Hsp90α and cell death in cancers: a review.

Heat shock protein 90α (Hsp90α), an important molecular chaperone, plays a crucial role in regulating the activity of various intracellular signaling pathways and maintaining the stability of various signaling transduction proteins. In cancer, the expression level of Hsp90α is often significantly upregulated and is recognized as one of the key factors in cancer cell survival and proliferation. Cell death can help achieve numerous purposes, such as preventing aging, removing damaged or infected cells, facilitating embryonic development and tissue repair, and modulating immune response. The expression of Hsp90α is closely associated with specific modes of cell death including apoptosis, necrotic apoptosis, and autophagy-dependent cell death, etc. This review discusses the new results on the relationship between expression of Hsp90α and cell death in cancer. Hsp90α is frequently overexpressed in cancer and promotes cancer cell growth, survival, and resistance to treatment by regulating cell death, rendering it a promising target for cancer therapy.

Extrachromosomal circular DNA (eccDNA): from carcinogenesis to drug resistance.

Extrachromosomal circular DNA (eccDNA) is a circular form of DNA that exists outside of the chromosome. Although it has only been a few decades since its discovery, in recent years, it has been found to have a close relationship with cancer, which has attracted widespread attention from researchers. Thus far, under the persistent research of researchers from all over the world, eccDNA has been found to play an important role in a variety of tumors, including breast cancer, lung cancer, ovarian cancer, etc. Herein, we review the sources of eccDNA, classifications, and the mechanisms responsible for their biogenesis. In addition, we introduce the relationship between eccDNA and various cancers and the role of eccDNA in the generation and evolution of cancer. Finally, we summarize the research significance and importance of eccDNA in cancer, and highlight new prospects for the application of eccDNA in the future detection and treatment of cancer.

ITGB6 promotes pancreatic fibrosis and aggravates the malignant process of pancreatic cancer via JAK2/STAT3 signaling pathway.

Integrin ß6 (ITGB6) is upregulated in multiple tumor types and elevated ITGB6 levels have been detected in patients with chronic pancreatitis. However, the role of ITGB6 in pancreatic fibrosis and cancer remains to be elucidated. In the present study, ITGB6 expression was assessed using western blotting and qRT-PCR. Besides, cell proliferation, cycling, migration, and invasion were evaluated using CCK-8, flow cytometry, wound healing, and transwell assays, respectively. The expression of fibrosis and JAK2/STAT3 signaling markers was detected by western blotting and immunofluorescence analysis. Moreover, nude mice were subcutaneously injected with co-cultured cell suspensions to establish an in vivo model. The results showed that ITGB6 was highly expressed in pancreatic cancer tissues and TGF-ß-induced pancreatic stellate cells (PSCs). Inhibition of ITGB6 expression in PSCs resulted in clear inhibition of activated PSC proliferation, migration, and fibrogenesis. Additionally, reduced ITGB6 expression inhibits the JAK2/STAT3 signaling pathway. Interestingly, activators of the JAK2/STAT3 signaling pathway reversed the effects of ITGB6 disruption on PSCs. Activated PSCs notably promoted the proliferation, invasion, and migration of pancreatic cancer cells in a co-culture assay. In contrast, activated PSCs with low ITGB6 expression failed to significantly affect the malignancy of pancreatic cancer cells. Moreover, in vivo results showed that interference with ITGB6 inhibited the activation of PSCs and promoted the development of pancreatic cancer. Silencing ITGB6 inhibited the proliferation, migration, and fibrosis-like effects of activated PSCs and indirectly inhibited the metastasis and malignant process of pancreatic cancer by inhibiting the JAK2/STAT3 signaling pathway. Therefore, ITGB6 is a potential candidate target for pancreatic cancer prevention and treatment.

Study on the application value of fluorescent laparoscopy in pancreatic tumor surgery.

Background: Fluorescent laparoscopy is rarely used in pancreatic surgery. The aim of this study was to investigate the value of fluorescent laparoscopy in pancreatic tumor surgery. Methods: A total of 19 patients with pancreatic tumors who were treated in the Department of Hepatobiliary Surgery at the First Affiliated Hospital of Wannan Medical College from January 2021 to August 2022 were selected. Fluorescent laparoscopy was used intraoperatively, and the imaging characteristics of different tumors were recorded and analyzed. Results: Among the 19 participants, postoperative pathology confirmed 12 cases of pancreatic cancer (8 cases of moderately differentiated adenocarcinoma, 3 cases of moderately-poorly differentiated adenocarcinoma, and 1 case of acinar cell carcinoma), 4 cases of pancreatic cystic tumors (1 case of microcystic serous cystadenoma, 1 case of serous cystadenoma, 1 case of solid pseudopapillary tumor, and 1 case of solid-cystic pseudopapillary tumor), 1 case of pancreatic neuroendocrine tumor (G1 stage), and 2 cases of inflammatory lesions. There were 8 cases of pancreaticoduodenectomy, 6 cases of distal pancreatectomy, 3 cases of middle pancreatectomy, 1 case of local pancreatectomy, and 1 case of duodenum-preserving pancreatic head resection. One minute after intravenous injection of indocyanine green (ICG), 10 of the 12 patients with pancreatic cancer showed tumor peritumor imaging; 2 cases of pancreatic serous cystic tumors did not show imaging; 2 cases of solid pseudopapillary tumors had tumor body imaging; 1 case of neuroendocrine tumor had tumor body imaging, with complete fluorescence imaging after specimen dissection; there were 2 cases pathologically confirmed as inflammatory lesions, 1 case with tumor body imaging, and 1 case with capsule imaging. Conclusions: By reasonably controlling the administration time and dose of ICG during surgery, some pancreatic tumors can be fluorescently imaged, which is beneficial for intraoperative tumor localization and margin determination.

SMYD2 Imparts Gemcitabine Resistance to Pancreatic Adenocarcinoma Cells by Upregulating EVI2A.

Although gemcitabine (GEM) is the first­line drug for advanced pancreatic adenocarcinoma (PAAD), the development of GEM resistance severely limits the effectiveness of this chemotherapy. This study investigated the mechanisms of ecotropic viral integration site 2 A (EVI2A) for resistance to GEM and immune evasion in PAAD. GEM resistance-related biomarkers were predicted using GEO datasets, and GEM-resistant PAAD cells were generated. EVI2A was found expressed highly in GEM-resistant PAAD cells. Gain-of-function analyses revealed that EVI2A encouraged the proliferation and motility of GEM-resistant cells and prevented apoptosis. In addition, EVI2A reduced T cell effector activation. SMYD2 was overexpressed in GEM-resistant cells, and SMYD2 enhanced H3K36me2 modification of EVI2A, thereby promoting EVI2A expression. SMYD2 reduced the sensitivity of GEM-resistant cells, which was reversed by EVI2A knockdown. SMYD2 increased the amount of M2 macrophages (co-cultured with PAAD cells) and decreased T cell effector activation (co-cultured with macrophage supernatant), and the number of M2 macrophages was decreased and T cell effectors were activated following EVI2A knockdown. Our findings indicate that EVI2A, manipulated by the SMYD2-H3K36me2 epigenetic axis, promoted GEM resistance and M2 macrophage-mediated immune evasion in PAAD. Therefore, EVI2A might represent a therapeutic target for overcoming GEM resistance and immunosuppressive environment in PAAD.

Application of a sectional U-shaped reinforcement combined with penetrating pancreaticojejunostomy (U-PPJ) for soft pancreas in laparoscopic pancreatic surgery.

Laparoscopic techniques have been widely used in pancreatic surgery, such as laparoscopic pancreaticoduodenectomy (LPD) and laparoscopic central pancreatectomy (LCP). Laparoscopic pancreaticojejunostomy (LPJ) is a common procedure for LPD and LCP, and is also the most critical. The quality of LPJ is associated with the occurrence of clinically relevant postoperative pancreatic fistula (CR-POPF). Although LPJ technology has been greatly improved, CR-POPF cannot be completely avoided especially to soft pancreas, which is an important reason for the high risk of laparoscopic pancreatic surgery. To date, there is a lack of standard LPJ approaches. Here, we report a U-shaped suture reinforcement for soft pancreatic section combined with penetrating pancreaticojejunostomy (PPJ) technique, called U-PPJ. Twenty-three patients with soft pancreas who underwent laparoscopic pancreatic surgery adopting U-PPJ method between 2017 and 2022 were enrolled (LPD = 19, LCP = 4). Preoperative, intraoperative and postoperative indexes were collected and analyzed. The results showed that all patients treated with U-PPJ were discharged without drainage tube or a small amount of exudate in the drainage tube does not require clinical treatment, but only needs to be removed after 2 days of observation. The average operation time was 417.35 min. The intraoperative blood loss was 171.74 ml. The pancreatic duct diameter was 3.41 mm. The average postoperative hospitalization days were 11.83 days. The average postoperative drainage tube removal time was 13.26 days. The incidence of postoperative B-grade pancreatic fistula was 4.3%, and no C-grade pancreatic fistula occurred. In our experience, U-PPJ can be completed by a skilled surgeon in less than 20 min. U-PPJ is safe, reliable, convenient and has a low incidence of CR-POPF in soft pancreas, which is worthy of clinical application. It also provides more options for laparoscopic pancreatic surgery. Since this is a retrospective study with a small number of cases, more prospective multicenter studies are needed to further verify its safety and efficacy.

Bone marrow-derived mesenchymal stem cells alleviate severe acute pancreatitis-induced multiple-organ injury in rats via suppression of autophagy.

Patients with severe acute pancreatitis (SAP) represent a substantial challenge to medical practitioners due to the high associated rates of morbidity and mortality and a lack of satisfactory therapeutic outcomes. In a previous study, our group demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) can ameliorate SAP; however, the mechanisms of action remain to be fully understood. BMSCs were intravenously injected into SAP rats 12 h after experimental induction of SAP using sodium taurocholate (NaT). Histopathological changes and the levels of pro-inflammatory mediators were assessed by hematoxylin and eosin (H&E) staining and ELISA, respectively. Autophagy levels were assessed using qRT-PCR, western blotting, immunohistochemistry, immunofluorescence, and transmission electron microscopy. AR42J cells and human umbilical vein endothelial cells (HUVECs) were administered BMSC-conditioned media (BMSC-CM) after NaT treatment, and cell viability was measured using a Cell Counting Kit-8 (CCK-8) and flow cytometry. In vivo, BMSCs effectively reduced multiple systematic inflammatory responses, suppressed the activation of autophagy, and improved intestinal dysfunction. In vitro, BMSC-CM significantly improved the viability of injured cells, promoted angiogenesis, and decreased autophagy. We therefore propose that the administration of BMSCs alleviates SAP-induced multiple organ injury by inhibiting autophagy.

Bone marrow-derived mesenchymal stem cells ameliorate severe acute pancreatitis by inhibiting necroptosis in rats.

The treatment and prognosis for severe acute pancreatitis (SAP) is currently unsatisfactory showing a high incidence of morbidity and mortality. Here, we investigated the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on SAP in rats and explored the possible mechanisms. The common bile duct of each model rat was occluded at the liver hilum, and the induction of SAP was achieved by retrograde perfusion of 3% sodium taurocholate (NaT). Prepared BMSCs were intravenously injected via the tail vein. Pancreatic acinar cells (PACs) were isolated from rat pancreas, and induced by TNF-α. In the present study, we found that necroptosis was activated in NaT-induced acute-necrotized pancreatitis, and transplanted BMSCs could inhibit necroptosis, repair pancreatic injury, and reduce systemic inflammatory response. In addition, necrostatin-1 (Nec-1), as the inhibitor of receptor-interacting protein kinase 1 (RIPK1), could also reduce SAP to some extent. Besides, we detected that BMSCs could also promote regeneration of damaged pancreatic tissues. Furthermore, in vitro, we also investigated that BMSCs could suppress TNF-α-induced necroptosis and improve the viability of PACs. In addition, Nec-1 and knockdown of receptor-interacting protein kinase 3 (RIPK3) or mixed lineage kinase domain-like protein (MLKL) could also inhibit necrosis of PACs induced by TNF-α. BMSCs ameliorated SAP and reduced injury of PACs by suppressing the activation of the necroptosis signaling pathway.

Bone marrow-derived mesenchymal stem cells attenuate severe acute pancreatitis via regulation of microRNA-9 to inhibit necroptosis in rats.

AIMS: Severe acute pancreatitis (SAP) is an acute disease of the digestive system accompanied by pancreatic necrosis. We have found that bone marrow-derived mesenchymal stem cells (BMSCs) can attenuate SAP, but the underlying mechanism remains unclear. The present study was conducted to explore the possible mechanisms by which BMSCs alleviate SAP. MAIN METHODS: BMSCs and BMSCs engineered to overexpress microRNA (miR)-9 (miR-9-BMSCs) were transplanted into rat models of SAP via the tail vein. Pancreatic acinar cells (PACs) were isolated from rat pancreatic tissues and induced by tumor necrosis factor-α (TNF-α) in vitro. KEY FINDINGS: miR-9-BMSCs significantly reduced the systemic inflammatory response, impeded the necroptosis signaling pathway and promoted regeneration of damaged pancreas in vivo. miR-9-BMSCs secreted miR-9, which targeted the gene encoding receptor interacting protein kinase 1 in PACs induced by TNF-α, to inhibit necroptosis and ameliorate SAP. SIGNIFICANCE: miR-9-BMSCs can reduce SAP-induced injury to pancreatic tissues and PACs by regulating miR-9 to suppress necroptosis.

N-Acetylcysteine enhances the therapeutic efficacy of bone marrow-derived mesenchymal stem cell transplantation in rats with severe acute pancreatitis.

BACKGROUND: Severe acute pancreatitis (SAP) is a high mortality disease, for which there is a lack of effective therapies. Previous research has demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs), which have immunomodulatory and antioxidant properties, have potential for the treatment of SAP. It remains unclear, however, whether the free radical scavenger N-acetylcysteine (NAC) can enhance the therapeutic efficacy of BMSC transplantation in SAP. In this study, we investigated the effect of combining treatment with NAC and BMSCs in a rat model of SAP. METHODS: SAP was induced by injection of sodium taurocholate into the pancreatic duct and, after successful induction of SAP, the rats were treated with BMSCs and NAC, either singly or in combination. RESULTS: After 3 days, serum levels of amylase, proinflammatory factors, malondialdehyde, and reactive oxygen species were significantly decreased in animals treated with BMSCs or NAC, compared with vehicle-treated animals. In contrast, total glutathione, superoxide dismutase and catalase were markedly increased after treatment with BMSCs or NAC. However, oxidative stress markers and inflammatory factors were significantly improved in the SAP + BMSCs + NAC group compared with those in the SAP + NAC group and the SAP + BMSCs group. CONCLUSIONS: Combined NAC and BMSC therapy was found to alleviate oxidative stress damage to the pancreas and to inhibit the inflammatory response to a significantly greater extent than single therapy with either BMSCs or NAC. Because NAC enhances the therapeutic efficacy of BMSC transplantation in a rat model of SAP, combined therapy may provide a promising new approach for the treatment of SAP.

Bone marrow-derived mesenchymal stromal cells ameliorate severe acute pancreatitis in rats via hemeoxygenase-1-mediated anti-oxidant and anti-inflammatory effects.

BACKGROUND AND AIMS: It has been previously verified that mesenchymal stromal cells (MSCs) have a good therapeutic effect on severe acute pancreatitis (SAP) and the potential for regeneration of damaged pancreatic tissue, but the exact molecular mechanism remains unclear. In this study, we demonstrated the therapeutic effect of bone morrow MSCs (BMSCs) on SAP, probably by targeting heme oxygenase-1 (HO-1). METHODS: Six hours after SAP induction, either phosphate-buffered saline (PBS) or BMSCs were transfused into the caudal vein of rats, zinc protoporphyrin (ZnPP) was administered intraperitoneally. Pancreatic pathological scoring, serum levels of amylase and inflammatory factors, as well as levels of reactive oxygen species (ROS), malondialdehyde (MDA) and myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT) activity in the pancreas were evaluated. RESULTS: Our data showed that BMSCs significantly reduce inflammation and oxidative stress, reduce apoptosis and promote angiogenesis of damaged pancreas. Moreover, BMSCs increased the level of HO-1 in the serum and pancreatic tissue in rats with SAP. In addition, the protective effect of BMSCs was partially neutralized by the HO-1 activity inhibitor ZnPP, suggesting a key role of HO-1 in the therapeutic effect of BMSCs on SAP. CONCLUSIONS: BMSCs ameliorated SAP, probably by inducing expression of HO-1, which can exert anti-inflammatory and anti-oxidant effects, reduce apoptosis and promote angiogenesis.

MicroRNA-9 modified bone marrow-derived mesenchymal stem cells (BMSCs) repair severe acute pancreatitis (SAP) via inducing angiogenesis in rats.

BACKGROUND: Severe acute pancreatitis (SAP) is an acute abdominal disease characterized by pancreatic necrosis and systemic disease. In a previous study, we showed that bone marrow-derived mesenchymal stem cells (BMSCs) can reduce SAP by secreting microRNA (miR)-9; however, the underlying mechanism remains unclear. The present study investigated the mechanism underlying BMSC-induced pancreatic regeneration. METHODS: BMSCs were isolated, and miR-9 modified/antagonized BMSCs (pri-miR-9-BMSCs/TuD-BMSCs) were generated and injected into SAP rats. The levels of inflammatory cytokines and histopathologic changes were examined using ELISA and H&E staining. Angiogenesis was analyzed by qRT-PCR, western blotting, and immunohistochemistry. Cell function tests, dual luciferase reporter assays, cell co-culture, western blotting, and cell tracing were used to explore the mechanisms underlying miR-9 induced angiogenesis. RESULTS: Pri-miR-9-BMSCs induced angiogenesis in SAP rats (Ang-1↑, TIE-2↑, and CD31↑) and repaired damaged vascular endothelial cells (VECs) in vitro, promoting angiogenesis (Ang-1↑, TIE-2↑, PI3K↑, AKT↑, p-AKT↑, CD31↑, and CD34↑). Pri-miR-9-BMSCs released miR-9 into VECs or injured pancreatic tissue, targeting the VE-cadherin gene and promoting PI3K/AKT signaling to treat SAP (VE-cadherin↓, ß-catenin↓, PI3K↑, p-AKT↑), whereas antagonizing miR-9 in BMSCs did not alleviate or aggravated SAP. CONCLUSIONS: Pri-miR-9-BMSCs can repair injured pancreatic tissue by secreting miR-9 and promoting angiogenesis.

Crosstalk of LKB1- and PTEN-regulated signals in liver morphogenesis and tumor development.

Liver kinase B 1 (LKB1 or STK11) and PTEN (phosphatase and tensin homologue deleted on chromosome 10) are two tumor suppressors that regulate the mTOR signaling pathway. Deletion studies show that loss of either Lkb1 (Lkb+/- ) or Pten (PtenloxP/loxP; Alb-Cre+ ) leads to liver injury and development of hepatocarcinoma. In this study, we investigated the crosstalk of LKB1 and PTEN loss during tumorigenesis and liver development. We show here that haplo-insufficiency of Lkb1 in the liver leads to advanced tumor development in the Pten null mice (PtenloxP/loxP; LkbloxP/+; Alb-Cre+ ). Our analysis shows that LKB1 and PTEN interacted with each other in their regulation of fatty acid synthase as well as p21 expression. The combined loss of LKB1 and PTEN (PtenloxP/loxP; LkbloxP/loxP; Alb-Cre+ ) also led to the inability to form zonal structures in the liver. The lack of metabolic zonal structures is consistent with the inability of the livers to store glycogen as well as elevated plasma bilirubin and alanine aminotransferase (ALT), indicative of liver dysfunction. These structural and functional defects are associated with cytoplasm distribution of a canalicular membrane protein MRP2 (multidrug resistant protein 2) which is responsible for clearing bilirubin. This observed regulation of MRP2 by LKB1 likely contributed to the lack of cellular polarity and the early lethality phenotype associated with homozygous loss of Lkb1 alone or in combination with Pten. Finally, Pten deletion does not rescue the precocious ductal plate formation reported for Lkb1 deleted livers. CONCLUSION: Our study dissected the functional and molecular crosstalk of PTEN and LKB1 and elucidate key molecular targets for such interaction.

Bone marrow-derived mesenchymal stem cells (BMSCs) repair acute necrotized pancreatitis by secreting microRNA-9 to target the NF-κB1/p50 gene in rats.

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-1ß↓, IL-6↓, HMGB1↓, MPO↓, CD68↓, IL-4↑, IL-10↑, and TGF-ß↑) 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↑, IκBß↑). 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.

Intravenous hMSCs Ameliorate Acute Pancreatitis in Mice via Secretion of Tumor Necrosis Factor-α Stimulated Gene/Protein 6.

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.

Stump Invagination Versus Simple Ligation in Open Appendicectomy: A Systematic Review and Meta-Analysis.

The aim of this meta-analysis was to compare the superiority of stump closure between stump invagination (SI) and simple ligation (SL) during open appendicectomy (OA). The literature searching was conducted in MEDLINE, EMBASE, the Cochrane Library, and http://scholar.google.com . Available data was extracted by 3 independent reviewers. The clinical outcomes were analyzed by meta-analytic software to compare the difference between 2 methods during OA. The pooled odds ratios (ORs) and weighted mean differences (WMDs) with 95% confidence intervals (95% CIs) were obtained by using fixed effect model. Eleven randomized controlled trials (RCTs) were finally included in this study involving 2634 patients. Postoperative pyrexia and infections were similar between SL and SI groups, respectively, but the former group had a shorter operative time (WMD: 8.72; 95% CI: 6.87-10.56; P < 0.00001); less incidence of postoperative ileus (WMD: 2.02; 95% CI: 1.36-3.01; P = 0.0005); and quicker postoperative recovery (WMD: 0.30; 95% CI: 0.11-0.48; P = 0.002). The above results were based on 5, 11, 4, 11, and 9 articles, respectively. The clinical results revealed that SL was significantly superior to SI. SL should be suggested during OA.

Duct-to-Mucosa Versus Invagination Pancreaticojejunostomy Following Pancreaticoduodenectomy: a Systematic Review and Meta-Analysis.

BACKGROUND: Postoperative pancreatic fistula (POPF) is one of the most common complications after pancreaticoduodenectomy (PD). The ideal choice of pancreaticojejunostomy (PJ) anastomosis remains a matter of debate. METHODS: A meta-analysis of randomized controlled trials (RCTs) comparing duct-to-mucosa with invagination PJ following PD was performed. Pooled odds ratio (OR) with 95 % confidence intervals (CI) were calculated using fixed-effects or random-effects models. RESULTS: In total, five RCTs involving 654 patients were included. Meta-analysis revealed no significant difference in POPF rate between the duct-to-mucosa and invagination PJ techniques (OR = 1.23, 95 % CI = 0.78-1.93; P = 0.38). Two of five trials applied the POPF definition proposed by the International Study Group of Pancreatic Surgery (ISGPS). Using this definition, the incidence of clinically relevant POPF was lower in patients undergoing invagination PJ than in those undergoing duct-to-mucosa PJ (OR = 2.94, 95 % CI = 1.31-6.60; P = 0.009). There was no significant difference in terms of delayed gastric emptying, intra-abdominal collection, overall morbidity and mortality, reoperation rate, and length of hospital stay between the two groups. CONCLUSION: 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.

Bone Marrow-Derived Mesenchymal Stem Cells Repair Necrotic Pancreatic Tissue and Promote Angiogenesis by Secreting Cellular Growth Factors Involved in the SDF-1 α /CXCR4 Axis in Rats.

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-ß, 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-1ß↓, IL-6↓, IL-4↑, IL-10↑, and TGF-ß↑), and promote tissue repair and angiogenesis (VEGF↑, ANG-1↑, HGF↑, TGF-ß↑, 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.

Primary closure and rate of bile leak following laparoscopic common bile duct exploration via choledochotomy.

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.