[Standardized use of sphincter preservation resection for rectal cancer].

Sphincter preservation resection has been the first choice for rectal cancer, not only for high and mid-rectal cancer, but also for low rectal cancer. Were sphincter preservation resection indicated and suitable for all of the patients with rectal cancer? The aim of this paper is to discuss when sphincter preservation resection should be chosen? Firstly we should have a thorough preoperative assessment for the patients. After that we should determine the indications of sphincter preservation resection according to the NCCN guideline. Meanwhile, surgical approach should be balanced between long term survival and functional outcomes.As a result, what is most important in sphincter preservation resection is reaching satisfaction both in curative resection and functional outcomes. These are also the reasons for rational utilization of sphincter preservation resection for rectal cancer.

[Diagnostic significance and management principles of colorectal intraepithelial neoplasia].

OBJECTIVE: To discuss the significance of pathological diagnosis of colorectal intraepithelial neoplasia and its treatment principles. METHODS: One hundred and fifty-eight cases with colorectal tumors were treated between January 2004 and June 2008, among them 73 cases of tumors were diagnosed as low grade intraepithelial neoplasia and 89 tumors as high grade intraepithelial neoplasia on biopsy. Five patients with adenoma were treated with endoscopic polypectomy, 49 patients with radical colectomy, 74 patients with low anterior resection (LAR), 16 patients with local excision, 2 patients with Hartmann operation, 4 patients with abdominal perineal resection, 7 patients with Parks coloanal anastomosis and 1 patient with sigmoid colostomy. The postoperative pathological examination result was compared with preoperative biopsy examination. RESULTS: With postoperative pathological examination, 109 cases (67.3%) were identified as infiltrative adenocarcinoma, among them 80 cases (89.9%) had been diagnosed as high grade intraepithelial neoplasia and the other 29 cases (39.7%) had been diagnosed as low grade intraepithelial neoplasia before the operation. In patients with infiltrative adenocarcinomas, 2 cases developed hepatic metastasis, 18 were classified as phase T4, and 26 cases (23.9%) were found with lymph nodes metastasis after the operation. CONCLUSIONS: We should pay more attention to tumors with a diagnosis of intraepithelial neoplasia due to its high potential of malignancy. When the lesion was highly suspected to be malignant, and the resection of the tumor would save the anal sphincter, the tumor should be treated with segmental resection. If the tumor could be confirmed as a infiltrating one then a curative resection is the first choice.

[Effect of neoadjuvant chemoradiotherapy on the healing of anastomosis following low anterior resection in locally advanced rectal cancer].

OBJECTIVE: To investigate the effect of the neoadjuvant chemoradiotherapy (NCR) on the healing of anastomosis following low anterior resection in patients with locally advanced rectal cancer. METHODS: Between May 2001 and August 2007, 192 patients with T3 and T4 low rectal cancer (distance from the tumor to anal verge 0.05). Anastomotic leakage occurred in 2 - 10 days post operation, and were managed properly and got desirable results. CONCLUSION: Neoadjuvant chemoradiotherapy would not affect the healing of anastomosis obviously if being applied reasonably in locally advanced low rectal cancer.

[Exploration on neoadjuvant chemoradiation in the treatment for locally advanced low rectal cancer].

OBJECTIVE: To explore the possibility of further improvement of the efficacy of neoadjuvant chemoradiotherapy in locally advanced lower rectal cancer and the management of patients with clinical complete regression. METHODS: From May 2001 to August 2007, 192 cases with locally advanced lower rectal cancer (T3/T4 or N(+)) received preoperative radiotherapy 40 - 46 Gy/20 - 23 fractions and concomitant oral capecitabine 625 mg/m(2) bid for 10 weeks prior to surgery. Curative resection with total mesorectal excision (TME) was carried out 6 weeks after the end of radiation. RESULTS: As a result, 117 cases (60.9%) experienced adverse events but only 2 suffered from G3 side effects. Seventeen cases (8.9%) had a clinical complete tumor regression without surgery; 175 patients underwent curative resection, of them 134 cases with low anterior resection (LAR), 32 cases with ultra-low anterior resection with Park's coloanal anastomosis (6 cases with diverting temporary colostomy) and 9 cases with abdominal pelvic resection (APR). Sphincter preservation was achieved in 94.9%. Twenty-four patients (12.5%) got pathological complete response (CR), 17 patients with clinical CR and the overall CR rate was 21.4%. According to the pathological staging post operation: T0N0 41 cases, T2N0 43 cases, T3N0 77 cases, T4N0 5 cases, T2N1 11 cases, T3N1 13 cases, T4N1 2 cases; Graded under Dworak's tumor regression: TRG0 8 patients, TRG1 32 patients, TRG2 28 patients, TRG3 83 patients and TRG4 24 patients, with an overall pathological tumor downstaging in 77.14%. No operative death occurred, 5 patients suffered from rectovaginal fistulas and 4 anastomotic leakages with an overall anastomotic leakage rate of 5.1% (9/175) and all the patients recovered uneventfully after properly managed. All patients were followed up for a median time of 42 months (range, 12 - 87 months). During the time, 11 patients developed lung metastases, 6 liver metastases and 7 had local recurrences. The 3 years disease-free survival (DFS) was 86.6% and overall survival (OS) was 92.6%. CONCLUSIONS: Neoadjuvant chemoradiotherapy has high efficacy in locally advanced lower rectal cancer, resulting in tumor down-staging, improved resectability and sphincter preservation, and reduced local recurrences. Meanwhile the cases with clinical complete response can be followed up closely and safely without surgery.

[Efficacy of neoadjuvant radiochemotherapy in treatment of locally advanced low rectal cancer].

OBJECTIVE: To explore efficacy of neoadjuvant radiochemotherapy in locally advanced low rectal cancer. METHODS: From May 2001 to August 2005, 105 patients with locally advanced low rectal cancer (T3, T4) were treated by preoperative radiotherapy to pelvis, 2.0 Gy daily up to 40-46 Gy in 4-5 weeks concomitantly with oral capecitabine at 1250 mg x m(-2) x d(-1) for 10 weeks up to surgery. In all patients surgery was carried out under the rule of total mesorectal excision technique. RESULTS: All patients finished the course of neoadjuvant radiochemotherapy. Among them, 36 patients experienced adverse effects. Thirteen patients resulted in complete tumor response and spared the operation. Ninety-two patients were operated on with radical resection, among them 71 patients with low anterior resection, 17 with Parks' colo-anal anastomosis and 4 with abdomino-perineal resection, so sphincter preservation was achieved in 96.2%. In postoperative pathological studies, 11 cases showed complete tumor regression. According to the TNM staging system, 24 cases were ranged T0N0, and 23 cases T2N0, 43 cases T3N0, 2 cases T4N0, 5 cases T2N1, 8 cases T3N1; and according to Dworak's tumor regression grading, 5 cases were ranked TGR0, and 18 cases TGR1, 11 cases TGR2, 47 cases TGR3, 24 cases TGR4. Pathologic downstaging was achieved in 78.1%, including complete response (TGR4) and intermediate response (TGR2 + 3). No operative death occurred. Anastomotic leakage was found in 5 cases, including 3 rectovaginal fistula. All patients have been followed up for 16-67 months, and lung metastasis occurred in 4 cases, liver metastasis in 2 patients and local recurrence in 4 patients. Three patients died of distant metastasis. The 3-year disease-free survival was 82.8% and overall survival was 96.5%. CONCLUSIONS: Neoadjuvant radiochemotherapy brings tumor down-staging and increases resectability and sphincter preservation, decreases recurrence and improves survival in locally advanced low rectal cancer.

[Irinotecan combined with fluoropyrimidine in treatment for advanced/metastatic colorectal carcinoma].

OBJECTIVE: To explore the efficacy and safety of CPT-11 combined with fluoropyrimidine in treatment for advanced or metastatic colorectal carcinoma. METHODS: From January 2001 to September 2003, 43 patients with advanced or metastatic colorectal carcinoma were randomized into two groups, group A [CPT-11 90 - 25 mg/m(2) continuous infusion for 10 h and folinic acid (FA) 30 mg x m(-2) x d(-1) + 5-FU 425 mg x m(-2) x d(-1) x 2 d continuous infusion for 48 h, every two weeks as a cycle in total of no less than six cycles] and group B (CPT-11 90 - 125 mg/m(2) continuous infusion for 10 h every two weeks as a cycle in total of no less than six cycles and capecitabine 1250 mg x m(-2) x d(-1) by oral divided into two doses, continuously taken without interruption for three months). RESULTS: In this study, overall response rate (ORR) was 44.2%, disease control achieved in 83.7%, Time to progression (TTP) was 11.0 months and overall survival (OS) was 14.6 months. Response rate in group A was 31.3% and 51.9% in group B. TTP of group A was 8.4 months and that of group B was 12.5 months; OS in group A was 14.2 months and 17.9 months in group B. In 43 cases with 502 cycles of chemotherapy, grade III side effect occurred only in 3.0% and no therapy-related death occurred. Nausea and vomiting was the most common side effect with an occurrence rate of 31.9% in group A and 2 cases of grade III, and 22.7% in group B with no case of grade III. Occurrence of side effect was much lower in group B than that of group A except hand-foot syndrome, which was 16.1% in group B with 2 cases of grade III as compared to 1.4% in group A with no case of grade III. CONCLUSIONS: Combination of CPT-11 and fluoropyrimidine is effective and safe in treatment for advanced/metastatic colorectal carcinoma. CPT-11 combined with capecitabine are not only more effective, but also its occurrence of side effect is lowered, and are especially high effective for lung metastasis. There is reasonable to recommend that combination of CPT-11 with capecitabine may be as first choice in treatment for such cases.

[Application of urinary nucleosides in the diagnosis and surgical monitoring of colorectal cancer].

OBJECTIVE: To evaluate the value of urinary normal and modified nucleosides in diagnosis and surgical monitoring of colorectal cancer (CRC). METHODS: Between October 2002 and July 2003, 52 consecutive patients with pathological confirmed CRC were included in this study. Spontaneous urine samples were collected 1 d before and 8 d after surgery and 14 kinds of urinary nucleosides in the samples were determined by reversed-phase high-performance liquid chromatography (RP-HPLC) method. Another 62 healthy volunteers were also enrolled as controls. The routine clinical tumor markers, including serum CEA, CA199, CA125 and AFP levels of CRC patients were evaluated by electrochemical-luminescence immunoassay simultaneously. RESULTS: The mean levels of pseudouridine (Pseu), adenosine (A), cytidine (C), 1-methyladenosine (m1A), 1-methylinosine (m1I), 3-methyluridine + 5-methyluridine (mU), 2,2-methylguanosine (m22G), inosine (I), 1-methylguanosine (m1G), N4-acetylcytidine (ac4C), N6-methyladenosine (m6A) among 14 kinds of determined urinary nucleosides in CRC group were much higher than those of controls (P < 0.05). Based on principal component analysis, 76.9% of CRC patients were correctly identified, which was much higher than that of CEA (38.5%), CA199 (40.4%), CA125 (15.4%), and AFP (17.3%) (P < 0.01). ROC curve analysis of m1G, and Pseu showed good sensitivity-specificity profiles to CRC. Two classification equations, Y(normal) = -3.009 + 0.0272 x Pseu + 4.918 x m1G and Y(CRC) = -8.057 + 0.0667 x Pseu + 8.258 x m1G, were established by Bayes stepwise discriminate analysis for predicting carcinogenesis of CRC. The elevated levels of Pseu, C, U (uridine), m1A, m1I, m1G, ac4C, A, m22G dramatically decreased after curative resection of 40 cases of CRC. And our data also showed that the preoperative levels of Pseu, m1G, m1A and m22G were positively related with tumor size and the preoperative levels of m1A, m22G and ac4C were positively related with Duke's staging of CRC (P < 0.05). CONCLUSIONS: Normal and modified urinary nucleosides may become additional tumor markers which are feasible in the clinical setting and will prove helpful in the diagnosis, management and follow-up of CRC, and Pseu and m1G may be more promising for clinical application.

Effects and possible anti-tumor immunity of electrochemotherapy with bleomycin on human colon cancer xenografts in nude mice.

AIM: To evaluate the anti-tumor effects and possible involvement of anti-tumor immunity of electrochemotherapy (ECT) employing electroporation and bleomycin in human colon cancer xenografts in nude mice, and to establish the experimental basis for clinical application of ECT. METHODS: Forty nude mice, inoculated subcutaneously human colon cancer cell line LoVo for 3 wk, were allocated randomly into four groups: B+E+ (ECT), B+E- (administration of bleomycin alone), B-E+ (administration of electric pulses alone), and B-E- (no treatment). Tumor volumes were measured daily. The animals were killed on the 7th d, the weights of xenografts were measured, and histologies of tumors were evaluated. Cytotoxicity of spleen natural killer (NK) and lymphokine-activated killer (LAK) cells was then assessed by lactic dehydrogenase release assay. RESULTS: The mean tumor volume of group B+E+ was statistically different from the other three groups after the treatment (F = 36.80, P<0.01). There was one case of complete response, seven cases of partial response (PR) in group B+E+, one case of PR in group B+E- and group B-E+ respectively, and no response was observed in group B-E-. The difference of response between group B+E+ and the other three groups was statistically significant (chi2 = 25.67, P<0.01). Histologically, extensive necrosis of tumor cells with considerable vascular damage and inflammatory cells infiltration were observed in group B+E+. There was no statistical difference between the cytotoxicity of NK and LAK cells in the four treatment groups. CONCLUSION: ECT significantly enhances the chemosensitivity and effects of chemotherapy in human colon cancer xenografts in nude mice, and could be a kind of novel treatment modality for human colon cancer. The generation of T-cell-dependent, tumor-specific immunity might be involved in the process of ECT.

Laparoscopic versus open right hemicolectomy with curative intent for colon carcinoma.

AIM: Laparoscopic surgery, especially laparoscopic rectal surgery, for colorectal cancer has been developed considerably. However, due to relatively complicated anatomy and high requirements for surgery techniques, laparoscopic right colectomy develops relatively slowly. This study was designed to compare the outcomes of laparoscopic right hemicolectomy (LRH) with open right hemicolectomy (ORH) in the treatment of colon carcinoma. METHODS: Between September 2000 and February 2003, 30 patients with colon cancer who underwent LRH were compared with 34 controls treated by ORH in the same period. All patients were evaluated with respect to surgery-related complications, postoperative recovery, recurrence and metastasis rate, cost-effectiveness and survival. RESULTS: Among 30 LRH, 2 (6.7%) were converted to open procedure. No significant differences were observed in terms of mean operation time, blood loss, post-operative complications, and hospital cost between LRH and ORH groups. Mean time for bowel movement, hospital stay, and time to resume early activity in the LRH group were significantly shorter than those in the ORH group (2.24+/-0.56 vs 3.25+/-1.29 d, 13.94+/-6.5 vs 18.25+/-5.96 d, 3.94+/-1.64 vs 5.45+/-1.82 d respectively, P<0.05). As to the lymph node yield, the specimen length and total cost for operation and drugs, there was no significant difference between the two groups. Local recurrence rate and metachronous metastasis rate had no marked difference between the two groups. Cumulative survival probability at 40 mo in LRH group (76.50%) was not obviously different compared to the ORH group (74.04%). CONCLUSION: LRH in patients with colon cancer has statistically and clinically significant advantages over ORH. Thus, LRH can be regarded as a safe and effective procedure.

[First-line Xeloda (Capecitabine) treatment for advanced and recurrent colorectal cancer].

OBJECTIVE: To evaluate the efficacy and safety of capecitabine as first-line therapy in patients with advanced and recurrent colorectal cancer. METHODS: From December 2000 to November 2001, sixty patients with advanced and recurrent colorectal cancer received first-line capecitabine treatment given at a dose of 1250 mg/m(2) twice daily, on days 1 - 14 every 21 days. At least 2 cycles were administered. RESULTS: The overall response rate was 23.3% with 14 PR, 24 SD (40.0%) and 15 PD. The median survival time was 14.7 months. The survival rate was 63.9% at 12-months and 33.4% at 24-months. Grade III-IV adverse effects were diarrhea in 4 patients (6.6%), anemia in 2 (3.3%) and hand-foot syndrome (HFS) in 1 (1.7%); Grade I-II adverse effects were hyperpigmentation in 20 (33.3%), HFS in 18 (30.0%) and diarrhea in 10 (16.7%). CONCLUSION: Capecitabine is an efficacious and better-tolerated alternative treatment for the patients with advanced and recurrent colorectal cancer.

[Single-dose ceftriaxone versus multiple-dose cefuroxime for prophylaxis of surgical site infection].

OBJECTIVE: To compare the effects and pharmacoeconomics of single-dose of ceftriaxone versus 3-day cefuroxime prophylaxis in patients undergoing gastric or colorectal resection. METHODS: Three hundred and five consecutive patients with gastric or colorectal cancer from 5 medical centers were randomly divided into ceftriaxone group (n = 153, receiving intravenously 1 g ceftriaxone 0.5 - 1 h prior to operation only) and cefuroxime group (n = 152, receiving 0.75 g cefuroxime preoperatively and the same dose q8h for 3 d). The patients' intra- and postoperative status, adverse responses and infectious complications were observed and documented, and pharmacoeconomic parameters were analyzed. RESULTS: The disease distribution, operative procedures and patients' conditions in the 2 groups were comparable. No adverse responses to the test antibiotics were observed. Postoperative infectious complications occurred in 7 cases in the ceftriaxone group (4.58%) and 14 cases in the cefuroxime group (9.21%), respectively (P = 0.992), among which, 12 cases were surgical site infections (incisional, intra-abdominal): 2 cases in the ceftriaxone group (1.31%), and 10 cases in the cefuroxime group (6.58%), (chi(2) = 5.607, P = 0.018). The direct cost related to prevention and treatment of surgical site infections was 283.5 RMB in the ceftriaxone group and 811.1 RMB in the cefuroxime group (Z = 14.51, P = 0.000). CONCLUSION: Both ceftriaxone and cefuroxime are safe and effective for prevention of surgical site infections. Single-dose ceftriaxone prophylaxis is sufficient for gastric and colorectal operations, with a better cost-effectiveness ratio.

Upregulation of vascular endothelial growth factor by hydrogen peroxide in human colon cancer.

AIM: To evaluate the effect of reactive oxygen species such as hydrogen peroxide on the progression of human colon cancer. METHODS: Human colon carcinoma cell lines, LS174T and HCT8, were treated respectively with 10(-5), 10(-7) or 10(-9) mol x L(-1) hydrogen peroxide for 24h,and co-cultured with human endothelial cell line ECV-304. The migration of ECV-304 induced by cancer cells was calculated and the expression level of vascular endothelial growth factor in cancer cells was determined by RT-PCR analysis and ELISA. Dactinomycin of 1.5mg x L(-1) which could block transcription of cancer cells was applied to observing the effects of H(2)O(2) on transcriptional activity and the relative half-life of VEGF mRNA. Finally,to evaluate the effect of H2O2 on NF-kappaB activity in colon cancer cells, NF-kappaB in cytoplasm and nucleus of the cells were detected with FITC-tagged antibody and its presence in the nucleus(Fn) vs cytoplasm(Fc) was monitored by measuring the green fluorescence integrated over the nucleus by laser scanning cytometry(LSC). RESULTS: Exogenouse hydrogen peroxide of low concentration increased the migration of endothelial cell induced by colon cancer cells. When cancer cells were treated with 10(-5) mol x L(-1) H2O2, the migration number of endothelial cells induced by LS174T cells was 203+/-70 and the number induced by HCT8 cells was 145+/-65. The two values were significantly higher than those treated with other concentrations of H2O2 (P<0.01). The expression of vascular endothelial growth factor in cancer cells, which could be blocked by dactinomycin, were increased to a certain degree, while the relative half-life of VEGF mRNA was not prolonged after treatment with hydrogen peroxide. The activity of NF-kappaB in colon cells rose after the cells were exposed to hydrogen peroxide for 24h. The Fn values in HCT8 cells were 91+/-13 (0 mol x L(-1) H2O2) and 149+/-40(10(-5) mol x L(-1) H2O2)(P<0.05), in LS174T cells were 127+/-35(0 mol x L(-1) H2O2) and 192+/-11(10(-5)mol x L(-1) H2O2) (P<0.05). It is similar to the case of VEGF expression in cancer cells. CONCLUSION: Hydrogen peroxide increases vascular endothelial growth factor expression in colon cancer cells, and it is likely that reactive oxygen species such as hydrogen peroxide facilitates the development of colon cancer.

Detection of aberrant p16 methylation in the serum of colorectal cancer patients.

PURPOSE: This study was designed to detect aberrant p16 promoter methylation in the serum of patients with colorectal cancer (CRC) and to explore the possibility of using this assay in early detection or as a prognostic marker of CRC patients. EXPERIMENTAL DESIGN: Methylation-specific PCR was used to detect p16 methylation in DNA extracted from 52 CRCs and matching serum samples and control serum samples from 34 patients with adenomatous polyps and 10 healthy individuals. The association of p16 hypermethylation in serum DNA of CRC patients with clinicopathological characteristics was then analyzed. RESULTS: P16 hypermethylation was found in 20 of 52 (38%) CRCs. Among the 20 cases with aberrant methylation in the tumor tissues, similar changes were also detected in the serum of 14 (70%) cases. No methylated p16 sequences were detected in the peripheral serum of the other 32 CRC cases without these changes in the tumor, in 34 patients with adenomatous polyps, or in 10 healthy control subjects. Clinicopathological analysis revealed that p16 methylation in serum was significantly associated with later Dukes' stage (P = 0.03). CONCLUSIONS: This assay offers a potential means for the serum-based detection and/or monitoring of CRC patients.