SMAD4 endows TGF-ß1-induced highly invasive tumor cells with ferroptosis vulnerability in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy prone to recurrence and metastasis. Studies show that tumor cells with increased invasive and metastatic potential are more likely to undergo ferroptosis. SMAD4 is a critical molecule in the transforming growth factor ß (TGF-ß) pathway, which affects the TGF-ß-induced epithelial-mesenchymal transition (EMT) status. SMAD4 loss is observed in more than half of patients with PDAC. In this study, we investigated whether SMAD4-positive PDAC cells were prone to ferroptosis because of their high invasiveness. We showed that SMAD4 status almost determined the orientation of transforming growth factor ß1 (TGF-ß1)-induced EMT via the SMAD4-dependent canonical pathway in PDAC, which altered ferroptosis vulnerability. We identified glutathione peroxidase 4 (GPX4), which inhibited ferroptosis, as a SMAD4 down-regulated gene by RNA sequencing. We found that SMAD4 bound to the promoter of GPX4 and decreased GPX4 transcription in PDAC. Furthermore, TGF-ß1-induced high invasiveness enhanced sensitivity of SMAD4-positive organoids and pancreas xenograft models to the ferroptosis inducer RAS-selective lethal 3 (RSL3). Moreover, SMAD4 enhanced the cytotoxic effect of gemcitabine combined with RSL3 in highly invasive PDAC cells. This study provides new ideas for the treatment of PDAC, especially SMAD4-positive PDAC.

Hernandezine induces autophagic cell death in human pancreatic cancer cells via activation of the ROS/AMPK signaling pathway.

Hernandezine (Her) is a bisbenzylisoquinoline alkaloid extracted from the traditional Chinese herbal medicine Thalictrum glandulosissimum. Evidence shows that Her is a natural agonist of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and induces apoptosis and autophagy in tumor cells. In this study, we investigated the role of autophagy in Her-induced cell death in human pancreatic cancer cell lines. We showed that Her dose-dependently suppressed cell proliferation, promoted autophagy and induced autophagic death in pancreatic ductal adenocarcinoma (PDAC) cell lines Capan-1 and SW1990. The IC50 values of Her in inhibition of Capan-1 and SW1990 cells were 47.7 µM and 40.1 µM, respectively. Immunoblotting showed that Her (1-40 µM) promoted the conversion of LC3-I to LC3-II, and Her exerted concentration-dependent and time-dependent effects on autophagy activation in PDAC cells. In transmission electron microscopy and fluorescence image analysis, we found that autophagic vacuoles were significantly increased in Her-treated cells. Knockdown of ATG5, a key gene in the autophagy pathway, alleviated the activation of autophagy by Her. These results demonstrated that Her induced autophagy in PDAC cells. Intensely activated autophagy could promote cell death. The autophagy inhibitors, BafA1 and HCQ significantly inhibited Her-induced cell death, implying that Her induced autophagic cell death in PDAC cells. Moreover, we showed that Her activated autophagy by increasing the phosphorylation of AMPK and decreasing the phosphorylation of mTOR/p70S6K. Knockdown of AMPKα relieves the autophagic cell death induced by Her. Furthermore, Her concentration-dependently enhanced reactive oxygen species (ROS) generation in PDAC cells. Antioxidants could reduce the phosphorylation of AMPK and suppress autophagic cell death induced by Her. Our study provides evidence for the development of Her as a therapeutic agent for the treatment of pancreatic cancer.

A new glance at autophagolysosomal-dependent or -independent function of transcriptional factor EB in human cancer.

Autophagy-lysosome system plays a variety of roles in human cancers. In addition to being implicated in metabolism, it is also involved in tumor immunity, remodeling the tumor microenvironment, vascular proliferation, and promoting tumor progression and metastasis. Transcriptional factor EB (TFEB) is a major regulator of the autophagy-lysosomal system. With the in-depth studies on TFEB, researchers have found that it promotes various cancer phenotypes by regulating the autophagolysosomal system, and even in an autophagy-independent way. In this review, we summarize the recent findings about TFEB in various types of cancer (melanoma, pancreatic ductal adenocarcinoma, renal cell carcinoma, colorectal cancer, breast cancer, prostate cancer, ovarian cancer and lung cancer), and shed some light on the mechanisms by which it may serve as a potential target for cancer treatment.

Mutations in key driver genes of pancreatic cancer: molecularly targeted therapies and other clinical implications.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with a minimal difference between its incidence rate and mortality rate. Advances in oncology over the past several decades have dramatically improved the overall survival of patients with multiple cancers due to the implementation of new techniques in early diagnosis, therapeutic drugs, and personalized therapy. However, pancreatic cancers remain recalcitrant, with a 5-year relative survival rate of <9%. The lack of measures for early diagnosis, strong resistance to chemotherapy, ineffective adjuvant chemotherapy and the unavailability of molecularly targeted therapy are responsible for the high mortality rate of this notorious disease. Genetically, PDAC progresses as a complex result of the activation of oncogenes and inactivation of tumor suppressors. Although next-generation sequencing has identified numerous new genetic alterations, their clinical implications remain unknown. Classically, oncogenic mutations in genes such as KRAS and loss-of-function mutations in tumor suppressors, such as TP53, CDNK2A, DPC4/SMAD4, and BRCA2, are frequently observed in PDAC. Currently, research on these key driver genes is still the main focus. Therefore, studies assessing the functions of these genes and their potential clinical implications are of paramount importance. In this review, we summarize the biological function of key driver genes and pharmaceutical targets in PDAC. In addition, we conclude the results of molecularly targeted therapies in clinical trials and discuss how to utilize these genetic alterations in further clinical practice.

Complete Genome Sequences of Leclercia sp. W6 and W17 Isolated from a Gastric Cancer Patient.

Leclercia sp. W6 and W17, which belong to the Enterobacteriaceae, were isolated from a stomach sample from a 78-year-old female gastric cancer patient, and genomic sequencing and analysis were performed. The genome of Leclercia sp. W6 consists of one chromosome with a size of 4,945,486 bp, while that of Leclercia sp. W17 contains one chromosome and two plasmids with a total size of 5,125,645 bp. Average nucleotide identity (ANI) calculations indicated that strains W6 and W17 exhibited similarities < 91.0% to other strains within the Enterobacteriaceae, except for six Leclercia strains. Phylogenomic analysis based on core-genome showed that strains W6 and W17 belong to the genus Leclercia, and phylogenetic analysis based on ANI values revealed that strains W6 and W17 formed an independent clade from those six Leclercia strains. Furthermore, comparative genomic analysis revealed that strains W6 and W17 had 5086 orthologous clusters (OCs) in their pan-genomes, and 59 exclusive OCs which were absent in their closest relatives. Genomic annotations revealed that the genomes of strains W6 and W17 encoded genes related to multidrug resistance clusters, multiple antibiotic resistance loci, and multidrug efflux pumps and had an identical urease gene cluster and a dissimilatory nitrate reduction pathway. Bioinformatic analyses indicated that strains W6 and W17 represented a novel species within the genus Leclercia. Genomic annotations revealed that these strains encoded genes related to multidrug resistance, nitrate reduction, and urease activity, which contribute to gastric malignant transformation. This will broaden our knowledge of the genetic mechanisms of the Enterobacteriaceae and help improve the clinical conditions of gastric cancer patients.

Actibacterium pelagium sp. nov., a novel alphaproteobacterium, and emended description of the genus Actibacterium.

A Gram-stain-negative, non-motile, rod-shaped bacterium, designated JN33T, was isolated from seawater collected from the western Pacific Ocean. Strain JN33T was positive for hydrolysis of aesculin and gelatin. On the basis of 16S rRNA gene sequence analysis, strain JN33T showed high 16S rRNA gene sequence similarity to Actibacterium atlanticum 22II-S11-z10T (97.3 %), A. mucosum KCTC 23349T (96.6 %) and A. ureilyticum LS-811T (95.7 %) and exhibited less than 97.0 % 16S rRNA gene sequence similarity with respect to the other type strains within the family Rhodobacteraceae. Phylogenetic analysis revealed that strain JN33T fell within the cluster of the genus Actibacterium. The average nucleotide identity and in silico DNA-DNA hybridization values between strain JN33T and the type strains of Actibacterium species were 73.1-73.8 % and 19.8-20.1 %, respectively. The sole respiratory quinone was ubiquinone 10 (Q-10). The principal fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) and C16 : 0. The major polar lipids were phosphatidylglycerol, one unidentified phospholipid and two unidentified aminolipids. The DNA G+C content was 57.8 mol%. Distinctly different phylogenetic characteristics, chemotaxonomic differences, as well as phenotypic properties, revealed that strain JN33T could be differentiated from the Actibacterium species with validly published names. Therefore, it is proposed that strain JN33T represents a novel species of the genus Actibacterium, for which the name Actibacterium pelagium sp. nov. (type strain, JN33T=CGMCC 1.16012T=KCTC 52653T) is proposed.

Comparison of clinical outcomes and quality of life between laparoscopic and open central pancreatectomy with pancreaticojejunostomy.

BACKGROUND: The studies comparing laparoscopic and open central pancreatectomy with pancreaticojejunostomy are limited. This study aimed to compare clinical outcomes and quality of life of patients undergoing laparoscopic and open central pancreatectomy with pancreaticojejunostomy. METHODS: Between December 1997 and December 2015, patients who underwent central pancreatectomy with pancreaticojejunostomy were reviewed. Patients were divided into 2 groups as laparoscopic central pancreatectomy (LCP) and open central pancreatectomy (OCP). Data considered for comparison analysis were patient demographics, intraoperative variables, morbidity, postoperative hospital stay, mortality, pathologic findings, and quality of life (SF-36 questionnaire). RESULTS: Thirty-six patients (17 LCP and 19 OCP) were included in the final analysis. Baseline characteristics were similar in the 2 groups. The operating time (280.4 ± 33.6 vs. 290.5 ± 62.5 min, p = 0.455) were similar between two groups. LCP group showed significantly lower estimated blood loss (76.4 ± 70.3 vs. 390.3 ± 279.0 ml, p = 0.001), shorter first flatus time (2.4 ± 0.9 vs. 3.9 ± 1.3 days, p = 0.001), and shorter diet start time (4.1 ± 2.2 vs. 6.1 ± 2.4 days, p = 0.030). However, the postoperative hospital stay was not significantly different between two groups (15.6 ± 12.1 vs. 24.0 ± 27.5 days, p = 0.347). Postoperative outcomes, including morbidity (58.8 vs. 52.6%, p = 0.749), pancreatic fistula rates (≥grade B: 17.6 vs. 36.8%, p = 0.106), and mortality, were similar in the 2 groups. The median follow-up period was 45 months (range 4-216 months). No local recurrence or distant metastasis was detected in either group. On the follow-up survey, the total quality of life score (702.9 ± 47.9 vs. 671.8 ± 94.1), physical health score (353.9 ± 24.8 vs. 326.6 ± 67.6) and mental health score (349.0 ± 26.5 vs. 345.2 ± 34.6) were higher in the LCP group compared with the OCP group. However, these differences were not statistically significant (p > 0.05). The score in role physical (100 vs. 73.1 ± 4.8, p = 0.042) was significantly higher in LCP group, and not statistically significant in other areas (p > 0.05). CONCLUSIONS: LCP with pancreaticojejunostomy is safe and feasible for benign or borderline malignant lesions in the pancreatic neck and proximal body. Compared to OCP, LCP is associated with lower estimated blood loss, faster recovery, and better quality of life.

Laparoscopic ligation of celiac trunk and splenic artery aneurysms with function preservation.

Celiac trunk aneurysms (CTAs) are rare and usually asymptomatic. Although most of these aneurysms can be treated with percutaneous embolization, some uncommon locations of the aneurysm may make this approach impossible. We report a patient with a celiac trunk aneurysm (CTA) and a proximal splenic artery aneurysm (SAA). Due to the size and location of these two aneurysms, after multidisciplinary discussion, endovascular management was considered inappropriate and they were treated by laparoscopic ligation of the two aneurysms and revascularization. This procedure offers good postoperative recovery with good preservation of the visceral function. Some collateral vessels in the viscera were obvious on postoperative day 7.

Upregulation of HOXB7 promotes the tumorigenesis and progression of gastric cancer and correlates with clinical characteristics.

Several examples of aberrant homeobox gene expression have been found across a range of cancers, and it is also confirmed that homeobox genes play a critical roles in tumorigenesis and progression. Notwithstanding homeobox B7 (HOXB7) has been documented that its deregulation promotes carcinogenesis and development in gastrointestinal tract, its function in gastric cancer has not been investigated. In this study, HOXB7 expression was examined to be distinctly upregulated in gastric carcinoma GC cell lines and in the tumor relative to normal gastric tissue. High HOXB7 expression was correlated with tumor differentiation (P = 0.025) and TNM stage (P = 0.008). HOXB7 knockdown in BGC-823 and SGC-7901 resulted in decreased migration and invasion with alteration of epithelial-mesenchymal transition (EMT) proteins and influenced proliferation, apoptosis, and cell cycle. Furthermore, complementary DNA (cDNA) microarray, qPCR, and Western blotting were performed to explore potential downstream target genes of HOXB7. HOXB7 is generally overexpressed in GC, associated with patient clinical characteristics, and specifically promotes GC cell malignant biological properties through PIK3R3/AKT signaling pathways, indicating HOXB7 as a causal factor in promoting tumor progression.

Comparison of short-term surgical outcomes between totally laparoscopic and laparoscopic-assisted distal gastrectomy for gastric cancer: a 10-y single-center experience with meta-analysis.

BACKGROUND: Laparoscopic-assisted distal gastrectomy (LADG) and totally laparoscopic distal gastrectomy (TLDG) are two commonly used methods of laparoscopic gastrectomy for gastric cancer. This study aimed to compare the short-term surgical outcomes of these two methods. METHODS: A prospectively maintained gastric cancer database between October 2004 and February 2014 was reviewed and 115 patients underwent LADG and 198 patients underwent TLDG were included. The clinical characteristics and perioperative clinical outcomes of two groups were compared. Moreover, a systematic review and meta-analysis were conducted. RESULTS: The mean operation time and blood loss were similar in two groups, as was the number of retrieved lymph nodes. There was no significant difference in time to first flatus, the time to restart oral intake, the length of the hospital stay after surgery, and postoperative complications. The meta-analysis revealed no significant differences in the operative time, surgical margin, time to first flatus, length of hospital stay, mortality, overall, and anastomosis-related complications among the groups. However, the intraoperative blood loss was lower in TLDG (weighted mean difference = 21.50 mL; 95% confidence interval: 9.79-33.22; P < 0.01), and number of retrieved lymph nodes was higher in TLDG (weighted mean difference = -1.56; 95% confidence interval: -2.69 to -0.44; P < 0.01). CONCLUSIONS: TLDG is safe and feasible compared with LADG. However, it is difficult to identify the clinical advantages of TLDG over LADG based on our study. Thus, the choice of surgical approach mainly depends on the patient conditions and the preference of the patients or surgeons.

Systematic review and meta-analysis of safety and efficacy of laparoscopic resection for gastrointestinal stromal tumors of the stomach.

OBJECTIVE: To evaluate the safety and efficacy of laparoscopic resection for gastrointestinal stromal tumors (GISTs) of the stomach with systematic review and meta-analysis. METHODS: The literature database before March, 2014 was extensively searched to retrieve the comparative studies of laparoscopic (LAP) and open resection (OPEN) for GISTs with a relevance of study goal. The inclusion and exclusion criteria were formulated. After a quality evaluation, the data were extracted. The Cochrane collaboration RevMan5.1 version software was used for meta-analysis. RESULTS: There are nineteen studies meeting the inclusion criteria for meta-analysis. The total sample size of these studies was 1,060 cases. The operation time was similar between the two groups [weighted mean difference (WMD) -7.20 min, 95 % confidence interval (CI) -25.65 to 11.25, P = 0.44)]. Compared to OPEN, however, LAP experienced less blood loss (WMD -54.21 ml, 95 % CI -82.65 to -25.77, P < 0.01), earlier time to flatus (WMD -1.34 days, 95 % CI -1.62 to -1.06, P < 0.01) and oral diet (WMD -1.80 days, 95 % CI -2.18 to -1.42, P < 0.01), shorter hospital stay (WMD -3.68 days, 95 % CI -4.52 to -2.85, P < 0.01) and decrease in overall complications [relative risk (RR) 0.51, 95 % CI 0.32-0.80, P < 0.01)]. In addition, the long-term follow-up result shows that there is no significant difference in the two groups of patients. CONCLUSION: Laparoscopic resection for gastric GISTs is a safe and feasible procedure with less blood loss, less overall complications and quicker recovery. The long-term survival situation of patients mainly depends on the tumor itself risk, and laparoscopic surgery will not increase the risks of tumor relapse and metastasis.

Cruciferous vegetable consumption and the risk of pancreatic cancer: a meta-analysis.

BACKGROUND: Previous studies regarding the association between cruciferous vegetable intake and pancreatic cancer risk have reported inconsistent results. We conducted a meta-analysis to demonstrate the potential association between them. METHODS: A systematic literature search of papers was conducted in March 2014 using PubMed, EMBASE, and Web of Science, and the references of the retrieved articles were screened. The summary odds ratios (ORs) with 95% confidence interval (CI) for the highest versus the lowest intake of cruciferous vegetables were calculated. RESULTS: Four cohort and five case-control studies were eligible for inclusion. We found a significantly decreased risk of pancreatic cancer associated with the high intake of cruciferous vegetables (OR 0.78, 95% CI 0.64-0.91). Moderate heterogeneity was detected across studies (P = 0.065). There was no evidence of significant publication bias based on Begg's funnel plot (P = 0.917) or Egger's test (P = 0.669). CONCLUSIONS: Cruciferous vegetable intake might be inversely associated with pancreatic cancer risk. Because of the limited number of studies included in this meta-analysis, further well-designed prospective studies are warranted to confirm the inverse association between cruciferous vegetable intake and risk of pancreatic cancer.

Laparoscopic versus open wedge resection for gastrointestinal stromal tumors of the stomach: a single-center 8-year retrospective cohort study of 156 patients with long-term follow-up.

BACKGROUND: The aim of this study was to compared laparoscopic (LWR) and open wedge resection (OWR) for the treatment of gastric gastrointestinal stromal tumors (GISTs). METHODS: The data of 156 consecutive GISTs patients underwent LWR or OWR between January 2006 and December 2013 were collected retrospectively. The surgical outcomes and the long-term survival rates were compared. Besides, a rapid systematic review and meta-analysis were conducted. RESULTS: Clinicopathological characteristics of the patients were similar between the two groups. The LWR group was associated with less intraoperative blood loss (67.3 vs. 142.7 ml, P < 0.001), earlier postoperative flatus (2.3 vs. 3.2 days, P < 0.001), earlier oral intake (3.2 vs. 4.1 days, P < 0.001) and shorter postoperative hospital stay (6.0 vs. 8.0 days, P = 0.001). The incidence of postoperative complications was lower in LWR group but did not reach statistical significance (4/90, 4.4% vs. 8/66, 12.1%, P = 0.12). No significant difference was observed in 3-year relapse-free survival rate between the two groups (98.6% vs. 96.4%, P > 0.05). The meta-analysis revealed similar results except less overall complications in the LWR group (RR = 0.49, 95% CI, 0.25 to 0.95, P = 0.04). And the recurrence risk was similar in two group (RR = 0.80, 95% CI, 0.28 to 2.27, P > 0.05). CONCLUSIONS: LWR is a technically and oncologically safe and feasible approach for gastric GISTs compared with OWR. Moreover, LWR appears to be a preferable choice with mini-invasive benefits.

Short-term surgical and long-term survival outcomes after laparoscopic distal gastrectomy with D2 lymphadenectomy for gastric cancer.

BACKGROUND: Laparoscopic distal gastrectomy (LDG) for gastric cancer has gradually gained popularity. However, the long-term oncological outcomes of LDG have rarely been reported. This study aimed to investigate the survival outcomes of LDG, and evaluate the early surgical outcomes of laparoscopy-assisted distal gastrectomy (LADG) and totally laparoscopic distal gastrectomy (TLDG). METHODS: Clinical outcomes of 240 consecutive patients with gastric cancer who underwent LDG at our institution between October 2004 and April 2013 were analyzed. Early surgical outcomes of LADG and TLDG were compared and operative experiences were evaluated. RESULTS: Of the 240 patients, 93 underwent LADG and 147 underwent TLDG. There were 109 T1, 36 T2, 31 T3, and 64 T4a lesions. The median follow-up period was 31.5 months (range: 4-106 months). Tumor recurrence was observed in 40 patients and peritoneal recurrence was observed most commonly. The 5-year disease-free survival (DFS) and overall survival (OS) rates according to tumor stage were 90.3% and 93.1% in stage I, 72.7% and 67.6% in stage II, and 34.8% and 41.5% in stage III, respectively. No significant differences in early surgical outcomes were noted such as operation time, blood loss and postoperative recovery between LADG and TLDG (P >0.05). CONCLUSIONS: LDG for gastric cancer had acceptable long-term oncologic outcomes. The early surgical outcomes of the two commonly used LDG methods were similar.

Immunoglobulin G4-associated cholangitis mimicking cholangiocarcinoma treated by laparoscopic choledochectomy with intracorporeal Roux-en-Y hepaticojejunostomy.

Immunoglobulin G4 (IgG4)-associated disease is a recently recognized disease entity that is characterized by elevated serum IgG4 concentrations, abundant IgG4 lymphoplasmacytic infiltration, and dramatic steroid responses. IgG4-associated cholangitis is one manifestation of IgG4-associated disease. However, it is clinically challenging to make a preoperative differentiation between this rare disease and cholangiocarcinoma, especially for those with serum concentrations of IgG4 in the normal range. This article reports on a 57-year-old man with jaundice and upper abdominal discomfort. Imaging examination showed biliary stricture that closely resembled cholangiocarcinoma, and the patient's serum IgG4 concentration was normal. The patient underwent a laparoscopic choledochectomy with Roux-en-Y hepaticojejunostomy using an intracorporeal hand-sewn technique. He recovered quickly without any complications. We also present our experience in laparoscopic intracorporeal hand-sewn hepaticojejunostomy.

A rare case of mixed mucinous cystadenoma with serous cystadenoma of the pancreas treated by laparoscopic central pancreatectomy.

Mixed mucinous cystadenoma with serous cystadenoma of the pancreas is rare. There have been only two previous case reports in the English-language literature. We present a case of a 46-year-old woman who was diagnosed with mixed mucinous cystadenoma with serous cystadenoma of the pancreas. Computed tomography and magnetic resonance imaging showed a cystic neoplasm in the dorsal/proximal body of the pancreas with a clear-margin multilocular cavity and enhanced internal septum. The patient underwent laparoscopic central pancreatectomy. The diagnosis of mixed mucinous cystadenoma with serous cystadenoma of the pancreas was confirmed by pathological examination. The patient was followed up for 3 months and there were no signs of recurrence, or pancreatic exocrine or endocrine insufficiency. To the best of our knowledge, this is the first reported case treated by laparoscopic central pancreatectomy.

Three cases of laparoscopic total gastrectomy with intracorporeal esophagojejunostomy for gastric cancer in remnant stomach.

Gastric cancer in remnant stomach is a rare tumor but with poor prognosis. Compared with conventional open surgery, laparoscopic gastrectomy has potential benefits for these patients due to advantages resulting from its minimally invasive approach. Herein, we report on three patients with gastric cancer in remnant stomach who underwent laparoscopic total gastrectomy with intracorporeal esophagojejunostomy successfully. The operative time was 280, 250 and 225 minutes, the estimated blood loss was 100, 80 and 50 ml and the length of postoperative hospital stay was seven, eight and nine days respectively. Our experience has suggested that laparoscopic total gastrectomy with intracorporeal esophagojejunostomy can be a safe, feasible and promising option for patients with gastric cancer in remnant stomach.

[Effect of Ginkgo biloba extract on the function of alveolar polymorphonuclear neutrophils in severe acute pancreatitis rats complicated with lung injury].

OBJECTIVE: To explore the effect of Ginkgo biloba extract (GBE) on the function of alveolar polymorphonuclear neutrophils (PMN) in severe acute pancreatitis (SAP) rats complicated with lung injury (LI). METHODS: Forty-eight adult SD rats were randomly divided into three groups, i.e., the sham-operation group, the SAP group, and the GBE treatment group, 16 in each group. The SAP model was successfully induced by retrograde injection of 5% sodium taurocholate solution into the biliopancreatic duct. Rats in the sham-operation group only received flipping of the duodenum. Those in the GBE treatment group received GBE intervention based on SAP model. Equal volume of normal saline was given to rats in the sham-operation group and the SAP group. Rats were sacrificed at 6 and 12 h after operation respectively. The lung tissue was sampled to evaluate the LI score. The wet/dry ratio (W/D) of lung tissues was detected. The activity of myeloperoxidase (MPO) was measured. Alveolar PMN was harvested by bronchoalveolar lavage. The content of neutrophil elastase (NE) in bronchoalveolar lavage fluid (BALF) was measured by enzyme-linked immunoabsorbent assay (ELISA). The percentage of CD11b/CD18 double positive PMN was detected using flow cytometry. The expression of intercellular adhesion molecule-1 (ICAM-1) and NE protein in the lung tissue was detected by Western blot. RESULTS: Compared with the sham-operation group, significant pathologic lesion occurred in the lung tissue of rats in the SAP group; the pathologic LI score, lung tissue W/D ratio, MPO, and NE content in BALF significantly increased, the expression of ICAM-1 and NE in the lung tissue was obviously up-regulated, and the percentage of CD11b/CD18 double positive PMN significantly increased (P < 0.01). Compared with the SAP group, pathological lesion of the lung tissue was obviously attenuated, and the above indices were all significantly declined in the GBE treatment group (P < 0.01). CONCLUSIONS: Expression of ICAM-1 in the lung tissue and the percentage of D11b/ CD18 double positive PMN were up-regulated in SAP rats complicated with LI, resulting in the adherence of PMN to pulmonary vascular endothelial cells, and then activating PMN to release NE and aggravate LI. GBE could alleviate LI through down-regulating the expression ICAM-1 and CD11b/CD18, and hindering the adherence and activation of PMN to pulmonary vascular endothelial cells.

[Totally laparoscopic versus laparoscopic assisted distal gastrectomy for gastric cancer: a meta-analysis].

OBJECTIVE: To compare the safety and efficacy of totally laparoscopic distal gastrectomy (TLDG) with laparoscopic assisted distal gastrectomy (LADG) for gastric cancer by meta-analysis. METHODS: The literature on comparative studies of TLDG and LADG up to June 2014 were extensively retrieved from database PubMed, Cochrane library, Web of Science, and Biosis Previews. The operation time, blood loss, time to flatus, time to first oral intake, postoperative hospital stay, postoperative morbidity, times of analgestic requirement, pain score, and the level of C-reactive protein (CRP) on postoperative day 1 and 7 were analyzed. The statistical analysis was performed with RevMan 5.1 software. RESULTS: Seven studies met the inclusion criteria for meta-analysis. A total of 1783 Patients were included for meta-analysis, among whom 727 cases underwent TLDG and 1056 underwent LADG. Comparing with LADG, TLDG experienced less blood loss [weighted mean difference (WMD)=22.86 ml，95% confidence interval (CI): 12.0-33.72, P<0.01)], less times of analgesic requirement (WMD=0.58, 95% CI: 0.35-0.81, P< 0.01)，less pain score on postoperative day 1 and day 3 (day1: WMD=0.60, 95% CI: 0.20-0.99, P < 0.01; day3: WMD=0.36, 95% CI: 0.24-0.48, P < 0.01), earlier beginning to take diet (WMD=0.66, 95% CI: 0.13-1.19, P=0.01). The operation time, postoperative hospital stay, overall morbidity and anastomosis-related morbidity, and the level of CRP on postoperative day 1 and 7 were similar between two groups (Ps>0.05). CONCLUSION: TLDG is a safe and feasible procedure with less blood loss, less pain, and quicker recovery than those of LADG.

Systematic review and meta-analysis of laparoscopic and open gastrectomy for advanced gastric cancer.

BACKGROUND: The use of laparoscopic gastrectomy (LG) in advanced gastric cancer (AGC) remains a controversial topic, mainly because of doubts about its oncologic validity. This study is a systematic review and meta-analysis of the available evidence. METHODS: A comprehensive search was performed until June 2013 to identify comparative studies evaluating survival rates, recurrence rates, surgical outcomes and complications. Pooled risk ratios (RR) and weighted mean differences (WMD) with 95% confidence intervals (CI) were calculated using the random effects model. Data synthesis and statistical analysis were carried out using RevMan 5.1 software. RESULTS: Fifteen trials were involved in this analysis. Compared to open gastrectomy (OG), LG involved a longer operating time (WMD = 48.67 min, 95% CI 34.09 to 63.26, P < 0.001); less blood loss (WMD = -139.01 ml, 95% CI -174.57 to -103.44, P < 0.001); earlier time to flatus (WMD = -0.79 days, 95% CI -1.14 to -0.44, P < 0.001); shorter hospital stay (WMD = -3.11 days, 95% CI -4.13 to -2.09, P < 0.001); and a decrease in complications (RR = 0.74, 95% CI 0.61 to 0.90, P = 0.003). There was no significant difference in the number of harvested lymph nodes, margin distance, mortality, cancer recurrence rate and long-term survival rate between the AGC patients treated with LG or OG (P > 0.05). CONCLUSIONS: Despite a longer operation, LG is a safe technical alternative to OG for AGC with a lower complication rate and enhanced postoperative recovery. Moreover, there were similar outcomes between both approaches in terms of cancer recurrence and the long-term survival rate. Because of the limitation of this study, methodologically high-quality studies are needed for further evaluation.