Pancreatectomy: A Meta-Analysis of Short-Term Outcomes.

AIM: To compare the safety and efficacy of robotic-assisted distal pancreatectomy (RADP) and laparoscopic distal pancreatectomy (LDP). METHODS: A literature search of PubMed, EMBASE, and the Cochrane Library database up to June 30, 2015 was performed. The following key words were used: pancreas, distal pancreatectomy, pancreatic, laparoscopic, laparoscopy, robotic, and robotic-assisted. Fixed and random effects models were applied. Study quality was assessed using the Newcastle-Ottawa Scale. RESULTS: Seven non-randomized controlled trials involving 568 patients met the inclusion criteria. Compared with LDP, RADP was associated with longer operating time, lower estimated blood loss, a higher spleen-preservation rate, and shorter hospital stay. There was no significant difference in transfusion, conversion to open surgery, R0 resection rate, lymph nodes harvested, overall complications, severe complications, pancreatic fistula, severe pancreatic fistula, ICU stay, total cost, and 30-day mortality between the two groups. CONCLUSION: RADP is a safe and feasible alternative to LDP with regard to short-term outcomes. Further studies on the long-term outcomes of these surgical techniques are required. CORE TIP: To date, there is no consensus on whether laparoscopic or robotic-assisted distal pancreatectomy is more beneficial to the patient. This is the first meta-analysis to compare laparoscopic and robotic-assisted distal pancreatectomy. We found that robotic-assisted distal pancreatectomy was associated with longer operating time, lower estimated blood loss, a higher spleen-preservation rate, and shorter hospital stay. There was no significant difference in transfusion, conversion to open surgery, overall complications, severe complications, pancreatic fistula, severe pancreatic fistula, ICU stay, total cost, and 30-day mortality between the two groups.

LDP vs ODP for pancreatic adenocarcinoma: a case matched study from a single-institution.

BACKGROUND: Laparoscopic distal pancreatectomy (LDP) showed advantage of perioperation outcomes for benign and low-grade tumor of the pancreas. The application of LDP for pancreatic ductal adenocarcinoma (PDAC) didn't gain popular acceptance and the number of LDP for PDAC remains low. We designed a case-matched study to analysis the short- and long-term outcomes of the patients undergoing either Laparoscopic distal pancreatectomy or open distal pancreatectomy for PDAC. METHOD: From 2003 to 2013, 17 patients were underwent LDP and 34 patients were underwent ODP for PDAC were matched by tumor size, age and body mass index (BMI). The two groups' demographic information, perioperative outcomes and survival data were compared. RESULTS: Baseline characteristics were comparable between the LDP and ODP groups. The intraoperative blood loss, first flatus, first oral intake and postoperative hospital stay were significantly less in LDP group than ODP group (50 ml vs400ml, P = 0.000; 3d vs 4d, P = 0.001; 3d vs 4d, P = 0.003; 13d vs 15.5d, P = 0.022). The mean operation time, overall postoperative morbidity and postoperative pancreatic fistula rates were similar in the two groups. 5 patients (29.4 %) in LDP group and 7 patients (20.6 %) in ODP group underwent extended resections. There were no significant differences in tumor sizes (3.5 cm vs 3.9 cm, P = 0.664) and number of harvested lymph nodes (9 vs8 P = 0.534). The median overall survival for both groups was 14.0 months. Cox proportional hazards analysis showed extended resections, R1 resection, perineural invasion and tumor differentiation were associated with worse survival. CONCLUSION: LDP is technically feasible and safe for PDAC in selected patients and the short-term oncologic outcomes were not inferior to ODP in this small sample study. However the long-term oncologic safety of LDP for PDAC has to be further evaluated by multicenter or randomized controlled trials.