Epigallocatechin gallate inhibits dimethylhydrazine-induced colorectal cancer in rats.

BACKGROUND: Epigallocatechin gallate (EGCG) is a polyhydroxy phenolic compound extracted from tea and its antitumor effect has received widespread attention. We explored the inhibitory effect of EGCG on dimethylhydrazine (DMH)-induced colorectal cancer (CRC) using a rat model, predicted the interaction between EGCG and CRC target genes using a database, and explained the EGCG associated target pathways and mechanisms in CRC. AIM: To understand the inhibitory mechanisms of EGCG on CRC cell proliferation and identify its pharmacological targets by network pharmacology analysis. METHODS: DMH (40 mg/kg, s.c., twice weekly for eight weeks) was used to induce CRC in rats. After model establishment, the rats were administered with EGCG (50, 100, or 200 mg/kg, p.o., once daily for eight weeks) and killed 12 and 20 wk after the start of the experiment. Formation of aberrant crypt foci and tumor was studied by histological analysis. Using network pharmacology analysis, candidate and collective targets of EGCG and CRC were identified, and Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses were used to predict the pathways altered by EGCG. RESULTS: At week 12, high-dose EGCG treatment significantly reduced the tumor formation rate, total number of tumors, cancerous and non-cancerous tumors, tumor volume, ascites formation, and aberrant crypt foci count. At week 20, all three doses of EGCG were effective. Seventy-eight collective targets of EGCG and CRC were identified, of which 28 genes were dysregulated in CRC. Kyoto Encyclopedia of Genes and Genomes and GO analyses showed that the dysregulated genes were enriched in hsa05210 (CRC), hsa04115 (p53 signaling pathway), and hsa04151 (PI3K-Akt signaling pathway), GO:0043124 (negative regulation of I-kappaB kinase/NF-kappaB signaling pathway), GO:0043409 (negative regulation of mitogen-activated protein kinase cascade), and GO:2001244 (positive regulation of intrinsic apoptotic signaling pathway) respectively. CONCLUSION: EGCG inhibits the formation of DMH-induced CRC by regulating key pathways involved in tumorigenesis.

Measurement system that improves the accuracy of polyp size determined at colonoscopy.

AIM: To assess the accuracy of polyp size using an endoscopic lesion measurement system (ELMS). METHODS: The accuracy of polyp size assessment was compared among measurements acquired by visual estimation, disposable graduated biopsy forceps (DGBF; used as a "scale-plate") and the ELMS. RESULTS: There were 192 polyps from 166 cases included in this study. The mean diameter of the post polypectomy measurement was 0.85±0.53 cm (range: 0.2-3.0 cm). The mean diameter by visual estimation was 1.10±0.53 cm, which was significantly different compared to the actual size of the polyp (P<0.001). The mean diameters obtained using DGBF (0.87±0.54 cm) and ELMS (0.85±0.53 cm) did not significantly differ from the actual size of the polyp. The difference between the measurements from the ELMS and DGBF was not significant. CONCLUSION: Unlike visual estimations at colonoscopy, endoscopic graduated biopsy forceps and the endoscopic lesion measurement system are accurate methods to estimate polyp size.

Use of disposable graduated biopsy forceps improves accuracy of polyp size measurements during endoscopy.

AIM: To determine the accuracy of endoscopic polyp size measurements using disposable graduated biopsy forceps (DGBF). METHODS: Gradations accurate to 1 mm were assessed with the wire of disposable graduated biopsy forceps. When a polyp was noted, endoscopists determined the width of the polyp; then, the graduated biopsy forceps was inserted and the largest diameter of the tumor was measured. After excision, during surgery or endoscopy, the polyp was measured using the vernier caliper. RESULTS: One hundred and thirty-three colorectal polyps from 119 patients were studied. The mean diameter, by post-polypectomy measurement, was 0.92 ± 0.69 cm; 83 were < 1 cm, 36 were between 1 and 2 cm, and 14 were > 2 cm. The mean diameter, by visual estimation, was 1.15 ± 0.88 cm; compared to the actual size measured using vernier calipers, the difference was statistically significant. The mean diameter measured using the DGBF was 0.93 ± 0.68 cm; compared to the actual size measured using vernier calipers, this difference was not statistically significant. The ratio between the mean size estimated by visual estimation and the actual size was significantly different from that between the mean size estimated using the DGBF and the actual size (1.26 ± 0.30 vs 1.02 ± 0.11). CONCLUSION: The accuracy of polyp size estimation was low by visual assessment; however, it improved when the DGBF was used.

[Manufacture and application of laparoscopic extraperitoneal sigmoid colostomy].

OBJECTIVE: To investigate the safety and feasibility of laparoscopic extraperitoneal sigmoid colostomy. METHODS: Thirty-six patients with low rectal cancer undergoing laproscopic abdominoperineal resection from July 2011 to July 2012 were prospectively enrolled in the study and randomly divided into extraperitoneal colostomy group(EPC, n=18) and internal peritoneal colostomy group(IPC, n=18). Follow-up period was 4-16 (median, 7) months and postoperative complications were compared between two groups. RESULTS: One case in EPC group was converted to IPC because of poor blood supply of the proximal sigmoid, who was eliminated from the subsequent analysis. Compared with the IPC group, the surgery time was longer in EPC group [(25.3±8.5) min vs. (14.7±6.4) min], while the difference was not statistically significant(P>0.05). Each group had 1 case of stoma ischemia, who both received the colostomy reconstructive surgery. The incidence of stoma edema was significantly higher in EPC group[35.3%(6/17) vs. 0, P<0.05). The early postoperative complications rate did not significantly different between the two groups[58.8%(10/17) vs. 27.8%(5/18), P>0.05]. The late postoperative complications rate was 22.2%(4/18) in IPC group, including 1 case of stoma prolapse, 1 case of stoma stenosis and 2 cases of parastomal hernia. No later postoperative complication occurred in EPC group. CONCLUSION: Extraperitoneal sigmoid colostomy is an easy and safe procedure with lower late complications as compared to internal peritoneal sigmoid colostomy.

[Experimental study of the impact of hyperlipidemia on the chemotherapy in colorectal cancer model].

OBJECTIVE: To study the effect of hyperlipidemia on the prognosis and therapeutic response for colorectal cancer and to explore the associated mechanism. METHODS: The hyperlipidemic subcutaneous heterotopic colorectal cancer orthotopic transplant model of nude mice was established by feeding high fat diet and performing transplantation. Seventy mice were divided into 7 groups with 10 mice in each group. Two groups were used as pre-experiment. The remaining 5 groups included 4 high-fat groups (G1 to G4), and 1 normal-diet control group (G5). G1, G2, G3, G4, and G5 received normal saline, capecitabine, simvastatin, capecitabine plus simvastatin and capecitabine respectively for 3 weeks. Changes of tumor volume, tumor weight, tumor growth rate and blood lipid parameters (TC, TG, HDL, LDL, Lpa, apoA and apoB) were observed. RESULTS: In G1 to G4, TC, HDL, apoA, TG, LDL, Lpa, apoB increased, but only TC, HDL, apoA were significantly different as compared with G5 (P=0.020, P=0.001, P=0.001, P=0.911, P=0.249, P=0.681, P=0.053). The tumor in G1 grew fastest, and its growth rate was significantly different as compared with G2, G4, G5 except G3 (P=0.001, P=0.806, P=0.001, P=0.010). The tumor growth rate of G3 was lower than group G1, but higher than G2, G4, G5 with significant difference (P=0.001, P=0.002, P=0.016). The tumor of G5 grew faster than G2 and G4, but without significant differences (P=0.051, P=0.070). The tumor of G4 grew slowest without significant difference as compared to G2 (P=0.438). Compared with pre-administration, at the third week, the TC of G1 was increased [(3.8±0.4) mmol/L], while the other 4 groups decreased [G2 (2.8±1.8) mmol/L, G3 (2.9±0.7) mmol/L, G4 (1.4±0.9) mmol/L, G5 (2.1±0.2) mmol/L]. G4 decreased significantly (P=0.004). At the fifth week, the TC of all the 5 groups decreased, while the lipids of G4 were higher as compared to those at the third week. The TG, Lpa, ApoA were significantly decreased at the third week (all P<0.05), while no significant differences were found in HDL and apoB. CONCLUSIONS: A hyperlipidemia colon tumor model involving subcutaneous colon translocation and orthotopic transplantation of nude mice is successfully established. This model is an ideal research model for hyperlipidemia and colorectal cancer. The effect of capecitabine on tumors in hyperlipidemia groups is better as compared to normal diet group. The proliferation of tumor cells can increase serum total serum cholesterol.

[Expression of JAG1 and DLL1 genes in colorectal cancer and its clinical significance].

OBJECTIVE: To study the expression of JAG1 and DLL1 in colorectal cancer and its clinical significance. METHODS: Patients with colorectal cancer were treated in the Center of Colorectal Surgery of the Third Affiliated Hospital of Nanjing University of TCM were collected prospectively and followed up. A tissue microarray was made and expressions of JAG1 and DLL1 were detected by immunohistochemical staining. RESULTS: A total of 146 cases with colorectal cancer were included. The differences in JAG1 expression were significant among different tumor differentiation types and the differences in DLL1 expression were significant among different tumor locations(all P<0.05). There were no significant differences in the expression of the two genes and microsatellite instability(MSI)(P>0.05). One hundred and thirty-four (91.8%) cases were followed up and the mean follow-up time was (42.3±13.3) months. Tumor-free survival was noticed in 86 patients. The overall survival was 93% at 1 year, 74% in 3 years, and 67% in 5 years. Multivariate analysis showed that long-term survival rate was related to TMN stage, pathology types, MSI status and expression of JAG1. The prognosis of patients with high expression of JAG1 was better than those with low and negative expression(P<0.05). CONCLUSIONS: The expressions of JAG1 and DLL1 are related to tumor differentiation and tumor location. The expression of JAG1 gene is associated with long-term survival.

Expression and clinical significance of Notch signaling genes in colorectal cancer.

The objective of this study was to explore the expression and clinical significance of Notch signaling genes in colorectal cancer. Colorectal cancer samples were prospectively collected from patients post-surgery at the 3rd Affiliated Hospital, Nanjing University of Traditional Chinese Medicine. Immunohistochemistry of tissue arrays was used to analyze the samples and genes involved in the Notch signaling pathway. Microsatellite instability (MSI) was detected by fluorescence multiplex polymerase chain reaction. A total of 146 colorectal cancer samples were collected, including 84 men (57.7%) and 62 women (42.5%). The average age of the study population was 60.8 ± 10.5 years. Notch1 and Notch2 gene expression correlated with tumor pathology type and degree of differentiation. In addition, Jagged 1 (JAG1) and hairy enhancer of split 1 gene expression correlated with the degree of tumor differentiation. Delta-like 1 gene expression varied significantly with tumor location. There was a significant difference between gene expression and MSI. Of the 138 patients, 134 (91.8%) participated in on-site visits, and the average follow-up time was 42.3 ± 13.3 months. During this period, 86 patients (71.6%) were tumor-free. At 1 year post-surgery, 93% of patients were alive, 74% of patients lived for 3 years, and 67% of patients lived for 5 years. The log-rank test was used to perform univariate analysis, and the COX proportional hazards model was used for the multivariate analysis. Based on these analyses, tumor prognosis correlated with the TNM stage, pathological type, microsatellite status as well as Notch2 and JAG1 gene expression. Patients expressing high levels of Notch2 and JAG1 presented with a significantly better prognosis compared to patients expressing negative or weak levels of Notch2 and JAG1. The expression levels of genes associated with the Notch signaling pathway correlated with tumor pathology and the degree of differentiation. In addition, Notch2 and JAG1 expression levels correlated with survival; however, the underlying mechanism for these correlations remains unclear.

Anal fistula plug vs mucosa advancement flap in complex fistula-in-ano: A meta-analysis.

AIM: To investigate the efficacy of the anal fistula plug (AFP) compared to the mucosa advancement flap (MAF), considered the best procedure for patients with a complex anal fistula. METHODS: The literature search included PubMed, EMBASE, Cochrane Library and OVID original studies on the topic of AFP compared to MAF for complex fistula-in-ano that had a deadline for publication by April 2011. Randomized controlled trials, controlled clinical trials and prospective cohort studies were included in the review. After information collection, a meta-analysis was performed using data on overall success rates as well as incidence of incontinence and morbidity. The quality of postoperative life was also included with the clinical results. RESULTS: Six studies involving 408 patients (AFP = 167, MAF = 241) were included in the meta-analysis. The differences in the overall success rates and incidence of fistula recurrence were not statistically significant between the AFP and MAF [risk difference (RD) = -0.12, 95%CI: -0.39 - 0.14; RD = 0.13; 95%CI: -0.18 - 0.43, respectively]. However, for the AFP, the risk of postoperative impaired continence was lower (RD = -0.08, 95%CI: -0.15 - -0.02) as was the incidence of other complications (RD = -0.06, 95%CI: -0.11 - -0.00). The postoperative quality of life, for patients treated using the AFP was superior to that of the MAF patients. Patients treated with the AFP had less persistent pain of a shorter duration and the healing time of the fistula and hospital stay were also reduced. CONCLUSION: The AFP is an effective procedure for patients with a complex anal fistula; it has the same success rate but a lower risk of complications than the MAF and may also be associated with an improved postoperative quality of life. Additional evidence is needed to confirm these findings.

[Inhibitory effect and mechanism of (-)-epigallocatechin-3-gallate on HT29 and HCT-8 colorectal cancer cell lines and expression of HES1 and JAG1].

OBJECTIVE: To study the inhibitory effect of (-)-epigallocatechin-3-gallate (EGCG) on cancer cells line HCT-8 and HT29 and its influence on the expression of HES1 and JAG1. METHODS: Colorectal cancer cells line HCT-8 and HT29 were cultured in vitro and treated with different concentrations of EGCG(10 mg/L, 20 mg/L, 35 mg/L). The inhibition of proliferation was tested by MTT analysis. Influence of EGCG on the cell apoptosis and cell cycle of HCT-8 and HT29 were detected with flow cytometry, and gene expression of HCT-8 and HT29 after EGCG treatment with real-time polymerase chain reaction. RESULTS: EGCG affected the proliferation and apoptosis of HCT-8 and HT29. The inhibition rates of the three different concentrations of EGCG were(28.894±5.076)%, (34.903±1.794)%, and (39.028±0.105)% on HCT-8, and (14.682±4.244)%, (22.429±3.847)%, and (29.840±5.076)% on HT29. EGCG caused G(2)/M phase arrest and M phase transition in HCT-8 cell line, and S phase arrest and G2 phase transition in HT29 cell line. EGCG down-regulated HES1 gene expression in both cell lines, however, the differences were not statistically significant(both P>0.05). EGCG upregulated JAG1 gene expression in both cell lines, however only the difference in HCT-8 was statistically significant(0.201±0.018 vs. 0.440±0.077, P=0.029). CONCLUSIONS: EGCG can significantly inhibit the proliferation of HT29 cells and HCT-8 cells by changing cell cycle and inducing cell apoptosis. The mechanism may be related to the upregulation of JAG1 gene expression.

[Influence of microsatellite instability on survival of patients with sporadic colorectal cancer in China].

OBJECTIVE: To investigate the role of microsatellite instability(MSI) in Chinese sporadic coloretal cancer. METHODS: A total of 146 patients with colorectal cancer were treated surgically from August 2004 to September 2006 in the Third Affiliated Hospital of Nanjing University of Traditional Chinese Medicine. Data were collected prospectively. Univariate and multivariable analyses were performed for parameters such as age, gender, tumor location, differentiation, MSI, tumor type, lymph node metastasis, TNM stage, and survival. RESULTS: Follow-up was available in 134 patients including telephone call and office visit. MSI(P=0.029), tumor type(P=0.000), TNM stage(P=0.000) were independently associated with survival on Cox regression model. There were 26 patients with MSI, and the 1-, 3-, and 5-year survival rates were 100%, 92.3%, and 92.3%, respectively. The remaining 108 patients had microsatellite stable tumor, and the 1-, 3-, and 5-year survival rates were 96.3%, 72.2%, and 63.5%, respectively. The difference was statistically significant(P=0.016). CONCLUSION: Microsatellite instability is an important factor associated with patient survival in Chinese sporadic colorectal cancer.

[Expression pattern and clinical significance of hairy enhancer of split 1 in colorectal cancer].

OBJECTIVE: To explore the roles of hairy enhancer of split 1 (Hes1) gene in colorectal cancer and analyze its clinical significance. METHODS: A total of 146 cases with colorectal cancer at our hospital were collected prospectively and followed up. There were 84 males and 62 females with an average age of (61 ± 11) years old. Tissue microarray was prepared and the expression of Notch signal genes were detected by immunohistochemical staining. RESULTS: The differential expressions of Hes1 were significant among various types [negative or weakly positive: 8% (12/146), positive(+): 77% (112/146), positive(++): 15% (22/146)]. Among all, 134 were followed up successfully for an average duration of (42 ± 13) months. According to the Kaplan-Meier life curve, the overall 1, 3 and 5-year survival rates were 93% (136/146), 74% (108/146) and 67% (98/146) respectively. The long-term survival rate was correlated with TNM stage and pathological types (all P = 0.000), but not with Hes1 (P = 0.267). CONCLUSION: The expression of Hes1 is correlated with pathological types and differentiation types. However the long-term survival rate is not correlated with its expression.

Retrorectal tumors in adults: magnetic resonance imaging findings.

AIM: To retrospectively evaluate the magnetic resonance imaging (MRI) features of adult retrorectal tumors and compare with histopathologic findings. METHODS: MRI features of 21 patients with preoperative suspicion of retrorectal tumors were analyzed based on the histopathological and clinical data. RESULTS: Fourteen benign cystic lesions appeared hypointense on T1-weighted images, and hyperintense on T2-weighted images with regular peripheral rim. Epidermoid or dermoid cysts were unilocular, and tailgut cysts were multilocular. Presence of intracystic intermediate signal intensity was observed in one case of tailgut cyst with a component of adenocarcinoma. Six solid tumors were malignant lesions and showed heterogeneous intensity on MRI. Mucinous adenocarcinomas showed high signal intensity on T2-weighted and mesh-like enhancing areas on fat-suppressed T2-weighted images. There was a fistula between the mass and anus with an internal opening in mucinous adenocarcinomas arising from anal fistula. Gastrointestinal stromal tumors displayed low signal intensity on T1-weighted images, and intermediate to high signal intensity on T2-weighted images. Central necrosis could be seen as a high signal on T2-weighted images. CONCLUSION: MRI is a helpful technique to define the extent of the retrorectal tumor and its relationship to the surrounding structures, and also to demonstrate possible complications so as to choose the best surgical approach.

[Distribution characteristics of colorectal neoplasm in 4450 patients and implication for colorectal cancer screening].

OBJECTIVE: To study the distribution characteristics of colorectal neoplasm and evaluate the implication for colorectal cancer screening. METHODS: A total of 17,939 colonoscopies were performed in the National Center of Colorectal Surgery between October 2004 and June 2009. Characteristics of colorectal neoplasm including anatomical distribution, sex, and age were investigated. RESULTS: Colorectal neoplasm was found in 24.8% (4450/17,939) of the patients during colonoscopy, including adenomatous polyp (n=3410, 19.0%) and adenocarcinoma (n=1040, 5.8%). The prevalence of colorectal neoplasm was higher in male and significantly increased in patients older than 40 years. 63.3% of the lesions located at the distal colon (sigmoid colon and rectum) and 36.7% at the proximal colon (36.7%). In patients with adenomatous polyp, 52.8% (1802/3410) of the lesions were at the distal colon, 30.8% (1049/3410) at the proximal colon, and 16.4% (559/3410) at both distal and proximal colon. In patients with carcinoma (n=1040), 921 (88.6%) lesions located at the distal colon, 118 (11.3%) at the proximal colon, and 1 (0.1%) at both segments. CONCLUSION: Sigmoidoscopy is inadequate for colorectal cancer screening as compared to colonoscopy.

[Tea polyphenol inhibits colorectal cancer with microsatellite instability by regulating the expressions of HES1, JAG1, MT2A and MAFA].

OBJECTIVE: To investigate the mechanism of tea polyphenol in inhibiting microsatellite instability (MSI) of colorectal cancer. METHODS: Using LoVo cells and SW480 cells treated with aqueous solution of tea polyphenol, cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) method, changes in microsatellite sequences were detected by genescan method and changes in gene expression of LoVo cells were detected by illumina expression arrays and quantitative real-time polymerase chain reaction (PCR). RESULTS: The proliferation inhibition rates of LoVo and SW480 cells treated with tea polyphenol increased with the increasing of drug concentration and showed an increasing tendency with time. The proliferation inhibition rate of LoVo cells with tea polyphenol was higher than that of SW480 cells, and there was a significant difference in the proliferation inhibition rates at 24 h, 72 h and one week. The microsatellite sequence of LoVo cells treated with tea polyphenol remained stable. The gene expression arrays and quantitative real-time PCR suggested that tea polyphenol inhibited the gene expressions of MT2A, MAFA, HES1 and JAG1 nearly two-fold over controls. It was also found that tea polyphenol inhibited the BAX and p38 genes with a more than two-fold difference but did not significantly inhibit the nuclear factor-κB pathway. CONCLUSION: Tea polyphenol significantly inhibited the proliferation of MSI colorectal cancer cells and stably maintained the microsatellite state in MSI colorectal cancer. Tea polyphenol inhibited the gene expressions of HES1, JAG1, MT2A and MAFA, up-regulated the gene expression of BAX and down-regulated that of P38. Further research is required to investigate how these pathways are interrelated.

[Impact of polyamidoamine dendrimer liposome on the cellular uptake and cytotoxicity of colonic cancer cells].

OBJECTIVE: To evaluate the effects of polyamidoamine dendrimer (PAMAM) liposome as gene carriers on the cellular uptake and its cytotoxicity in colonic cancer cell. METHODS: The liposome modified PAMAM was synthesized with liposome and polyamidoamine dendrimer. Plasmid PEGFP-N1 was mixed with the liposome-modified PAMAM or unmodified PAMAM to form nanoparticle complexes. The shape and size of the nanoparticle complexes were observed by transmission electron microscope and the zeta potential was measured by analytical tool. The encapsulating efficiency was determined by ultraviolet spectrophotometer in centrifuging method. After the cell lines SW620 (colonic cancer cell), MCF-7 (breast cancer cell), ECV304 (vascular endothelial cell) were transfected by the two kinds of PAMAM nanoparticle complexes, the flow cytometry was used to determine the uptake of enhanced green fluorescent protein (EGFP) gene. The cytotoxicity of PAMAM liposome nanoparticles and PAMAM nanoparticles was evaluated by MTT assay. RESULTS: The diameter of liposome modified PAMAM complex was (192 ± 16) nm, and that of PAMAM complex was (189 ± 19) nm (P > 0.05); and the zeta potential of liposome modified PAMAM complex was higher than that of PAMAM complex [(42 ± 7) mV vs. (32 ± 7) mV, P < 0.05]. There was no significant difference in envelopment rate between the two groups [(82 ± 7)% vs. (84 ± 6)%, P > 0.05]. After the colonic cancer cell line SW620 was transfected with the two kinds of PAMAM nanoparticle complexes, the cellular uptake of the cells with the liposome-modified PAMAM complex was significantly higher than that of the cell with PAMAM complex (P < 0.05). The cellular survival rate of the cell lines with liposome-modified PAMAM complex was significantly higher than that of cell lines with PAMAM complex (P < 0.05). CONCLUSION: The liposome modified PAMAM can improve gene transfection efficiency and suppress its cytotoxicity.

[Establishment of colostomy orthotopic transplantation mice and study on their biological characteristics].

OBJECTIVE: To establish a colorectal cancer colostomy orthotopic transplantation mice model. METHODS: A colostomy was preformed in BALB/C nu-nu nude mice. After two weeks, when the stoma healed, tumor tissues developed from Lovo cells were implanted into the submucosa of the stoma. When tumor grew up to 5 mm, fluorouracil(5-FU, 20 mg/kg) was administrated by intraperitoneal injection. Tumor developed at the colostomy was observed and its biological characteristics and behaviour were evaluated. RESULTS: Colostomy was performed in 10 mice and stoma healed at two weeks. Ten colostomies developed detectable tumor in two to three weeks. Three to five weeks later, the tumors grew up to 5 mm. Survival time of mice injected with 5-FU was(15.2+/-3.7) weeks (ranged:11-21 weeks), and the survival time of the no-treatment group was(12.3+/-2.8) weeks(ranged:9-19 weeks). The difference was statistically significant(P=0.001). The rate of mesenteric metastasis was 1/5 and 2/5 in the treatment and no-treatment group respectively. CONCLUSION: Colostomy orthotopic transplantation mice model is an ideal mice model with the advantages of having high success rate, visualization of implanted tumor in living animal, long survival time and significant tumor response to common chemotherapeutic agent.

Symptomatic gallstones after sleeve gastrectomy.

BACKGROUND: Cholelithiasis is a common complication after bariatric surgery. Pure restrictive procedures such as sleeve gastrectomy and gastric banding theoretically should result in less gallstone formation because the food continues to follow the normal gastrointestinal transit, maintaining the enteric-endocrine reflex intact. To the authors' knowledge, the literature has no studies that analyze the incidence of gallstone formation after sleeve gastrectomy. This study aimed to compare the rates of symptomatic gallstones between laparoscopic Roux-en-Y gastric bypass (RYGBP) and sleeve gastrectomy (SG). METHODS: A retrospective chart review of patients who underwent laparoscopic RYGBP and SG between 2004 and 2006 was performed. The patients with previous cholecystectomy, known gallstones with or without concomitant cholecystectomy, and previous weight-reduction operations were excluded from the analysis. The outcome measures were the numbers of patients who had experienced symptomatic and complicated gallstones. Using Cox regression analysis, comparisons was made between the patients with laparoscopic RYGBP (group A) and those with laparoscopic SG (group B). RESULTS: Groups A excluded 174 (26%) of 670 patients, and group B excluded 27 (34.2%) of 79 patients. The patients in group A had a significantly higher preoperative body mass index (BMI) than those in group B. Additionally, more group A than group B patients had a BMI exceeding 45 and more than a 25% loss of original weight. No significant difference in the development of symptomatic (8.7% vs. 3.8%; p = 0.296) or complicated (1.8% vs. 1.9%; p = 0.956) gallstones was noted between the two groups CONCLUSIONS: There was no significant difference in symptomatic or complicated gallstone disease between the patients treated with laparoscopic SG and those treated with laparoscopic RYGBP. Routine prophylactic cholecystectomy should not be recommended for weight reduction during laparoscopic SG.

[Anticancer effects of tea polyphenols on colorectal cancer with microsatellite instability in nude mice].

OBJECTIVE: To study the anticancer effects of tea polyphenols on colorectal cancer with microsatellite instability (MSI) in nude mice and to explore its mechanism. METHODS: A colostomy was performed on the caecum of nude mice. Tumor fragments collected from the subcutaneous tumor of hMSH2-absence colon carcinoma Lovo cell line were surgically implanted onto the submucosa of the caecum during colostomy to establish the model. Then, the nude mice were divided into untreated group and 50, 75 and 100 mg/kg tea polyphenols groups. The mice in tea polyphenols-treated groups were given intra-abdominal injection of 50, 75 and 100 mg/kg tea polyphenols respectively. The inhibition rates of tumors were calculated, and microsatellite instability (MSI) and the alteration of transforming growth factor-beta1 (TGF-beta1), TGF-beta2 and insulin-like growth factor (IGF) were detected by Genescan method at different times after the injection. RESULTS: The tumor volumes of the three groups began to decrease at the 1st week and decreased most greatly from 2 to 3 weeks after treatment, and then the tumors tended to increase. The study found that tea polyphenols could inhibit the tumor growth. The tumor inhibition rates in the three treated groups were significantly higher than those in untreated group 1, 2, 3 and 4 weeks after treatment (P<0.01). Detection of MSI showed that the colorectal tumor in the untreated group presented with four MSI signs, including BAT-25, D2S123, D5S346 and D17S250, and TGF-beta1, TGF-beta2, IGF expressions. After using the tea polyphenols, the microsatellite tended to become stable. CONCLUSION: Tea polyphenols can inhibit the mismatch-repair-gene deficient colorectal cancer in nude mice by down-regulating the microsatellite instability.

[Application of magnetic resonance imaging in the diagnosis of complex anal fistula].

OBJECTIVE: To evaluate the value of magnetic resonance imaging (MRI) in the diagnosis of complex anal fistula. METHODS: The preoperative digital examination and MRI with the phased-array coil were implemented for 28 patients who were clinically suspected with complex anal fistula. The final diagnosis were based on surgical findings. Outcomes of MRI and digital examination were compared with surgical results. RESULTS: Twenty-five patients were diagnosed as complex anal fistula, 1 presacral cyst and 2 chronic anorectal fistula combined with perianal mucinous adenocarcinoma. All the patients were correctly diagnosed by MRI,while the patients with presacral cyst and perianal mucinous adenocarcinoma could not be diagnosed correctly by digital examination. According to the Parks classification, 3 patients were suffered from trans-sphincteric fistula, 10 intersphincteric, 5 supra- sphincteric and 7 extra-sphincteric. The diagnosis rates of the internal opening with digital examination and MRI were 48% and 84%, the rates of the primary tract were 76% and 100%, and the rates of the secondary extensions were 57.9% and 94.7% respectively. The differences in detection of internal opening, primary tract and secondary extensions between MRI and digital examination were significant (P<0.01). CONCLUSION: MRI with the phased-array coil can correctly orient the internal opening and direction of the complex anal fistula, and find the relationship between anorectal sphincters and the complex fistula.

[Study of germline mutation of hMSH2, hMSH6 and hMLH1 and methylation of hMLH1 in microsatellite instability colorectal cancer].

OBJECTIVE: To study the characteristics of germline mutations of hMLH1, hMSH2 and hMSH6 and promoter methylation status of MLH1 in patients with MSI colorectal cancer. METHODS: Sequence analysis of germline mutation and promoter methylation of MLH1 in 34 prospective collected patients with MSI colorectal cancer were performed. RESULTS: Nineteen out of 34 patients with MSI colorectal cancer were detected with hypermethylation of MLH1,which accounted for 55.9%. 73.7% MSI-H colorectal cancer cases and 33.3% MSI-L colorectal cancer cases were detected with hypermethylation of MLH1 and the difference was significant. Eight germline mutations were found, including 3 MSH6 mutations and 5 MSH2 mutations. CONCLUSION: There are some different characteristics of the germline mutations of hMLH1, hMSH2 and hMSH6 and promoter methylation of MLH1 in Chinese MSI colorectal patients.