A Substage Increase in The AJCC Classification System Improves Prognostic Prediction in Stage III Gastric Cancer With Insufficient Lymph Nodes Removed.

BACKGROUND: The impact of lymph nodes (LNs) removed on the survivals of patients with stage III gastric cancer, especially on that of those who undergo the adjuvant chemotherapy as a compensation for a possibly insufficient lymphadenectomy, is still unclear. METHODS: Consecutive patients (n = 488) with stage III gastric cancer under R0 curative resection followed by adjuvant chemotherapy were analyzed. The overall survival (OS) was compared between patients with insufficient LNs removed (ILNr, <16 LNs) and sufficient LNs removed (SLNr, ≥16 LNs). Performance of the prediction systems was evaluated using the Likelihood ratio χ2 test, Akaike information criterion (AIC), Harrell's concordance index (C-index), and area under the receiver operating characteristic curves (AUC). RESULTS: The OS of patients were significantly longer in those with SLNr relative to those with ILNr (for stage IIIA, 68.2 vs. 43.2 months, P = 0.042; for stage IIIB, 43.7 vs. 24.9 months, P < 0.001; for stage IIIC, 23.9 vs. 8.3 months, P < 0.001; and for total stage III, 37.7 vs. 21.7 months, P < 0.001). However, the OS were similar between stage IIIA patients with ILNr and stage IIIB patients with SLNr (P = 0.928), between IIIB patients with ILNr and IIIC patients with SLNr (P = 0.962), and IIIC patients with ILNr and stage IV (P = 0.668), respectively. A substage increase in the AJCC classification system, from IIIA to IIIB, from IIIB to IIIC, and from IIIC to IV in patients with ILNr, enhanced the accuracy of prognostic prediction in patients with stage III gastric cancer compared to the current TNM system (Likelihood ratio χ2, 188.6 vs. 184.8; AIC, 4336.4 vs. 4340.6; C-index, 0.695 vs. 0.679, P = 0.002). The ROC curves revealed that the performance of prognostic prediction was better in the new prediction system (AUC = 0.699) compared with the current TNM system (AUC = 0.676). CONCLUSIONS: ILNr (LNs <16) impairs the long-term outcomes of stage III gastric cancer underwent adjuvant chemotherapy. The status of LNs removal adds values to the current TNM system in prognostic prediction of stage III gastric cancer.

Anti-EGFR therapy in metastatic colorectal cancer: mechanisms and potential regimens of drug resistance.

Cetuximab and panitumumab, as the highly effective antibodies targeting epidermal growth factor receptor (EGFR), have clinical activity in the patients with metastatic colorectal cancer (mCRC). These agents have good curative efficacy, but drug resistance also exists at the same time. The effects of KRAS, NRAS, and BRAF mutations and HER2 amplification on the treatment of refractory mCRC have been elucidated and the corresponding countermeasures have been put forward. However, the changes in EGFR and its ligands, the mutations or amplifications of PIK3CA, PTEN, TP53, MET, HER3, IRS2, FGFR1, and MAP2K1, the overexpression of insulin growth factor-1, the low expression of Bcl-2-interacting mediator of cell death, mismatch repair-deficient, and epigenetic instability may also lead to drug resistance in mCRC. Although the emergence of drug resistance has genetic or epigenetic heterogeneity, most of these molecular changes relating to it are focused on the key signaling pathways, such as the RAS/RAF/mitogen-activated protein kinase or phosphatidylinositol 3-kinase/Akt/mammalian target of the rapamycin pathway. Accordingly, numerous efforts to target these signaling pathways and develop the novel therapeutic regimens have been carried out. Herein, we have reviewed the underlying mechanisms of the resistance to anti-EGFR therapy and the possible implications in clinical practice.

Tumor Immune Microenvironment and Chemosensitivity Signature for Predicting Response to Chemotherapy in Gastric Cancer.

Current gastric cancer staging alone cannot predict prognosis and adjuvant chemotherapy benefits in stage II and III gastric cancer. Tumor immune microenvironment biomarkers and tumor-cell chemosensitivity might add predictive value to staging. This study aimed to construct a predictive signature integrating tumor immune microenvironment and chemosensitivity-related features to improve the prediction of survival and adjuvant chemotherapy benefits in patients with stage II to III gastric cancer. We used IHC to assess 26 features related to tumor, stroma, and chemosensitivity in tumors from 223 patients and evaluated the association of the features with disease-free survival (DFS) and overall survival (OS). Support vector machine (SVM)-based methods were used to develop the predictive signature, which we call the SVM signature. Validation of the signature was performed in two independent cohorts of 445 patients. The diagnostic signature integrated seven features: CD3+ cells at the invasive margin (CD3 IM), CD8+ cells at the IM (CD8 IM), CD45RO+ cells in the center of tumors (CD45RO CT), CD66b+ cells at the IM (CD66b IM), CD34+ cells, periostin, and cyclooxygenase-2. Patients fell into low- and high-SVM groups with significant differences in 5-year DFS and OS in the training and validation cohorts (all P < 0.001). The signature was an independent prognosis indicator in multivariate analysis in each cohort. The signature had better prognostic value than various clinicopathologic risk factors and single features. High-SVM patients exhibited a favorable response to adjuvant chemotherapy. Thus, this SVM signature predicted survival and has the potential for identifying patients with stage II and III gastric cancer who could benefit from adjuvant chemotherapy.

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.

Systemic immune-inflammation index for predicting prognosis of colorectal cancer.

AIM: To investigate the clinical significance of preoperative systemic immune-inflammation index (SII) in patients with colorectal cancer (CRC). METHODS: A retrospective analysis of 1383 cases with CRC was performed following radical surgery. SII was calculated with the formula SII = (P × N)/L, where P, N, and L refer to peripheral platelet, neutrophil, and lymphocyte counts, respectively. The clinicopathological features and follow-up data were evaluated to compare SII with other systemic inflammation-based prognostic indices such as the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in patients with CRC. RESULTS: The optimal cut-off point for SII was defined as 340. The overall survival (OS) and disease-free survival (DFS) were better in patients with low NLR, PLR, and SII (P < 0.05). The SII was an independent predictor of OS and DFS in multivariate analysis. The area under the receiver-operating characteristics (ROC) curve for SII (0.707) was larger than those for NLR (0.602) and PLR (0.566). In contrast to NLR and PLR, SII could effectively discriminate between the TNM subgroups. CONCLUSION: SII is a more powerful tool for predicting survival outcome in patients with CRC. It might assist the identification of high-risk patients among patients with the same TNM stage.

Up-regulation of long non-coding RNA XLOC_010235 regulates epithelial-to-mesenchymal transition to promote metastasis by associating with Snail1 in gastric cancer.

We previously performed long non-coding RNA (lncRNA) expression microarray analyses to identify novel indicators for gastric cancer (GC) metastasis and prognosis in which we identified lncRNA XLOC_010235 (XLOC) as a candidate RNA. However, XLOC_010235 molecular mechanism of action remains unclear. Gain and loss of function approaches were used to investigate the biological role of XLOC in vitro. The effects of XLOC on cell viability were assessed by CCK-8 proliferation assays. Real-time PCR, western-blot and immunofluorescence were used to evaluate the mRNA and protein expression of Snail and multiple EMT related molecules. The positive XLOC/Snail1 interaction was identified and verified by immunohistochemistry assay and bivariate correlation analysis. Ectopic expression of XLOC facilitate cell viability, migration and invasion, leading to the acceleration of metastasis, while depletion of XLOC expression hindered cell migration and invasion. Moreover, over-expression of XLOC was found to play a important role in epithelial-to-mesenchymal transition (EMT) through the regulation of E-cadherin, N-cadherin and Vimentin expression, in which transcriptional factor Snail1 was involved. These results advance our understanding of the role of lncRNA XLOC_010235 as a active regulator of EMT by associating with Snail1, which may help in the development of new therapeutics.

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.

Case of metachronous bilateral isolated adrenal metastasis from colorectal adenocarcinoma and review of the literature.

Rarely has a solitary, metachronous bilateral adrenal metastasis of colorectal cancer been reported. We depict a 41-year-old man who underwent sigmoid colon cancer radical surgery followed by adjuvant chemotherapy for a locally ulcerative sigmoid adenocarcinoma with metachronous bilateral adrenal metastasis revealed by a computed tomography scan. Histopathological examination showed adenocarcinoma, compatible with metastasis from the rectal cancer. The level of serum carcinoembryonic antigen had indicative significance for the presence of adrenal metastasis in the reported series. We performed a literature analysis related to this pathological characteristic and attach importance to consistent, vigilant radiological surveillance of the adrenal glands in the patients' follow up for colorectal cancer with or without subsequent adrenal metastasis.

Identification of differentially expressed signatures of long non-coding RNAs associated with different metastatic potentials in gastric cancer.

BACKGROUND: Gastric cancer (GC) is known for its lymph node metastasis and outstanding morbidity and mortality. Thus, improvement in the current knowledge regarding the molecular mechanism of GC is urgently needed to discover novel biomarkers involved in its progression and prognosis. Several long, non-coding RNAs (lncRNAs) play important roles in gastric tumorigenesis and metastasis. However, the signature of lncRNA-associated metastasis in GC is not fully clarified. METHODS: We determined the lncRNA and mRNA expression profiles correlating to GC with or without lymph node-metastasis based on microarray analysis. Twelve differentially expressed lncRNAs and six differentially expressed mRNAs were validated by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay. RESULTS: The relationships between the aberrantly expressed lncRNAs XLOC_010235 or RP11-789C1.1 and lymph node metastasis, pathologic metastasis status, distal metastasis and TNM (tumour, node, and metastasis) stage were found to be significantly different. Via survival analysis, patients who had high-expressed XLOC_010235 or low-expressed RP11-789C1.1 showed significantly worse survival than patients with inverse-expressed XLOC_010235 or RP11-789C1.1. CONCLUSION: In summary, this current study highlights some evidence regarding the potential role of lncRNAs in GC and posits that specific lncRNAs can be identified as novel, poor prognostic biomarkers in GC.

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.

Survival prognosis and clinicopathological features of the lymph nodes along the left gastric artery in gastric cancer: implications for D2 lymphadenectomy.

The Japanese Gastric Cancer Treatment Guidelines (third edition) have assigned No. 7 station left gastric artery lymph nodes (LNs) to the D1 range of lymphatic dissection. We investigated the clinicopathological characteristics, survival impact, and appropriateness of ascribing No. 7 station LNs to D1 lymphadenectomy in gastric cancer. Patients (n=608) undergoing radical resection with No. 7 station LN dissection were recruited between January 1997 and June 2008. They were subdivided into four groups: N0, no LN metastasis; D1, LN without No. 7 station LN metastasis in the D1 lymphadenectomy region; No. 7, No. 7 station LN without LN metastasis in the D2 lymphadenectomy region; and D2, LN without No. 7 station LN metastasis in the D2 lymphadenectomy region. Of these, 17.2% (n=105) were positive for No. 7 LN metastasis, an important, independent prognostic factor associated with poor clinicopathological parameters, advanced tumor stage, and reduced survival. Tumor behavior in the No. 7 group was similar to that in the D2 group, but poorer than in the D1 group in terms of advanced tumor stage, with 5-year survival rates of 34.3%, 25.9% and 54.6%, respectively. Five-year survival rates in the No. 7 group were comparable to those in the D2 group (P>0.05), but significantly lower than in the D1 group (P<0.05). Logistic multivariate regression analysis established No. 3 and 9 station LN metastasis, node classification, and tumor-node-metastasis stage as independent risk factors for No. 7 station LN metastasis. Thus, No. 7 station LNs should be ascribed to D2 lymphadenectomy in gastric cancer.

Effect of somatostatin in advanced gastric cancer after D2 radical gastrectomy.

AIM: To study the effect of somatostatin in patients with advanced gastric cancer who received D2 lymphadenectomy and vagina vasorum dissection. METHODS: Using a prospective, single-blind, placebo-controlled design, patients with advanced gastric cancer were randomized into a study group (n = 61) and a control group (n = 59). Patients in the study group were given somatostatin for 5-7 d starting 6 h after the operation, and patients in the control group were given normal saline. Preoperative and nonoperative complications in the perioperative period, as well as different types of postoperative drainage in the two groups were compared. RESULTS: There was no significant difference between the study group and the control group for preoperative clinicopathological indicators. We found no significant difference between the two groups for the overall incidence of complications, but a lower percentage of peritoneal effusion was observed in the treatment group (1.6% vs 10.2%, P < 0.05). There were no significant differences between the two groups in the incidence of postoperative pancreatic dysfunction and chylous fistula. However, there were significant differences in the amylase concentration in drainage fluid, volume and duration of drainage, volume and duration of chylous fistula and peritoneal drainage, and volume and duration of gastric tube drainage. The study group did not show any increase in mean hospitalization cost and the cost reduced when the postoperative complications occurred. CONCLUSION: Postoperative somatostatin reduces volume and duration of surgical drainage and related complications. Somatostatin may improve safety of gastric cancer surgery, reducing postoperative complications and promoting recovery.

Efficacy and complications of polyethylene glycols for treatment of constipation in children: a meta-analysis.

Constipation is a common childhood complaint. In 90% to 95% of children, constipation is functional, which means that there is no objective evidence of an underlying pathological condition. Polyethylene glycol (PEG or macrogol) solution is an osmotic laxative agent that is absorbed in only trace amounts from the gastrointestinal tract and routinely used to treat chronic constipation in adults. Here, we report the results of a meta-analysis of PEG-based laxatives compared with lactulose, milk of magnesia (magnesium hydroxide), oral liquid paraffin (mineral oil), or acacia fiber, psyllium fiber, and fructose in children. This meta-analysis was conducted in accordance with PRISMA guidelines and involved searches of MEDLINE, Cochrane, EMBASE, and Google Scholar databases up to February 10, 2014, using the keywords (Constipation OR Functional Constipation OR Fecal Impaction) AND (Children) AND (Polyethylene Glycol OR Laxative). Primary efficacy outcomes included a number of stool passages/wk and percentage of patients who reported satisfactory stool consistency. Secondary safety outcomes included diarrhea, abdominal pain, nausea or vomiting, pain or straining at defecation, bloating or flatulence, hard stool consistency, poor palatability, and rectal bleeding. We identified 231 articles, 27 of which were suitable for full-text review and 10 of which were used in the meta-analysis. Patients who were treated with PEG experienced more successful disimpaction compared with those treated with non-PEG laxatives. Treatment-related adverse events were acceptable and generally well tolerated. PEG-based laxatives are effective and safe for chronic constipation and for resolving fecal impaction in children. Children's acceptance of PEG-based laxatives appears to be better than non-PEG laxatives. Optimal dosages, routes of administration, and PEG regimens should be determined in future randomized controlled studies and meta-analyses.

RAD51 potentiates synergistic effects of chemotherapy with PCI-24781 and cis-diamminedichloroplatinum on gastric cancer.

AIM: To explore the efficacy of PCI-24781, a broad-spectrum, hydroxamic acid-derived histone deacetylase inhibitor, in the treatment of gastric cancer (GC). METHODS: With or without treatment of PCI-24781 and/or cis-diamminedichloroplatinum (CDDP), GC cell lines were subjected to functional analysis, including cell growth, apoptosis and clonogenic assays. Chromatin immunoprecipitation and luciferase reporter assays were used to determine the interacting molecules and the activity of the enzyme. An in vivo study was carried out in GC xenograft mice. Cell culture-based assays were represented as mean ± SD. ANOVA tests were used to assess differences across groups. All pairwise comparisons between tumor weights among treatment groups were made using the Tukey-Kramer method for multiple comparison adjustment to control experimental-wise type I error rates. Significance was set at P < 0.05. RESULTS: PCI-24781 significantly reduced the growth of the GC cells, enhanced cell apoptosis and suppressed clonogenicity, and these effects synergized with the effects of CDDP. PCI-24781 modulated the cell cycle and significantly reduced the expression of RAD51, which is related to homologous recombination. Depletion of RAD51 augmented the biological functions of PCI-24781, CDDP and the combination treatment, whereas overexpressing RAD51 had the opposite effects. Increased binding of the transcription suppressor E2F4 on the RAD51 promoter appeared to play a major role in these processes. Furthermore, significant suppression of tumor growth and weight in vivo was obtained following PCI-24781 treatment, which synergized with the anticancer effect of CDDP. CONCLUSION: These data suggest that RAD51 potentiates the synergistic effects of chemotherapy with PCI-24781 and CDDP on GC.

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.

Pathological diagnosis is maybe non-essential for special gastric cancer: case reports and review.

Histopathological results are critical for the diagnosis and surgical decision regarding gastric cancer. However, opposite opinions from radiology and pathology can sometimes affect clinical decisions. The two cases reported in this article were both highly suspected as gastric cancer by clinical manifestations and radiologic findings, although both showed negative results in the first biopsy examination. One was confirmed as gastric cancer by the time of the 6(th) biopsy, while the other was still negative even after 8 biopsies. With a definite pathologic result and the agreement of the patient for the latter case, both of them finally received surgery. Postoperative pathological examination revealed findings that were the same as Borrmann type IV gastric cancer. We believed that duplicate biopsies under radiologic guidance were necessary for highly suspected gastric cancer cases in the absence of a definite pathology result, and patients should be under close follow-up. We propose that, if gastric cancer is highly suspected when typical radiology changes of widely diffuse gastric parietal lesions suffice to exclude lymphoma and other similar situations, and even in absence of a positive biopsy result, a diagnostic laparotomy under laparoscopy and even radical gastrectomy may be reasonably performed by an experienced gastric cancer center with the agreement of the patient after being decided by a multidisciplinary discussion team.

[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.

[Risk factors and prognostic impact of No.12 lymph node metastasis in cases with curable advanced distal gastric cancer].

OBJECTIVE: To explore the risk factors and prognostic impact of duodenal hepatic ligamentous lymph node (No.12 LN) metastasis in cases with curable advanced distal gastric cancer. METHODS: The data of 379 cases with advanced distal gastric cancer undergoing radical resection were screened from the Database of Gastric Cancer Center of Sun Yat-sen University from January 1997 to December 2010. According to No.12 LN metastasis, they were divided into negative (n = 339) and positive (n = 40) groups. Their clinicopathological parameters and surgical regimens were compared. And the risk factors and prognostic impact of No.12 LN metastasis were analyzed. RESULTS: No significant inter-group difference existed in gender, age, infiltration depth or differentiation degree (all P > 0.05). In negative and positive groups, the percent of tumor size ≥ 5 cm was 30.1% (102/339) vs 55.0% (22/40), lymph node metastasis N3 stage 8.3% (28/339) vs 42.5% (17/40), other lymph nodes except for No.12 metastasis 70.2% (238/339) vs 92.5% (37/40), distal metastasis M1 10.9% (37/339) vs 32.5% (13/40), TNM stage IV 18.6% (63/339) vs 65.0% (26/40), infiltration Borrmann type 74.3% (252/339) vs 92.5% (37/40), non-adenocarcinoma 15.9% (54/339) vs 35.0% (14/40) and positive serum-carcinoembryonic antigen (S-CEA) 12.7% (43/339) vs 32.5% (13/40). There were all with significant difference (all P < 0.01). Logistic regression analysis showed tumor size ≥ 5 cm, lymph node (except for No.12) metastasis, distal metastasis and positive S-CEA were independent risk factors of No.12 LN metastasis (OR = 2.144, 3.581, 2.597, 2.552; P = 0.035, 0.042, 0.019, 0.022 respectively). Cox regression analysis showed lymph nodes (except for No.12) and No.12 metastasis, distal metastasis and Borrmann type were independent prognostic factors for all cases. In negative and positive groups, median survival time was 63.0 versus 12.0 months with significant difference (P = 0.000). CONCLUSIONS: For cases with curable advanced distal gastric cancer, No.12 LN metastasis was an independent prognostic factor. No.12 LN should be dissected thoroughly in cases with tumor size ≥ 5 cm, lymph nodes (except No.12) metastasis, distal metastasis and positive S-CEA.