Kupffer cells: increasingly significant role in nonalcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is considered to be a manifestation of liver metabolic damage and is related to insulin resistance and genetic susceptibility. Inflammation mediated by Kupffer cells (KCs) is of critical importance to the development of NAFLD. The primary role of KCs in NAFLD is considered to be the perturbation of the C-Jun N-terminal kinase (JNK) and nuclear factor-kappa B (NF-κB) pathways as a result of lipopolysaccharide (LPS) recognition by Toll-like receptor 4 (TLR4). Simultaneously, the activation of NF-κB, as mediated by oxidative and endoplasmic reticulum (ER) stress and free fatty acid (FFA) or free cholesterol (FC) crystal formation, heavily relies on NF-κB regulatory factors and TLR4. Additionally, the imbalance of certain pro-inflammatory cytokines and chemokines released by innate immunity is deemed to promote the steatosis of hepatocytes. In conclusion, this review indicates that the inflammatory and oxidative stress of KCs play a significant role in the development of NAFLD.

Comparison of patient outcomes with and without stenting tube in pancreaticoduodenectomy.

Objective To evaluate the clinical effect of different pancreaticojejunostomy techniques in the treatment of pancreaticoduodenectomy and investigate the applicability of pancreaticojejunostomy without pancreatic duct stenting. Methods From January 2012 to December 2015, 87 patients who underwent pancreaticoduodenectomy were randomly assigned to either Group A (duct-to-mucosa anastomosis with pancreatic duct stenting, n = 43) or Group B (pancreas-jejunum end-to-side anastomosis without stenting (n = 44). The operative duration of pancreaticojejunostomy, postoperative hospital stay, and incidence of postoperative complications were compared between the two methods. Results The operative duration of pancreaticojejunostomy without use of the pancreatic duct stent was significantly shorter in Group B than in Group A (t = 7.137). The postoperative hospital stay was significantly shorter in Group B than in Group A (t = 2.408). The differences in the incidence of postoperative complications such as pancreatic fistula, abdominal bleeding, abdominal infection and delayed gastric emptying were not significantly different between the two groups (χ2 = 0.181, 0.322, 0.603, and 0.001, respectively). Conclusion Pancreaticoduodenectomy without pancreatic duct stenting is safe and reliable and can reduce the operative time and hospital stay. No significant differences were observed in the incidence of postoperative complications.

Effects of Amarogentin on Residual Liver Cancer Stem Cells After Insufficient Thermal Ablation and Related Mechanism / 肿瘤防治研究

Objective To observe the effects of amarogentinon liver cancer stem cells (LCSCs) after insufficient thermal ablation and its mechanism. Methods A insufficient thermal ablation model of HepG2 cells was established by water bath method.The percentage of CD133-positive LCSCs and the mRNA and protein levels of CD133 were detected by flow cytometry, qRT-PCR and Western blot.The insufficient thermal ablation model of HepG2 cells was treated with variable doses of amarogentin for 24 h; the percentage of CD133-positive LCSCs, the proliferation and apoptosis of liver cancer cells, and the mRNA and protein levels of CD133, TBC1D15, and p53were detected by flow cytometry, qRT-PCR and Western blot. Results The percentage of CD133-positive HepG2 cells and the mRNA and protein levels of CD133 and TBC1D15in the insufficient thermal ablation model were significantly higher than those in the normal HepG2 cells.Amarogentin then markedly decreased the percentage of CD133-positive LCSCs, the proliferation rate of HepG2 cells, and the mRNA and protein levels of CD133 and TBC1D15 in the insufficient thermal ablationresidual model (all P < 0.05);inversely, the apoptosis rate of HepG2 cells and the phosphorylated levels of p53 in the insufficient thermal ablation model were significantly increased (all P < 0.05). Conclusion Amarogentin could reduce the proportion of LCSCs after insufficient thermal ablation, inhibit the proliferation, and promote the apoptosis of LCSCs, which maybe associated with increasing the phosphorylation of p53 and inhibiting the expression of TBC1D15.

Clinical Efficacy of Concept of Membrane Anatomy with Complete Mesangectomy in Radical Resection of Rectal Cancer / 肿瘤防治研究

Objective To compare the clinical efficacy between traditional laparoscopic surgery and laparoscopic surgery under the guidance of membrane anatomy with complete mesangectomy in the treatment of rectal cancer. Methods A retrospective cohort study was conducted on 60 patients with rectal cancer who were randomly divided into control group (n=30) and observation group (n=30) in accordance with the principle of randomization.The control group received traditional laparoscopic radical resection of rectal cancer, and the observation group received laparoscopic radical resection of rectal cancer under the guidance of membrane anatomy with complete mesangectomy.The different clinical application effects of the two groups were analyzed by comparing the general data, operation time, intraoperative blood loss, and postoperative rehabilitation. Results All the 60 patients underwent the laparoscopic radical resection of rectal cancer.No operation-related complications, conversion to laparotomy, or perioperative death cases were reported.No statistically significant differences in age, gender, operation time, postoperative exhaust time, drainage tube removal time, or postoperative complications were found between the two groups (all P > 0.05).Compared with the control group, the observation group had significantly less intraoperative blood loss and more lymph node dissected (P < 0.05). Conclusion Laparoscopic radical resection of rectal cancer guided by the membrane anatomy with complete mesangectomy can completely remove the mesorectum, enlarge and clear the surgical field, reduce intraoperative bleeding, thoroughly remove lymph nodes, and improve the quality of surgery.

Imidazoline I2 receptor inhibitor idazoxan regulates the progression of hepatic fibrosis via Akt-Nrf2-Smad2/3 signaling pathway.

Liver fibrosis is a global health problem and its relationship with imidazoline I2 receptor has not been reported. This study aimed to investigate the effects and underlying mechanisms of imidazoline I2 receptor (I2R) inhibitor idazoxan (IDA) on carbon tetrachloride (CCl4)-induced liver fibrosis. In vivo liver fibrosis in mice was induced by intraperitoneally injections of CCl4 for eight weeks, and in vitro studies were performed on activated LX2 cells treated with transforming growth factor-ß (TGF-ß). Our results showed that IDA significantly improved liver inflammation, ameliorated hepatic stellate cells activation and reduced collagen accumulation by suppressing the pro-fibrogenic signaling of TGF-ß/Smad. Further investigation showed that IDA significantly balanced oxidative stress through improving the expressions and activities of anti-oxidant and detoxifying enzymes and activating Nrf2-the key defender against oxidative stress with anti-fibrotic potentials. Even more impressively, knock out of Nrf2 or suppression of Akt by perifosine (PE) eliminated the anti-oxidant and anti-fibrotic effects of IDA in vivo and in vitro, suggesting that Akt/Nrf2 constitutes a critical component of IDA's protective functions. Taken together, IDA exhibits potent effects against liver fibrosis via Akt-Nrf2-Smad2/3 signaling pathway, which suggests that specifically targeting I2R may be a potentially useful therapeutic strategy for liver fibrosis.

Changes of Foxo3a in PBMCs and its associations with stress hyperglycemia in acute obstructive suppurative cholangitis patients.

OBJECTIVE: The levels of Foxo3a in the peripheral blood mononuclears cells (PBMCs) before and after treatment were detected in acute obstructive suppurative cholangitis (AOSC) patients to evaluate the associations between Foxo3a and stress hyperglycemia (SHG). METHODS: PBMCs were obtained from AOSC patients (n=28) on admission (AP), from patients at 1 week after cure (RP) and from healthy volunteers (HV) (n=14) to evaluate the relationship between the protein levels of Foxo3a and the serum levels of glucose. Signaling pathways, which link inflammation and glycometabolism, simultaneously affecting the expression of Foxo3a, were detected. In addition, cytokines were detected in PBMCs and AOSC mouse models, which were pre-treated with Foxo3a agonist. RESULTS: The levels of glucose and p-Foxo3a in the AP were significantly higher than those in the RP and HV, where as the levels of Foxo3a in the AP were lower than those in the RP and HV. Foxo3a levels in the AP normalized against RP were strongly negatively correlated with the glucose levels in the AP normalized against RP. The levels of sphingosine-1-phosphate receptor 2 (S1PR2) in the AP were higher than those in the RP and HV. In addition, inhibition of Foxo3a phosphorylation, coupled with the down-regulation of S1PR2, attenuated the LPS-induced inflammatory response in the PBMCs and AOSC mouse models. CONCLUSIONS: Foxo3a is correlated with the dysregulation of glucose homeostasis in the pathogenesis of AOSC-induced sepsis by inhibiting the activation of PI3K/Akt-S1PR2 and NF-κB pathways, hinting at a switched role and therapeutic potentialities in the early stage of sepsis.

Diagnosis and treatment of pancreatic duct stone / 国际外科学杂志

Pancreatic duct stones are closely related to chronic pancreatitis. Although the incidence is low, they can cause intractable abdominal pain and may lead to pancreatic cancer. Changes in the composition of pancreatic juice are the essential causes for the formation of pancreatic duct stones, while local inflammation and pancreatic ductal stenosis are the direct causes of the progression of stones and the recurrence of the symptoms, and they are also the main targets of treatment. Endoscopic treatment combined with extracorporeal shock-wave lithotripsy has a good therapeutic effect on most pancreatic duct stones. More complex stones require surgical intervention. The choice of specific surgical methods is related to the size and distribution of the stones. Treatment schemes should aim at reducing long-term stones or pain recurrence, and preserving more endocrine and exocrine functions of the pancreas, in order to bring greater benefits to patients.

Advances in the comprehensive treatment of pancreatic cancer / 国际外科学杂志

Pancreatic cancer is one of the most malignant digestive cancer with high morbidity and mortality. Surgical treatment is considered the only way to cure pancreatic cancer. For resectable pancreatic cancer, the principles of "artery-frst approach" and "systematic mesopancreas dissection" have improved the increase the local radicality and reduce the local recurrence rate. For borderline resectable pancreatic cancer and locally advanced pancreatic cancer, neoadjuvant chemotherapy can be used before surgical resection. Although there are no targeted and immunotherapeutic drugs for pancreatic cancer, clinical studies on monoclonal antibodies are ongoing. Chimeric antigen receptor T cell therapy and irreversible electroporation are emerging therapies in the treatment of pancreatic cancer. In the present study, the status and progress of comprehensive treatment for pancreatic cancer are reviewed.

Research advances in neoadjuvant therapy for resectable pancreatic cancer / 国际外科学杂志

Pancreatic cancer is highly malignant, and surgical resection is the only cure method at present. In recent years, neoadjuvant therapy has enabled some patients to be successfully downgraded with surgical treatment, which increased the R0 surgical resection rate and prolonged the survival time of patients, has become an important part in the treatment of pancreatic cancer. However, the applicability and standardization of neoadjuvant therapy for pancreatic cancer still need more advanced evidence. This article reviews whether neoadjuvant therapy should be used for resectable pancreatic cancer, the choice of neoadjuvant chemotherapy, and the progress, advantages and disadvantages of neoadjuvant chemoradiotherapy.

Down-Regulated Receptor Interacting Protein 140 Is Involved in Lipopolysaccharide-Preconditioning-Induced Inactivation of Kupffer Cells and Attenuation of Hepatic Ischemia Reperfusion Injury.

BACKGROUND: Lipopolysaccharide (LPS) preconditioning is known to attenuate hepatic ischemia/reperfusion injury (I/RI); however, the precise mechanism remains unclear. This study investigated the role of receptor-interacting protein 140 (RIP140) on the protective effect of LPS preconditioning in hepatic I/RI involving Kupffer cells (KCs). METHODS: Sprague-Dawley rats underwent 70% hepatic ischemia for 90 minutes. LPS (100 µg/kg) was injected intraperitoneally 24 hours before ischemia. Hepatic injury was observed using serum and liver samples. The LPS/NF-κB (nuclear factor-κB) pathway and hepatic RIP140 expression in isolated KCs were investigated. RESULTS: LPS preconditioning significantly inhibited hepatic RIP140 expression, NF-κB activation, and serum proinflammatory cytokine expression after I/RI, with an observation of remarkably reduced serum enzyme levels and histopathologic scores. Our experiments showed that protection effects could be effectively induced in KCs by LPS preconditioning, but couldn't when RIP140 was overexpressed in KCs. Conversely, even without LPS preconditioning, protective effects were found in KCs if RIP140 expression was suppressed with siRNA. CONCLUSIONS: Down-regulated RIP140 is involved in LPS-induced inactivation of KCs and hepatic I/RI attenuation.

Etiology and recent treatment progress of acute liver failure / 国际外科学杂志

Acute liver failure (ALF) is commonly used to describe the emergence or development of an acute attack of abnormal liver function. It is a rare but severely life-threatening clinical syndrome that often causes jaundice, coagulopathy and hepatic encephalopathy. Encephalopathy(HE) and multiple organ failure. ALF has a wide range of etiological factors. In the global scope, different regions often show different epidemiological characteristics. With the gradual improvement of specialized diagnosis and intensive care, the prognosis of ALF has improved significantly. The current clinical treatment methods of ALF include etiology treatment, symptomatic supportive treatment, immunotherapy, artificial liver and liver transplantation. This article will summarize the causes of ALF and discuss the latest treatment progresses of ALF.

Pathogenesis and treatment progress of hepatocellular carcinoma / 国际外科学杂志

The global disease burden of hepatocellular carcinoma (HCC) is increasing gradually. HCC can be categorized into proliferation and non-proliferation classes. The occurrence and development of HCC are closely associated with both genetic and epigenetic changes. However, the underlying mechanisms remain unclear. CT/MRI is the most commonly used imaging modality for diagnosis of HCC. Barcelona clinic liver cancer staging system is widely used to stage HCC worldwide. The treatment options of HCC include surgery, liver transplantation, radiofrequency ablation, transcatheter arterial chemoembolization and systematic therapy. This review will focus on the progress in mechanisms and treatments of HCC.

Research progress on protective effect of liver ischemia-reperfusion injury after liver transplantation / 国际外科学杂志

Hepatic ischemia-reperfusion injury is the most common complication after liver transplantation. Oxidative stress, autophagy, and inflammatory response caused by excessive reactive oxygen species production are significant steps that cause liver ischemia-reperfusion injury. What′s more, nuclear factor erythroid 2-related factor 2 is considered to be a major regulator of the antioxidant response, the PI3K-Akt-mTOR signaling pathway is considered to be an important pathway of autophagy, and the HMGB1-TLR4-NF-κB signaling pathway is considered to be a key signaling pathway which leads to inflammation. Based on the above signaling pathways and regulatory factor, this article shows that the antioxidant, anti-inflammatory and autophagy regulation effects of genes, molecules and drugs on hepatic ischemia-reperfusion cells, to explore the protective effects on hepatic ischemia-reperfusion cells.

Meta-analysis of duct-to-mucosa and invagination of pancreaticoduodenectomy / 国际外科学杂志

Objective To systematically evaluate the surgical effect in duct-to-mucosa and invagination groups of pancreaticojejunostomy after pancreaticoduodenectomy.Methods The Cochrane Library,PubMed,EMbase and CBM data bases were searched to identify randomized controlled trials that compared the postoperative pancreatic fistula,mortality,incidence of complications,delayed gastric emptying,postoperative haemorrhage,infection,reoperate rate,postoperative hospital stay of duct-to-mucosa and invagination for pancreaticcoduodenectomy.Meta-analysis was performed using the software RevMan 5.3.Results Nine trials with 1 163 patients comparing the duct-to-mucosa group with invagination group were included,the duct-to-mucosa group with 579 patients and the invagination group with 584 patients.The meta-analysis revealed that,compared the duct-to-mucosa group with the invagination group,the rate of postoperative pancreatic fistula was not significantly reduced (RR =1.13,95 ％ CI:0.88-1.45,P =0.34),there was no significa nt difference between the two group.To systematically evaluate the total mortality (RR =0.80,95 ％ CI:0.42-1.52,P =0.49),incidence of complications (RR =1.04,95 ％ CI:0.88-1.24,P =0.63),delayed gastric emptying (RR =1.26,95 ％ CI:0.90-1.76,P =0.18),postoperative haemorrhage (RR =0.86,95 ％ CI:0.51-1.44,P =0.57),postoperative infection (RR =1.20,95％ CI:0.86-1.69,P =0.29),reoperate rate (RR =1.05,95％ CI:0.62-1.78,P =0.84),postoperative hospital stay (WMD =-1.36,95％ CI:-2.91-0.20,P =0.09) in duct-to-mucosa and invagination groups.There was no significant difference between the two group.Conclusions There was no significant difference of postoperative pancreatic fistul and mortality,incidence of complications,delayed gastric emptying,postoperative haemorrhage,postoperative infection,reoperate rate,postoperative hospital stay in duct-to-mucosa and invagination groups of pancreaticojejunostomy after pancreaticoduodenectomy.

Meta-analysis of duct-to-mucosa and invagination of pancreaticoduodenectomy / 国际外科学杂志

Objective@#To systematically evaluate the surgical effect in duct-to-mucosa and invagination groups of pancreaticojejunostomy after pancreaticoduodenectomy.@*Methods@#The Cochrane Library, PubMed, EMbase and CBM data bases were searched to identify randomized controlled trials that compared the postoperative pancreatic fistula, mortality, incidence of complications, delayed gastric emptying, postoperative haemorrhage, infection, reoperate rate, postoperative hospital stay of duct-to-mucosa and invagination for pancreaticcoduodenectomy. Meta-analysis was performed using the software RevMan 5.3.@*Results@#Nine trials with 1 163 patients comparing the duct-to-mucosa group with invagination group were included, the duct-to-mucosa group with 579 patients and the invagination group with 584 patients. The meta-analysis revealed that, compared the duct-to-mucosa group with the invagination group, the rate of postoperative pancreatic fistula was not significantly reduced (RR=1.13, 95%CI: 0.88-1.45, P=0.34), there was no significant difference between the two group. To systematically evaluate the total mortality (RR=0.80, 95%CI: 0.42-1.52, P=0.49), incidence of complications (RR=1.04, 95%CI: 0.88-1.24, P=0.63), delayed gastric emptying (RR=1.26, 95%CI: 0.90-1.76, P=0.18), postoperative haemorrhage (RR=0.86, 95%CI: 0.51-1.44, P=0.57), postoperative infection (RR=1.20, 95%CI: 0.86-1.69, P=0.29), reoperate rate (RR=1.05, 95%CI: 0.62-1.78, P=0.84), postoperative hospital stay (WMD=-1.36, 95%CI: -2.91-0.20, P=0.09) in duct-to-mucosa and invagination groups. There was no significant difference between the two group.@*Conclusions@#There was no significant difference of postoperative pancreatic fistul and mortality, incidence of complications, delayed gastric emptying, postoperative haemorrhage, postoperative infection, reoperate rate, postoperative hospital stay in duct-to-mucosa and invagination groups of pancreaticojejunostomy after pancreaticoduodenectomy.

Drainage procedure for pancreatolithiasis: re-examination of the pancreatic duct diameter standard

Purpose@#Pancreatic duct decompression relieves pancreatic duct stone (PDS)-associated abdominal pain, though a consensus indication for the drainage procedure of the main pancreatic duct (MPD) is lacking. Moreover, major prognostic factors for postsurgical long-term pain relief and recurrence are largely unknown. @*Methods@#The clinical outcomes of 65 consecutive PDS patients undergoing surgery from 2008–2012 with 3+ years of follow-up were assessed. @*Results@#At postsurgical follow-up (median, 4.5 years; range, 3–7 years; procedure: Partington, n = 32; Frey, n = 27; pancreatoduodenectomy, n = 3; distal pancreatectomy, n = 3), the early complication and complete stone clearance rates were 29.2% and 97%, respectively. Long-term, complete and partial pain relief were 93.9%, 83.1%, and 10.8%, respectively. The risk of pancreatic fistula was higher in the 8 mm group (P < 0.05), and 80% of the pancreatic fistula cases occurred in the <8 mm group. A shorter pain duration (P = 0.007), smaller MPD diameter (P = 0.04), and lower Izbicki pain score (P < 0.001) predicted long-term pain relief. Pain recurrence after initial remission occurred in 5 patients and was only related to pain duration (P = 0.02). Stone recurrence and pancreatic exocrine functional and endocrine functional deterioration occurred in 2, 5, and 11 patients, respectively. @*Conclusion@#Surgery provides excellent stone clearance, long-term pain relief, and acceptable postoperative morbidity. Using 8 mm as the criterion for drainage surgery can minimize the postoperative pancreatic fistula risk. Individualized and timely surgical treatment may improve the effect of surgery.

Rise and mix of membrane anatomy / 中华胃肠外科杂志

Membrane anatomy is in broad sense the anatomy of the mesentery and its bed, both of which are consisted of fascia membrane or/and serous membrane. Although the traditional mesentery has the definition of mesentery, people unconsciously identify them according to their "fan-shaped" and "free" characteristics. The "generalized mesentery" we propose refers to the fascia and/or serosa, envelope-like organs and their blood vessels, suspending to the posterior wall of the body, regardless of its shape, free or not. So the main points of the anatomy are as follows.(1) Organs or tissues with their feeding structures are enveloped by the fascia membrane or/and serous membrane, suspending to posterior wall of the body, to form different shapes of the mesentery in broad sense, and most of them are buried in the mesentery bed. (2) Cancer metastasis type V of in the gut moves in the envelop of the mesentery in broad sense.(3) Intraoperative breach of the envelop membrane not only results in intraoperative bleeding, but also cancer cell leakage from the mesentery. (4) The cancer of gut can be divided into cancer in the mesentery, cancer out of the mesentery and cancer at edge of the mesentery based on this anatomy. Radical tumor resection is effective for cancer in the mesentery, which should not be artificially breached into those of cancer out of the mesentery. The essence of neoadjuvant chemoradiation is to push cancer at edge of the mesentery back inside the mesentery.(5) Based on such anatomy, radical gut tumor operations are divided into D2/D3 procedure, without emphasizing the integrity of the mesentery during lymphatic dissection; CME procedure, which emphasizes the integrity of the mesentery but does not strictly define the extent of lymphatic dissection; D2/D3 + CME procedure, which strictly defines the integrity of the mesentery and the extent of lymphatic dissection.(6)For gastrointestinal tumors of the same T stage, shorter mesentery indicates worse prognosis.(7) For gastrointestinal tumors with the same T stage and the same length of mesentery, the more mesentery buried in the mesentery bed, the worse prognosis. (8) The above seven principles are universal in the organs of the body cavity (and even all internal organs).Membrane anatomy, unlike traditional "plane surgery" , is completely different from the "anatomy of the membrane..." described by Japanese scholars, but mainly bases on generalized mesentery and mesentery bed, meanwhile inherent life events can be accurately defined and confirmed.

Minimally invasive therapies for hepatocellular carcinoma / 中华肝脏病杂志

Over 70% of hepatocellular carcinoma patients have not received traditional surgery because of their own disease characteristics and the limitations of traditional surgical methods. With the advancement of medical technology and the development of minimally invasive concepts, minimally invasive surgery, transcatheter arterial chemoembolization, and local ablation have received increasing attention. The combination of various treatment methods can help to strengthen the characteristics of each treatment, but the guiding standard of comprehensive treatment still needs further exploration and research.

Progress in surgical treatment for severe acute pancreatitis complicated with abdominal compartment syndrome / 国际外科学杂志

Acute pancreatitis is a clinically common acute abdomen,mild acute pancreatitis is a self-limiting disease,while severe acute pancreatitis (SAP) requires multidisciplinary treatment and the mortality rate remains high.A special complication of SAP is intra-abdominal hypertension,as the disease progresses,the intraabdominal pressure is further increased,leading to abdominal compartment syndrome (ACS),which eventually leads to multiple organ dysfunction syndrome.This current surgical intervention for SAP combined with ACS has gradually replaced the conventional medical treatment program.This article reviews the various options for surgical treatment of SAP with ACS.

Progress in surgical treatment for severe acute pancreatitis complicated with abdominal compartment syndrome / 国际外科学杂志

Acute pancreatitis is a clinically common acute abdomen, mild acute pancreatitis is a self-limiting disease, while severe acute pancreatitis (SAP) requires multidisciplinary treatment and the mortality rate remains high. A special complication of SAP is intra-abdominal hypertension, as the disease progresses, the intra-abdominal pressure is further increased, leading to abdominal compartment syndrome (ACS), which eventually leads to multiple organ dysfunction syndrome. This current surgical intervention for SAP combined with ACS has gradually replaced the conventional medical treatment program. This article reviews the various options for surgical treatment of SAP with ACS.