Search

Purpose: This study aimed to investigate the effectiveness of postoperative chemotherapy in pT1bN0 and pT2N0 gastric cancer patients with high risk factors., Materials and Methods: Clinicopathological data of gastric cancer patients, who had undergone gastrectomy in high volume centers in Korea and China and were finally diagnosed with pT1bN0 and pT2N0 between 2006 and 2010, were analyzed retrospectively. Survival analyses stratified by risk factors and multivariable analyses were performed., Results: A total of 1509 patients were enrolled, with 41 (2.7%) patients receiving adjuvant chemotherapy after gastrectomy and 1468 (97.3%) patients undergoing surgery alone. The adjuvant chemotherapy group showed higher percentages of tumor with maximal diameter >3 cm (51.2% vs. 25.8%), poor differentiation (68.3% vs. 49.8%), and less harvested lymph nodes (17.1% vs. 5.2%) compared to the surgery alone group. The overall survival rates were 95.1% in the adjuvant chemotherapy group and 93.3% in the surgery alone group, without significant difference. In multivariable analysis, age was found to be an independent prognostic factor. However, there were no difference in the overall survival between patients with risk factors and those without risk factors, even in terms of age. Meanwhile, patients with more than two risk factors who received chemotherapy showed better survival trend, especially for pT2N0 patients, compared to the surgery alone group, although no significant differences were observed., Conclusion: In pT1bN0 and pT2N0 patients, age was found to be an independent prognostic factor. However, adjuvant chemotherapy seemed to be unnecessary, while postoperative chemotherapy might offer survival benefits to pT2N0 patients with more than two risk factors., Competing Interests: Dr. Woo Jin Hyung is a consultant for Ethicon and Verb Surgical, and has grants from Medtronic & GC Pharma and stocks in Hutom. Doctors Kun Yang, Mo-Xi Chen, Yoon Young Choi, Zong-Guang Zhou, Jian-Kun Hu, and Sung Hoon Noh have no conflicts of interest or financial ties to disclose., (© Copyright: Yonsei University College of Medicine 2021.)

Differential expressions and functions of various micoRNAs (miRNAs) have been intensively studied in both colon and rectal cancers. However, the importance of miRNAs on radiotherapy (RT) response and clinical outcome in rectal cancer patients remains unclear. In this study, we used real-time polymerase chain reaction to examine the expressions of miR-302a, miR-105, and miR-888 in normal mucosa and cancer tissue from rectal cancer patients with and without preoperative RT. The biological function of miR-302a, miR-105, and miR-888 expression was further analyzed and identified through the public databases: TCGA (The Cancer Genome Atlas) and GEPIA (Gene Expression Profiling Interactive Analysis). The results showed that the expression of miR-105 in rectal cancer was higher than that in normal mucosa in RT ( P = 0.042) and non-RT patients ( P = 0.003) and was associated with mucinous histological type ( P = 0.004), COX-2 ( P = 0.042), and p73 expression ( P = 0.030). The expression of miR-302a was shown more frequently in cancers with necrosis ( P = 0.033) and with WRAP53 expression ( P = 0.015), whereas miR-888 expression occurred more frequently in tumors with protein the expression of survivin ( P = 0.015), AEG-1 (astrocyte elevated gene-1) ( P = 0.003), and SATB1 (special AT-rich sequence binding protein 1) ( P = 0.036). Moreover, TargetScan also predicted AEG-1 and SATB1 as putative targets for miR-888. The miRNA-gene network analysis showed that ABI2 was associated with all the three miRNAs, with lower expression and good diagnostic value in rectal cancers. The TCGA database demonstrated the association of miR-105 expression with high carcinoembryonic antigen level ( P = 0.048). RT reduced the expressions of miR-302a, miR-105, and miR-888. Prognostic analysis showed that miR-888 expression was independently associated with worse survival of patients without RT [overall survival, P = 0.001; disease-free survival, P = 0.009]. Analysis of biological function revealed that the protein serine/threonine kinase activity and PI3K-AKT signaling pathway were the most significantly enriched functions and pathways, respectively. Our findings suggest that miR-105 is involved in rectal cancer pathogenesis and miR-888 is associated with prognosis. MiR-302a, miR-105, and miR-888 have potential influence on the pathogenesis, RT, and prognosis of rectal cancer., (Copyright © 2020 Meng, Pathak, Zhang, Adell, Jarlsfelt, Holmlund, Wang, Zhang, Zhang, Zhou and Sun.)

Background: Deregulation of HER2 expression could affect the biological characteristics of gastric cancer cells and treatment option for gastric cancer patients. This research aims to investigate the impact of HER2 on biological characteristics of gastric cancer stem cells (GCSCs) and prognosis of gastric cancer patients., Methods: HER2 knockdown in GCSCs were constructed by lentivirus transfection. Alterations of proliferation, self-renewal, invasion, migration, colony formation, and tumorigenicity of GCSCs were examined. The changes of gene expressions after HER2 interference in GCSCs were detected by gene microarray. The impact of concentration of serum HER2 and expression of HER2 in tumor tissues on survival of 213 gastric cancer patients was also analyzed., Results: Down-regulation of HER2 decreased the self-renewal, colony formation, migration, invasion, proliferation, and chemotherapy resistance of GCSCs. However, the tumorigenicity of GCSCs in vivo was increased after down-regulation of HER2. The results of gene microarray showed that HER2 gene might regulate the signal transduction of mTOR, Jak-STAT, and other signal pathways and affect the biological characteristics of GCSCs. Furthermore, survival analyses indicated that patients with high concentration of HER2 in serum had a favorable overall survival. However, there was no significant correlation between expression of HER2 in tumor tissue and overall survival., Conclusion: Interference of HER2 in GCSCs decreased the capacity of self-renewal, proliferation, colony formation, chemotherapy resistance, invasion, and migration but might increase the tumorigenicity in vivo . Patients with high concentration of HER2 in serum seemed to have a favorable prognosis., (Copyright © 2020 Sun, Yang, Wang, Liu, Hou, Lu, Chen, Zhang, Zhou, Mo and Hu.)

Objective: The prognostic significance of serum CA19-9 levels in gastric cancer patients remains a matter debate. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative serum CA19-9 levels in patients with gastric cancer. Methods: A total of 1,046 gastric cancer patients who underwent curative gastrectomy in West China Hospital of Sichuan University from January 2011 to December 2016 were analyzed retrospectively. Patients were categorized by minimum P -value using X-tile, while the baseline confounders for CA19-9 changes were balanced through propensity score matching (PSM). The relationships between CA19-9 changes and other clinicopathologic features were measured. Univariate and multivariate analysis were performed to explore the risk factors associated with survival outcomes. Results: We included 653 patients. Changes in CA19-9 levels significantly correlated with age, tumor size, macroscopic type, histological grade, T stage and TNM stage. Kaplan-Meier curves revealed that patients with CA19-9 changes <20% had significant better overall survival than those with changes more than 20% ( p < 0.001); Cox regression analysis revealed the CA19-9 change ( p = 0.010), gender ( p = 0.031), histological grade ( p = 0.036) and TNM stage ( p < 0.001) were independent risk factors for survival after PSM. Stratification analysis indicated that patients with CA19-9 change more than 20% had worse prognosis that those with CA19-9 change no more than 20% in male ( p = 0.002), poorly differentiated or undifferentiated type ( p = 0.031) and TNM stage III ( p = 0.006). Conclusion: Changes in preoperative and postoperative serum CA19-9 levels were closely associated with clinicopathological traits and was an independent prognostic factor in gastric cancer patients. This parameter may be a reliable marker for prediction of survival., (Copyright © 2020 Song, Liu, Yang, Zhang, Chen, Zhao, Chen, Yang, Zhou and Hu.)

Background: The aim of this systematic review and meta-analysis is to assess the efficacy of adjuvant chemotherapy in patients with stage IIB/C CRC and defective mismatch repair (dMMr) status, and to evaluate what is the determinant risk factor for adjuvant chemotherapy in those patients., Method: A systematic search of PubMed, EMBASE, Web of science, Cochrane Library databases will be performed. All RCTs published in electronic databases from inception to March 19, 2020, with language restricted in English will be included in this review study. Two reviewers will independently perform the Study selection, data extraction, quality assessment, and assessment of risk bias and will be supervised by third party. Outcomes consisted of overall survival, progression-free survival and sufficient information to extract hazard ratios and their 95% confidence intervals and it will be calculated to present the prognostic role of adjuvant chemotherapy in patients with stage IIB/C CRC and dMMR status using Review Manager version 5.3 when there is sufficient available data., Results: The results of this systematic review and meta-analysis will be submitted to a peer-reviewed journal for publication., Conclusion: This study will summarize up-to-date evidence to assess the efficacy of adjuvant chemotherapy in patients with stage IIB/C CRC and dMMR status and provide a scientific and practical suggestions for treatment decision-making., Registration: This protocol has been registered on the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) with a registration number of INPLASY202050019.

Our previous study demonstrated that miR-124 was downregulated in colorectal cancer (CRC) compared with normal mucosa, and the downregulated expression of miR-124 was an independent prognostic factor in CRC patients. However, the function of miR-124 in CRC patients treated with chemotherapy is currently unclear. The aim of this study was to determine the miR-124 expression and its regulative role in oxaliplatin (L-OHP)-based chemotherapy of CRC patients. We observed that low miR-124 expression was correlated with worse overall survival (OS) in the 220 patients who received postoperative chemotherapy of 5-fluorouracil [5-FU]+leucovorin+L-OHP (FOLFOX) or capecitabine+L-OHP (XELOX). miR-124 overexpression promoted L-OHP-induced, but not 5-FU-induced, cytotoxicity and apoptosis in HT29 and SW480 cells. CAPN2 was a direct target of miR-124, and its protein expression was reduced by forced expression of miR-124. miR-124 inhibited tumorigenesis and promoted OS of mice bearing xenograft tumors, especially upon L-OHP treatment. miR-124 also promoted L-OHP-induced apoptosis and restrained CAPN2 protein expression in xenograft tumors. Our results suggest that miR-124 could be considered as both a predictor of L-OHP-based chemotherapy for personalized treatment and a therapeutic target for CRC., (© 2020 The Author(s).)

Background: MRE11 plays an important role in DNA damage response for the maintenance of genome stability, and is becoming a prognostic marker for cancers, including colorectal cancer (CRC). However, the correlations of MRE11 to prognosis and tumor-infiltrating inflammatory cells (TIICs) in different locations of CRC remains unclear. Methods: Among Swedish and TCGA-COREAD patients, we investigated the association of MRE11 expression, tumor-infiltrating inflammatory cells (TIICs) and microsatellite status with survival in right-sided colon cancer (RSCC) and left-sided colon and rectal cancer (LSCRC). The signaling of MRE11-related was further analyzed using weighted gene co-expression network analysis and ClueGO. Results: High MRE11 expression alone or combination of high MRE11 expression with high TIICs was related to favorable prognosis in LSCRC. Moreover, high MRE11 expression was associated with favorable prognosis in LSCRC with microsatellite stability. The relationships above were adjusted for tumor stage, differentiation, and/or TIICs. However, no such evidence was observed in RSCC. Several signaling pathways involving MRE11 were found to be associated with cell cycle and DNA repair in RSCC and LSCRC, whereas, the activation of the immune response and necrotic cell death were specifically correlated with LSCRC. Conclusions: High MRE11 expression is an independent prognostic marker in LSCRC and enhanced prognostic potency of combining high MRE11 with high TIICs in LSCRC, mainly due to differential immune signaling activated by MRE11 in RSCC and LSCRC, respectively., (Copyright © 2020 Fan, Kopsida, Liu, Zhang, Gao, Arbman, Cao, Li, Zhou and Sun.)

Rationale : The sustained and severe endoplasmic reticulum (ER) stress in cancer cells may contribute to apoptotic cell death, thus representing a potential target for cancer therapy. Brigatinib is an anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of ALK-positive non-small-cell lung cancer (NSCLC). However, it remains unclear if brigatinib has alternative model of action to exert antitumor effect in ALK-negative cancers. Methods : ALK-positive NSCLC cells and various human ALK-negative cancer cells, especially human colorectal cancer (CRC) cells were used to examine the tumor suppression effect of brigatinib alone or in combination with autophagy inhibitors in vitro and in vivo . A variety of biochemical assays were conducted to elucidate the underlying mechanisms of brigatinib in CRC cells. Results : Here, we show the significant anti-cancer effect of brigatinib in CRC through induction of apoptosis by sustained ER stress. Mechanistically, brigatinib induces ER stress via promoting the interaction between ubiquitin-specific peptidase 5 (USP5), a deubiquitinase, and oxysterol-binding protein-related protein 8 (ORP8), leading to ORP8 deubiquitination, accumulation and growth inhibition. Furthermore, we find that brigatinib-mediated ER stress simultaneously induces autophagic response via ER-phagy that acts as a protective mechanism to relieve excessive ER stress. As such, combination of brigatinib with autophagy inhibitors significantly enhances the anti-CRC effect of brigatinib both in vitro and in vivo , supporting the repurposing of brigatinib in CRC, independently of ALK. Conclusion : The unearthed new molecular action of brigatinib suggests that therapeutic modulation of ER stress and autophagy might represent a valid strategy to treat CRC and perhaps other ALK-negative cancers., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: The tumor location-modified Lauren classification (mLC) has been proposed recently, but its clinical significance remains under debate. This study aimed to elucidate the clinical relevance of mLC and evaluate its superiority to the Lauren classification (LC) for gastric cancer patients with gastrectomy., Methods: This study retrospectively evaluated 2764 consecutive gastric cancer patients from three comprehensive medical institutions. The patients were categorized into training, inner-validation, and independent validation sets. The relationships between mLC and other clinicopathologic factors were analyzed, and independent prognostic factors were identified. Survival prognostic discriminatory ability and predictive accuracy were compared between mLC and LC using the concordance index (C-index) and Akaike's information criterion (AIC), and a nomogram based on mLC was constructed to compare its prognostic improvement with the tumor-node metastasis (TNM) staging system., Results: A significant association between mLC and gender, age, histologic type, T stage, N stage, and M stage was found. The findings showed that mLC, not LC, is an independent prognostic factor, with a smaller AIC and a higher C-index than LC. The nomogram based on mLC showed a better predictive ability than TNM alone., Conclusions: Compared with LC, mLC, which could be considered a more reliable prognostic factor, may improve the prognostic discriminatory ability and predictive accuracy for gastric cancer patients with gastrectomy.

Objective: To improve the apoptosis/necrosis In vitro model of ascites-induced acute pancreatitic (AP) acinar cells by using the co-culture system and mixed ascites technology for the first time. Furthermore, we compared this improved model with cerulein and cerulein+LPS models, and observed the effects of three models on acinar apoptotic/necrotic-related indicators., Methods: The In vitro cultured rat acinar cells AR42J were divided in four groups: control group (medium+PBS), cerulein group (medium+10 nmol/L cerulein), cerulein+LPS group (medium+10 nmol/L cerulein+10 mg/L LPS) and improved ascites group. In the improved ascites group, the ascites of sodium taurocholate-induced rat model was mixed and added into the co-culture system to stimulated In vitro cultured homogenous acinar cells. The co-culture system was set as follows: the chambers with the pore size of 1 μm were placed in the cultue plate, and the culture medium and mixed ascites were respectively added to the culture plate and the chamber at a ratio of 1:1. The acinar cells in each group were collected after 24 h stimulation. The apoptotic/necrotic rates, the expressions of apoptosis/necrosis related proteins [B-cell lymphoma protein 2 (Bcl-2), Bcl-2-associated X protein (Bax) and receptor interacting protein 1 (RIP1)], and the ultra-structure of acinar cells were detected by flow cytometry, Western blot and transmission electron microscopy (TEM)., Results: The acinar cells in the improved ascites model were mainly characterized by necrosis; compared with the other 3 groups, the apoptosis rate and necrosis rate were both up-regulated, RIP1 and BAX protein expression levels were up-regulated, and Bcl-2 protein was down-regulated. TEM results showed the organelle structure of acinar cells was destroyed, and the cell membrane was degraded in the improved ascites model. Compared with the control group, apoptosis rate of acinar cells in the cerulein and cerulein+LPS models were increased and necrosis rate were not changed. The expression of pro-apoptotic protein Bax was increased, while the expression level of RIP1 was not significantly increased. TEM results showed that in cerulein group and cerulein+LPS group, the chromatin of the cells was condensed into a mass, the cytoplasm was degraded and the cell membrane was intact, showing typical apoptosis characteristics., Conclusion: Compared with cerulein and cerulein +LPS models, which mainly focus on apoptosis of acinar cells and applied to mild acute pancreatitis study, the improved ascites model mainly focuses on the necrosis of acinar cells and is a good model for studying acinar cell necrosis and severe acute pancreatitis., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Background: The prognosis of remnant gastric cancer (RGC) is significantly poor. However, the mechanism and some clinical features of RGC have not been fully understood and are still under debate., Materials and Methods: From January 2000 to January 2014, 90 RGC patients were enrolled in this retrospective study. Patients were divided into two groups according to primary disease. Clinicopathological features and survival outcomes were compared between two groups., Results: A total of 34 (37.8%) patients were diagnosed with remnant gastric cancer following benign disease (RGCB) and 56 (62.2%) were diagnosed with remnant gastric cancer following malignant disease (RGCM). The mean time interval from the primary operation to the development of RGC was 12.5 ± 13.3 years in all RGC patients. The mean time interval in RGCB was significantly longer than that in RGCM (P < 0.01). The 1-, 2-, and 3- year overall survival rates of all patients were 56.1%, 38.2% and 33.2%, respectively. Univariate analysis indicated that tumor size, curability, histology type, serosa invasion, nodal involvement and distant metastasis were prognostic factors for RGC. The multivariate Cox regression analysis revealed that distant metastasis was an independent prognostic factor for RGC., Conclusion: RGC occurred earlier in patients with gastrectomy for primary malignant disease than for primary benign disease, even though the primary disease made no difference to the survival of RGC. Nonetheless, RGC patients experienced dismal overall survival. Therefore, early diagnosis plays a significant role in successfully carrying out curative resection and improving the prognosis for RGC., (Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Studies comparing Billroth-I (B-I) with Roux-en-Y (R-Y) anastomosis are still lacking and inconsistent. The aim of this trial was to compare the quality of life (QoL) of B-I with R-Y reconstruction after curative distal gastrectomy for gastric cancer. A total of 140 patients were randomly assigned to the B-I group (N = 70) and R-Y group (N = 70) with the comparable baseline characteristics. The overall postoperative morbidity rates were 18.6% and 25.7% in the B-I group and R-Y group without significant difference. More estimated blood loss and longer surgical duration were found in the R-Y group. At the postoperative 1 year time point, the B-I group had a higher score in pain, but lower score in global health. However, the R-Y anastomosis was associated with lower incidence of reflux symptoms at postoperative 6 months (P = 0.002) and postoperative 9 months (P = 0.007). The multivariable analyses of variance did not show any interactions between the time trend and grouping. For the results of endoscopic examination, the degree and extent of remnant gastritis were milder significantly in the R-Y group. The stronger anti-reflux capability of R-Y anastomosis contributes to the higher QoL by reducing the reflux related gastritis and pain symptoms, and promotes a better global health.

Background: Obesity has become an epidemic in developing countries including China. The use of bariatric surgery to treat obesity has grown in popularity worldwide, but it is still a new concept in China. This study aims to investigate the trends in bariatric surgery in China., Methods: An electronic search of the MEDLINE, EMBASE, and Chinese National Knowledge Infrastructure was conducted to select studies for this survey., Results: A total of 7779 bariatric procedures were reported from 2001 to 2015, most of which (89.2 %) were performed in the most recent 5 years. Further, 70.9 % of all procedures were performed to treat obesity and related comorbidities, defined as metabolic surgery. The data showed 89.4 % of all operations were performed laparoscopically. The absolute number of bariatric surgeries increased 148.7 times in the last 5 years compared to the 2001-2005 period. The percentage of laparoscopic Roux-en-Y gastric bypasses performed increased from 0 to 62.2 %, and the percentage of laparoscopic sleeve gastrectomies from 0 to 12.7 %. The percentage of laparoscopic adjustable gastric bands increased dramatically from 0 to 73.3 % in the 2006-2010 period, but it dropped quickly to 12.9 % in the 2011-2015 period. Most operations (66.7 %) were conducted in the East area, which is the most developed economic region in China. There was limited surgical innovation or original research reported in China., Conclusions: Bariatric surgery is still at an early stage in China, but is now experiencing an explosive growth. A national registry system needs to be established to record and provide precise data.

Serpina family A member 4 (SERPINA4), also known as kallistatin, exerts important effects in inhibiting tumor growth and angiogenesis in many malignancies. However, the precise role of SERPINA4 in CRC has not been fully elucidated. The present study aimed to investigate the expression of SERPINA4 and its clinical significance in CRC. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses showed that the mRNA and protein expression of SERPINA4 in colorectal cancer (CRC) specimens was significantly decreased than that in adjacent normal mucosa. Immunohistochemistry (IHC) was conducted to characterize the expression pattern of SERPINA4 by using a tissue microarray (TMA) containing 327 archived paraffin-embedded CRC specimens. Statistical analyses revealed that decreased SERPINA4 expression was significantly associated with invasion depth, nodal involvement, distant metastasis, American Joint Committee on Cancer (AJCC) stage, and tumor differentiation. SERPINA4 was also an independent prognostic indicator of disease-free survival and overall survival in patients with CRC. Furthermore, the impact of altered SERPINA4 expression on CRC cells was analyzed with a series of in vitro and in vivo assays. The results demonstrated that SERPINA4 significantly inhibits malignant tumor progression and serves as a novel prognostic indicator and a potential therapeutic target for CRC.

Acute pancreatitis is an inflammatory condition that may lead to multisystemic organ failure with considerable mortality. Recently, resolvin D1 (RvD1) as an endogenous anti-inflammatory lipid mediator has been confirmed to protect against many inflammatory diseases. This study was designed to investigate the effects of RvD1 in acute pancreatitis and associated lung injury. Acute pancreatitis varying from mild to severe was induced by cerulein or cerulein combined with LPS, respectively. Mice were pretreated with RvD1 at a dose of 300 ng/mouse 30 min before the first injection of cerulein. Severity of AP was assessed by biochemical markers and histology. Serum cytokines and myeloperoxidase (MPO) levels in pancreas and lung were determined for assessing the extent of inflammatory response. NF-κB activation was determined by Western blotting. The injection of cerulein or cerulein combined with LPS resulted in local injury in the pancreas and corresponding systemic inflammatory changes with pronounced severity in the cerulein and LPS group. Pretreated RvD1 significantly reduced the degree of amylase, lipase, TNF-α, and IL-6 serum levels; the MPO activities in the pancreas and the lungs; the pancreatic NF-κB activation; and the severity of pancreatic injury and associated lung injury, especially in the severe acute pancreatitis model. These results suggest that RvD1 is capable of improving injury of pancreas and lung and exerting anti-inflammatory effects through the inhibition of NF-κB activation in experimental acute pancreatitis, with more notable protective effect in severe acute pancreatitis. These findings indicate that RvD1 may constitute a novel therapeutic strategy in the management of severe acute pancreatitis., (Copyright © 2016 the American Physiological Society.)

Background/aims: Facing with the high incidence rate and the poor outcomes of the postoperative pulmonary complications (PPCs), we sought to evaluate potential risk factors for developing the PPCs of gastric cancer patients., Methodology: Retrospective study was carried out to analyze consecutive gastric cancer patients who had a preoperative pulmonary function test and underwent gastrectomy in the West China Hospital (January, 2000 - December, 2009). Potential risk factors to the development of the PPCs and the survival outcomes of these patients were also analyzed., Results: Totally, one hundred and twenty four patients (18.1%) were developed the PPCs after gastrectomy. For the development of the PPCs, univariate analysis identified the following risk factors is associated with the development of the PPCs: age ≥ 70 years (p < 0.001); male patients (p = 0.041); FEV1/FVC < 60 (p < 0.001); with the history of pulmonary disease (p < 0.001); hemoglobin < 90g/L (p = 0.025); serum albumin < 35g/L (p = 0.002); combined organoectomy (p = 0.036). Multivariate analysis identified FEV1/FVC < 60 (p = 0.004); with the history of pulmonary disease (p < 0.002); serum albumin < 35g/L (p = 0.004) were risk factors for the incidence of the PPCs., Conclusions: For the early detection of the PPCs, extra attention should be paid to those gastric cancer patients with FEV1/FVC < 60; history of pulmonary disease and .serum albumin < 35g/L.

Background/aims: This study aimed to compare the short and long-term outcomes of hand-assisted laparoscopic gastrectomy (HALG) to those of laparoscopy assisted gastrectomy (LAG)., Methodology: From June 2009 to October 2011, fifteen pairs of patients with gastric carcinoma who underwent LAG or HALG were included for analysis retrospectively. Overall survival, morbidity and mortality, and operative variables were analyzed., Results: The characteristics baselines were comparable between two groups. There was no difference in morbidity or mortality between two groups. There were also no significant differences in terms of mean number of harvested lymph nodes, postoperative hospital stay, intraoperative blood lost volume, operation time, reoperation, intraoperative conversion, mean time to first flatus and mean time to liquid diet intake between the two groups. The median survival months for patients were 28.9 and 31.7 in HALG and LAG group respectively, and the estimated 3 year overall survival rates were 73.3% in HALG group and in 80.0% LAG group without any statistic significant (P=0.779)., Conclusions: There was no difference in overall morbidity and mortality, postoperative recovery or overall survival between the HALG group and LAG group. Well-designed randomized controlled trials should be needed to prove the results further.

Background/aims: The aim of this study was to investigate the association of human epidermal growth factor receptor 2 (HER2) expression with clinicopathological characteristics of resectable gastric cancer patients., Methodology: A total of 394 stage I-III surgical gastric cancer patients who were detected of immunohistochemical (IHC) HER2 expression postoperatively were included in this retrospective study. Association of IHC HER2 over-expression (3+) rate with clinicopathological characteristics was tested by univariate and multivariate analyses., Results: IHC HER2 over-expression rate was 5.1% (95% CI 3.1%-7.7%). By univariate analyses, none of the clinicopathological characteristics was associated with the IHC HER2 over-expression compared to negative expression (0/1+) (p>0.05), with the exception of a higher rate (12.2%) of IHC HER2 (3+) in moderate differentiation subset (p=0.02). However, the multivariate analyses didn’t selected any characteristic as an independent risk factor of IHC HER2 over-expression or the combination of IHC HER2 (2/3+)., Conclusions: IHC HER2 over-expression rate is relatively low among stage I-III gastric cancer patients, and might be generally not associated with clinicopathological characteristics.

The objective of this study is to quantitatively analyze the predictive strength among the conventional serological tumor biomarkers for gastric cancer in Chinese population. Thirty-three hospital-based case-control studies were searched out through Chinese databases and PubMed during 1999-2009. Gastric cancer cases and healthy volunteers or benign gastric diseases controls were detected of any of serological CA724, CA242, CEA, CA199, CA125, or CA153. Areas under the curve (AUC) and optimal Q indexes of summary receiver operating characteristics (sROC) curves were quantitatively compared. The summary positive and negative likelihood ratios (sLR + and sLR-) were pooled. Totally, 2,390 gastric cancer cases and 2,893 controls were analyzed. CA724 and CA242 both had the greatest AUCs (0.88), respectively, followed by the combination CA724 + CEA + CA199 (0.85), CA125 (0.82), CEA (0.80), and CA199 (0.76), but all of them had no statistical significance to CA153 (negative control) by Z tests, possibly due to relatively great standard errors. The results of Q index analyses were similar to those of AUCs, that CA724 and CA242 had the optimal strength. The sLR + of CA724 (16.08, 95 % confidence interval (CI) 7.86-32.86) or CA242 (11.03, 95 % CI 7.12-17.08) was strong to judge the gastric cancer status based on its positive result. The combination of CA724 + CEA + CA199 had the prior sLR- (0.33, 95 % CI 0.25-0.43) to the others. Serological CA724 or CA242 has predictive effect for screening gastric cancer and can be recommended into the screening program of population-based or symptomatic cases. However, prospective epidemiological studies are required before confirmative conclusion.

Objective: To study the safety and survival outcome of surgical management for elderly gastric cancer patients. Methods: Patients proven of gastric cancer who aged ≥80 years during November 2002 to July 2011 were retrospectively analyzed. The detailed information of patients’ characteristics and surgical management was retrieved. Follow-up of overall survival status was performed to analyze the surgical effectiveness., Results: Totally, 92 (48 in surgery and 44 in non-surgery group) out of 187 eligible patients recorded adequate information and analyzed finally. There were 34 patients undergone radical gastrectomy, 6 palliative gastrectomy, 1 gastrojejunostomy and 7 exploratory laparotomy. Median follow-up durations were 25 (9-111) and 28 (8-114) months in surgery and non-surgery groups, respectively (p=0.797). Clinical-pathological T stage and node status were comparable. Clinical-pathological distal metastasis status was 15 and 26 M1 cases for surgery and nonsurgery, respectively (p=0.006). Incidence of postoperative complications and hospital mortality were 25.0% and 2.1%, respectively. The 2-year survival rates of M0 subgroups were 35.7% and 0% for surgery and nonesurgery, respectively (HR=3.98, p=0.022)., Conclusions: The safety of surgery for well-selected ≥ 80-year elderly gastric cancer patients was potentially acceptable and the patients of early or locally advanced diseases could obtain survival benefits by surgery.

Aim: To perform a meta-analysis to quantitatively summarize the evidence for the association between the Notch signaling pathway and gastric cancer (GC)., Methods: An electronic search of the MEDLINE, EMBASE and Chinese National Knowledge Infrastructure, which contain articles published from 1966 onwards, was conducted to select studies for this meta-analysis., Results: Fifteen studies with a total of 1547 gastric cancer cases and 450 controls were included in this meta-analysis. Overall, the expression of Notch1, Notch2, Delta-like 4 and Hes1 was significantly higher in tumor tissues of GC compared to normal tissues. Specifically, stratified analyses showed that significantly increased expression of Notch1 was associated with non-cardia location, > 5 cm size, diffuse type, positive lymphovascular invasion and distal metastasis. Statistically significant higher expression of Notch3 was found in diffuse type GC. Jagged1 was also significantly over-expressed in diffuse type and poor differentiation type of GC. DLL4 was significantly over-expressed in advanced T stage, N stage and TNM stage in GC patients. However, the stratified analysis showed that there was no statistically significant difference in Hes1 expression between different subgroups. Sporadic reports showed that Notch1 and Jagged1 were independent poor prognostic predictors in GC., Conclusion: The Notch signaling pathway plays an important role in tumor progression of gastric cancer.

Background/aims: To investigate a proper preoperative assessment and management of preoperative cardiac, pulmonary and digestive comorbidities in morbidly obese patients undergoing bariatric surgery., Methodology: A general description of comorbidities in bariatric patients was reviewed and a clinical practice path in assessment and management of comorbidities was summarized., Results: Morbidly obese patients frequently carried serious comorbidities in cardiovascular, pulmonary and digestive systems. The most common abnormalities included hypertension, left ventricular wall hypertrophy, ST and T wave abnormalities, obstructive sleep apnea, ventilatory dysfunction, and nonalcoholic fatty liver disease. A routine specialized preoperative evaluation could find the potential abnormality and screen the appropriate patients. Prophylactic treatments obviously reduced the morbidity of peri-operative complications, Conclusion: Comprehensive preoperative evaluation and proper management is essential to appropriately select and prepare bariatric patients, and minimize surgical risk.

Objective: To investigate the effect of down-regulation of Notch1 by Notch1 small interfering RNA (siRNA) on chemosensitivity to gemcitabine in pancreatic cancer cells and its mechanism., Methods: Notch1 siRNA was transfected to pancreatic cancer cell lines AsPC-1, BxPC-3, MIAPaCa-2 and Panc-1. The transfected pancreatic cancer cells were treated with 10 μmol/L gemcitabine in vitro. The relative quantity of Notch1 mRNA of pancreatic cancer cells was detected by real-time PCR. The inhibition rates of gemcitabine-treated cells were evaluated by CCK-8 method. The expression of Bax protein was examined by Western blot, and the caspase 3 activity was detected by CaspACETM assay system kit., Results: The relative quantity of Notch1 mRNA was the highest in BxPC-3 cell line and the lowest in Panc-1 cells. The inhibition rates of gemcitabine treated-cells were significantly higher in Notch1 siRNA transfection groups than in corresponding siRNA control groups (AsPC-1: 67.5±6.7 vs 47.5±6.8; BxPC-3: 90.5±4.4 vs 70.2±4.2; MIAPaCa-2: 80.9±5.7 vs 58.1±6.0; Ps<0.05), with the overexpression of protein Bax. The activity of caspase 3 was also significantly increased in Notch1 siRNA transfection groups compared with corresponding siRNA control groups (AsPC-1: 28.90±2.70 vs 12.82±3.44; BxPC-3: 59.87±6.77 vs 27.27±11.88; MIAPaCa-2: 29.34±4.06 vs 14.59±4.25; P<0.05)., Conclusion: Inhibition of Notch signaling pathway by Notch1 siRNA can enhance chemosensitivity to gemcitabine in pancreatic cancer cells through activating apoptosis activity．

Objective: To explore the effect of DAPT, a gamma-secretase inhibitor on the proliferation of pancreatic cancer cells and its underlying mechanism., Methods: Three human pancreatic cancer cell lines as AsPC-1, BxPC-3 and MIAPaCa-2 were employed for in vitro experiments. Cell proliferation was tested by CCK-8 and cell apoptosis was examined by Annexin V/PI staining after the treatment of various concentrations of DAPT at different time., Results: DAPT of 100 micromol/L significantly inhibited the proliferation of these 3 cell lines from day 3 to 5. DAPT of 50 micromol/L inhibited the proliferation of BxPC-3 and MIAPaCa-2 cells from day 3 to 5, whereas the effect of inhibition was only observed at day 5 in AsPC-I cell. DAPT of 10 micromol/L inhibited the proliferation of BxPC-3 and MIAPaCa-2 cells at day 5, whereas no effect was found in AsPC-1. Flow cytometry test showed that cell apoptosis rate was higher in DAPT treatment groups compared with control group., Conclusion: DAPT could suppress the proliferation of pancreatic cancer cell, with the mechanism of promoting cell apoptosis.

Previous studies from our laboratory identified a number of miRNAs that were aberrantly expressed in colorectal cancer (CRC) tissue. However, their diagnostic and prognostic value in serum has not been fully evaluated. In the present study, we measured the levels of five miRNAs (miR-21, miR-31, miR-92a, miR-18a, and miR-106a) in serum samples from 200 CRC patients, 50 advanced adenoma patients, and 80 healthy controls by real-time quantitative polymerase chain reaction (RT-PCR). In our study, the levels of miR-21 and miR-92a in patients with CRC and advanced adenoma were significantly higher than those in healthy controls (all P < 0.05). MiR-21 yielded an area under the receiver-operating characteristics (ROC) curve (AUC) of 0.802 and miR-92a yielded an AUC of 0.786 in discriminating CRCs from the controls. Additionally, miR-21 and miR-92a yielded an AUC of 0.709 and 0.701, respectively, in discriminating advanced adenomas from the controls. Combined ROC analyses using both miRNAs, revealed an elevated AUC of 0.847 in discriminating CRCs, and an AUC of 0.722 in discriminating advanced adenomas from the controls. In the multivariate Cox proportional hazards analysis, high miR-92a expression in CRC was independently associated with poor survival (P = 0.03; hazard ratio 4.36; 95 % confidence interval = 1.64-11.57). No significant difference was observed in the levels of miR-18a, miR-31, and miR-106a among CRC, advanced adenoma, and control samples. In summary, our data indicate that miR-21 and miR-92a serum levels have potential value for early detection of CRC. Furthermore, miR-92a has prognostic value in CRC patients.

Background/aims: The incidence of acute pancreatitis has been increasing recently. This study aims to elucidatethe role of TRAIL signal pathway in the process of acute pancreatitis., Methodology: Pancreatitis models were constructed by cerulein or cerulein plus lipopolysaccharide. Amylase and lipidase were measured in different groups. The mRNA expression of TRAIL, DR5, DcR1 and DcR2 were studied by means of relative Quantitative-Real-Time PCR. In addition, the expression of TUNEL and Caspase 3 was studied by immunohistochemistry., Results: The establishment of pancreatitis model was successful. There were significant differences of amylase and lipidase in the three groups (p<0.05), with highest in MAP group. The mRNA expression of TRAIL was upregulated in SAP group and downregulated in MAP group. The expressions of DcR1 were detected to be statistically upregulated in MAP group and SAP group. The expressions of DR5 and DcR2 were not significant different from each other among the three groups (p>0.05). There were no siginificant differences among the three groups for the expression of Caspase 3 which indicated the apoptosis of acinar cell. The correlation coefficient between the expression of TUNEL and Caspase 3 was 0.383 (p=0.037)., Conclusions: TRAIL signal pathway might play a role in the process of acute pancreatitis which needs to be explored further.

Background/aims: To evaluate the feasibility and safety of early removal of nasogastric tube after total gastrectomy for gastric cancer., Methodology: Data of 142 gastric cancer patients who underwent total gastrectomy from January 2011 to March 2012 were retrospectively collected and analyzed. Early removal ER group n=57 of nasogastric tube was defined as removal within postoperative 48 h, and conventional placement CP group n=85 of nasogastric tube was defined as removal till flatus and less than 300 cc gastric juice drainage. Outcome measures included postoperative temperature, hospital stay length, days to passage of flatus, days to semi-liquid diet, postoperative complications and mortality., Results: No statistically significant difference was found between the ER group and the CP group in postoperative highest temperature p=0,456 the incidence of temperature over 38.5C p=0,772 postoperative hospital stay length p=0,102 and time to flatus p=0,163 There was no death or reoperation in patients of both groups. There were no significant differences in postoperative complications between the two groups 22,8% vs 30,6%, p=0,309 There was no anastomotic leakage, hemorrhage or stenosis. There was a trend of decreased risk of postoperative pneumonia in the ER group 10,5% vs 21,2% despite no significance p=0,097 CONCLUSIONS: The early removal of nasogastric tube within postoperative 48 h after total gastrectomy is feasible and safe in common practice and might also have a potential benefit in preventing postoperative pneumonia.

Our aim in the present study was to investigate the potential roles of the 78-kDa glucose-regulated protein (GRP78) and the X-linked inhibitor of apoptosis protein (XIAP) in the regulation of apoptosis during cerulein-induced acute pancreatitis (CAP). A rat CAP model was induced by injection of cerulein (50 µg/kg), and the severity of CAP was estimated by measuring serum amylase and lipase, pancreatic edema and histological changes. Pancreatic acinar cell apoptosis was determined by terminal-deoxynucleotidyl-transferase-mediated dUTP nick-end labeling (TUNEL) assay, and the expression of GRP78, XIAP and the apoptotic genes caspase-3, -7 and -9 were determined by real‑time quantitative PCR and western blotting. After induction with cerulein, increased serum amylase and lipase, pancreatic edema, inflammation and apoptosis were observed in CAP rats. Furthermore, the mRNA and protein levels of GRP78 and XIAP were significantly downregulated in CAP rats, while the mRNA levels of caspase-3, -7 and -9, as well as the cell apoptotic index were markedly increased when compared with control rats (P<0.05). The expression of GRP78 and XIAP was negatively correlated with caspase expression in CAP (P<0.05). This study suggests that the downregulation of GRP78 and XIAP were correlated with apoptosis in pancreatic acinar cells, and that this may occur through the regulation of caspase activation during CAP.

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors. Of this family, PPARδ has been implicated in the pathogenesis of colorectal cancer, whereas its exact role is highly controversial as available studies yield conflicting results. Therefore, further studies using powerful and duplicable methods are needed to clarify the functions of PPARδ in colorectal cancer. RNA interference (RNAi) is such a powerful tool for specific suppression of gene expression at the posttranscriptional level. Of available RNAi methods, lentivirus has been shown to mediate RNAi most efficiently and stably based on its remarkable advantages, such as powerful transduction efficiency and a wider range of target cells, integration of expression cassette into host genomics, low immunogenicity and self-inactivated and replication-incompetent after integrating into host genomics. In this chapter, we will introduce the details of using lentivirus-mediated RNAi to specifically knockdown the expression of PPARδ in colon cancer cell lines. This method includes: designing and cloning short-hairpin RNA cassette into lentivector, constructing and titrating lentiviral particles, infecting target cells with lentivirus and assaying the knockdown efficiency.

Rectal cancer is one of the most malignant tumors in gastrointestinal tract, while low rectal cancer with locally advanced stage is the most common type in China. The concept of neo-adjuvant therapy has challenged the traditional treatment strategy for rectal cancer, and has showed encouraging effects in local relapse control, radical resection and sphincter preservation. However, some important issues still remain controversial, including course and dose of radiotherapy, choice of chemotherapy regimen, long-term benefits. This article aims to review and discuss related issues of neo-adjuvant therapy.

Background/aims: To study the potential role of the 78kDa glucose regulated protein (GRP78) in the pathogenesis of acute pancreatitis (AP) in vitro., Methodology: AR42J cells were stimulated by cerulein or cerulein plus lipoplysaccharide (LPS). The severity of pancreatic inflammation was evaluated by amylase, lipase, TNF-a, and IL-6. Apoptosis was determined by flow cytometry; the expressions of apoptotic genes, GRP78 and the downstream molecules were determined by real-time quantitative PCR and Western blot., Results: After cerulein stimulation, the levels of amylase, lipase, TNF-a and IL-6 were all increased, with a more pronounced increase after cerulein plus LPS stimulation. Apoptosis was different in two cell models, high apoptosis in cerulein group; whereas cerulein plus LPS induced relatively less apoptosis. Apoptotic gene expressions revealed more pronounced increase in the cerulein group than those in cerulein plus LPS group. The expressions of GRP78 and downstream molecules were different in two cell models. GRP78 expression was down-regulated in cerulein group and upregulated in cerulein plus LPS group., Conclusions: GRP78 expression was associated with apoptosis and the severity of cerulein-induced pancreatic inflammation, indicating that GRP78 might prevent apoptosis in pancreatic acinar cells thereby deteriorating the severity of AP.

Objective: To design and construct a lentiviral vector containing shRNA against rat glucose-regulated protein 78 gene (GRP78), and to establish rat pancreatic acinar cell line with stable knockdown of GRP78 expression., Methods: Constructed three plasmid expression vectors coding shRNA against GRP78, and converted them into lentiviral particles using three plasmid package systems. Then, AR42J cells were transduced with produced lentiviral particles. The green fluorescent protein (GFP) positive cells were selected by fluorescence-activated cell sorting (FACS), the GRP78 gene mRNA and protein expression were detected by real-time PCR and Western blot., Results: The DNA sequencing showed that the lentiviral vectors containing shRNA against GRP78 gene were constructed correctly. After the transduction, highly efficient transduction (> 85%) of lentivirus in AR42J cells was observed by fluorescent microscopy and FACS. Quantitative real-time PCR showed that GRP78 mRNA expression in AR42J cells was suppressed by LVshGRP78-1, LVshGRP78-2 and LVshGRP78-3 lentivirus about 69.4% +/- 1.42%, 74.7% +/- 1.69% and 86.6% +/- 1.73% as compared with that of the untreated cells (P < 0.05), while LV-Non Target had no significant effect on the GRP78 mRNA level (P > 0.05). Western blot showed that the suppressed effect of LVshGRP78 lentivirus on GRP78 protein was consistent with GRP78 mRNA., Conclusion: The results demonstrated that lentiviral vectors containing the shRNA against GRP78 gene were successfully constructed, which could stably knock down the GRP78 expression in AR42J cells. This study will provide a new cell model for further study of the role of GRP78 in the pathogenesis of acute pancreatitis.

Background/aims: To evaluate the correlation between the expression of stem cell makers and prognosis in colorectal cancer., Methodology: Eligible studies evaluating the correlation between stem cell makers and prognosis were selected based on the references in PubMed, Embase and Cochrane libraries. Outcome measures included overall survival, relevant pathological parameters. Meta-analyses were performed by RevMan 5.0., Results: Seventeen eligible articles involving 3098 patients were included. Meta-analysis showed CD44 expression is not significant difference of 5-year overall survival rate (OR=0.69, p=0.22) and relevant clinical parameters, such as histological grade (OR=1.98, p=0.06), dukes grade (OR=0.77, p=0.43) and metastasis (OR=1.03, p=0.89). Likewise, there is no correlation between CD44v6 and dukes stage (OR=0.56, p=0.23), metastasis (OR= 2.81, p=0.33), except for histological grade (OR=0.48, p=0.02). However, CD44v6 positive cells (OR=0.36, p=0.02) were significantly associated with poor overall survival., Conclusions: Based on current retrospective evidence, a stem cell maker, CD44 cannot become a prognostic marker in colorectal cancer. In contrast, CD44v6, an isoform of CD44 plays a significant role to predict clinic outcome.

The aim of the present study to evaluate the application of sentinel lymph node (SLN) pathology in rectal cancer using ex vivo mapping and to investigate the incidence and prognostic value of occult SLN metastasis in routine node-negative specimens. Specimens (n=117) of rectal cancer were examined using a combination of routine pathology and ex vivo SLN mapping. The inspected SLNs were further treated with immunohistochemical staining for occult cancer foci. The log-rank test was used to assess survival. SLNs were examined in 112 of the included specimens with a total number of 212, resulting in an identification rate of 95.7% (112/117). The status of SLNs accurately reflected N stage in 93.8% (105/112) of cases and the sensitivity was 75.6% (31/41) in detecting nodal metastasis. The accuracy of SLN pathology decreased in cancers of more advanced TNM stages (P=0.001). In 74 cases with routine node-negative (N0) disease, SLN micrometastasis (MIC) and isolated tumor cells (ITC) were examined in 9 and 4 cases, while the remaining 61 were regarded as negative (NEG). The log-rank test revealed poorer disease-free and overall survival of the MIC group compared with the NEG group. However, the findings from the ITC group were not significant compared with those from the MIC and NEG groups. In conclusion, ex vivo SLN pathology is practical and accurate in rectal cancer; however, its utility is limited in cases of advanced disease. Immunohistochemically detected SLN micrometastasis in node-negative cases is therefore a predictor of poorer outcome, and may therefore be listed as a marker for adjuvant therapy.

Background/aims: To study lymph node metastasis and micrometastasis within the mesorectum and lateral pelvic area in lower rectal cancer., Methodology: Specimens of 96 patients, who underwent total mesorectal excision (TME) and lateral lymph node dissection (LLND), were included., Results: An average of 19.4 mesorectal lymph nodes were examined. Horizontally, more than 30 percent of involved lymph nodes were located in the outer layer of the mesorectum. Longitudinally, metastasized lymph nodes were harvested from the distal, paratumoral and proximal mesorectum of 6, 42 and 29 specimens, respectively. Fourteen specimens were observed to have circumferential resection margin involvement, while another 3 had micrometastasis. The average amount of harvested lateral pelvic lymph nodes was 12.1. Most (1052/1159) of the lateral nodes were defined as negative. Fourteen and 11 specimens were examined to contain lateral node metastasis and micrometastasis, respectively. Among regions of the lateral pelvic area, middle rectal root (44%), internal iliac (28%) and obturator (20%) were more likely to be involved by cancer spread., Conclusions: Complete excision of the mesorectum is essential for local clearance of lower rectal cancer. Mesorectal margin involvement and lateral metastasis underlined the limitation of single surgical procedure, thus suggesting the significance of neoadjuvant therapy.

Objective: To design and construct a lentiviral vector containing shRNA against rat myeloid differentiation protein 88 gene (MyD88), and to establish rat pancreatic ductal cell line with stable knockdown of MyD88 expression., Methods: Constructed two plasmid expression vectors coding shRNA against MyD88 and converted them into lentiviral particles using three-plamid package system, named as Lenti-sh MyD88-1 and LentishMyD88-2. Rat pancreatic ductal cell, ARIP were divided into untreated group, Lenti-Non Target group, LentishMyD88-1 and LentishMyD88-2 treated groups, and transduced with corresponding lentiviral particles. The GFP positive cells were selected by fluorescence-activated cell sorting and puromycin, the MyD88 gene silencing efficiency was detected by real-time RT-PCR., Results: After the transduction, we observed highly efficient transduction (reach to 100%) of lentivirus in ARIP cells by fluorescent microscopy and FACS. Quantitative RT-PCR showed that Lenti-shMyD88-1 reduced MyD88 mRNA expression by about 82.73% +/- 1.203% in ARIP cells, and LentishMyD88-2, reduced 75.56% +/- 1.176% as compared with that of the untreated cells (P < 0.05)., Conclusion: The results demonstrated that lentivector containing the short hairpin RNA expression cassette specifically targeting MyD88 (pLVshMyD88-1,-2) were successfully constructed, which could stably knock down the MyD88 expression in ARIP cells. This study finally provided a new and stable cell model for the study of MyD88's function in acute pancreatitis.

Objective: To investigate the expression of apoptosis related gene glycogen synthase kinase-3B (GSK-3B) in acute edematous pancreatitis (AEP), and the relationship between GSK-3B and AEP., Methods: The AEP rat model was established by the injection of caerulein [50 microg/(kg x h)] intraperitoneally per hour for 4 times. There were total 36 rats, every 6 rats were sacrificed at 0 h, 1 h, 3 h, 6 h, 12 h and 18 h after the injection of caerulein. Blood samples were taken from portal vein for ELISA examination of pancreatic amylase and lipase, pancreatic mRNA was extracted for RT-PCR analysis of GSK-3B, caspase-3, 9. The expression of GSK-3B protein was examed by Western blot, and acinar cell apoptosis was measured by TUNEL assay., Results: AEP was successfully induced and pancreatic lesions were most severe at 6 h after the injection of caerulein. Immunohistochemistry assay showed that GSK-3B protein located in cytoplasm of pancreatic acinar cells and endothelial cells, but not in islet cells. The mRNA levels of GSK-3B, caspase-3, 9, the protein level of GSK-3B, as well as cell apoptotic index in AEP rats were significantly increased when compared with the control rats received normal saline. Acinar cell apoptosis index was positively correlated with serum amylase, lipase, ratio of dry/wet of pancreas and GSK-3B mRNA expression, while GSK-3B mRNA level was positively correlated with caspase-3, 9 mRNA expression., Conclusion: The expression levels of GSK-3B mRNA and protein were related to the severity of AEP and acinar cell apoptotic index.

Background: Toll-like receptor 4 (TLR4) plays an important role in the occurrence and development of acute pancreatitis (AP). Apoptosis of pancreatic cells is closely related to the severity of AP. TLR4 is known to induce apoptosis in some cell types and therefore it is of importance to investigate potential associations between TLR4 activity and apoptosis in the setting of AP., Methods: A total of 50 wild-type (C57BL/10J) and TLR4-deficient (C57BL/10ScNJ) mice were divided into three groups: 2-hour, 4-hour, and control groups. Each group was divided into two equal subgroups: TLR4-wild-type mice and TLR4-deficient mice. AP was experimentally induced by 7 intraperitoneal injections of 50 μg/kg cerulein at hourly intervals. Control mice received 7 injections of equal volumes of saline. The severity of pancreatic injury during AP was assessed by serum amylase concentration and histopathology. The level of apoptosis of pancreatic cells in response to AP was evaluated by calculating the apoptotic index (AI) and comparing the expression levels of cytochrome C and Fas-associated protein with death domain (FADD) between TLR4-wild-type and TLR4-deficient mice at 2 time points., Results: The AI was found to be significantly lower in the pancreas of TLR4-deficient mice with AP compared to TLR4-wild-type mice at two hours after the last treatment injection. Enzyme-linked immunosorbent assay and real-time reverse transcription-polymerase chain reaction also revealed significantly lower expression of cytochrome C and FADD in the pancreas of TLR4-deficient mice than in TLR4-wild-type animals at the same time point. Serum amylase concentration and morphological severity of AP in pancreatic tissue were found to be similar in the two strains of mice at both time points., Conclusion: We postulate that TLR4 can mediate apoptosis of pancreatic cells during the early stages of AP, via the activation of both intrinsic and extrinsic apoptotic signaling pathways.

The knowledge of anatomical variations in hepatic artery is of importance to surgeons in planning effective therapeutic strategies for general surgery. Apart from the different source and number variations, the unusual course was also discovered during the angiography and anatomical dissection. The present case report shows a rare case in which the common hepatic artery arising from the celiac trunk, crossed the portal vein, positioning itself at the back of this structure, found in a male patient undergoing distal partial gastrectomy.

Objective: To explore the feasibility and safety of laparoscopic extended gastrectomy through the transhiatal approach in patients with esophagogastric junction cancer., Methods: From Feb 2008 to May 2010, 55 cases with Siewert type II or III esophagogastric junction cancer underwent laparoscopic transhiatal extended gastrectomy at the West China hospital. Clinical data were analyzed retrospectively., Results: Esophagogastric junction cancer was Siewert type II in 36 patients and Siewert type III in 19. Thirty-five cases underwent proximal gastrectomy, 20 total gastrectomy. There were 53 D2 lymph node excisions and 2 palliative resections. Fifty patients underwent laparoscopic extended gastrectomy successfully, with 5 converted to open operations. A safe anastomosis between inferior pulmonary vein and pulmonary hilum was achieved in the majority of patients. The mean operative time was(236.2±35.5) min and the mean estimated blood loss was(60.6±33.9) ml. There were no postoperative mortalities or anastomotic leakage/stenosis. No reoperations were required. Pleural laceration occurred in 11 cases during operation, of whom 10 were repaired intraoperatively and one was managed with drainage postoperatively. There were 3 patients developed pulmonary infection and one wound infection. Postoperative recovery was uneventful in other patients., Conclusion: Laparoscopic transhiatal extended gastrectomy is feasible and safe for patients with esophagogastric junction cancer.

Background: Acute pancreatitis is an acute inflammatory process of the pancreas that frequently involves peripancreatic tissues and at times remote organ systems. For a long time, the etiology and pathogenesis of acute pancreatitis has been intensively investigated worldwide, but the pathogenetic theories are controversial. The integrity of the pancreatic duct-acinar system might play an important role in the pathogenesis of this disease., Data Sources: Web of Science and PubMed databases were searched for published studies (between January 1966 and June 2009) to identify relevant articles using the keywords "acinar hyperstimulation", "pathogenesis", "acute pancreatitis", "pancreatic duct-acinar system", and "pancreatic duct pressure". Most of the relevant articles were reviewed., Results: From critical reading of the relevant articles, we found that the underlying mechanisms involved in the pathogenesis of acute pancreatitis are still under debate and ill-understood. On the basis of the relevant studies, we propose a hypothesis for the pathogenesis of acute pancreatitis, in which the integrity of the pancreatic duct-acinar system plays an essential role in the onset and progression of various forms of the disease., Conclusions: In our hypothesis, pancreatic duct obstruction and hyperstimulation of the exocrine pancreas are preconditions for the onset of acute pancreatitis; under the common conditions of pancreatic duct obstruction and acinar hyperstimulation, acute pancreatitis arises and develops. This may be an important common pathophysiological mechanism causing various forms of acute pancreatitis.

There was no literature reporting the relationship between AKAP13 and colorectal carcinoma. This study is aim to investigate the expression and role of AKAP13 in human colorectal cancers. This study investigated 94 pair-matched human colorectal cancers and adjacent normal mucosa, as well as 36 adenomas, of which mRNA expression of AKAP13 was detected by relative Quantitative-Real-Time RT-PCR and protein expression by immunohistochemical staining. AKAP13 gene was upregulated in colorectal cancer group by 2.259 times compared to control group without significant difference (P = 0.081), and no expression was detected in adenoma by RT-PCR. The positive expression rate of AKAP13 protein in colorectal carcinoma (52.3%) was significantly higher than those in adenoma (9.1%) and normal tissue (34.7%) (P = 0.006) by immunohistochemical staining. Either the mRNA or protein expressions of AKAP13 were correlated with histological types and differentiation grade (P < 0.05). Our results suggest AKAP13 protein may be related to the carcinogenesis of human colorectal cancer. However, more deeply and larger scale research are required to prove the correlation.

Objective: To investigate the expression of microRNA(miR)-21 and miR-125 in colorectal cancer (CRC) and its relationship with clinicopathological features., Methods: Quantitative real-time PCR was applied to examine the expression of miR-21 and miR-125 in 100 primary CRC specimens which were diagnosed and operated in West China Hospital between 2006 and 2007, in comparison with the corresponding normal mucosa specimens. The relationship between the expression of miRNAs and clinicopathological features was analyzed., Results: The expression of miR-21 in CRC was up-regulated by 2.3 times compared to normal mucosa (P =0.025), while the expression of miR-125 was down-regulated by 3.3 times in comparison with normal mucosa (P =0.005). Furthermore, the expression of miR-21 was related to TNM stage (P =0.028) and local invasion (P =0.023). On the other hand, no significant relationship was found between the expression of miR-125 and clinicopathological features (P >0.05)., Conclusion: The over-expression of miR-21 may play a role in the development and progression of CRC, while miR-125 may not be related to the pathogenesis of CRC.

Objective and Design: Toll-like receptor 4 (TLR4) is potentially associated with acute pancreatitis (AP), but its exact role remains controversial. IL-1 receptor-associated kinase 4 (IRAK-4) is a common mediator of Toll-like receptors pathways, with an essential role in transducing downstream signals. This study investigates the potential role of the TLR4 pathway, in particular IRAK-4, in a murine model of AP., Methods: Acute pancreatitis was induced in wild-type and TLR4-deficient mice by intraperitoneal injections of caerulein (50 microg/kg). Pancreatic pathological scores and myeloperoxidase activity were dynamically measured, along with pancreatic TLR4 and IRAK-4 mRNA and protein., Results: In wild-type mice, pathological scores and myeloperoxidase activity were rapidly increased at 1, 2 and 4 h, followed by alleviation at 12 and 24 h. In TLR4-deficient mice, they were slightly increased within 2 h, but became more severe at 12 and 24 h. IRAK-4 mRNA and protein were significantly down-regulated at 1, 2 and 4 h in wild-type mice. Unexpectedly, TLR4-deficient mice showed more profound reductions of IRAK-4 mRNA and protein at the same time., Conclusions: TLR4 deficiency delayed the initiation of pancreatitis, implying a potential role for TLR4 during AP. IRAK-4 might function during AP, but independently of TLR4.