Preoperative Anemia Is a Predictor of Worse Postoperative Outcomes Following Open Pancreatoduodenectomy: A Propensity Score-Based Analysis.

Background: Preoperative anemia is a common clinical situation proved to be associated with severe outcomes in major surgeries, but not in pancreatic surgery. We aim to study the impact of preoperative anemia on morbidity and mortality in patients undergoing open pancreatoduodenectomy and use propensity score matching (PSM) to balance the basal data and reduce bias. Methods: We analyzed the data of consecutive patients undergoing open pancreatoduodenectomy with a complete record of preoperative hemoglobin, at two pancreatic centers in China between 2015 and 2019. Anemia is defined as hemoglobin less than 12 g/dl for male and 11 g/dl for female, following Chinese criteria. We compared clinical and economic outcomes before and after PSM and used logistic regression analysis to assess the correlation between variables and anemia. Results: The unmatched initial cohort consisted of 517 patients. A total of 148 cases (28.6%) were diagnosed with anemia at admission, and no case received a preoperative blood transfusion or anti-anemia therapy. After PSM, there were 126 cases in each group. The rate of severe postoperative complications was significantly higher in the anemia group than in the normal group (43.7% vs. 27.0%, p = 0.006), among which the differences in prevalence of clinically relevant postoperative pancreatic fistula (CR-POPF) (31.0% vs. 15.9%, p = 0.005) and cardiac and cerebrovascular events (4.0% vs. 0.0%, p = 0.024) were the most significant. The costs involved were more in the anemia group (26958.2 ± 21671.9 vs. 20987.7 ± 10237.9 USD, p = 0.013). Among anemic patients, receiver operating characteristic (ROC) curve analysis shows the cut-off value of hemoglobin, below which, patients are prone to suffer from major complications (104.5 g/l in male and 90.5 g/l in female). Among all patients, multivariate analysis showed that preoperative obstructive jaundice [odds ratio (OR) = 1.813, 95% confidence interval (CI) (1.206-2.725), p = 0.004] and pancreatic ductal adenocarcinoma [OR = 1.861, 95% CI (1.178-2.939), p = 0.008] were predictors of anemia. Among paired patients, preoperative anemia [OR = 2.593, 95% CI (1.481-5.541), p = 0.001] and malignant pathology [OR = 4.266, 95% CI (1.597-11.395), p = 0.004] were predictors of postoperative severe complications. Conclusion: Preoperative anemia is a predictor of worse postoperative outcomes following open pancreatoduodenectomy and needs to be identified and treated.

Preoperative Nutrition Support May Reduce the Prevalence of Postoperative Pancreatic Fistula after Open Pancreaticoduodenectomy in Patients with High Nutritional Risk Determined by NRS2002.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a severe complication which may be caused by a perioperative nutrition problem. We aimed to study whether patients with high nutritional risk (NRS2002 score ≥ 5) might benefit from preoperative nutrition support regarding the risk of CR-POPF after open pancreaticoduodenectomy. METHODS: Consecutive patients undergoing open pancreaticoduodenectomy with complete record of NRS2002 at two Chinese institutions between 2013 and 2018 were analysed. CR-POPF was diagnosed following the 2016 ISGPS criteria. Nutrition support included oral nutrition supplement and enteral and parenteral nutrition. Clinical and economic outcomes were analysed. RESULTS: 522 cases were included. 135 cases (25.9%) were at high nutritional risk (NRS2002 score ≥ 5), among which 41 cases (30.4%) received preoperative nutrition support. The CR-POPF rate was significantly lower in the preoperative nutrition support group compared with the no nutrition support group (12.2% versus 28.7%, P = 0.038). Multivariate analysis showed that preoperative nutrition support was a protective factor for CR-POPF in patients at high risk [OR 0.339, 95% CI (0.115-0.965), P = 0.039]. Higher albumin and a larger diameter of the main pancreatic duct were found to be other protectors for CR-POPF. CONCLUSIONS: Patients with high nutritional risk (NRS2002 score ≥ 5) may profit from preoperative nutritional support manifested in the reduction of CR-POPF.

Anatomic versus non-anatomic resection of hepatocellular carcinoma with microvascular invasion: A systematic review and meta-analysis.

The efficacy of anatomical resection (AR) and non-anatomical resection (NR) in the treatment of hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) remains unknown. This study compared the safety and outcomes of these surgical procedures. A systematic literature search was conducted. The main outcomes were overall survival (OS), disease-free survival (DFS). Overall hazard ratio (HR) was calculated from Kaplan-Meier plots and outcomes using random-effects models. There was no significant difference in postoperative complications between the AR and NR groups (risk ratio [RR]: 0.92, 95% confidence interval [CI]: 0.72-1.17, p = 0.496). OS was higher with AR at 1 year (RR: 0.66, 95% CI: 0.45-0.98, p = 0.037), 3 years (RR: 0.64, 95% CI: 0.50-0.82, p = 0.000), and 5 years (RR: 0.76, 95% CI: 0.65-0.89, p = 0.001). AR was associated with a higher OS rate (HR: 0.62, 95% CI: 0.47-0.82, p = 0.001). AR was associated with improved DFS at 1 year (RR: 0.65, 95% CI: 0.52 to 0.82, p = 0.000), 3 years (RR: 0.75, 95% CI: 0.66 to 0.86, p = 0.000), and 5 years (95% CI: 0.75 to 0.94, p = 0.002). Compared with NR, AR had significant advantages on overall HR of DFS (HR: 0.64, 95% CI: 0.45 to 0.91, p = 0.012). In conclusion, AR was associated with higher rates of OS and DFS in HCC patients with MVI. Thus, for well-presented liver function HCC patients which are predicted to have positive MVI, AR is recommended.

Repression of lncRNA NEAT1 enhances the antitumor activity of CD8+T cells against hepatocellular carcinoma via regulating miR-155/Tim-3.

BACKGROUND: Immunotherapy is a promising method for the treatment of hepatocellular carcinoma (HCC), in which CD8+T cells play a key role. The influence of long noncoding RNA (lncRNA) nuclear-enriched autosomal transcript 1(NEAT1) on the antitumor activity of CD8+T cells was clarified in this study. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from HCC patients, and the expressions of NEAT1 and Tim-3 were determined by qRT-PCR and western blot, respectively. CD8+T cell apoptosis and cell percentage were analyzed via flow cytometry. The cytolysis activity of CD8+T cells against HCC cells was examined. RNA immunoprecipitation (RIP) and RNA pull-down assay were performed to explore the interaction between NEAT1 and miR-155. RESULTS: NEAT1 and Tim-3 were up-regulated in the PBMCs of patients with HCC (n = 20) compared with healthy subjects (n = 20). Down-regulation of NEAT1 restrained CD8+T cell apoptosis and enhanced the cytolysis activity, while interference of miR-155 showed the opposite effects by up-regulating Tim-3. Binding and interaction between NEAT1 and miR-155 were validated in CD8+T cells. Down-regulation of NEAT1 restrained CD8+T cell apoptosis and enhanced the cytolysis activity through the miR-155/Tim-3 pathway. Repression of NEAT1 suppressed tumor growth in HCC mice. CONCLUSION: Via modulating the miR-155/Tim-3 pathway, repression of NEAT1 restrained CD8+T cell apoptosis and enhanced the cytolysis activity against HCC, implying an effective target for improving the outcome of immunotherapy.

[FTY720-induced lymphocyte apoptosis inhibits acute graft versus host disease in rat small bowel transplantation].

OBJECTIVE: To investigate the effect and mechanism of FTY720 on acute graft versus host disease (GVHD) in rat small bowel transplantation (SBTx). METHODS: Heterotopic SBTx was performed using a parent (WF)-into-F1 (WFxACI) rat combination. Recipient rats were divided into experimental group (n=6) and control group (n=6). Rats in the experimental group were administered with FTY720 at 0.5 mg/kg for 14 days. Lymphocyte apoptosis in the liver and the mucosa of intestine and graft was detected by TUNEL and flow cytometry 15 days after transplantation. Recipient survival and lymphocyte apoptosis were compared between the two groups. RESULTS: Recipients in the control group died of GVHD after a mean survival time of (16+/-2.1) days. FTY720-treated recipients had a significantly longer survival (>100 days). After administration of FTY720, the percentage of apoptotic lymphocytes was significantly increased in the graft as compared to that in the control group by flow cytometry. The ratio of apoptotic lymphocyte in the liver and graft was also significantly higher in the experimental group by TUNEL. CONCLUSION: FTY720 effectively induces the lymphocyte apoptosis, inhibits the lesion of target tissues by GVHD, and prolongs the recipient survival.

[Alternation and significance of CD4(+)CD45RA(+) and CD4(+)CD45RO(+) T cells in peripheral blood of colorectal cancer patients].

OBJECTIVE: To investigate the alternation and significance of CD4(+)CD45RA(+) T cells and CD4(+)CD45RO(+) T cells in peripheral blood of colorectal cancer patients. METHODS: The expression of CD4(+) T cells, CD4(+)CD45RA(+) T cells and CD4(+)CD45RO(+) T cells in peripheral blood of 60 colorectal cancer patients were detected with flow cytometry pre-operatively and 1, 3 months post-operatively, compared with those of 10 healthy persons. RESULTS: CD4(+) T cells expression of colorectal cancer patients was the same as the healthy persons. The proportion of CD4(+)CD45RO(+) T cells of colorectal cancer patients was higher, which descended post-operatively, especially in Dukes A and B patients, while CD4(+)CD45RA(+) T cells showed the opposite findings. CONCLUSION: CD4(+)CD45RA(+) T cells and CD4(+)CD45RO(+) T cells, playing an important immune effect in colorectal cancer patients, is closely related to stage and prognosis.