Gastrosplenic Fistula and/or Splenic Abscess: A Rare and Refractory Complication Following Sleeve Gastrectomy.

Splenic abscess is a rare complication often associated with sleeve gastrectomy (SG) due to factors including local infections, distant infections, tumors, ischemia, and trauma, which presents substantial challenges. We report four cases of gastrosplenic fistula and/or splenic abscess after SG. Patient data, including demographics, comorbidities, diagnostic procedures, treatments, and outcomes, were recorded. Surgical techniques for SG adhered to established protocols. Four patients had a male-to-female ratio of 2:2, with an average age of 39.8 years and an average preoperative BMI of 38.9 kg/m2. All patients were readmitted due to recurrent fever and chills caused by splenic abscesses detected on CT scans, with an average admission duration of 16.5 weeks. Treatments varied from fasting and antibiotics to percutaneous drainage and surgical interventions. The average treatment duration post-diagnosis of splenic abscess was 37.25 weeks. Managing gastrosplenic fistula and/or splenic abscess is complex, underscoring the significance of prompt diagnosis and proper treatment. This highlights the need for heightened awareness among healthcare professionals to promptly recognize and manage this rare complication after SG.

Hand-Sewn Gastrojejunostomy In Situ to Solve Acute Anastomotic Stricture Due to Submucosal Tunneling in Gastric Bypass.

Roux-en-Y gastric bypass (RYGB) is the second most widely used bariatric surgical procedure for morbid obesity and its related comorbidities. Anastomotic stricture is one of the major complications after RYGB. Submucosal tunneling is a rare cause of anastomotic stricture or occlusion, and clinical symptoms will appear soon after surgery. We present our technical suggestions to perform a hand-sewn gastrojejunostomy in situ when the gastric pouch is too small and the tissue is not enough to be resected to solve acute anastomotic stricture due to submucosal tunneling in gastric bypass.

Metabolic and bariatric surgery in China: A summary of the Greater China Metabolic and Bariatric Surgery Database and comparison with other international registry databases.

AIMS: To summarize the Greater China Metabolic and Bariatric Surgery Database (GC-MBD) and to compare patient characteristics and different procedures performed with data from published reports from other international bariatric surgery registries. MATERIALS AND METHODS: Data were extracted from the GC-MBD registry in 2021. Baseline demographic characteristics, obesity-related comorbidities and operational information were analysed. Descriptive comparisons of these data were made with the published reports from four other international/national databases, including the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) registry, the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database of the United States, the National Bariatric Surgical Registry (NBSR) of the United Kingdom, and the Scandinavian Obesity Surgery Registry (SOReg). RESULTS: Fifty-three centres in China registered 6807 cases in the GC-MBD. Compared with published data from the IFSO registry, MBSAQIP, NBSR and SOReg, patients in China undergoing surgery were younger and had a lower body mass index. The incidence of other obesity-related comorbidities, except for gastroesophageal reflux disease, was also higher than in Western countries. Furthermore, more patients underwent sleeve gastrectomy, less revisional bariatric surgery was reported in China, and jejunojejunal bypass with sleeve gastrectomy, uncommon in other countries, was China's second-leading bariatric procedure. CONCLUSIONS: By establishing comprehensive national registries such as the GC-MBD, real-world information can be gathered on clinical practice and patient outcomes. Insights into variations in clinical practice can be identified by comparing reports from different countries, which can help in making and evaluating healthcare policies on the best clinical practices at a national level.

Current status of gastroesophageal reflux disease after sleeve gastrectomy: Still a long way to go.

Obesity is a public health concern that is becoming increasingly more serious around the world. Bariatric surgery has become more prevalent due to the obesity epidemic worldwide. Sleeve gastrectomy (SG) is one of the most popular procedures which is safe and efficient. Despite all its favorable features, however, there is an increasing evidence from the literature that the long-term incidence of gastroesophageal reflux disease (GERD) is likely to represent the Achilles' heel of this procedure. Management of severe reflux after SG usually requires revisional surgery. The relationship between SG and GERD needs to be better ascertained in order to prevent related complications, such as esophageal adenocarcinoma. This review attempts to elucidate the effect of SG on GERD and the postoperative management of reflux disease according to recent literature in the hope of drawing the attention of clinicians to postoperative gastroesophageal reflux and guiding the optimal management strategy associated with this "troublesome complication".

Alterations in the Serum Urate Concentrations after Bariatric Surgery: a Short-Term Prospective Observational Study.

BACKGROUND: Bariatric surgery is associated with a reduced incidence of hyperuricaemia during the long follow-up time. However, few studies have elucidated the alterations in serum urate (SU) levels in the short-term post-surgery period. PURPOSE: To identify the alterations in SU concentrations in individuals with obesity at 1 week, 1 month, and 3 months after bariatric surgery and determine the risk factors for alterations during the first 3 post-surgery months. METHODS: Thirty-four patients were enrolled. Pre- and post-operative variables were collected at baseline and at each follow-up point. A paired t-test was applied to investigate the relationship between the major parameters. A linear mixed model was performed to analyse the variations of SU concentrations with time. RESULTS: Compared with baseline levels, SU levels significantly increased at 1 week, then declined significantly at 1 month after surgery (P < 0.05). At the 3-month follow-up, a significant decrease in SU levels was detected compared with that in baseline levels (P < 0.001). In univariate regression analysis, age, sex, weight, body mass index, triglyceride (TG), total cholesterol (TC), creatinine (Cr), and medications were all risk factors for alterations in SU concentrations post-surgery. In the final model, sex, weight, Cr, age, TC, Cr * age, and Cr * TC were established. CONCLUSIONS: Surgeons should be cognizant of the significant increase in SU levels in the first postoperative week. Alterations in SU concentrations during the first 3 post-operative months were associated with sex, age, weight, Cr, and TC levels at baseline.

Leukemia inhibitory factor promotes gastric cancer cell proliferation, migration, and invasion via the LIFR-Hippo-YAP pathway.

The long-term outcome of gastric cancer (GC) patients remains unsatisfactory despite some recent improvements. Leukemia inhibitory factor (LIF) is a prognostic biomarker for some solid tumors, however its role in GC remains unknown. In this study, we demonstrated that LIF and LIF receptor (LIFR) are overexpressed in GC tissues and established that a correlation exists between them. LIF and LIFR expression are associated with tumor differentiation, lymphovascular invasion, tumor stage, lymph node metastasis, and pTNM stage, indicating that they may be useful prognostic factors. LIF promoted GC cell proliferation, colony formation, invasion, migration, and tumor growth; it also promoted cell cycle progression and inhibited apoptosis; and knocking out the LIFR gene reversed the effects of LIF. LIF inhibited the activity of the Hippo pathway, resulting in reduced phosphorylation of YAP, increased YAP nuclear translocation, and increased cell proliferation. Finally, silencing YAP mRNA expression suppressed cell proliferation. Overall, the results demonstrate that LIF promotes the malignant biological behavior of GC cells through LIFR-Hippo-YAP signaling. LIF may therefore be a useful biomarker for GC.

The Clinical Value and Appropriateness Criteria of Upper Abdominal Magnetic Resonance Examinations in Patients Before and After Bariatric Surgery: a Study of 837 Images.

PURPOSE: The abdominal magnetic resonance (MR) examinations have been increasingly applied in patients with obesity. However, few studies analyzed the appropriateness of this examination. This study is aimed to evaluate the feasibility and clinical value of upper abdominal MR in quantification of visceral/subcutaneous adipose tissue (VAT/SAT) and liver fat fraction (LFF) in patients before and after bariatric surgery. METHODS: All patients who underwent bariatric surgery from November 2017 to November 2019 in the prospectively maintained, IRB-approved database of our institution were queried. The images of all MR studies were retrospectively reviewed and analyzed. RESULTS: In total, 570 patients with 837 upper abdominal MR examinations were analyzed. The VAT/SAT can be clearly visualized and quantified on fat liver acquisition with volume acceleration-flexible (LAVA-Flex) sequence. The present rate of a single axial slice at the level of the L1-L2 intervertebral disc was 93.1% (779/837). The LFF could be quantitatively evaluated on all of the proton density fat fraction (PDFF) maps (100%, 837/837). Occasional findings may include cholelithiasis, cysts, hepatic hemangioma, and renal angiomyolipoma, which can be clearly diagnosed by MR. CONCLUSION: The upper abdominal MR is featured by well feasibility and clear clinical value when applying in patients with obesity. We can use the results to do clinical research and evaluate obesity-related disease risks before and after surgery, thus providing suggestions to choose the type of surgery for patients with different risk levels in the future. MR scanning including fat LAVA-Flex images with the inclusion of L1-L2 level and PDFF measurements is suggested for the VAT/SAT/LFF quantification. TRIAL REGISTRATION: NCT03520699.

Laparoscopic Proximal Gastrectomy Versus Laparoscopic Total Gastrectomy for Proximal Gastric Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: To compare laparoscopic proximal gastrectomy (LPG) and laparoscopic total gastrectomy (LTG) with regard to outcomes, including efficacy and safety, in patients with proximal gastric cancer. METHODS: Original English-language articles comparing LPG and LTG for proximal gastric cancer up to November 2019 were systematically searched in the Embase, PubMed, Cochrane Library, Web of Knowledge, and ClinicalTrials.gov databases by two independent reviewers. Our main endpoints were surgery-related features (operation time, blood loss, harvested lymph nodes, and postoperative hospital stay), postoperative complications (anastomotic leakage, anastomotic bleeding, anastomotic stenosis, and reflux esophagitis), and oncologic outcomes (5-year overall survival and recurrent cancer). RESULTS: Fourteen studies including a total of 1,282 cases (510 LPG and 772 LTG) were enrolled. Fewer lymph nodes were harvested (WMD = -13.33, 95% CI: -15.66 to -11.00, P < 0.00001) and more postoperative anastomotic stenosis (OR = 2.03, 95% CI: 1.21 to 3.39, P = 0.007) observed in LPG than LTG. There were no significant differences in other explored parameters between the two methods. However, based on a subgroup analysis of digestive tract reconstruction, LPG with esophagogastrostomy (LPG-EG) had shorter operative time (WMD = -42.51, 95% CI: -58.99 to -26.03, P < 0.00001), less intraoperative blood loss (WMD = -79.52, 95% CI: -116.63 to -42.41, P < 0.0001), and more reflux esophagitis (OR = 3.92, 95% CI: 1.56 to 9.83, P = 0.004) than was observed for LTG. There was no difference between LPG performed with the double tract anastomosis/double-flap technique (DT/DFT) and LTG. CONCLUSION: LPG can be performed as an alternative to LTG for proximal gastric cancer, especially LPG-DT/DFT, with comparable safety and efficacy.

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.

Endothelin-A receptor in gastric cancer and enhanced antitumor activity of trastuzumab in combination with the endothelin-A receptor antagonist ZD4054.

Endothelin-A receptor (ETAR) is overexpressed in cancers and can function through transactivation of the epidermal growth factor receptor. We explored ETAR in gastric cancer and investigated the antitumor effect of trastuzumab in combination with the ETAR antagonist ZD4054. The expression of ETAR was significantly correlated with the expression of vascular endothelial growth factor. Univariate and multivariate analyses further showed that ETAR expression correlated with reduced survival in gastric cancer patients. In vitro, ZD4054 increased the antiproliferative effect of trastuzumab in gastric cancer cell lines. Moreover, the addition of ZD4054 to trastuzumab significantly increased apoptosis in gastric cancer cell lines. In vivo, tumor growth was considerably inhibited by treatment with ZD4054 and trastuzumab, and the tumor volume in the trastuzumab and ZD4054 combination group was smaller than in the other groups. The detection of ETAR could help predict the prognosis of gastric cancer patients. Additionally, this study provides support for the therapeutic use of the combination of ZD4054 and trastuzumab as an anticancer treatment, especially for gastric cancer.

[Corrigendum] Increased expression of Lgr5 is associated with chemotherapy resistance in human gastric cancer.

An interested reader drew to the attention of the Journal that the western blot featured in Fig. 3B of the above paper also appeared as Fig. 3D in the following publication, featuring many of the same authors: Xi HQ, Cai AZ, Wu XS et al: Leucine­rich repeat­containing G­protein­coupled receptor 5 is associated with invasion, metastasis, and could be a potential therapeutic target in human gastric cancer. Br J Cancer 110: 2011­2020, 2014. After having consulted the authors about this matter, they conceded that there was a data sharing violation here, and that the image should not have been reproduced in the above article without having received the prior permission of the British Journal of Cancer. This permission has now been sought after and obtained, and Fig. 3 is reproduced opposite, now including the appropriate credit for the original source of Fig. 3B. The authors apologize to the Editors of the British Journal of Cancer and Oncology Reports, and to the readership for any inconvenience caused. [the original article was published in Oncology Reports 32: 181­188, 2014; DOI: 10.3892/or.2014.3204].

Increased Expression of 58-kDa Microspherule Protein (MSP58) in Human Gastric Cancer Promotes Cell Proliferation and Correlates with Poor Patient Survival.

BACKGROUND: Gastric cancer (GC) is one of the most frequently occurring malignancies with poor prognosis because of its huge heterogeneity and limited available therapeutic options. The nucleolar 58-kDa microspherule protein (MSP58) is involved in a variety of cellular processes. Though MSP58 was identified as a candidate oncogene in many cancer types, it has both oncogenic and tumor suppressive properties. The oncogenic effect of MSP58 in GC is currently unclear. The present study identified MSP58 expression in GCs and investigated its role in tumor proliferation and patient survival. METHODS: MSP58 expression in GCs was identified using western blotting and immunochemistry methods and correlations with clinicopathological features. Patient survival was calculated by multivariate survival analysis. Small interference RNA transfection, CCK8, and clonogenic assays were performed to investigate the roles of MSP58 in cell proliferation. RESULTS: MSP58 was highly expressed in MGC803, BGC823, and NCI-N87 cell lines compared with normal gastric mucosa cells. The study thus provided evidence that knockdown of MSP58 expression significantly suppressed cell proliferation and colony-forming ability. Immunohistochemical analysis showed MSP58 was highly expressed in 51.5% of GC tissues and in 11.9% of normal corresponding mucosal tissues. Significant positive correlations between MSP58 expression and differentiation grade, depth of invasion, and pathological tumor node metastasis (TNM) stage was further identified. The overall 5-year survival rate for the MSP58-positive group was lower than that of the MSP58-negative group. Depth of invasion, lymph node metastasis, and MSP58 expression were found to be independent prognostic factors. CONCLUSIONS: These findings suggested that MSP58 plays an important role in tumorigenesis and progression and may help predict the prognosis of GC patients.

Ability of Serum C-Reactive Protein Concentrations to Predict Complications After Laparoscopy-Assisted Gastrectomy: A Prospective Cohort Study.

Inflammatory markers, including C-reactive protein (CRP) and white blood cell (WBC), are widely available in clinical practice. However, their predictive roles for infectious complications following laparoscopy-assisted gastrectomy (LAG) have not been investigated. Our aim was to investigate the diagnostic accuracy of CRP concentrations and WBC counts for early detection of infectious complications following LAG and to construct a nomogram for clinical decision-making.The clinical data of consecutive patients who underwent LAG with curative intent between December 2013 and March 2015 were prospectively collected. Postoperative complications were recorded according to the Clavien-Dindo classification. The diagnostic value of CRP concentrations and WBC counts was evaluated by area under the curve of receiver-operating characteristic curves. Optimal cutoff values were determined by Youden index. Univariate and multivariate logistic regression analyses were performed to identify risk factors for complications, after which a nomogram was constructed.Twenty-nine of 278 patients (10.4%) who successfully underwent LAG developed major complications (grade ≥III). CRP concentration on postoperative day 3 (POD 3) and WBC count on POD 7 had the highest diagnostic accuracy for major complications with an area under the curve value of 0.86 (95% confidence interval [CI], 0.79-0.92] and 0.68 (95% CI, 0.56-0.79) respectively. An optimal cutoff value of 172.0 mg/L was identified for CRP, yielding a sensitivity of 0.79 (95% CI, 0.60-0.92) and specificity 0.74 (95% CI, 0.68-0.80). Multivariate analysis identified POD3 CRP concentrations ≥172.0 mg/L, Eastern Cooperative Oncology Group Performance Status ≥1, presence of preoperative comorbidity, and operation time ≥240 min as risk factors for major complications after LAG.The optimal cut-off value of CRP on POD3 to predict complications following LAG was 172.0 mg/L and a CRP-based nomogram may contribute to early detection of complications after LAG.

Palliative Therapy for Gastric Outlet Obstruction Caused by Unresectable Gastric Cancer: A Meta-analysis Comparison of Gastrojejunostomy with Endoscopic Stenting.

BACKGROUND: Gastrojejunostomy (GJJ) and endoscopic stenting (ES) are palliative treatments for gastric outlet obstruction (GOO) caused by gastric cancer. We compared the outcomes of GJJ with ES by performing a meta-analysis. METHODS: Clinical trials that compared GJJ with ES for the treatment of GOO in gastric cancer were included in the meta-analysis. Procedure time, time to resumption of oral intake, duration of hospital stay, patency duration, and overall survival days were compared using weighted mean differences (WMDs). Technical success, clinical success, procedure-related mortality, complications, the rate of re-obstruction, postoperative chemotherapy, and reintervention were compared using odds ratios (OR s). RESULTS: Nine studies were included in the analysis. Technical success and clinical success were not significantly different between the ES and GJJ groups. The ES group had a shorter procedure time (WMD = -80.89 min, 95% confidence interval [CI] = -93.99 to -67.78,P < 0.001), faster resumption of oral intake (WMD = -3.45 days, 95% CI = -5.25 to -1.65,P < 0.001), and shorter duration of hospital stay (WMD = -7.67 days, 95% CI = -11.02 to -4.33,P < 0.001). The rate of minor complications was significantly higher in the GJJ group (OR = 0.13, 95% CI = 0.04-0.40,P < 0.001). However, the rates of major complications (OR = 6.91, 95% CI = 3.90-12.25,P < 0.001), re-obstruction (OR= 7.75, 95% CI = 4.06-14.78,P < 0.001), and reintervention (OR= 6.27, 95% CI = 3.36-11.68,P < 0.001) were significantly lower in the GJJ group than that in the ES group. Moreover, GJJ was significantly associated with a longer patency duration (WMD = -167.16 days, 95% CI = -254.01 to -89.31,P < 0.001) and overall survival (WMD = -103.20 days, 95% CI = -161.49 to -44.91, P= 0.001). CONCLUSIONS: Both GJJ and ES are effective procedures for the treatment of GOO caused by gastric cancer. ES is associated with better short-term outcomes. GJJ is preferable to ES in terms of its lower rate of stent-related complications, re-obstruction, and reintervention. GJJ should be considered a treatment option for patients with a long life expectancy and good performance status.

LKB1 inhibits the proliferation of gastric cancer cells by suppressing the nuclear translocation of Yap and ß-catenin.

Liver kinase B1 (LKB1) is known to suppress the proliferation, energy metabolism and mesenchymal transition of various cancer cells, and is involved in the regulation of Hippo-Yes-associated protein (Yap) and the Wnt/ß-catenin signaling pathways. However, the role of LKB1 in gastric cancer (GC) was not fully understood. Thus, in the present study, we studied LKB1 and found that protein expression (0.37±0.061 vs. 0.59±0.108, P=0.006) and the protein ratio of p-Yap/Yap (0.179±0.085 vs. 0.8±0.126, P=0.001) were reduced in 54 gastric adenocarcinoma (GAC) tissues compared with the matched adjacent non-cancerous tissues, using western blotting and RT-qPCR assays. LKB1 expression was also observed decreased in 109 GAC tissues compared with 54 adjacent non-cancerous tissues (χ2=4.678, P=0.0306), and negatively correlated with the nuclear expression of Yap (r=-0.6997) and ß-catenin (r=-0.3510), using immunohistochemical analysis. In GC patients, LKB1 expression was negatively associated with tumor size, tumor infiltration, lymph node metastasis and the TNM stage. LKB1 expression was determined to be positively correlated with longer overall survival of GC patients using Kaplan-Meier analysis (P=0.001). Subsequently, LKB1 expression in human GAC AGS cells was enhanced with a full­length LKB1 transfection. In vitro and in vivo proliferation was inhibited in LKB1-overexpressing GC cells compared with the control cells. Yap and ß-catenin expression were assessed by western blotting and RT-qPCR, and were found to be increased in the cytoplasm but decreased in the nucleus in LKB1-overexpressing GC cells compared with the control cells. The increase in cytoplasmic ß-catenin was reversed by the silencing of LKB1 or Yap with shRNAs in LKB1-overexpressing GC cells. Moreover, Yap and ß-catenin mRNA were barely altered by LKB1 overexpression. Thus, we concluded that LKB1 expression was reduced in GAC tissues but that it correlated positively with better prognosis for GC patients. LKB1 inhibits the proliferation of GC cells by suppressing the nuclear translocation of Yap and ß-catenin.

The Role of No. 10 Lymphadenectomy for Advanced Proximal Gastric Cancer Patients Without Metastasis to No. 4sa and No. 4sb Lymph Nodes.

BACKGROUND: There is no consensus in the impact of No. 10 lymph node dissection (LND) for advanced proximal gastric cancer (APGC) and the status of negative No. 4sa and No. 4sb lymph nodes (No. 4s LNs) is reportedly associated with no metastasis to No. 10 LN. We aimed to evaluate the role of No. 10 LND in APGC patients with negative No. 4s LNs and the diagnostic accuracy of intraoperative pathologic examination. METHODS: We analyzed data on 727 patients with APGC who had undergone D2 lymphadenectomy with No. 10 LND (n = 380) or without No. 10 LND (n = 347) between January 2005 and December 2010. Additionally, from January to July 2014, we prospectively enrolled 48 patients with APGC and examined their No. 4s LNs intraoperatively. RESULTS: The negative predictive efficacy of No. 4s LN status for no metastasis to No. 10 LN was 98.09 %. Operation time, blood loss, time to first solid diet, hospital stay, and postoperative complication rate differed significantly between patients with negative No. 4s LNs who underwent No. 10 LND (n = 260) and those who did not undergo No. 10 LND (n = 243). Differences between the two groups in 5-year overall and disease-free survival were not statistically significant. The sensitivity, specificity, and accuracy of intraoperative pathological examination of LNs were 93.42, 96.56, and 95.86 %, respectively. CONCLUSIONS: The No. 10 lymphadenectomy may not be recommended in patients with APGC who are found by intraoperative pathological examination to have negative No. 4s LNs.

Fat4 suppression induces Yap translocation accounting for the promoted proliferation and migration of gastric cancer cells.

Fat4 functions as a Hippo signaling regulator which is involved in mammalian tissue development, differentiation and tumorigenesis. Loss of Fat4 due to frequent gene mutation was detected in a variety of tumors including gastric cancer, where Fat4 was recognized as a tumor suppressor, repressing cancer cell proliferation and adhesion. However, the detailed mechanisms linking Fat4 to its diverse functions and clinicopathological characteristics in gastric cancer remain unclear. Here, we silenced Fat4 using Fat4-shRNA in gastric cancer cells and found that this suppression led to the increase in phosphorylated Yap and nuclear accumulation of Yap, which associated to the promoted proliferation, migration and cell cycle progression. Then we transfected a full-length Fat4 into the Fat4-silenced cells, and found the decrease in phosphorylated Yap and inhibition of the cell cycle progression. Intriguingly, Fat4 reduction also leads to the accumulation of cytoplasmic ß-catenin via the loss of restraining to cytoplasmic Yap instead of ß-catenin transcription promotion. The Fat4-silenced cells which were treated with 5-FU, Cisplatin, Oxaliplatin and Paclitaxel individually demonstrated less sensitivities to these chemotherapy drugs compared with the control cells. Furthermore, immunohistochemical analysis revealed that Fat4 expression was significantly reduced in gastric cancer tissues compared with adjacent noncancerous tissues, and negatively correlated with tumor infiltration, lymph node metastasis and cumulative survival rate. In conclusion, Fat4 expression is deceased in gastric cancer cells, leading to nuclear translocation of Yap and correlates with poor prognosis.

Robotic versus laparoscopic gastrectomy for gastric cancer: comparison of short-term surgical outcomes.

BACKGROUND: Robot-assisted gastrectomy (RAG) is a new minimally invasive surgical technique for gastric cancer. This study was designed to compare RAG with laparoscopy-assisted gastrectomy (LAG) in short-term surgical outcomes. METHODS: Between October 2011 and August 2014, 423 patients underwent robotic or laparoscopic gastrectomy for gastric cancer: 93 RAG and 330 LAG. We performed a comparative analysis between RAG group and LAG group for clinicopathological characteristics and short-term surgical outcomes. RESULTS: RAG was associated with a longer operative time (P < 0.001), lower blood loss (P = 0.001), and more harvested lymph nodes (P = 0.047). Only three patients in LAG group had positive margins, and R0 resection rate for RAG and LAG was similar (P = 0.823). The RAG group had postoperative complications of 9.8 %, comparable with those of the LAG group (P = 0.927). Proximal margin, distal margin, hospital stay, days of first flatus, and days of eating liquid diet for RAG and LAG were similar. In the subgroup of serosa-negative patients, RAG had a longer operation time (P = 0.003), less intraoperative blood loss (P = 0.005), and more harvested lymph nodes (P = 0.04). However, in the subgroup of serosa-positive patients, RAG had a longer operation time (P = 0.001), but no less intraoperative blood loss (P = 0.139) and no more harvested lymph nodes (P = 0.139). Similarly, in the subgroup of total gastrectomy patients, RAG had a longer operation time (P = 0.018), but no less intraoperative blood loss (P = 0.173). CONCLUSIONS: The comparative study demonstrates that RAG is as acceptable as LAG in terms of surgical and oncologic outcomes. With lower estimated blood loss, acceptable complications, and radical resection, RAG is a promising approach for the treatment of gastric cancer. However, the indication of patients for RAG is critical.

Serum HER2 Is a Potential Surrogate for Tissue HER2 Status in Gastric Cancer: A Systematic Review and Meta-Analysis.

Determining the expression level of human epidermal growth factor receptor 2 (HER2) in tumor tissue is of great importance for personalized therapy in gastric cancer. Although several studies have investigated whether serum HER2 can serve as a surrogate for tissue HER2 status, results have been inconsistent. We therefore performed a meta-analysis of published clinical studies in an attempt to address this problem. PubMed, Embase, Web of Science, the Cochrane Library and Science Direct were queried for eligible studies that could provide sufficient data to construct 2 × 2 contingency tables. The quality of the studies included in the meta-analysis was assessed in accordance with the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. The pooled sensitivity, specificity and diagnostic odds ratio (DOR) were calculated for the eligible studies. The summary receiver operating characteristic (SROC) curve was constructed and the area under the SROC (AUSROC) was used to evaluate overall diagnostic performance. Eight studies comprising a total of 1170 participants were included in our meta-analysis. The pooled sensitivity, specificity and DOR were 0.39 (95% CI: 0.21-0.61), 0.98 (95% CI: 0.87-1.00), and 27 (95% CI: 9-81), respectively. The AUSROC was 0.77 (95% CI: 0.73-0.80) and Deeks funnel plot suggested the absence of publication bias (p = 0.91). Meta-regression analysis indicated that threshold effect was the main source of heterogeneity. Assays for evaluating serum HER2 levels are highly specific and demonstrate moderate diagnostic performance for HER2 tissue status in gastric cancer.

Increased expression of Lgr5 is associated with chemotherapy resistance in human gastric cancer.

Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5), a marker of adult stem cells and cancer stem cells, plays important roles in tumor progression. Furthermore, Lgr5 also contributes to chemoradiotherapy resistance. However, the function of Lgr5 in the prediction of preoperative chemotherapy efficacy has not been reported. We evaluated the potential of Lgr5 in predicting tumor response and overall survival in advanced gastric cancer treated with preoperative chemotherapy. The association between Lgr5 and chemotherapy resistance was also investigated in gastric cancer cell lines. Hematoxylin and eosin staining and immunohistochemical analysis of Lgr5 expression were performed in 68 cases of gastric cancer treated with preoperative chemotherapy. Lgr5 expression was specifically silenced in the AGS gastric cancer cell lines by RNA interference. Levels of Lgr5 mRNA and protein in cell lines were detected by quantitative reverse transcription-polymerase chain reaction or western blotting. Cell viability was evaluated by an MTT assay. Cell apoptosis was assessed by Annexin V-FITC/propidium iodide dual staining analysis. We found that Lgr5 expression was significantly associated with tumor regression grade after preoperative chemotherapy. The rate of positive Lgr5 expression was significantly higher in patients with poor tumor regression compared with those exhibiting tumor regression (P=0.001). Lgr5-positive patients had a significantly shorter survival time than Lgr5-negative patients (P=0.001). Inhibition of Lgr5 expression with small interfering RNA increased the sensitivity of AGS gastric cancer cells to chemotherapy. Our findings suggest that Lgr5 expression may be implicated in the chemoresistance of gastric cancer cells and is a potential novel biomarker for predicting response to chemotherapy and prognosis in gastric cancer patients, and may also represent a potential new therapeutic target for cancer therapy.