OBJECTIVETo investigate the prognostic value of thymidylate synthase (TS), topoisomerase-1 (Topo-1), and proliferating index Ki-67 in advanced colorectal cancer patients on irinotecan (CPT-11) in combination with fluorouracil treatment (5-Fu).

METHODSThe biomarker expression of TS, Topo-1 and Ki-67 in 78 patients detected immunohistochemically were correlated with the clinical outcome.

RESULTSThe expressions of those biomarkers were not correlated with clinical therapeutic response, but with time to progression (TTP) and/or overall survival (OS). Patients with low expression of TS had significantly longer TTP (P < 0.05) and in OS (P < 0.05). The low expression of Ki-67 was also significantly predictive of longer survival (P < 0.05). As compared with any biomarker, the combination of any two biomarkers still possessed no predictive value to therapeutic response, but an enhanced predictive value to prognosis. The median time to progression in patients with low expression of TS, or Ki-67, or both were 9, 8 and 17 months, respectively; in patients with low expression of TS, or Topo-1, or both were 9, 9 and 13 months; in patients with low expression of Topo-1, or Ki-67, or both were 8, 9 and 11 months. TTP was significantly longer in patients with low expression of two biomarkers as compared with those with high expression (P = 0.031).

CONCLUSIONTS, Topo-1, and Ki-67 are not predictive for chemotherapy response to CPT-11 combined with 5-Fu, but valuable in predicting prognosis. The combination of any two biomarkers can provide more powerful prognostic information for advanced colorectal cancer patients.

Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; metabolism ; Camptothecin ; administration & dosage ; analogs & derivatives ; Colorectal Neoplasms ; drug therapy ; enzymology ; DNA Topoisomerases, Type I ; metabolism ; Female ; Fluorouracil ; administration & dosage ; Humans ; Ki-67 Antigen ; metabolism ; Male ; Middle Aged ; Prognosis ; Thymidylate Synthase ; metabolism ; Treatment Outcome

Background/Aims: Patients with diverticular disease (DD) frequently have abnormal bowel movements. However, it is unknown whether the entity of these alterations is associated with the severity of DD. We aimed to assess bowel habits and their relationship with the severity of DD according to Diverticular Inflammation and Complication Assessment (DICA) classification, Combined Overview on Diverticular Assessment (CODA) score, and fecal calprotectin (FC). Methods: An international, multicenter, prospective cohort study was conducted in 43 centers. A 10-point visual analog scale (VAS) was used to assess the severity of constipation and diarrhea. The association of constipation and diarrhea with DICA classification, CODA score, and basal FC was tested using non-parametric tests. Survival methods for censored observations were applied to test the association of constipation and diarrhea with the incidence of acute diverticulitis over a 3-year follow-up. Results: Of 871 patients with DD were included in the study. Of these, 208 (23.9%) and 199 (22.9%) reported a VAS score for constipation and diarrhea at least 3 at baseline, respectively. Higher constipation and diarrhea scores were associated with increasing DICA classification, CODA score and basal FC (P< 0.001). Constipation and diarrhea scores were independently associated with an increased hazard of developing acute diverticulitis (hazard ratio [HR]constipation = 1.15 per 1-VAS point increase, 95% confidence interval [CI], 1.04–1.27; P=0.004; and HRdiarrhea =1.14; 95% CI, 1.03–1.26; P=0.014, respectively). Conclusions In newly diagnosed patients with DD, higher endoscopic and combined scores of DD severity were associated with higher scores of constipation and diarrhea at baseline. Both constipation and diarrhea were independent prognostic factors of acute diverticulitis.

Background/Aims: Patients with diverticular disease (DD) frequently have abnormal bowel movements. However, it is unknown whether the entity of these alterations is associated with the severity of DD. We aimed to assess bowel habits and their relationship with the severity of DD according to Diverticular Inflammation and Complication Assessment (DICA) classification, Combined Overview on Diverticular Assessment (CODA) score, and fecal calprotectin (FC). Methods: An international, multicenter, prospective cohort study was conducted in 43 centers. A 10-point visual analog scale (VAS) was used to assess the severity of constipation and diarrhea. The association of constipation and diarrhea with DICA classification, CODA score, and basal FC was tested using non-parametric tests. Survival methods for censored observations were applied to test the association of constipation and diarrhea with the incidence of acute diverticulitis over a 3-year follow-up. Results: Of 871 patients with DD were included in the study. Of these, 208 (23.9%) and 199 (22.9%) reported a VAS score for constipation and diarrhea at least 3 at baseline, respectively. Higher constipation and diarrhea scores were associated with increasing DICA classification, CODA score and basal FC (P< 0.001). Constipation and diarrhea scores were independently associated with an increased hazard of developing acute diverticulitis (hazard ratio [HR]constipation = 1.15 per 1-VAS point increase, 95% confidence interval [CI], 1.04–1.27; P=0.004; and HRdiarrhea =1.14; 95% CI, 1.03–1.26; P=0.014, respectively). Conclusions In newly diagnosed patients with DD, higher endoscopic and combined scores of DD severity were associated with higher scores of constipation and diarrhea at baseline. Both constipation and diarrhea were independent prognostic factors of acute diverticulitis.

Background/Aims: Patients with diverticular disease (DD) frequently have abnormal bowel movements. However, it is unknown whether the entity of these alterations is associated with the severity of DD. We aimed to assess bowel habits and their relationship with the severity of DD according to Diverticular Inflammation and Complication Assessment (DICA) classification, Combined Overview on Diverticular Assessment (CODA) score, and fecal calprotectin (FC). Methods: An international, multicenter, prospective cohort study was conducted in 43 centers. A 10-point visual analog scale (VAS) was used to assess the severity of constipation and diarrhea. The association of constipation and diarrhea with DICA classification, CODA score, and basal FC was tested using non-parametric tests. Survival methods for censored observations were applied to test the association of constipation and diarrhea with the incidence of acute diverticulitis over a 3-year follow-up. Results: Of 871 patients with DD were included in the study. Of these, 208 (23.9%) and 199 (22.9%) reported a VAS score for constipation and diarrhea at least 3 at baseline, respectively. Higher constipation and diarrhea scores were associated with increasing DICA classification, CODA score and basal FC (P< 0.001). Constipation and diarrhea scores were independently associated with an increased hazard of developing acute diverticulitis (hazard ratio [HR]constipation = 1.15 per 1-VAS point increase, 95% confidence interval [CI], 1.04–1.27; P=0.004; and HRdiarrhea =1.14; 95% CI, 1.03–1.26; P=0.014, respectively). Conclusions In newly diagnosed patients with DD, higher endoscopic and combined scores of DD severity were associated with higher scores of constipation and diarrhea at baseline. Both constipation and diarrhea were independent prognostic factors of acute diverticulitis.