The administration of mesenchymal stem cells/multipotent mesenchymal stromal cells (MSCs) to enhance tissue repair is currently undergoing clinical trials. Some studies, including our previous work, have also revealed the beneficial effect of MSCs in severe acute pancreatitis (SAP); however, their mechanisms or mode of action remain controversial. In this study, we demonstrated that intravenously (i.v.)-administered human MSCs (hMSCs) remarkably promoted recovery from experimental SAP without significant engraftment of hMSCs in the damaged pancreas. Interestingly, we found that i.v.-administered hMSCs with knockdown of TSG-6 expression lost most of their anti-inflammatory effects and thus could not significantly ameliorate SAP. As expected, the effects of hMSCs were also duplicated by i.v. infusion of recombinant TSG-6. Furthermore, our results showed that the increase of oxidative stress, activation of the NLRP3 inflammasome and NF-κB signaling in SAP was substantially inhibited following administration of hMSCs or TSG-6, which was dependent on the presence of CD-44 receptors in acinar cells. In conclusion, our study, for the first time, revealed that novel mechanisms are responsible for the immunomodulatory effect of i.v. hMSCs.

Acute pancreatitis (AP), a common acute abdominal disease, 10%–20% of which can evolve into severe acute pancreatitis (SAP), is of significant morbidity and mortality. Bone marrow-derived mesenchymal stem cells (BMSCs) have been reported to have a potential therapeutic role on SAP, but the specific mechanism is unclear. Therefore, we conducted this experiment to shed light on the probable mechanism. We validated that SDF-1α significantly stimulated the expressions of VEGF, ANG-1, HGF, TGF-β, and CXCR4 in BMSCs, which were inhibited by its receptor agonist, AMD3100. The capacities of proliferation, migration, and repair of human umbilical vein endothelial cells were enhanced by BMSCs supernatant. Meanwhile, BMSCs supernatant could also promote angiogenesis, especially after the stimulation with SDF-1α. In vivo, the migration of BMSCs was regulated by SDF-1α/CXCR4 axis. Moreover, transplanted BMSCs could significantly alleviate SAP, reduce the systematic inflammation (TNF-α↓, IL-1β↓, IL-6↓, IL-4↑, IL-10↑, and TGF-β↑), and promote tissue repair and angiogenesis (VEGF↑, ANG-1↑, HGF↑, TGF-β↑, and CD31↑), compared with the SAP and anti-CXCR4 groups. Taken together, the results showed that BMSCs ameliorated SAP and the SDF-1α/CXCR4 axis was involved in the repair and regeneration process.

Acute pancreatitis (AP) is a common acute abdominal disease, 10–20% of which can evolve into severe AP (SAP) causing significant morbidity and mortality. Bone marrow-derived mesenchymal stem cells (BMSCs) have the potential of repairing SAP, but the detailed mechanism remains unknown. We demonstrate here that microRNA-9 (miR-9) modified BMSCs (pri-miR-9-BMSCs) can significantly reduce the pancreatic edema, infiltration, hemorrhage, necrosis, the release of amylase and lipase. Meanwhile, decreased local/systemic inflammatory response (TNF-α↓, IL-1β↓, IL-6↓, HMGB1↓, MPO↓, CD68↓, IL-4↑, IL-10↑, and TGF-β↑) and enhanced regeneration of damaged pancreas (Reg4↑, PTF1↑, and PDX1↑) are also promoted. But these effects diminish or disappear after antagonizing miR-9 (TuD). Besides, we find that miR-9 is negatively correlated with AP and miR-9 agomir which can mimic the effects of pri-miR-9-BMSCs and protect injured pancreas. Furthermore, we investigate that BMSCs deliver miR-9 to the injured pancreas or peripheral blood mononuclear cell (PBMC), which can target the NF-κB1/p50 gene and inhibit the NF-κB signaling pathway (p-P65↓, NF-κB1/p50↓, IκBα↑, IκBβ↑). Taken together, these results show that miR-9 is a key paracrine factor of BMSCs attenuating SAP targeting the NF-κB1/p50 gene and suppressing the NF-κB signaling pathway.

Background: Choledocholithiasis is traditionally managed by endoscopic retrograde cholangiopancreatography or T-tube insertion following common bile duct exploration. This study examined the efficacy and safety of primary duct closure following laparoscopic common bile duct exploration (LCBDE) via choledochotomy. Methods: Between September 2011 and September 2013, 157 consecutive patients underwent LCBDE via choledochotomy. Results: Of 157 LCBDE procedures, 138 (87.9%) were successfully completed with primary closure of the choledochotomy. Eight patients (5.1%) underwent closure with T-tube drainage after choledochotomy and 11 patients (7.0%) were converted to open surgery. The biliary tree was free of stones at the end of surgery in 154 patients (98.1%). Postoperative bile leak occurred in 6 patients (3.8%). The median follow-up period was 18 (2-33) months, with no evidence of further bile duct stones or bile duct stricture in any patients. Univariable analysis revealed that successful duct clearance (p = 0.010) and diameter of the common bile duct (p < 0.001) were two significant risk factors for bile leak. Conclusions: Primary duct closure following LCBDE is effective and safe for the management of choledocholithiasis. The postoperative bile leak rate may be low in skilled laparoscopic surgeons with a careful selection of patients.

Invagination PJ is not superior to duct-to-mucosa PJ in terms of POPF and other complications but appears to reduce clinically relevant POPF. Further well-designed RCTs that use ISGPS definition are still required before strong evidence-based recommendations can be formulated.

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ObjectiveA distal pancreatectomy has routinely been used for removing benign/borderline malignant tumors of the body and tail of the pancreas; however, controversy exists whether or not the spleen should be saved. Therefore, we conducted this meta-analysis for comparing the clinical outcomes of patients who underwent distal pancreatectomy with or without splenectomy.MethodsA literature research from the databases of Medline, Embase, and Cochrane library was performed to evaluate and compare the clinical outcomes between spleen-preserving distal pancreatectomy (SPDP) and distal pancreatectomy with splenectomy (DPS). Pooled odds ratio (OR) and weighted mean difference (WMD) with 95% confidence interval (95% CI) were calculated using fixed-effects or random-effects models.ResultsEleven non-randomized controlled studies involving 897 patients were selected to satisfy the inclusion criteria; 355 patients underwent SPDP and 542 patients underwent DPS. Compared with DPS, SPDP required a shorter hospital stay (WMD = 1.16, 95% CI = −2.00 to −0.31, P = 0.007), and had a lower incidence of intra-abdominal abscesses (OR = 0.48, 95% CI = 0.27 to 0.83, P = 0.009). In addition, spleen infarctions occurred in SPDP, most of which involved use of the Warshaw method for preserving the spleen. There were no differences between the SPDP and DPS groups with respect to operative time, operative blood loss, requirement for blood transfusion, pancreatic fistulas, thromboses, post-operative bleeding, wound infections and re-operation rates.ConclusionSPDP should be performed due to the benefits of the immune system and quick post-operative recovery. It is also essential to preserve the splenic artery and vein. Large randomized controlled trials are further needed to verify the results of this meta-analysis.

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