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.

(-)-Epigallocatechin-3-gallate inhibits VEGF expression induced by IL-6 via Stat3 in gastric cancer

AIM: To demonstrate that (-)-Epigallocatechin-3-gallate (EGCG) inhibits vascular endothelial growth factor (VEGF) expression and angiogenesis induced by interleukin-6 (IL-6) via suppressing signal transducer and activator of transcription 3 (Stat3) activity in gastric cancer. METHODS: Human gastric cancer (AGS) cells were treated with IL-6 (50 ng/mL) and EGCG at different concentrations. VEGF, total Stat3 and activated Stat3 protein levels in the cell lyses were examined by Western blotting, VEGF protein level in the conditionedmedium was measured by enzyme-linked immunosorbent assay, and the level of VEGF mRNA was evaluated by reverse transcription polymerase chain reaction (RTPCR). Stat3 nuclear translocation was determined by Western blotting with nuclear extract, and Stat3-DNA binding activity was examined with Chromatin immunoprecipitation (ChIP) assay. IL-6 induced endothelial cell proliferation was measured with 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazoliumbromide assay, in vitro angiogenesis was determined with endothelial cell tube formation assay in Matrigel, and IL-6-induced angiogenesis in vitro was measured with Matrigel plug assay. RESULTS: There was a basal expression and secretion of VEGF in AGS cells. After stimulation with IL-6, VEGF expression was apparently up-regulated and a 2.4-fold increase was observed. VEGF secretion in the conditioned medium was also increased by 2.8 folds. When treated with EGCG, VEGF expression and secretion were dose-dependently decreased. IL-6 also increased VEGF mRNA expression by 3.1 folds. EGCG treatment suppressed VEGF mRNA expression in a dose-dependent manner. EGCG dose-dependently inhibited Stat3 activation induced by IL-6, but did not change the total Stat3 expression. When treated with EGCG or AG490, VEGF expressions were reduced to the level or an even lower level in the tumor cells not stimulated with IL-6. However, PD98059 and LY294002 did not change VEGF expression induced by IL-6. EGCG inhibited Stat3 nucleus translocation, and Stat3-DNA binding activity was also markedly decreased by EGCG. Furthermore, EGCG inhibited IL-6 induced vascular endothelial cell proliferation and tube formation in vitro and angiogenesis in vitro . CONCLUSION: EGCG inhibits IL-6-induced VEGF expression and angiogenesis via suppressing Stat3 activity in gastric cancer, which has provided a novel mechanistic insight into the anti-angiogenic activity of EGCG.

Vagina vasorum dissection during D2 lymphadenectomy for gastric carcinoma

AIM: To explore the relationship between metastasis and vagina vasorum in the progress of gastric carcinoma and to find some facts and references for gastric surgeons. METHODS: One hundred and seven specimens of left or right gastric arteries (55 left and 52 right) were gathered from 59 patients undergoing radical gastrectomy for gastric carcinoma. All the frozen specimens were cut into 3 μm-thick sections and stained with hematoxylin-eosin (HE) and immunohistochemical method separately. Cytokeratin (CK) and mesothelial cells (MC) were stained with immunohistochemical method. Cancer cells inside vagina vasorum were detected and the structure of artery wall was observed under microscope. RESULTS: Metastatic cancer cells or tubercles were found inside vagina vasorum in some stage Ⅲ or Ⅳ specimens, but not in stageⅠor Ⅱ specimens. Tumor cells in vagina vasorum were CK positive in 26 specimens of 14 tumors. Among them, stage Ⅲ was found in 4 specimens of 2 tumors, and stage Ⅳ in 22 specimens of 12 tumors. None of these specimens was positive for MC. The positive rate of CK increased with TNM staging. Compared with the lower part, tumors in the upper and middle parts of stomach were more likely to metastasize into vagina vasorum. CONCLUSION: Vagina vasorum dissection should be performed during D2 lymphadenectomy for TNM stage Ⅲ or Ⅳ gastric carcinoma.

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 postinflammatory 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.

Detection of hMSH2 and hMLH1 mutations in Chinese hereditary non-polyposis colorectal cancer kindreds

AIM： To establish and validate the mutation testing for identification and characterization of hereditary non-polyposis colorectal cancer （HNPCC） in suspected Chinese patients. METHODS： Five independent Chinese kindreds with HNPCC fulfilling the classical Amsterdam criteria were collected. Genomic DNA was extracted after informed consent was obtained. The coding region of hMSH2 and hMLH1 genes was detected by polymerase chain reaction （PCR） and denaturing high-performance liquid chromatography （DHPLC）. Mutations identified in the proband by DHPLC were directly sequenced using a 377 DNA sequencer, analyzed with a basic local alignment tool （BLAST）, and tested in the corresponding family members by direct DNA sequencing. RESULTS： Mutations were identified in two Chinese HNPCC kindreds. One was the missense mutation of hMSH2 c.1808A→G resulting in Asp 603 Gly identified in the proband of the fifth HNPCC （HNPCCS） kindred. In the HNP5 kindred, three family members were found to have this mutation and two of them had colorectal cancer. The other mutation of hMLH1 c.1882A→G was identified in the HNP2 kindred＇s proband, which might be the nonsense mutation analyzed by BLAST. CONCLUSION： Pedigree investigation and mutation testing of hMSH2 and hMLH1 are the practical methods to identify high-risk HNPCC patients in China.

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,placebocontrolled 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 differenttypes 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.

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 alocally 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.

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. How-ever, 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 find-ings that were the same as Borrmann type Ⅳ gastric cancer. We believed that duplicate biopsies under ra-diologic guidance were necessary for highly suspected gastric cancer cases in the absence of a definite pathol-ogy result, and patients should be under close follow-up. We propose that, if gastric cancer is highly sus-pected when typical radiology changes of widely diffuse gastric parietal lesions suffice to exclude lymphoma and other similar situations, and even in absence of a posi-tive biopsy result, a diagnostic laparotomy under lapa-roscopy and even radical gastrectomy may be reason-ably performed by an experienced gastric cancer center with the agreement of the patient after being decided by a multidisciplinary discussion team.

Effects of different Helicobacter pylori culture filtrates on growth of gastric epithelial cells

AIM:To study the effects of different Helicobacter pylori(H pylori) culture filtrates on growth of gastric epithelial cells. METHODS:Broth culture filtrates of H pylori were prepared. Gastric epithelial cells were treated with the filtrates,and cell growth was determined by growth curve and flow cytometry. DNA damage of gastric epithelial cells was measured by single-cell microgel electrophoresis. RESULTS:Gastric epithelial cells proliferated actively when treated by CagA-gene-positive broth culture filtrates,and colony formation reached 40%. The number of cells in S phase increased compared to controls. Comet assay showed 41.2% comet cells in GES-1 cells treated with CagA-positive filtrates(P < 0.05) . CONCLUSION:CagA-positive filtrates enhance the changes in morphology and growth characteristics of human gastric epithelial tumor cells. DNA damage maybe one of the mechanisms involved in the growth changes.

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

AIM:To explore the efficacy of PCI-24781,a broadspectrum,hydroxamic acid-derived histone deacetylase inhibitor,in the treatment of gastric cancer(GC).METHODS:With or without treatment of PCI-24781and/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 typeⅠ 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.

The effect of FasL gene transfer to islet cells on pancreatic islet allografts

OBJECTIVE: To investigate the effect of FasL gene transfer to islet cells on pancreatic islet allografts. METHODS: A recombinant and replication-deficient type-5 adenovirus encoding murine FasL (AdV- FasL) was constructed by the method of calcium phosphate precipitation. Pancreatic islets were infected with the recombinant adenovirus AdV-FasL, and transplanted into diabetic recipients. FasL expression was detected by RT-PCR and immunohistochemistry. The survival of allografts and the apoptosis of gene transferred islet allografts were analyzed. RESULTS: All animals receiving islet allograft alone returned to a diabetic state by several days (mean survival time 6.3±0.6 days). Compared with the control group, no delayed rejection and prolonged survival of allografts were observed in the group of FasL gene transfer. The rejection was accelerated and the allograft survival was shortened to 3.4±0.2 days (P<0.05). Pancreatic islets infected with AdV- FasL demonstrated positive staining of FasL at 24 h, with an increased intensity at 48 h, but not in AdV-5 infected or uninfected islets. TUNEL labeling of pancreatic islet allografts at 24, 48 h revealed apoptosis that was not in AdV-5 infected allografts. CONCLUSIONS: Though co-transplantation of FasL-expressing testicular cells can induce privilege of islet allografts and prolong allograft survival, direct expression of FasL on islet allografts infected with AdV-FasL may accelerate islets rejection by islet apoptosis and granulocyte infiltration.

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.