Background: Pancreatic cancer (PC) is a common malignancy of the digestive system and is characterized by poor prognosis and early metastasis. Tumor immune escape plays an important role in PC progression. Programmed death 1 (PD1) blockade therapy is a promising treatment for patients with PC, but is yet to achieve significant clinical effects so far. Interferon gamma (IFN-γ) is a soluble dimeric cytokine that is closely associated with tumor immune surveillance and cytotoxicity. IFN-γ suppresses a variety of tumor-derived cytokines in PC, such as CXCL8. In the present study, we investigated the therapeutic efficacy of combined anti-PD1 and IFN-γ treatment in PC. Methods: BxPC-3 and Panc-1 human PC cell lines were used to construct a murine PC model. Blood samples (n=44) and surgical resection specimens (n=36) from human patients with PC were also collected. χ² test, two-tailed unpaired t-test or Kaplan-Meier survival analysis was used to calculate p values. Results: PD1/PD-L1 signaling was overexpressed in PC tumor-bearing mice. Anti-PD1 prevented tumor growth if initiated early after tumor inoculation; however, delayed anti-PD1 treatment showed limited benefit. Murine PC model had a preferential expansion of CXCR2⁺CD68⁺ macrophages, and these cells showed an immunosuppressive nature (M2 polarization). PC tumors overexpressed CXCL8 and tumor-derived CXCL8 deficiency prohibited the trafficking of CXCR2⁺CD68⁺ macrophages. IFN-γ suppressed the expression of tumor-derived CXCL8, and combined with IFN-γ treatment, delayed anti-PD1 treatment showed significant antitumor effects. Thus, we conclude that murine CXCR2⁺CD68⁺ macrophages traffic to PC tumors by tumor-derived CXCL8 and mediate local immunosuppression, which limits the efficacy of PD1 blockade therapy. IFN-γ suppresses tumor-derived CXCL8 and inhibits the tumor trafficking of CXCR2⁺CD68⁺ macrophages by blocking the CXCL8–CXCR2 axis to enhance anti-PD1 efficacy. Human PC also produces high levels of CXCL8. Patients with PC present elevated CXCR2 expression on peripheral and tumor-infiltrating CD68⁺ macrophages, which are associated with advanced tumor stage and poor prognosis. Conclusion: Our findings suggest that IFN-γ is a translatable, therapeutic option to improve the efficacy of PD1 blockade therapy by preventing trafficking of CXCR2⁺CD68⁺ macrophages via blocking the CXCL8–CXCR2 axis.

Background: There are few widely accepted and operationally feasible models for predicting the mortality risk of patients in surgical intensive care unit (SICU). Although serum anion gap (AG) is known to be correlated with severe metabolic acidosis, no investigations have been reported about the association between AG level and the outcome during hospitalization in SICU. This study aimed to explore the predictive power of AG for 90-day all-cause mortality in SICU. Methods: Data of the eligible patients in SICU from 2008 to 2019 was obtained from the Medical Information Mart for Intensive Care IV version 2.0 (MIMIC-IV v2.0) database. Baseline clinical data of the selected patients was compared in different groups stratified by the outcome during their admission via univariate analysis. Restricted cubic spline (RCS) was drawn to confirm the relationship of AG and the short-term mortality. Kaplan-Meier survival curve was plotted in different AG level groups. Univariate and multivariate Cox analyses were performed, and Cox proportional-hazards models were built to investigate an independent role of AG to predict 90-day all-cause mortality risk in SICU. Receiver operating characteristics (ROC) curves analysis was performed to evaluate the predictive value of AG on the 90-day prognosis of patients. Results: A total of 6,395 patients were enrolled in this study and the 90-day all-cause mortality rate was 18.17%. Univariate analysis showed that elevated serum AG was associated with higher mortality (P < 0.001). RCS analysis indicated a positively linear relationship between serum AG and the risk of 90-day all-cause mortality in SICU (χ² = 4.730, P = 0.193). Kaplan-Meier survival analysis demonstrated that low-AG group (with a cutoff value of 14.10 mmol/L) had a significantly higher cumulative survival rate than the counterpart of high-AG group (χ² = 96.370, P < 0.001). Cox proportional-hazards models were constructed and confirmed the independent predictive role of AG in 90-day all-cause mortality risk in SICU after adjusting for 23 confounding factors gradually (HR 1.423, 1.246–1.625, P < 0.001). In the further subgroup analyses, a significant interaction was confirmed between AG and sepsis as well as surgery on the risk for the 90-day mortality. The ROC curve showed that the optimal cut-off value of AG for predicting 90-day mortality was 14.89 with sensitivity of 60.7% and specificity of 54.8%. The area under curve (AUC) was 0.602. When combined with SOFA score, the AUC of AG for predicting 90-day prognosis was 0.710, with a sensitivity and specificity of 70% and 62.5% respectively. Conclusions: Elevated AG (≥ 14.10 mmol/L) is an independent risk factor for predicting severe conditions and poor prognosis of critical ill surgical patients.

Previous gastrectomy can lead to an increased incidence of cholecystocholedocholithiasis (CCL) and increased morbidity rate. However, the appropriate treatment strategy for patients with CCL and a history of gastrectomy remains unclear. We performed a retrospective cohort study of patients with CCL and a history of gastrectomy who underwent either one-stage laparoscopic common bile duct (CBD) exploration with stone clearance and laparoscopic cholecystectomy (LCBDE+LC) or two-stage endoscopic retrograde cholangiopancreatography followed by LC (ERCP+LC) from May 2010 to March 2018. The success rate of ERCP for CBD stone clearance was 81.2% in patients with a history of Billroth I gastrectomy and 23.7% in patients with a history of Billroth II or Roux-en-Y esophagojejunostomy [χ2 = 97.67, P < 0.001, risk ratio (RR) = 3.43]. The success rate of second-step LC after successful ERCP for removal of CBD stones and the success rate of LCBDE+LC after ERCP treatment failure were 96.8 and 87.7%, respectively, in patients with preoperative intra-abdominal adhesion evaluation scores of ≤3 points. These success rates were 28.6 and 27.6%, respectively, in patients with scores of > 3 points (χ2 = 59.70, P < 0.001, RR = 3.38 and χ2 = 53.41, P < 0.001, RR = 3.27, respectively). Based on the results of this study, ERCP+LC seems to be an attractive strategy for treatment of CCL in patients with a history of Billroth I gastrectomy, and LCBDE+LC appears to be suitable for patients with a history of Billroth II or Roux-en-Y esophagojejunostomy. Preoperative evaluation of intra-abdominal adhesions helps to reduce the conversion rate of laparoscopic surgery.

Patients with previous gastrectomy have an increased incidence of gallstones and gallbladder morbidity requiring surgery. We investigated the possible risk factors that contribute to severe gallbladder disease in patients with previous gastrectomy and ...

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