Objective To review the relationship between histone modifications and gastrointestinal cancer. Methods Literatures on histone modifications and the relationship between histone modifications and gastrointestinal cancer were collected and reviewed. Results Histone modifications played an important role in the establishment of gene silencing during tumorgenesis. DNA methylation and histone modifications might interact with each other and form a complex network to establish and maintain gene silencing. Restoring gene function silenced by epigenetic changes in cancer had the potential of ‘normalizing’ cancer cells, which was named epigenetic therapy. Epigenetic therapy was very promising in prevention and treatment of gastrointestinal cancer, but many unsolved issues remain which need to be addressed in future studies. Conclusion Histone modifications are associated with the pathogenesis of gastrointestinal cancer. Restoring gene function silenced by epigenetic changes may have a great role in the prevention and treatment of gastrointestinal cancer.
【Abstract】 Objective To investigate the relationship between methylation of tumor suppressor gene and gastric cancer. Methods The literatures in recent years about the concept of methylation, its biological significance and the relationship between DNA methylation/demethylation and gastric cancer were reviewed. The effects of methylation of different tumor suppressor genes on gastric cancer were also analyzed. Results The effect of aberrant methylation on the development and the progression of gastric cancer was still unclear but it was supposed that the inactivation of genes related with cell cycle regulation, mitotic checkpoint, apoptosis, DNA mismatch repair, metastasis suppression and so on might be attributable to the aberrant methylation in gastric cancer. Conclusion Aberrant methylation of tumor suppressor genes plays an important role in the development and progression of gastric cancer. The status of methylation of tumor suppressor genes may be used as a useful molecule marker for diagnosis, assessing metastasis and evaluating prognosis, and demethylation could possibly be a new therapy for gastric cancer.
Objective To discuss the clinicopathologic risk factors related to local recurrence of rectal cancer after radical surgery. Methods The complete clinicopathologic data of 368 patients with rectal cancer from January 2004 to April 2011 in this hospital were retrospectively analyzed by univariate and multivariate analysis methods. Results There were 73 cases suffered from local recurrence and accounted for 19.84% （73/368） of rectal cancer during the same period. Univariate analysis results showed that gender， tumor from anal margin， tumor circumference， TNM staging， histology type， vessel infiltration， tumor perforation， stomal leak， and chemoradiotherapy were associated with postoperative recurrence （P＜0.05）. Multivariate analysis results showed that tumor from anal margin， tumor circumference， TNM staging， histology type， vessel infiltration， tumor perforation， and chemoradiotherapy were prognostic factor for local recurrence of rectal cancer （P＜0.05）. Conclusions There are many factors related to postoperative local recurrence， but the most dangerous factor is vessel infiltration.
ObjectiveTo investigate the expression of a disintegrin and metalloproteinase with thrombospondin typeⅠmotif (ADAMTS1) in colorectal cancer tissues, and to study the relationship with clinicopathological features and prognosis of it. MethodsExpression of ADAMTS1 was evaluated by immunohistochemistry (SP method) in 65 specimens, which obtained by resection from patients with colorectal cancer, including corresponding adjacent benign tissues. Chi-square test was used for analyzing the relationship between expression of ADAMTS1 and clinicopathological features of colorectal cancer tissues. Cox proportional hazard model was used to explore the relationship between expression of ADAMTS1, other clinicopathological parameters, and patients' survival situation. ResultsThe positive expression rate of ADAMTS1 was 40% (26/65) in the colorectal cancer tissues and 85% (55/65) in the adjacent benign tissues, which was significantly higher in adjacent benign tissues (χ2=27.546, P < 0.001). The positive expression rate of ADAMTS1 was significantly lower in the colorectal cancer tissues with lymph node metastasis than that of the colorectal cancer without lymph node metastasis (χ2=5.329, P=0.021). Results of survival analysis showed that median survival time were 27 months in the ADAMTS1-negative group and 70 months in the ADAMTS1-positive group respectively, and the survival situation was better in latter group (χ2=10.151, P=0.001). Results of multivariable prognostic analysis of Cox proportional hazard model showed that colorectal cancer withⅠ-Ⅱstage (RR=3.782, 95% CI:1.509-9.476, P=0.005), without lymph node metastasis (RR=3.107, 95% CI:1.186-8.138, P=0.021), and with positive-expression of ADAMTS1 (RR=2.020, 95% CI:1.071-3.809, P=0.030) had better survival situation. ConclusionsExpression of ADAMTS1 is down-regulated in colorectal cancer tissues and it is associated with lymph node metastasis. The prognosis of patients in ADAMTS1-positive group is better than that of ADAMTS1-negative group, suggesting that ADAMTS1 may be an independent prognostic factor in colorectal cancer.
Objective To investigate the pathological features， diagnosis， treatment， and prognosis of multiple primary colorectal cancer （MPCC）. Methods Clinical data of 41 patients with MPCC treated in The Fourth Affiliated Hospital and The First Affiliated Hospital of China Medical University from Aug. 1993 to Mar. 2009 were retrospectively analyzed. Results Forty one patients with MPCC， including 29 patients with synchronous colorectal cancer （SCC） and 12 patients with metachronous colorectal cancer （MCC）， accounted for 1.8% （41/2 340） of colorectal cancer during the same period of time， and with adenomatous polyps in 19 cases and polyps canceration in 10 cases. Among 29 patients with SCC， 15 cases （51.7%） were diagnosed by preoperative fiberoptic colonoscopy， 9 cases （31.0%） were diagnosed by preoperative fiberoptic colonoscopy， abdomen CT， and barium enema， 5 cases （17.2%） were diagnosed by intraoperative exploration and intraoperative fiberoptic colonoscopy， respectively. All of the 12 patients with MCC were diagnosed by preoperative fiberoptic colonoscopy and abdomen CT. For 29 patients with SCC， tumor locations were from proximal appendix to distal rectum， but 12 patients with MCC were adverse. Sixty-five （77.4%） tumors were tubular or papillary adenocarcinoma， and 56 （66.7%） tumors were well and moderately differentiated adenocarcinoma. The TNM stage of most tumors （72） was stageⅡ or Ⅲ phase， account for 85.7%. Radical surgeries were performed in 37 patients and palliative surgeries in 4 patients， and there were no complications after operation. During the follow-up for 3-5 years （mear 3.6 years）， the overall survival rate of 3- and 5-year were 48.8% （20/41） and 34.1% （14/41）， respectively. In detail， 3-year survival rate of SCC group and MCC group were 48.3% （14/29） and 50.0% （6/12）， respectively；5-year survival rate were 31.0% （9/29） and 41.7% （5/12）， respectively. Conclusions Cause of MPCC has not been clear， but it has possible relationship with adenomatous polyps. Preoperative fiberoptic colonoscopy， abdomen CT， and barium enema are very important for patients with SCC， and intraoperative fiberoptic colonoscopy is also necessary. Patients with MCC should enhance postoperative follow-up with fiberoptic colonoscopy. Further more， radical resection should be performed as early as possible.
Objective To detect the expression of thromhospondin-1 （TSP-1） in gastric cancer and metastaticlymph node tissues， and to study its relationship of TSP-1 to clinicopathologic parameters or tumor angiogenesis. Methods The TSP-1 and vascular endothelial growth factor （VEGF） expressions and microvessel density （MVD） were evaluated by immunohistochemistry in 72 specimens obtained by gastric resection from patients with gastric cancer， including corres-ponding adjacent normal gastric mucosa tissues （distant from cancer ≥5 cm） and lymph nodes surrounding cancer. A semiquantitative scoring system was used for evaluating the staining. The relationship of TSP-1 to VEGF expression， MVD， or clinicopathologic parameters was analyzed. Results ① TSP-1 positive expression rate was 45.8% （33/72） in the primary gastric cancer tissues， 90.3% （65/72） in the corresponding adjacent normal gastric mucosa tissues， and 50.8% （30/59） in the metastatic lymph nodes tissues. The expressions of TSP-1 in the primary gastric cancer tissues and metastatic lymph nodes tissues were significantly lower than those in the adjacent normal gastric mucosa tissues （χ2=32.710，P=0.000；χ2=25.298， P=0.000）. The expression of TSP-1 had no statistical significance in the primary gastric cancer tissues as compared with in the metastatic lymph nodes tissues （χ2=0.327， P=0.568）. ② The expression of TSP-1 in the metastatic lymph nodes tissues was significantly lower than that in the non-metastatic lymph nodes tissues （Z=-2.573， P=0.010）. ③The expression of TSP-1 in the primary gastric cancer tissues and metastatic lymph nodes tissues suggested a negative correlation with VEGF （rs=-0.309， P=0.008；rs=-0.269， P=0.040） and MVD （rs=-0.348， P=0.003；rs=-0.272， P=0.037）. Conclusions TSP-1 expression is down-regulated and has a negative correlation with VEGF and MVD in the primary gastric cancer and the metastatic lymph nodes tissues. According to the present results， it seems likely that TSP-1 is a tumor angiogenesis inhibitor.
Objective To analyze the influencing factors on postoperative complications and mortality of gastric cancer after total gastrectomy. Methods The clinical data of 622 patients with gastric cancer received total gastrectomy were collected. According to the extent of lymph node dissection, the patients were divided into 2 groups: D0/D1 group (n=35) and D2/D3 group (n=587). The risk factors influencing postoperative morbidity and mortality were determined by logistic multiple regression analysis. Results The total postoperative complication morbidity and mortality for all patients were 9.81% (61/622) and 2.89% (18/622), respectively. The postoperative complication morbidity was 8.57% (3/35) and 9.88% (58/587) in the two groups, the postoperative mortality was 2.86% (1/35) and 2.90% (17/587) in the two groups, there were no significant differences between the two groups (Pgt;0.05). The most common postoperative complication was intestinal obstruction (18.03%, 11/61). Multivariate analysis revealed that risk factors on the postoperative complications and mortality were age ≥ 70 years, TNM stage Ⅳ, preoperative complication, palliative excision, merely manual or mechanical anastomosis, and multivisceral resection (Plt;0.05), however, the extent of lymph node was not influencing factor (Pgt;0.05). Conclusions Patients with advanced gastric cancer have a high risk of postoperative complications and mortality. Multiple organ resection should be avoided for patients with gastric cancer of TNM stage Ⅳ.
ObjectiveTo investigate the values of serum CEA and CA19-9 in predicting postoperative recurrence and metastasis and prognosis for gastric cancer. MethodsPreoperative serum levels of CEA and CA19-9 were measured by electrochemiluminescence assay in 136 patients with gastric cancer. The relationships of serum CEA level, CA19-9 level to clinicopathologic features, postoperative recurrence and metastasis, and prognosis of gastric cancer were analyzed. Kaplan-Meier method (log-rank test) was used to survival analysis. ResultsThere were 67 patients with postoperative recurrence and metastasis in 136 patients with gastric cancer. The positive rate was 48.5% (66/136) for CEA and 43.4% (59/136) for CA19-9. There was a significant correlation between CEA level and T stage, TNM stage, lymph node metastasis, or vascular invasion (P=0.011, P=0.018, P=0.021, P=0.024). There was a significant correlation between CA19-9 level and T stage or lymph node metastasis (P=0.018, P=0.045). The rate of postoperative recurrence and metastasis was 60.6% (40/66) in positive CEA, 61.0% (36/59) in positive CA19-9, 38.6% (27/70) in negative CEA, and 40.3% (31/77) in negative CA19-9, respectively. The rate of postoperative recurrence and metastasis in the positive CEA or positive CA19-9 was significantly higher than those in the negative CEA or negative CA19-9 (P=0.010, P=0.016). Kaplan-Meier analysis showed that patients with positive CEA or positive CA19-9 had worse survival than those with negative CEA or CA19-9 (P=0.003, P=0.007). ConclusionsCEA and CA19-9 have important values in detecting recurrence and metastasis, predicting patient survival after gastric cancer surgery. Combined analysis of these markers is considered to be helpful for improving the prediction of the postoperative recurrence and metastasis and prognosis of gastric cancer.