Manufacture and application of laparoscopic extraperitoneal sigmoid colostomy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the safety and feasibility of laparoscopic extraperitoneal sigmoid colostomy.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>Extraperitoneal sigmoid colostomy is an easy and safe procedure with lower late complications as compared to internal peritoneal sigmoid colostomy.</p>

Experimental study of the impact of hyperlipidemia on the chemotherapy in colorectal cancer model / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the effect of hyperlipidemia on the prognosis and therapeutic response for colorectal cancer and to explore the associated mechanism.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Expression of JAG1 and DLL1 genes in colorectal cancer and its clinical significance / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the expression of JAG1 and DLL1 in colorectal cancer and its clinical significance.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

Influence of microsatellite instability on survival of patients with sporadic colorectal cancer in China / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the role of microsatellite instability(MSI) in Chinese sporadic coloretal cancer.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>Microsatellite instability is an important factor associated with patient survival in Chinese sporadic colorectal cancer.</p>

Inhibitory effect and mechanism of (-)-epigallocatechin-3-gallate on HT29 and HCT-8 colorectal cancer cell lines and expression of HES1 and JAG1 / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

Distribution characteristics of colorectal neoplasm in 4450 patients and implication for colorectal cancer screening / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the distribution characteristics of colorectal neoplasm and evaluate the implication for colorectal cancer screening.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>Sigmoidoscopy is inadequate for colorectal cancer screening as compared to colonoscopy.</p>

Impact of polyamidoamine dendrimer liposome on the cellular uptake and cytotoxicity of colonic cancer cells / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the effects of polyamidoamine dendrimer (PAMAM) liposome as gene carriers on the cellular uptake and its cytotoxicity in colonic cancer cell.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>The liposome modified PAMAM can improve gene transfection efficiency and suppress its cytotoxicity.</p>

Establishment of colostomy orthotopic transplantation mice and study on their biological characteristics / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To establish a colorectal cancer colostomy orthotopic transplantation mice model.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Application of magnetic resonance imaging in the diagnosis of complex anal fistula / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the value of magnetic resonance imaging (MRI) in the diagnosis of complex anal fistula.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>

Study of germline mutation of hMSH2, hMSH6 and hMLH1 and methylation of hMLH1 in microsatellite instability colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the characteristics of germline mutations of hMLH1, hMSH2 and hMSH6 and promoter methylation status of MLH1 in patients with MSI colorectal cancer.</p><p><b>METHODS</b>Sequence analysis of germline mutation and promoter methylation of MLH1 in 34 prospective collected patients with MSI colorectal cancer were performed.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>There are some different characteristics of the germline mutations of hMLH1, hMSH2 and hMSH6 and promoter methylation of MLH1 in Chinese MSI colorectal patients.</p>

Study the value of screening hereditary nonpolyposis colorectal cancer kindreds by detecting the expression of hMLH1/hMSH2 with tissue microarray / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the value of screening hereditary nonpolyposis colorectal cancer (HNPCC) kindreds by detecting the expressions of hMLH1/hMSH2 with tissue microarray.</p><p><b>METHODS</b>A tissue microarray with 22 colorectal cancers from HNPCC families and 15 sporadic colorectal cancers was established, and the expressions of hMLH1/hMSH2 were detected by immunohistochemistry (IHC).</p><p><b>RESULTS</b>The expressions of hMLH1 or hMSH2 were negative in 15 of 22 HNPCC and 1 of 15 sporadic colorectal cancers in routine IHC. The expressions of hMLH1 or hMSH2 were negative in 17 of 22 HNPCC and 2 of 15 sporadic colorectal cancers in tissue microarray. The examination of hMSH2 expression yielded same results between routine IHC and tissue microarray. There were no difference on the hMLH1 expressions between routine IHC and tissue microarray.</p><p><b>CONCLUSION</b>Tissue microarray is a high-throughput way to detect the expressions of hMLH1/hMSH2 and is applicable to screen HNPCC kindreds.</p>

Detection of microsatellite instability in colorectal cancer by fluorescence multiplex polymerase chain reaction and its clinical value / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To detect microsatellite instability(MSI) in colorectal cancer by fluorescence multiplex polymerase chain reaction(FM-PCR) and explore its clinical value.</p><p><b>METHODS</b>MSI of 110 colorectal cancer patients undergone surgical resection in our department from 2004 to 2005 were examined by FM-PCR, and the pathological characteristics were compared between MSI and microsatellite stable (MSS) colorectal cancer patients.</p><p><b>RESULTS</b>Among 110 cases, the male were 66 and the female were 44. Mean age was 60.8 (26-94) yrs. All 5 microsatellite markers were amplified. Out of them, 10 cases (8.1%) were MSI-H, 13 cases (11.8%) were MSI-L and 87 cases (79.1%) were MSS. Instability of BAT-26 was found in 9 cases (8.2%), BAT-25 was in 11 cases (10.0%), D2S123 was in 11 cases (10.0%), D5S346 was in 6 cases (8.2%) and D17S250 was in 8 cases (7.3%). Age between MSI and MSS colorectal cancer patients was significant and other pathological characteristics were not significant.</p><p><b>CONCLUSIONS</b>FM-PCR is a clinically stable method for MSI detection in colorectal cancer patients. There are no significant differences between MSI and MSS pathological characteristics of colorectal cancer patients.</p>

Indications for colonoscopy examination and its disease distribution: a report of 5690 cases / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the indications for colonoscopy examination and the distribution of diagnostic diseases.</p><p><b>METHOD</b>From Jan. 2000 to Dec. 2004, 5960 patients received colonoscopy examination in our colorectal center. The indications for colonoscopy examination and the distribution of its diagnostic diseases were analyzed.</p><p><b>RESULTS</b>There were 3096 males and 2594 females,and the mean age was (52+/-15) years. The reasons for colonoscopy included hemafecia (26.9%), atypical abdominal pain (25.8%), diarrhea or increased frequency of stool (11.1%), anal tenesmus or discomfort (7.6%), constipation (7.0%),mucous or bloody purulent stool (3.0%), intra-rectal mass or abdominal mass on physical examination (0.9%), re- examination after colonoscopic polypectomy (10.9%), re-examination after operation for colorectal cancer(1.5%), simple health examination (2.2%). Colonoscope reached the cecum in 97.7% of the cases,and at least one disease was found in 2283 cases (40.1%). Among them,colorectal cancer accounted for 10.3%, colorectal polyps 19.6%, ulcerative colitis 4.3%, and Crohn's disease 0.5% respectively.</p><p><b>CONCLUSION</b>The indications for colonoscopy are too strict to screen the early stage colorectal cancer. Colonoscopy should be performed in the cases with symptoms such as bloody stool, diarrhea, abdominal pain, constipation, or with colorectal polyps, after operation for colorectal cancer,or as members of hereditary colorectal cancer family.</p>

Analysis of the clinicopathological features of Chinese hereditary nonpolyposis colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological features of Chinese hereditary nonpolyposis colorectal cancer (HNPCC).</p><p><b>METHODS</b>Patients who met the Amsterdam criteria were enrolled in this study from several hospitals in China. Clinicopathological features of patients with HNPCC were compared between the patients with suspected HNPCC and sporadic colorectal cancer.</p><p><b>RESULTS</b>One hundred and sixty-seven individuals from 31 families met the Amsterdam criteria. The average age was 48.6 (22-78) years old. There were 43 cases (31.9%) with ascending colon cancer and 52 cases (38.5%) with rectal cancer. The 3-, 5-, 10- years survival rate was 70.3%, 49.9% and 39.7% respectively. The incidence of multiple primary neoplasms was 20.4% .</p><p><b>CONCLUSIONS</b>Chinese HNPCC is characterized by early disease onset. Rectal cancer and ascending colon cancer are the first and the secondly common cancer for Chinese HNPCC. Gastric cancer is the most common parenteral cancer in Chinese HNPCC families.</p>

The role of the immunohistochemistry for hMLH1 and hMSH2 with detection of microsatellite instability to identify the kindreds with hereditary nonpolyposis colorectal cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the specificity and sensitivity of the immunohistochemistry for hMLH1 and hMSH2 with detection of microsatellite instability (MSI) to identify the kindreds with hereditary nonpolyposis colorectal cancer and to analyse its value in clinical practice.</p><p><b>METHOD</b>Specimens of 16 cases with HNPCC and 16 cases with sporadic colorectal cancer were detected by immunostaining with hMLH1 and hMSH2 and MSI was also detected.</p><p><b>RESULTS</b>The specificity and sensitivity of the immunohistochemistry for hMLH1 and hMSH2 were 91.7% and 87.5% respectively. The specificity and sensitivity of MSI were 100% and 75.0%. By combining two methods, the specificity and sensitivity were 91.7% and 93.8% respectively.</p><p><b>CONCLUSIONS</b>By combination of the immunohistochemistry for hMLH1 and hMSH2 and detection of MSI to identify the kindreds with HNPCC, the specificity and sensitivity are improved which is better than to use either of them alone. And it is very easy and cheap that it can be used in clinics.</p>

Clinicopathological features of typical and non-typical hereditary non-polyposis colorectal cancer and their germline mutation of hMLH1 and hMSH2 / 中华外科杂志

<p><b>OBJECTIVE</b>To study the clinicopathological features of the Chinese hereditary non-polyposis colorectal cancer and its germline mutation of hMLH(1) and hMSH(2).</p><p><b>METHODS</b>Thirteen typical Chinese hereditary non-polyposis colorectal carcinoma (HNPC)C kindreds and 19 non-typical HNPCC families were registered and followed up. The germline mutation of the hMLH(1) and hMSH(2) of 12 index cases of 6 typical and 6 non-typical HNPCC were screened by PCR-SSCP. Samples with abnormal mobility were sequenced directly.</p><p><b>RESULTS</b>The average age of typical HNPCC was 47, no difference existed between sexes. Location of the tumors of typical HNPCC represented 44.7% on the right half colon and non-typical HNPCC 65.8% on the rectum. The rate of the metachronos cancer was 11.5%. The 3-, 5-and 10-year survival rate was 64.0%, 45.3% and 31.2% respectively. Among 12 cases, 8 showed abnormal mobility. Except for an intron polymorphism, six exons abnormalities were found in 5 of 12 proband. Sequencing showed 4 missense, 7 insertion and a nonsense mutations.</p><p><b>CONCLUSIONS</b>Chinese HNPCC is early onset, more common on proximal colon and better prognosis. Mutation of hMSH(2) is dominant in the Chinese typical HNPCC, but mutation of hMLH(1) is more common in the non-typical group.</p>