Th17 Cells Secrete TWEAK to Trigger Epithelial-Mesenchymal Transition and Promote Colorectal Cancer Liver Metastasis.

Liver metastasis is the leading cause of mortality in patients with colorectal cancer. Given the significance of both epithelial-mesenchymal transition (EMT) of tumor cells and the immune microenvironment in colorectal cancer liver metastasis (CRLM), the interplay between them could hold the key for developing improved treatment options. We employed multiomics analysis of 130 samples from 18 patients with synchronous CRLM integrated with external datasets to comprehensively evaluate the interaction between immune cells and EMT of tumor cells in liver metastasis. Single-cell RNA sequencing analysis revealed distinct distributions of nonmalignant cells between primary tumors from patients with metastatic colorectal cancer (mCRC) and non-metastatic colorectal cancer, showing that Th17 cells were predominantly enriched in the primary lesion of mCRC. TWEAK, a cytokine secreted by Th17 cells, promoted EMT by binding to receptor Fn14 on tumor cells, and the TWEAK-Fn14 interaction enhanced tumor migration and invasion. In mouse models, targeting Fn14 using CRISPR-induced knockout or lipid nanoparticle-encapsulated siRNA alleviated metastasis and prolonged survival. Mice lacking Il17a or Tnfsf12 (encoding TWEAK) exhibited fewer metastases compared with wild-type mice, while cotransfer of Th17 with tumor cells promoted liver metastasis. Higher TWEAK expression was associated with a worse prognosis in patients with colorectal cancer. In addition, CD163L1+ macrophages interacted with Th17 cells, recruiting Th17 via the CCL4-CCR5 axis. Collectively, this study unveils the role of immune cells in the EMT process and identifies TWEAK secreted by Th17 as a driver of CRLM. SIGNIFICANCE: TWEAK secreted by Th17 cells promotes EMT by binding to Fn14 on colorectal cancer cells, suggesting that blocking the TWEAK-Fn14 interaction may be a promising therapeutic approach to inhibit liver metastasis.

The value of a deep learning image reconstruction algorithm in whole-brain computed tomography perfusion in patients with acute ischemic stroke.

Background: Computed tomography perfusion (CTP) and computed tomography angiography (CTA) are valuable tools for diagnosing acute ischemic stroke (AIS). It is essential to obtain high-quality CTP and CTA images in short time. This study aimed to evaluate the image quality and diagnostic performance of brain CTP and CTA images generated from CTP reconstructed by a deep learning image reconstruction (DLIR) algorithm on patients with AIS. Methods: The study prospectively enrolled 54 patients with suspected AIS undergoing non-contrast CT and CTP within 24 hours. CTP datasets were reconstructed with three levels of adaptive statistical iterative reconstruction-Veo algorithm [ASIR-V 0% with filtered back projection (FBP), ASIR-V 40%, and ASIR-V 80%] and three levels of DLIR, including low (DLIR-L), medium (DLIR-M), and high (DLIR-H). CTA images were generated using the CTP datasets at the peak arterial phase. Objective parameters including signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and noise reduction rate. Subjective evaluation was assessed according to Abels scoring system. Perfusion parameters and detection accuracy for infarction core lesions were evaluated. The objective and subjective image quality of CTA images were also evaluated. Results: All reconstructions produced similar CT values (P>0.05). With the increase of ASIR-V and DLIR reconstruction strength, image noise decreased, while SNR and CNR increased for CTP images, especially in white matter. DLIR-H, DLIR-M, and ASIR-V80% yielded higher subjective scores than did ASIR-V40% and FBP. DLIR-H provided the highest noise reduction rate and detection accuracy. No significant difference was found in conventional parameters, the volume of infarct core, or ischemic penumbra among the 6 groups (P>0.05). The objective evaluation of reconstructed CTA images was comparable in DLIR-H, DLIR-M, and ASIR-V80% (P>0.05). The subjective scores of the DLIR-H and DLIR-M images were higher than those of the other groups, especially ASIR-V40% and FBP (P<0.05). Conclusions: Compared with FBP and ASIR-V40%, DLIR-H, DLIR-M, and ASIR-V80% improved the overall image quality of CTP and CTA images to varying degrees. Furthermore, DLIR-H and DLIR-M showed the best performance. DLIR-H is the best choice in diagnosing AIS with improved detection accuracy for cerebral infarction. Reconstructing CTA images using CTP datasets could reduce contrast agent and radiation dose.

TRIM52 aggravated inflammation and pyroptosis in dextran sulfate sodium-induced inflammatory bowel disease through activation of the TLR4/NF-κBs pathway.

INTRODUCTION: Inflammatory bowel disease (IBD), which mainly leads to diarrhea, fatigue, stool blood, abdominal pain, and cramping, is threatening public health. Tripartite motif-containing 52 (TRIM52) has been reported to play an important role in inflammatory responses via activating the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway. However, the causes of IBD need to be elucidated, and the function of TRIM52 in IBD remains unclear. Here, we demonstrated that TRIM52 aggravated inflammation and pyroptosis in dextran sulfate sodium (DSS)-induced IBD by activating TLR4/NF-κBs pathway. METHODS: The colitis model was established on mice through DSS induction. For the TRIM52 knockdown, the mice were infected with a recombinant adenoviral vector expressing sgRNAs targeting TRIM52. RT-qPCR, western blot, and immunohistochemistry were performed to verify TRIM52 expression in DSS-induced IBD. The body weight, disease activity index, colon length, and H&E staining were used to assess the IBD symptoms in mice with TRIM52 knockdown. The inflammatory responses were examined by RT-qPCR and ELISA measuring tumor necrosis factor-α (TNF-α), inter-leukin 6 (IL-6), and interleukin 1ß (IL-1ß). Furthermore, the pyroptosis in colon tissue was detected by western blot. Finally, the TLR4/NF-κBs pathway activity was also examined by western blot. RESULTS: TRIM52 expression was up-regulated in DSS-induced IBD, and knockdown of TRIM52 could alleviate the symptoms of IBD. TRIM52 knockdown retarded DSS-induced inflammatory response and inhibited DSS-induced pyroptosis in colon tissue. In addition, TRIM52 played a role in activating TLR4/NF-κBs pathway. CONCLUSION: Knockdown of TRIM52 alleviated inflammation and pyroptosis in IBD by regulating TLR4/NF-κBs pathway. TRIM52 is expected to be a novel diagnostic indicator for IBD and a target of therapeutic treatment.

An In Vitro Study on Extracellular Vesicles From Adipose-Derived Mesenchymal Stem Cells in Protecting Stress Urinary Incontinence Through MicroRNA-93/F3 Axis.

Since the potential roles of extracellular vesicles secreted by adipose-derived mesenchymal stem cells (ADSCs) are not well understood in collagen metabolism, the purpose of this research was to evaluate the effects of ADSCs-extracellular vesicles in stress urinary incontinence and the regulatory mechanism of delivered microRNA-93 (miR-93). ADSCs were isolated and cultured, and ADSCs-extracellular vesicles were extracted and identified. Stress urinary incontinence primary fibroblasts or satellite cells were treated with ADSCs-extracellular vesicles to detect the expression of Elastin, Collagen I, and Collagen III in fibroblasts and Pax7 and MyoD in satellite cells. After transfecting ADSCs with miR-93 mimics or inhibitors, extracellular vesicles were isolated and treated with stress urinary incontinence primary fibroblasts or satellite cells to observe cell function changes. The online prediction and luciferase activity assay confirmed the targeting relationship between miR-93 and coagulation factor III (F3). The rescue experiment verified the role of ADSCs-extracellular vesicles carrying miR-93 in stress urinary incontinence primary fibroblasts and satellite cells by targeting F3. ADSCs-extracellular vesicles treatment upregulated expression of Elastin, Collagen I, and Collagen III in stress urinary incontinence primary fibroblasts and expression of Pax7 and MyoD in stress urinary incontinence primary satellite cells. miR-93 expression was increased in stress urinary incontinence primary fibroblasts or satellite cells treated with ADSCs-extracellular vesicles. Extracellular vesicles secreted by ADSCs could deliver miR-93 to fibroblasts and then negatively regulate F3 expression; ADSCs-extracellular vesicles could reverse the effect of F3 on extracellular matrix remodeling in stress urinary incontinence fibroblasts. miR-93 expression was also increased in stress urinary incontinence primary satellite cells treated by ADSCs-extracellular vesicles. Extracellular vesicles secreted by ADSCs were delivered to satellite cells through miR-93, which directly targets F3 expression and upregulates Pax7 and MyoD expression in satellite cells. Our study indicates that miR-93 delivered by ADSCs-extracellular vesicles could regulate extracellular matrix remodeling of stress urinary incontinence fibroblasts and promote activation of stress urinary incontinence satellite cells through targeting F3.

Identification of Candidate Biomarkers and Prognostic Analysis in Colorectal Cancer Liver Metastases.

BACKGROUND: Colorectal cancer (CRC), one of the most common malignant tumors worldwide, has a high mortality rate, especially for patients with CRC liver metastasis (CLM). However, CLM pathogenesis remains unclear. METHODS: We integrated multiple cohort datasets and databases to clarify and verify potential key candidate biomarkers and signal transduction pathways in CLM. GEO2R, DAVID 6.8, ImageGP, STRING, UALCAN, ONCOMINE, THE HUMAN PROTEIN ATLAS, GEPIA 2.0, cBioPortal, TIMER 2.0, DRUGSURV, CRN, GSEA 4.0.3, FUNRICH 3.1.3 and R 4.0.3 were utilized in this study. RESULTS: Sixty-three pairs of matched colorectal primary cancer and liver metastatic gene expression profiles were screened from three gene expression profiles (GSE6988, GSE14297 and GSE81558). Thirty-one up-regulated genes and four down-regulated genes were identified from these three gene expression profiles and verified by another gene expression profiles (GSE 49355) and TCGA database. Two pathways (IGFBP-IGF signaling pathway and complement-coagulation cascade), eighteen key differentially expressed genes (DEGs), six hub genes (SPARCL1, CDH2, CP, HP, TF and SERPINA5) and two biomarkers (CDH2 and SPARCL1) with significantly prognostic values were screened by multi-omics data analysis and verified by Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) cohort. CONCLUSIONS: In this study, we identified a robust set of potential candidate biomarkers in CLM, which would provide potential value for early diagnosis and prognosis, and would promote molecular targeting therapy for CRC and CLM.

CircRPPH1 serves as a sponge for miR-296-5p to enhance progression of breast cancer by regulating FOXP4 expression.

Circular RNAs (circRNAs) have been demonstrated to play critical roles in the initiation and development of breast cancer (BC). This study aimed to uncover the regulatory roles of a novel circRNA, circRPPH1 (hsa_circ_0000514) in BC progression. CircRPPH1, miR-296-5p and FOXP4 levels were determined by qRT-PCR. CircRPPH1 stability was detected in response to ribonuclease (RNase) R digestion and actinomycin D treatment. Cell growth, migration and invasion were evaluated using various functional experiments. Protein levels of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP-9), hexokinase 2 (HK2) and forkhead box protein 4 (FOXP4) were measured by Western blotting. Metabolic alterations of BC cells were evaluated using commercial kits. The interaction between miR-296-5p and circRPPH1/FOXP4 was assessed using dual-luciferase assay, RNA pull-down, and RNA immunoprecipitation (RIP) assay. The in vivo tumorigenesis was assessed in nude mice. According to the results, up-regulation of circRPPH1 was closely correlated with the poor prognosis of BC patients. Functional experiments showed that knockdown of circRPPH1 repressed BC cell growth, migration, invasion, glycolysis, and in vivo tumor growth. In addition, circRPPH1 could sponge miR-296-5p to enhance FOXP4 expression in BC cells. miR-296-5p inhibition or FOXP4 overexpression restored the malignant properties of circRPPH1-silenced BC cells. Thus, circRPPH1 promoted BC malignant progression through regulating miR-296-5p/FOXP4 axis, indicating a possible novel therapeutic strategy involving circRNA for BC patients.

Association between the platelet to lymphocyte ratio, neutrophil to lymphocyte ratio and axillary lymph node metastasis in cT1N0 breast cancer patients.

OBJECTIVE: To investigate the relationship between platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and axillary lymph node metastasis in cT1N0 breast cancer patients. METHODS: The clinicopathological data of 154 patients with cT1N0 breast cancer from January 2015 to June 2020 were retrospectively analyzed. All patients underwent sentinel lymph node (SLN) biopsy. The differences of PLR and NLR levels among groups with different clinicopathological factors (age, tumor size, ER, PR, HER-2, Ki67, p53 expression levels, vascular tumor thrombus and SLN metastasis) were compared. The relationship between clinicopathological factors and metastasis of SLN and non-SLN was analyzed. RESULTS: There were 32 patients with SLN metastasis. The cut-off values of PLR and NLR for the whole group were 142.91 and 2.84. The PLR level was higher in patients with vascular tumor thrombus and SLN metastasis (P<0.05), and the NLR level was higher in patients with P53 negative and SLN metastasis groups (P<0.05). According to univariate analysis, there were significant differences in SLN metastasis among different tumor sizes, vascular tumor thrombus states, PLR and NLR levels (P<0.05), but there was no significant difference in SLN metastasis among patients with different ages, ER, PR, HER-2, Ki67, p53 expression groups (P>0.05). According to multivariate analysis, the risk of SLN metastasis in patients with vascular tumor thrombus was higher than that in patients without vascular tumor thrombus (P<0.05). The risk of SLN metastasis in patients with high level of PLR was higher than that in patients with low level of PLR (P<0.05). The difference was not significant in SLN metastasis status among patients with different ages and ER, PR, HER-2, Ki67, p53 expression and NLR level (P>0.05). CONCLUSION: High level of PLR and vascular tumor thrombus are the risk factors for SLN metastasis.

High expression of lncRNA-SNHG7 is associated with poor prognosis in hepatocellular carcinoma.

Expression of long non-coding RNA SNHG7 (lncRNA-SNHG7) and its clinical significance in hepatocellular carcinoma (HCC) were explored. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of lncRNA-SNHG7 in cancer tissues. Kaplan-Meier curves and multivariate Cox proportional models were used to study the impact on clinical outcome. Expression of lncRNA-SNHG7 was much higher in cancer tissues than that in para-cancer tissues. The lncRNA-SNHG7 expression was correlated with tumor number, lymph node metastasis and clinical stage (P<0.05). In addition, HCC patients with higher lncRNA-SNHG7 expression had significantly poorer progression-free survival time and overall survival time (P<0.001). Both univariate analysis and multivariate analysis indicated that high expression of lncRNA-SNHG7 was an independent predictor of poor prognosis in HCC. LncRNA-SNHG7 might contribute to the development of HCC and serve as a clinical biomarker and a therapeutic target for HCC patients.

Circ-ITGA7 sponges miR-3187-3p to upregulate ASXL1, suppressing colorectal cancer proliferation.

Background: As a class of endogenous noncoding RNAs, some circular RNAs (circRNAs) have recently been reported to play a role in the regulation of tumorigenesis and progression in colorectal cancer (CRC). However, the mechanisms by which most these circRNAs function in CRC are still unclear. Purpose: The objective of this study was to identify the role of circRNA-ITGA7 in CRC cell proliferation. Patients and methods: Human genome-wide circRNA microarray v2 analysis was used for expression profile analysis. Target genes were predicted using online bioinformatics database, including TargetScan, miRDB, miRTarbase and miRMap. Gene overexpression and silencing cell models were built using cell transfection. qRT-PCR and Western blot were performed for gene and protein expression assessment. CCK8, colony formation and cell cycle analysis were used for proliferation testing. Annexin V-FITC analysis was performed for apoptosis detection. Results: CircRNA sequencing analysis suggested that compared to that in adjacent normal control tissue, the expression of circ-ITGA7, a novel circRNA, is decreased significantly in CRC. Gain-of-function studies further demonstrated that circ-ITGA7 suppressed proliferation of CRC cells. Based on prediction and verification, we subsequently revealed that miR-3187-3p is a circ-ITGA7-associated miRNA. Furthermore, RNA sequencing and bioinformatics analyses showed that ASXL1-5'UTR, the target of miR-3187-3p, is upregulated in circ-ITGA7-overexpressed cells and mediates the circ-ITGA7-induced suppression of proliferation. Conclusion: Circ-ITGA7 might suppress CRC proliferation by sponging miR-3187-3p and increasing ASXL1 expression. Thus, circ-ITGA7 might be a potential diagnostic biomarker and a therapeutic target for CRC.

Evaluating the prognostic value and functional roles of transcription factor AP4 in colorectal cancer.

The basic helix-loop-helix transcription factor AP4 (TFAP4) gene serves an important function in the genesis and progression of tumors. However, few studies to date have defined the role of this gene in colorectal cancer (CRC). The aim of the present study was to assess the expression of TFAP4 in CRC and its impact on the prognosis of patients with CRC. In the present study, the expression of TFAP4 was detected in 30 matched pairs of fresh CRC tissues, 187 cases of clinical paraffin-embedded CRC tissues and CRC cell lines using the reverse transcriptase-quantitative polymerase chain reaction, immunohistochemistry or western blot analysis. Survival analysis was based on TFAP4 expression. The effects of TFAP4 on CRC cell function were investigated by ectopic expression or knockdown of TFAP4 in vitro. TFAP4 expression was revealed to be increased in human CRC tissues and cell lines. The overall survival (OS) time of patients with high TFAP4 expression was significantly decreased compared with patients with low TFAP4 expression (P<0.001). In addition, TFAP4 was revealed to be an independent prognostic factor for the OS time of patients with CRC (hazard ratio, 2.607; 95% confidence interval, 1.469-4.627; P=0.001). Ectopic TFAP4 expression promoted CRC cell proliferation, migration and invasion in vitro, and the silencing of TFAP4 expression resulted in the inhibition of these events. These results demonstrated that TFAP4, which was overexpressed in CRC tissues and cell lines, increased the malignant potential of CRC cells and may serve as an indicator for poor prognosis in patients with CRC.

[Retrospect and prospect: brief history and current status of gastrointestinal surgery in Guangdong Province, China].

The First Affiliated Hospital of Sun Yat-sen University has made many lasting contributions to gastrointestinal surgery in Guangdong Province and even in China. The Department of Gastrointestinal Surgery was established at the First Affiliated Hospital of Sun Yat-sen Medical College in 1965, which opened the prelude to the development of gastrointestinal surgery in Guangdong. This article summarizes the evolution of gastrointestinal surgery and highlights the milestones specific to the field of gastrointestinal surgery in Guangdong Province, China. Main features and trends of gastrointestinal surgery in Guangdong Province are analyzed as well.

Targeting CRMP-4 by lentivirus-mediated RNA interference inhibits SW480 cell proliferation and colorectal cancer growth.

The aim of the present study was to investigate the expression level of collapsin response mediator protein 4 (CRMP-4) in human colorectal cancer (CRC) tissue and to evauluate its impact on SW480 cell proliferation, in addition to tumor growth in a mouse xenograft model. Clinical CRC tissue samples were collected to detect the CRMP-4 protein expression levels using western blot and immunohistochemistry analyses. A specific small interfering RNA sequence targeting the CRMP-4 gene (DPYSL3) was constructed and transfected into an SW480 cell line using a lentivirus vector to obtain a stable cell line with low expression of CRMP-4. The effectiveness of the interference was evaluated using western blot and reverse transcription-quantitative polymerase chain reaction, and the cell proliferation was determined using MTT and BrdU colorimetric methods. Tumor growth was assessed by subcutaneously inoculating the constructed cells into BALB/c nude mice. The protein expression levels of CRMP-4 were markedly increased in colon tumor tissue of the human samples. The proliferation of SW480 cells and the tumor growth rate in nude mice of the si-CPMR-4 group were evidently depressed compared with the si-scramble group. Thus, the present results suggest that CRMP-4 may be involved in the pathogenesis of CRC.

VEGF promotes gastric cancer development by upregulating CRMP4.

This study aimed to investigate the precise role of CRMP4 in gastric tumor growth and patient survival. The mRNA and protein expression levels of CRMP4, VEGF and VEGFR2 were validated by qRT-PCR and immunohistochemistry. We investigated the effects on tumor growth of overexpression and knockdown of CRMP4 both in vitro and in vivo by constructing stable gastric cell lines using lentiviral-mediated transduction and shRNA interference-mediated knockdown of CRMP4 expression. We further validated the role of the ERK/AKT signaling pathways in VEGF and CRMP4 expression using ERK and PI3K inhibitors. Increased expression of VEGF and CRMP4 were observed in gastric cancer tissues compared with tumor-adjacent tissue. We found that higher CRPM4 expression was associated with lymph node metastasis, TNM stage, tumor differentiation and poorer prognosis in gastric cancer patients. In HGC27 and SGC7901 gastric cancer cells, VEGF upregulated CRMP4 in time and dose-dependent manners. Overexpression of CRMP4 increased cell proliferation, migration and invasion, whereas knockdown of CRMP4 expression had opposite effects. VEGF activated CRMP4 expression in gastric cancer cells, and this effect was significantly inhibited by MAPK and PI3K inhibitors (PD98059 and LY294002). In mice, CRMP4 overexpression also resulted in increased tumor growth. These results suggest that increased CRMP4 expression mediated by the activation of VEGF signaling facilitates gastric tumor growth and metastasis, which may have clinical implications associated with a reduced survival rate in gastric cancer patients.

Diagnosis and Treatment of Abdominal Arterial Bleeding After Radical Gastrectomy: a Retrospective Analysis of 1875 Consecutive Resections for Gastric Cancer.

BACKGROUND: Massive abdominal arterial bleeding is an uncommon yet life-threatening complication of radical gastrectomy. The exact incidence and standardized management of this lethal morbidity are not known. METHODS: Between January 2003 and December 2013, data from 1875 patients undergoing radical gastrectomy with D2 or D2 plus lymphadenectomy were recorded in a prospectively designed database from a single institute. The clinical data and management of both early (within 24 h) and late (beyond 24 h) postoperative abdominal arterial hemorrhages were explored. For late bleeding patients, transcatheter arterial embolization (TAE) and re-laparotomy were compared to determine the better initial treatment option. RESULTS: The overall prevalence of postoperative abdominal arterial bleeding was 1.92 % (n = 36), and related mortality was 33.3 % (n = 12). Early and late postoperative bleedings were found in 6 and 30 patients, respectively. The onset of massive arterial bleeding occurred on average postoperative day 19. The common hepatic artery and its branches were the most common bleeding source (13/36; 36.1 %). All the early bleeding patients were treated with immediate re-laparotomy. For late bleeding, patients from the TAE group had a significantly lower mortality rate than that of the patients from the surgery group (7.69 vs. 56.25 %, respectively, P = 0.008) as well as a shorter procedure time for bleeding control (2.3 ± 1.1 vs. 4.8 ± 1.7 h, respectively, P < 0.001). Four rescue reoperations were performed for TAE failures; the salvage rate was 50 % (2/4). Ten patients developed massive re-bleeding after initial successful hemostasis by either TAE (5/13) or open surgery (5/16). Three out of the 10 re-bleeding patients died of disseminated intravascular coagulation (DIC), while the other 7 recovered eventually by repeated TAE and/or surgery. CONCLUSION: Abdominal arterial bleeding following radical gastrectomy tends to occur during the later phase after surgery, with further complications such as abdominal infection and fistula(s). For late bleeding, TAE can be considered as the first-line treatment when possible.

[Expression and significance of miR-125a and Mcl-1 in intestinal tissue after massive small bowel resection in rat].

OBJECTIVE: To investigate the expression and significance of miR-125a and anti-apoptotic protein Mcl-1 in intestinal tissue after massive small bowel resection in intestinal adaptation. METHODS: Sprague-Dawley rats (54 male rats, 8-week old) were divided into 3 groups randomly, including two control groups. Rats in the experiment group were subjected to 70% massive small bowel resection. Rats in the resection group underwent simple intestinal resection and anastomosis. Rats in the control group underwent laparotomy alone. A 5 cm intestine approximately 1 cm distal to the anastomosis was harvested a week after operation. Expression of Mcl-1 was assessed by immunohistochemistry and real-time PCR was used to detect the expression of miR-125a in intestinal tissue. RESULTS: The positive expression of Mcl-1 in the experiment group was 18.8%(3/16), significantly lower than that in the control group(76.5%, 13/17) and the resection group (83.33%, 15/18)(both P<0.01). The expression of miR-125a in the experiment group was 1.92, significantly higher than that in the control group (1.01) and the resection group (1.05)(both P<0.01). CONCLUSION: miR-125a and anti-apoptotic protein Mcl-1 may play an important role in intestinal adaptation process and they may regulate each other through a certain pathway.

Rare case of an abdominal mass: Reactive nodular fibrous pseudotumor of the stomach encroaching on multiple abdominal organs.

Reactive nodular fibrous pseudotumor (RNFP), which presents abdominal clinical manifestations and malignant radiographic results, usually requires radical resection as the treatment. However, RNFP has been recently described as an extremely rare benign post-inflammatory lesion of a reactive nature, which typically arises from the sub-serosal layer of the digestive tract or within the surrounding mesentery in association with local injury or inflammation. In addition, a postoperative diagnosis is necessary to differentiate it from the other reactive processes of the abdomen. Furthermore, RNFP shows a good prognosis without signs of recurrence or metastasis. A 16-year-old girl presented with a 3-mo history of epigastric discomfort, and auxiliary examinations suggested a malignant tumor originating from the stomach; postoperative pathology confirmed RNFP, and after a 2-year follow-up period, the patient did not display any signs of recurrence. This case highlights the importance of preoperative pathology for surgeons who may encounter similar cases.

[Impact of clinicopathological features and extent of lymph node dissection on the prognosis in early gastric cancer patients].

OBJECTIVE: To explore the impact of clinicopathological features and extent of lymph node dissection on the prognosis in early gastric cancer (EGC) patients. METHODS: A total of 142 EGC cases screened from database of gastric cancer of Sun Yat-sen University, from Aug. 1994 to Jan. 2010, were included in this study. According to the lymph node metastasis status, they were divided into lymph node negative (n = 116) and lymph node positive (n = 26) groups. The clinicopathological features of the two groups and the impact of extent of lymph node dissection on the prognosis were analyzed. RESULTS: There were no significant differences in age, gender, tumor size and location, Borrmann typing, WHO TNM staging, histological typing, and CEA value between the two groups (P > 0.05). The TNM stages in the lymph node positive group were higher than that in the lymph node negative group (P < 0.001). Between the cases who underwent D1 (n = 21) and D2 (n = 121) dissection, there were no significant differences in postoperative hospital days, blood transfusion volume, and operation time (P > 0.05). The median numbers of LN dissected in D1 and D2 cases were 4 (0 to 16) and 20 (12 to 30), with a significant difference (P = 0.000), but the number of positive LN without significant difference (P = 0.502). The postoperative complication rates were 9.5% in the D1 and 3.3% in the D2 dissection groups, without a significant difference (P = 0.128). The median survival time of the lymph node negative and positive groups was 156 vs. 96 months (P = 0.010). In cases who received D2 and D1 lymph node dissection, the median survival time (MST) was 156 vs. 96 months (P = 0.0022). In the lymph node positive group, D2 dissection prolonged survival time significantly than D1 dissection (96 vs. 27months) (P = 0.001). Cox regression analysis showed that the extent of lymph node dissection and LN metastasis were independent prognostic factors for EGC patients. CONCLUSIONS: It is not able to accurately assess the LN metastasis status preoperatively according to the routine clinicopathological features. For the patients with unknown LN metastasis status, D2 dissection should be the first choice. Comparing with D1 dissection, the morbidity of D2 dissection are not increased, but survival time is prolonged.

[Effects of inhibition of Hedgehog signaling pathway for transforming growth factor-ß-induced epithelial-mesenchymal transition].

OBJECTIVE: To elucidate the mechanism of Hedgehog pathway in the metastasis of gastric cancer and examine particularly the effect on epithelial-mesenchymal transition (EMT). METHODS: Using pharmacological and siRNA knockdown approach, the Hedgehog pathway was inhibited. The cellular morphology, protein level, invasion and metastatic abilities were measured by microscope, Western blot, Transwell invasion assay and Transwell migration assay. RESULTS: Under the inhibition of Hedgehog pathway, the invasive and migration abilities of gastric cancer decreased. The transforming growth factor (TGF) -ß could induce spindle-like-shaped morphological changes with a down-regulation of epithelial characteristic (decreased E-cadherin protein level) and an up-regulation of mesenchymal characteristics (increased Vimentin protein level). There were concurrent increases of invasive and migration potentials by 3 and 4 folds respectively.However, under the continuous stimulation of TGF-ß, the inhibition of Hedgehog pathway could reverse the EMT changes, lower the expression of vimentin and reduce the invasion and metastatic abilities by 3 and 2 folds respectively. CONCLUSIONS: The inhibition of Hedgehog pathway can decrease the TGF-ß-inducing EMT.It suggests that Hedgehog pathway may play a critical role in the metastasis of gastric cancer.

[Details and technical considerations in pancreaticoduodenectomy].

Pancreaticoduodenectomy (PD) is one of the most challenging endeavor and formidable procedures in abdominal surgery. This procedure is inherently difficult and associated with high mortality and complication morbidity. The revolution of the concept of surgical oncology, the modifications in surgical techniques, introduction of advanced surgical equipment and the developments of critical care medicine have led to significant reduction in reduced surgical mortality and complication morbidity. Comprehensive evaluation before operation, precise dissection during operation and management of the stump of pancreas in pancreaticoduodenectomy procedure are reviewed and comments are provided in this article.

[Clinicopathological features and prognosis of young patients with gastric cancer].

OBJECTIVE: To summarize the clinicopathological characteristics and analyze the prognostic factors of young patients with gastric cancer. METHODS: A total of 99 patients with the age less than or equal to 40 were admitted in The First Affiliated Hospital of Sun Yat-sen University from August 2001 to December 2009. Their clinicopathological and follow-up data were compared with middle-aged and elderly patients with the age more than 40. RESULTS: There were statistically significant differences in gender, tumor location, Borrmann type, histological type, differentiated histology, depth of invasion, peritoneal metastasis between young patients and elder ones. The 5-year survival rates of young and elder patients were 49.1% and 44.4% respectively, and the difference was not statistically significant (P>0.05). Univariate and multivariate analyses showed that TNM stage (P=0.014) and surgical methods (P=0.012) were independent predictive factors of survival for young patients. For the young patients, the 5-year survival rate was 56.7% after curative resection, 11.1% after palliative resection. Those who underwent palliative surgery or biopsy alone died within 1 year after surgery. The difference between difference surgical procedures in survival were statistically significant (P<0.05). CONCLUSIONS: As compared to elder patients, young patients with gastric cancer have special clinicopathological features. However, no significant difference of survival rate is found between the young and the elder patients. TNM stage and surgical methods are independent prognostic factors of young patients with gastric cancer. Radical resection appears to confer the only chance of prolonged survival.