Acute kidney injury after radical gastrectomy: incidence, risk factors, and impact on prognosis.

Background: Acute kidney injury (AKI) is a serious adverse event often overlooked following major abdominal surgery. While radical gastrectomy stands as the primary curative method for treating gastric cancer patients, little information exists regarding AKI post-surgery. Hence, this study aimed to ascertain the incidence rate, risk factors, and consequences of AKI among patients undergoing radical gastrectomy. Methods: This was a population-based, retrospective cohort study. The incidence of AKI was calculated. Multivariate logistic regression was used to identify independent predictors of AKI. Survival curves were plotted by using the Kaplan-Meier method and differences in survival rates between groups were analyzed by using the log-rank test. Results: Of the 2,875 patients enrolled in this study, 61 (2.1%) developed postoperative AKI, with AKI Network 1, 2, and 3 in 50 (82.0%), 6 (9.8%), and 5 (8.2%), respectively. Of these, 49 patients had fully recovered by discharge. Risk factors for AKI after radical gastrectomy were preoperative hypertension (odds ratio [OR], 1.877; 95% CI, 1.064-3.311; P = 0.030), intraoperative blood loss (OR, 1.001; 95% CI, 1.000-1.002; P = 0.023), operation time (OR, 1.303; 95% CI, 1.030-1.649; P = 0.027), and postoperative intensive care unit (ICU) admission (OR, 4.303; 95% CI, 2.301-8.045; P < 0.001). The probability of postoperative complications, mortality during hospitalization, and length of stay in patients with AKI after surgery were significantly higher than those in patients without AKI. There was no statistical difference in overall survival (OS) rates between patients with AKI and without AKI (1-year, 3-year, 5-year overall survival rates of patients with AKI and without AKI were 93.3% vs 92.0%, 70.9% vs 73.6%, and 57.1% vs 67.1%, respectively, P = 0.137). Conclusions: AKI following radical gastrectomy is relatively rare and typically self-limited. AKI is linked with preoperative hypertension, intraoperative blood loss, operation time, and postoperative ICU admission. While AKI raises the likelihood of postoperative complications, it does not affect OS.

MT1M regulates gastric cancer progression and stemness by modulating the Hedgehog pathway protein GLI1.

Gastric cancer (GC) is a highly prevalent and aggressive malignancy with a poor prognosis. Recent evidence suggested that metallothionein 1 M (MT1M) may play a critical role in cancer development, progression, and drug resistance; however, its role in GC remains largely unknown. In this study, we investigated the expression and function of MT1M in GC both in vitro and in vivo. We found that MT1M expression was significantly downregulated in GC tissues and cell lines. Decreased expression of MT1M was associated with worse clinical prognosis, particularly in patients treated with 5-fluorouracil. Low expression of MT1M was indicative of poor overall survival (OS, HR 0.56 [95% CI 0.37-0.84], P < 0.005), first progression survival (FP, HR 0.54 [95% CI 0.36-0.79], P < 0.005), and post-progression survival (PPS, HR 0.65 [95% CI 0.45-0.94], P < 0.05). We also demonstrated that overexpression of MT1M inhibited cell proliferation and induced apoptosis in GC cells and in tumor xenografts, and it improved chemosensitivity to 5-fluorouracil. Furthermore, we found that MT1M overexpression could inhibit stem cell characteristics by targeting GLI1 and affecting GLI1 ubiquitination. Collectively, these findings indicated that MT1M may act as a tumor suppressor in GC and could serve as a potential therapeutic target to attenuate stemness and chemotherapy resistance of GC.

3D laparoscopic-assisted vs open gastrectomy for carcinoma in the remnant stomach: A retrospective cohort study.

BACKGROUND: Three-dimensional (3D) laparoscopic technique has gradually been applied to the treatment of carcinoma in the remnant stomach (CRS), but its clinical efficacy remains controversial. AIM: To compare the short-term and long-term results of 3D laparoscopic-assisted gastrectomy (3DLAG) with open gastrectomy (OG) for CRS. METHODS: The clinical data of patients diagnosed with CRS and admitted to the First Medical Center of Chinese PLA General Hospital from January 2016 to January 2021 were retrospectively collected. A total of 84 patients who met the inclusion and exclusion criteria were enrolled. All their clinical data were collected and a database was established. All patients were treated with 3DLAG or OG by experienced surgeons and were divided into two groups based on the different surgical methods mentioned above. By using outpatient and telephone follow-up, we were able to determine postoperative survival and tumor status. The postoperative short-term efficacy and 1-year and 3-year overall survival (OS) rates were compared between the two groups. RESULTS: Among 84 patients with CRS, 48 were treated with OG and 36 with 3DLAG. All patients successfully completed surgery. There was no significant difference between the two groups in terms of age, gender, body mass index, ASA score, initial disease state (benign or malignant), primary surgical anastomosis method, interval time of carcinogenesis, and tumorigenesis site. Patients in the 3DLAG group experienced less intraoperative blood loss (188.33 ± 191.35 mL vs 305.83 ± 303.66 mL; P = 0.045) and smaller incision (10.86 ± 3.18 cm vs 20.06 ± 5.17 cm; P < 0.001) than those in the OG group. 3DLAGC was a more minimally invasive method. 3DLAGC retrieved significantly more lymph nodes than OG (14.0 ± 7.17 vs 10.73 ± 6.82; P = 0.036), whereas the number of positive lymph nodes did not differ between the two groups (1.56 ± 2.84 vs 2.35 ± 5.28; P = 0.413). The complication rate (8.3% vs 20.8%; P = 0.207) and intensive care unit admission rate (5.6% vs 14.5%; P = 0.372) were equivalent between the two groups. In terms of postoperative recovery, the 3DLAGC group had a lower visual analog score, shorter indwelling time of gastric and drainage tubes, shorter time of early off-bed motivation, shorter time of postoperative initial flatus and initial soft diet intake, shorter postoperative hospital stay and total hospital stay, and there were significant differences, showing better short-term efficacy. The 1-year and 3-year OS rates of OG group were 83.2% [95% confidence interval (CI): 72.4%-95.6%] and 73.3% (95%CI: 60.0%-89.5%) respectively. The 1-year and 3-year OS rates of the 3DLAG group were 87.3% (95%CI: 76.4%-99.8%) and 75.6% (95%CI: 59.0%-97.0%), respectively. However, the 1-year and 3-year OS rates were similar between the two groups, which suggested that long-term survival results were comparable between the two groups (P = 0.68). CONCLUSION: Compared with OG, 3DLAG for CRS achieved better short-term efficacy and equivalent oncological results without increasing clinical complications. 3DLAG for CRS can be promoted safely and effectively in selected patients.

Rspondin-1 contributes to the progression and stemness of gastric cancer by LGR5.

Gastric cancer is a one of the most common malignant tumors with poor prognosis worldwide. Leucine-rich G-protein-coupled receptor 5 (LGR5) is determined as a modulator of Wnt signaling cascade and R-spondins are a family of secretory agonists in the Wnt signaling and act as ligands to interact with LGR5. However, the function of Rspondin-1 in GC remains obscure. Here, we identified the effect of Rspondin-1 on GC progression. Rspondin-1 and LGR5 were upregulated in clinical gastric cancer tissues. CCK-8 assay revealed that the viability of GC cells was reduced by Rspondin-1 depletion and enhanced by Rspondin-1 overexpression. The depletion of Rspondin-1 decreased while the overexpression of Rspondin-1 increased the numbers of colony formation and Edu-positive GC cells. The depletion of Rspondin-1 attenuated the invasion and migration ability of GC cells. Moreover, sphere formation assays revealed that the knockdown of Rspondin-1 reduced the stemness of GC cells. The expression of cancer stem cell markers, including Nanog, OCT3/4, and SOX2 were suppressed by Rspondin-1 depletion in GC cells. Rspondin-1 induced tumor growth of gastric cancer cells in vivo. Mechanically, the cell viability and invasion suppressed by the depletion of Rspondin-1 in GC cells were rescued by LGR5 overexpression. Besides, the overexpression of LGR5 reversed Rspondin-1 knockdown-inhibited Nanog and OCT3/4 expression. Consequently, we concluded that Rspondin-1 contributes to the progression and stemness of gastric cancer by LGR5.

The abdominal-transhiatal surgical approach versus the thoracoabdominal surgical approach in Siewert type II adenocarcinoma of the esophagogastric junction: protocol for a multicenter prospective, open, parallel, and randomized controlled trial.

BACKGROUND: To date, Siewert type II adenocarcinoma of the esophagogastric junction (ST-II AEG) can be removed radically utilizing either the abdominal-transhiatal (TH) or the right thoracoabdominal (RTA) approaches. Because of a paucity of high-quality direct evidence, the appropriate surgical approach for ST-II AEG remains debatable. In the present, only several retrospective studies are available, representing ambiguous results. Thus, prospective randomized clinical trials are demanded to compare the survival, oncological outcomes, safety and efficiency and life quality between the TH and RTA approach in patients with resectable AEG of Siewert type II. METHODS: A prospective, multicenter, open, randomized, and parallel controlled study named S2AEG will be conducted. Three hundred and twelve patients who match the inclusion criteria but not the exclusion criteria will be participating in the trial and randomly divided into the TH (156) and RTA (156) cohorts. The primary efficacy endpoint is the 3-year disease-free survival (DFS) following the operation. The rate of R0-resection, the number and site of lymph nodes infiltrated and dissected, postoperative complications, hospital days and life quality are the second endpoints. DISCUSSION: This study is the first prospectively randomized controlled trial aiming to compare the surgical outcomes between TH and RTA approaches in patients with resectable ST-II AEG. It is hypothesized that patients in the TH cohort would harvest equivalent oncological results and survival while maintaining acceptable life quality when compared to patients in the RTA cohort. Our findings will provide high-level clinical evidence for clinical decision-making on the appropriate surgical approach for patients with ST-II AEG. Embarked in November 2019, this research will be completed 3 years after the final participant's enrolment date. TRIAL REGISTRATION: Clinical Trial.gov ID: NCT04910789 May 29, 2021. Name: S2AEG.

Clinical significance and prognostic value of circulating B10 cells in colorectal cancer.

BACKGROUND: B10 cells, a subset of regulatory B cells, can inhibit antitumor response and thus promote tumor development. This study explored the clinical meaning and prognostic value of circulating B10 cells in colorectal cancer (CRC). MATERIALS AND METHODS: The proportion of B10 cells in peripheral blood in CRC patients and healthy controls was detected by multicolor flow cytometry. RESULTS: The proportion of circulating B10 cells was remarkably elevated in CRC patients compared to normal controls (% of CD19+ B cells; 16.6% (IQR 6.0%) versus 9.0% (IQR 5.7%), p < 0.001). B10 cells proportion was associated with tumor size, depth of invasion, lymph node metastasis, and TNM stage in CRC. Kaplan-Meier analysis indicated that CRC patients with high B10 cells proportion suffered worse overall survival than those with low B10 cells proportion. Multivariate analysis revealed that the proportion of B10 cells was an independent prognostic indicator for CRC patients. CONCLUSION: Our results indicate that the proportion of circulating B10 cells is an independent prognostic factor for patients with CRC and thus may help guide the clinical decision in CRC.

MiR-144-3p inhibits gastric cancer progression and stemness via directly targeting GLI2 involved in hedgehog pathway.

BACKGROUND: Gastric cancer (GC) is the fifth most commonly diagnosed cancer worldwide. Due to the dismal prognosis, identifying novel therapeutic targets in GC is urgently needed. Evidences have shown that miRNAs played critical roles in the regulation of tumor initiation and progression. GLI family zinc finger 2 (GLI2) has been reported to be up-regulated and facilitate cancer progression in multiple malignancies. In this study, we focused on identifying GLI2-targeted miRNAs and clarifying the underlying mechanism in GC. METHODS: Paired fresh gastric cancer tissues were collected from gastrectomy patients. GLI2 and miRNAs expression were detected in gastric cancer tissues and cell lines. Bioinformatics analysis was used to predict GLI2-targeted miRNAs and dual-luciferase reporter assay was applied for target verification. CCK-8, clone formation, transwell and flow cytometry were carried out to determine the proliferation, migration, invasion and cell cycle of gastric cancer cells. Tumorsphere formation assay and flow cytometry were performed to detail the stemness of gastric cancer stem cells (GCSCs). Xenograft models in nude mice were established to investigate the role of the miR-144-3p in vivo. RESULTS: GLI2 was frequently upregulated in GC and indicated a poor survival. Meanwhile, miR-144-3p was downregulated and negatively correlated with GLI2 in GC. GLI2 was a direct target gene of miR-144-3p. MiR-144-3p overexpression inhibited proliferation, migration and invasion of gastric cancer cells. Enhanced miR-144-3p expression inhibited tumorsphere formation and CD44 expression of GCSCs. Restoration of GLI2 expression partly reversed the suppressive effect of miR-144-3p. Xenograft assay showed that miR-144-3p could inhibit the tumorigenesis of GC in vivo. CONCLUSIONS: MiR-144-3p was downregulated and served as an essential tumor suppressor in GC. Mechanistically, miR-144-3p inhibited gastric cancer progression and stemness by, at least in part, regulating GLI2 expression.

CircRNAs in gastric cancer: current research and potential clinical implications.

Gastric cancer (GC) has a dismal prognosis and is also one of the most commonly diagnosed malignancies worldwide. circRNAs are covalently closed circular RNA molecules without 5'-cap and a 3'-tail, currently listed among the broad noncoding RNA family. circRNAs participate in a variety of pathophysiological processes relevant to human diseases, especially malignancies, including GC. Compelling evidence has shown that circRNAs can function by sponging miRNAs, interacting with RNA binding proteins, and encoding proteins or peptides. Yet, our current understanding of these RNA circles remains very limited. Here, we overview the biogenesis, characteristics, functions, and degradation of circRNAs. Moreover, we give an account of the circRNAs that have been linked with GC, describing their functions and mechanisms of action in the context of GC. Next, we discuss the potential value of circRNAs as diagnostic or prognostic GC biomarkers and summarize future prospects, important questions, and challenges of circRNA-based therapeutics.

GRSF1 promotes tumorigenesis and EMT-mediated metastasis through PI3K/AKT pathway in gastric cancer.

It is vital to identify effective therapeutic targets and explore the underlying mechanisms to curb the progression of Gastric cancer (GC) and improve the prognosis of GC patients. Guanine-rich RNA sequence binding factor 1 (GRSF1) is a member of the RNA-binding protein family. The present study showed that GRSF1 knockdown suppressed GC cells proliferation, migration and invasion in vitro, while GRSF1 overexpression enhanced the proliferation, migration and invasion of GC cells. Meanwhile, knockdown of GRSF1 inhibited tumor growth and tumor metastasis in vivo. Furthermore, we demonstrated that GRSF1 induced epithelial-mesenchymal transition (EMT) and activated PI3K/AKT pathway in vitro and in vivo through gain and loss of function. In conclusion, we demonstrated that GRSF1 promotes tumorigenesis and EMT-mediated metastasis through PI3K/AKT pathway in GC. Our study for the first time identified the functions of GRSF1 serving as an oncogene in GC, which may be a potential effective therapeutic target and malignant indicator in GC.

PAFAH1B3 Expression Is Correlated With Gastric Cancer Cell Proliferation and Immune Infiltration.

BACKGROUND: Platelet activating factor acetylhydrolase 1b catalytic subunit 3 (PAFAH1B3) is associated with a variety of human diseases. However, its function in gastric cancer remains uncertain. METHODS: PAFAH1B3 expression was analyzed in The Cancer Genome Atlas (TCGA) and genotype-tissue expression pan-cancer data. The association between PAFAH1B3 expression and patient prognosis was evaluated using TCGA clinical survival data. Enrichment analysis of PAFAH1B3 was performed using the clusterProfiler R software package. Moreover, the correlation between PAFAH1B3 expression and immune cell infiltration were evaluated by analyzing TCGA database. CCK8 assay and colony-formation assay were performed to assess the effect of PAFAH1B3 on the proliferation of gastric cancer cells. Transwell assay was used to evaluate the impact of PAFAH1B3 on gastric cancer cell migration. Western blot was performed to evaluate the role of PAFAH1B3 on signaling pathways in gastric cancer cells. RESULTS: PAFAH1B3 was highly expressed in many types of tumors including gastric cancer. High PAFAH1B3 expression was significantly correlated with proliferation-related gene sets involved in DNA replication, the cell cycle, and cell cycle checkpoints. Further analysis showed that high PAFAH1B3 expression was associated with high M1 macrophage and CD8-positive T cell infiltration scores. PAFAH1B3 knockdown inhibited the proliferation, migration, and the activation of oncogenic signaling in gastric cancer cells. CONCLUSIONS: Our findings suggest that PAFAH1B3 may be an oncogene in gastric cancer.

Macrophage Deficiency Makes Intestinal Epithelial Cells Susceptible to NSAID-Induced Damage.

OBJECTIVES: In Crohn's disease (CD), the mechanisms underlying the regulation by granulocyte-macrophage colony-stimulating factor (GM-CSF) of mucosal barrier function in the ileum are unclear. We analyzed the molecular mechanisms underlying the regulation by GM-CSF of the mucosal barrier function. METHODS: We examined the role of GM-CSF in the intestinal barrier function in CD at the molecular-, cellular-, and animal-model levels. RESULTS: Macrophages directly secreted GM-CSF, promoting intestinal epithelial proliferation and inhibiting apoptosis, which maintained intestinal barrier function. Macrophages were absent in NSAID-induced ileitis, causing GM-CSF deficiency, increasing the apoptosis rate, decreasing the proliferation rate, increasing inter- and paracellular permeabilities, decreasing the TJP levels, and reducing the numbers of mesenteric lymph nodes, memory T cells, and regulatory T cells in Csf1op/op transgenic mice. CONCLUSIONS: GM-CSF is required for the maintenance of intestinal barrier function. Macrophages directly secrete GM-CSF, promoting intestinal epithelial proliferation and inhibiting apoptosis.

Effects of early oral feeding after radical total gastrectomy in gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is a heavy burden in China. Nutritional support for GC patients is closely related to postoperative rehabilitation. However, the role of early oral feeding after laparoscopic radical total gastrectomy in GC patients is unclear and high-quality research evidence is scarce. AIM: To prospectively explore the safety, feasibility and short-term clinical outcomes of early oral feeding after laparoscopic radical total gastrectomy for GC patients. METHODS: This study was a prospective cohort study conducted between January 2018 and December 2019 based in a high-volume tertiary hospital in China. A total of 206 patients who underwent laparoscopic radical total gastrectomy for GC were enrolled. Of which, 105 patients were given early oral feeding (EOF group) after surgery, and the other 101 patients were given the traditional feeding strategy (control group) after surgery. Perioperative clinical data were recorded and analyzed. The primary endpoints were gastrointestinal function recovery time and postoperative complications, and the secondary endpoints were postoperative nutritional status, length of hospital stay and expenses, etc. RESULTS: Compared with the control group, patients in the EOF group had a significantly shorter postoperative first exhaust time (2.48 ± 1.17 d vs 3.37 ± 1.42 d, P = 0.001) and first defecation time (3.83 ± 2.41 d vs 5.32 ± 2.70 d, P = 0. 004). In addition, the EOF group had a significant shorter postoperative hospitalization duration (5.85 ± 1.53 d vs 7.71 ± 1.56 d, P < 0.001) and lower postoperative hospitalization expenses (16.60 ± 5.10 K¥ vs 21.00 ± 7.50 K¥, P = 0.014). On the 5th day after surgery, serum prealbumin level (214.52 ± 22.47 mg/L vs 204.17 ± 20.62 mg/L, P = 0.018), serum gastrin level (246.30 ± 57.10 ng/L vs 223.60 ± 55.70 ng/L, P = 0.001) and serum motilin level (424.60 ± 68.30 ng/L vs 409.30 ± 61.70 ng/L, P = 0.002) were higher in the EOF group. However, there was no significant difference in the incidence of total postoperative complications between the two groups (P = 0.507). CONCLUSION: Early oral feeding after laparoscopic radical total gastrectomy can promote the recovery of gastrointestinal function, improve postoperative nutritional status, reduce length of hospital stay and expenses while not increasing the incidence of related complications, which indicates its safety, feasibility and potential benefits for gastric cancer patients.

microRNA-582 Potentiates Liver and Lung Metastasis of Gastric Carcinoma Cells Through the FOXO3-Mediated PI3K/Akt/Snail Pathway.

BACKGROUND: The dysregulation of microRNA (miRNAs) is broadly participated in cancer progression, resulting in sustained cell proliferation by directly targeting various targets. This study investigated the expression of miR-582 in GC and its association with liver metastasis. METHODS: Firstly, differentially expressed miRNAs in gastric cancer (GC) tissues were predicted by microarray. Then, the relationship between miR-582 and clinical characteristics of GC patients was analyzed. By silencing of miR-582 in GC cells, the change in malignant biological behaviors of GC cells was detected. The upstream lncRNA, downstream targeting genes of miR-582 and the corresponding signaling pathway were predicted by online databases and verified by luciferase reporter assays, RT-qPCR and Western blot analysis. Finally, the effects of miR-582 on the growth and metastasis of GC cells were detected by in vivo tumorigenesis and metastasis tests. RESULTS: MiR-582 was highly expressed in GC tissues and related to the metastasis of patients with GC. Silencing of miR-582 expression blocked malignant biological behaviors of GC cells in vitro and in vivo. MiR-582 inhibited forkhead box protein O3 (FOXO3) to upregulate the PI3K/AKT/Snail signaling pathway in GC cells. Besides, GATA6-AS1 was found as an upstream lncRNA to modulate the expression of miR-582. CONCLUSION: MiR-582 induced by GATA6-AS1 silencing promotes the growth and metastasis of GC cells by targeting FOXO3 to induce the activation of the PI3K/AKT/Snail signaling pathway. MiR-582 could be a potential molecular therapy target for patients with GC.

LncRNA DSCAM-AS1 Promotes Colon Cancer Cells Proliferation and Migration via Regulating the miR-204/SOX4 Axis.

INTRODUCTION: Long non-coding RNA (lncRNA) DSCAM-AS1 was reported to be aberrantly expressed and play pivotal roles in various human cancers. The aim of the present study was to investigate the expression and roles of DSCAM-AS1 in colon cancer (CC). METHODS: Quantitative real-time PCR (qRT-PCR) was used to detect the expression of DSCAM-AS1, miR-204 and the mRNA level of SOX4. Cell proliferation and cell cycle were analyzed by MTT assay and flow cytometry, respectively. Transwell assay was used for migration capacity detection. Luciferase activity assay was conducted to verify the direct binding of DSCAM-AS1 and miR-204 or miR-204 and SOX4. The protein expression of SOX4 was determined by Western blot. Kaplan-Meier curves were calculated and the Log rank test was performed for the survival data analysis. RESULTS: DSCAM-AS1 was significantly upregulated in CC and high expression of DSCAM-AS1 was associated with poor prognosis in patients with colon cancer. Knockdown of DSCAM-AS1 significantly suppressed CC cells proliferation and migration. In addition, DSCAM-AS acted as a molecular sponge for miR-204 and SOX4 was identified as a direct target of miR-204 in CC. Moreover, the rescue assay revealed that miR-204 inhibition partly abolished the effects of DSCAM-AS1 knockdown on CC cells proliferation, migration and SOX4 expression. DISCUSSION: The present study demonstrated that DSCAM-AS1 acted as an oncogenic lncRNA in CC progression by regulating miR-204/SOX4 axis and DSCAM-AS1 may serve as a novel therapeutic target in the treatment of colon cancer.

Laparoscopy versus conventional laparotomy in the management of abdominal trauma: a multi-institutional matched-pair study.

BACKGROUND: Laparoscopy is being increasingly applied as either a diagnostic or therapeutic intervention in the management of abdominal trauma. However, its outcomes in comparison with conventional laparotomy remain unclear, especially in terms of therapeutic management. METHODS: This retrospective cohort study included patients from three trauma centers in Beijing, China. Fifty-four patients undergoing laparoscopic interventions for abdominal trauma by experienced laparoscopists were enrolled in the laparoscopy group (LP group). Another 54 patients who underwent laparotomy (LT group) were matched according to the patients' baseline characteristics, causes of injury, and hemodynamic parameters. Perioperative clinical parameters and short-term survival were compared between these two groups. RESULTS: The baseline characteristics were comparable between these two groups (LP vs. LT: Age, p = 0.112; Sex, p = 0.820; Injury severity score, p = 0.158; Cause distribution, p = 0.840). The most common cause was traffic accident (36.1%) and the most frequent surgical intervention was bowel repair/resection (34.3%) in our study. The operation time was similar in these two groups (LP vs. LT: 202.2 ± 72.58 vs. 194.11 ± 82.95 min, p = 0.295) while post-operative complication rate was slightly reduced in LP group (7.7% vs. 13.5%) with no statistical significance (p = 0.383). Opioid use was lower in the LP than LT group (11.67 ± 4.08 vs. 26.0 ± 13.42 morphine equivalents (MEQ), p = 0.034). The hospital stay was significantly shorter in the LP group (13.48 ± 10.9 vs. 18.64 ± 14.73 days, p = 0.021). One patient in the LT group died of an intra-abdominal abscess and multiple organ dysfunction syndrome 19 days postoperatively, while all patients in the LP group recovered and were discharged. CONCLUSION: Laparoscopy is feasible and safe in treating abdominal trauma patients in hemodynamically stable conditions performed by experienced surgeons. Laparoscopy might have the advantages of reduced pain and quicker recovery with similarly favorable clinical outcomes.

Glucagon-like peptide-1 receptor agonist exendin-4 mitigates lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages.

Macrophages play a critical role in the immune response against pathogen invasion and injury. However, under pathological stress, macrophages could have aberrant roles and contribute to the pathogenesis of inflammatory associated diseases. Exenatide is a glucagon-like peptide 1(GLP-1) agonist, which belongs to the family of synthetic exendin-based incretin mimetic. Exendin related compounds reduce glucose levels in type 2 diabetes patients. The purpose of this study was to examine the anti-inflammatory effects of exendin-4 in LPS-induced activation of macrophages. We show that exendin-4 inhibits LPS-induced expression of inflammatory mediators (iNOS, COX-2, PGE2 and NO) and pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in RAW264.7 macrophages. Exendin-4 pretreatment mitigates LPS induced cellular ROS production. Mechanistically, Exendin-4 suppresses the LPS-induced activation of the JNK and AP-1 pathway. Furthermore, exendin-4 suppresses both nuclear p65 accumulation and transfected NF-κB promoter activity, indicating it inhibits the activation of the NF-κB pathway. Our study demonstrates that the GLP-1 agonist exendin-4 has a potent anti-inflammatory effect independent on its glucose reducing ability, and exendin-4 has the potential implication to treat inflammatory associated diseases.

[Surgical strategy for adenocarcinoma of esophagogastric junction].

The incidence of adenocarcinoma of esophagogastric junction (AEG) has been increasing. The surgical strategy for AEG remains controversial. The Siewert definition of AEG facilitates decision of surgical approach, while TNM stage for AEG contributes to prognosis evaluation and clinical decision making. Generally, transthoracic procedure is suitable for Siewert I and transhiatal is suitable for Siewert III. The lymph node drainage of AEG is characterized by simultaneous drainage to the mediastinal and abdominal lymphatic pathways. The optimal lymphadenectomy depends on the distribution of lymph node metastasis. Reconstruction of the digestive tract requires safety as a precondition, taking into account of postoperative complications and quality of life. For AEG patients undergoing total gastrectomy, Roux-en-Y anastomosis is more common. For those undergoing proximal gastrectomy, esophageal residual stomach (tubular stomach) anastomosis is more common, but the proportion of postoperative reflux esophagitis is higher. Some documents have revealed advantages of minimally invasive laparoscopic operation for AEG, but higher level evidences is needed.

[Comparison of the superiority of different TNM staging systems in Siewert III adenocarcinoma of esophagogastric junction].

OBJECTIVE: To compare the prognostic value of TNM staging systems in the 7th edition and the 8th edition AJCC in Siewert III adenocarcinoma of esophagogastric junction (AEG). METHODS: Data of 160 patients with Siewert III AEG who underwent radical surgery (R0) from January 2009 to January 2013 in PLA General Hospital were collected retrospectively. Exclusion standards:(1)preoperative neoadjuvant chemoradiotherapy;(2)with distant metastasis before or during operation;(3)palliative operation or R1/R2 resection;(4)pathological type as non-adenocarcinoma;(5)number of retrieved lymph nodes less than 16;(6)diagnosed with other malignant tumors concurrently or within 5 years after operation;(7)incomplete clinical or follow-up data. According to the above criteria, 160 patients were included in this study finally. All the patients underwent radical total or proximal gastrectomy by abdominal approach. D1 or D1+ lymph node dissection was performed in early patients and D2 in advanced patients. All the patients were re-staged by the gastric cancer TNM7 (G7), the gastric cancer TNM8 (G8) and the esophageal cancer TNM7(E7). Univariate analysis and Cox regression analysis were performed. Kappa value and Akaike's information criterion (AIC, the less AIC, the better prognosis) value were compared between different staging systems in agreement and predicting prognosis. RESULTS: There were 128 males and 32 females(sex ratio 4:1), and the average age was (60.2±11.6) years and 17 patients with basic disease. Of all the patients, 133 cases (83.1%) underwent radical total gastrectomy and 27 cases (16.9%) underwent proximal gastrectomy. The median number of dissected lymph nodes were 31 and the median number of positive lymph nodes were 4. Multivariate analysis showed that the G7, G8, E7 staging systems were independent prognostic factors (HR=1.374, 1.407 and 1.305 respectively,all P<0.001). Stage migration between G7 and G8 were only observed in IIIA, IIIB and IIIC, and stage migration rate was 8.1% (13/160), and the agreement was very good (weighted Kappa 0.904, P<0.001). However, the difference between G8 and E7 was quite obvious, stage migration rate was 40.6%(65/160), and the agreement between G8 and E7 was not satisfied (weighted Kappa 0.536, P<0.001). AIC value was 811.4 in G8, 812.8 in G7 and 815.9 in E7, respectively. CONCLUSION: Compared with G7 and E7 staging systems, the G8 staging system is superior in predicting the prognosis of patients with Siewert III AEG.

Shikonin induces ROS-based mitochondria-mediated apoptosis in colon cancer.

Colon cancer is the third most common malignancy worldwide, and chemotherapy is a widely used strategy in clinical therapy. Chemotherapy-resistant of colon cancer is the main cause of recurrence and progression. Novel drugs with efficacy and safety in treating colon cancer are urgently needed. Shikonin, a naphthoquinone derived from the roots of the herbal plant Lithospermum erythrorhizon, has been determined to be a potent anti-tumor agent. The aim of the present study was to detect the underlying anti-tumor mechanism of shikonin in colon cancer. We found that shikonin suppressed the growth of colon cancer cells in a dose-dependent manner in vitro and in vivo. Shikonin induced mitochondria-mediated apoptosis, which was regulated by Bcl-2 family proteins. Shikonin increased the generation of intracellular ROS, which played an upstream role in shikonin-induced apoptosis. Our data indicated that generation of ROS, down-regulated expression of Bcl-2 and Bcl-xL, depolarization of the mitochondrial membrane potential and activation of the caspase cascade were components of the programmed event of shikonin-induced apoptosis in colon cancer cells. In addition, shikonin presented minimal toxicity to non-neoplastic colon cells and no liver injury in xenograft models, showing safety in the control of colon cancer cell growth in vitro and in vivo. Taken together, our findings suggest that shikonin might serve as a potential novel therapeutic drug in the treatment of human colon cancer.