Soung Min Jeon

The effects of metformin on the survival of colorectal cancer patients with diabetes mellitus

Metformin use has been associated with decreased cancer risk and mortality. However, the effects of metformin on clinical outcomes of colorectal cancer (CRC) are not defined. This study aimed to evaluate the association between metformin use and mortality of CRC in diabetic patients. We identified 595 patients who were diagnosed both CRC and diabetes mellitus. Patients were compared by two groups; 258 diabetic patients taking metformin and 337 diabetic patients not taking metformin. Patients demographics, clinical characteristics, overall mortality and CRC‐specific mortality were analyzed. After a median follow‐up of 41 months, there were 71 total deaths (27.5%) and 55 CRC‐specific deaths (21.3%) among 258 patients who used metformin, compared with 136 total deaths (40.4%) and 104 CRC‐specific deaths (30.9%) among 337 patients who did not use metformin. Metformin use was associated with decreased overall mortality (p = 0.018) and CRC‐specific mortality (p = 0.042) by univariate analysis. After adjustment for clinically relevant factors, metformin use showed lower risk of overall mortality (HR, 0.66; 95% CI 0.476–0.923; p = 0.015) and CRC‐specific mortality (HR, 0.66; 95% CI 0.45–0.975; p = 0.037) in CRC patients with diabetes. Metformin use in CRC patients with diabetes is associated with lower risk of CRC‐specific and overall mortality.

Prognostic factors and long‐term clinical outcomes for surgical patients with intestinal Behcet's disease

Background: To date there have been few studies regarding the efficacy of surgical treatment and related prognostic factors following intestinal resection in patients with intestinal Behcets disease (BD). Here we investigated the long‐term clinical outcomes and related prognostic factors after surgical treatment for intestinal BD. Methods: We reviewed the medical records of 72 patients with intestinal BD who underwent surgery between March 1986 and May 2010. Prognostic factors were identified by univariate analysis using the Kaplan‐Meier method, the log‐rank test, and multivariate analysis using Cox proportional hazards regression models. Results: Recurrence after surgical treatment was observed in 42 (58.3%) patients and reoperations were performed in 22 (30.6%) patients. The cumulative recurrence rates after surgical treatment were 29.2% at 2 years and 47.2% at 5 years; the cumulative reoperation rates were 12.5% at 2 years and 22.2% at 5 years. Multivariate analysis identified volcano‐shaped ulcers, higher C‐reactive protein (CRP) levels (≥4.4 mg/dL), and the presence of intestinal perforations detected by pathology as independent predictive factors for recurrence. Moreover, volcano‐shaped ulcers, higher CRP levels (≥4.4 mg/dL), and a history of postoperative steroid therapy were independent predictive factors for reoperation. Conclusions: According to the current study, volcano‐shaped ulcers, higher CRP levels, a history of postoperative steroid therapy, and the presence of intestinal perforations detected by pathology were factors of a poor prognosis. Careful follow‐up is required in surgical patients with these risk factors, who are at high risk for recurrence and reoperation. (Inflamm Bowel Dis 2010;)

Abrogation of galectin-4 expression promotes tumorigenesis in colorectal cancer

BackgroundAlthough it has been well established that galectin-4 is selectively expressed by intestinal epithelial cells, the role of galectin-4 in colorectal cancer (CRC) development is, as yet, poorly understood. Here, we aimed to explore the role of galectin-4 in CRC development, both in vitro and in vivo.MethodsGalectin-4 expression was investigated in tissue specimens from patients with adenoma, carcinoma and ulcerative colitis (UC) using immunohistochemistry. Colorectal cancer-derived HT-29 cells, in which galectin-4 expression was knocked down, were established using shRNA. mRNA and protein expression levels of galectin-4 and several downstream cancer-related genes were analyzed using RT-PCR, qPCR array, Western blotting, and immunofluorescence assays. To investigate the effect of galectin-4 expression abrogation on tumorigenesis in vivo, xenograft assays were performed.ResultsImmunohistochemistry analyses showed high expression levels of galectin-4 in normal colon mucosa tissues. Conversely, the expression levels of galectin-4 were significantly lower in CRC samples and its precursor lesions with dysplasia or inflammation. We found that shRNA-mediated galectin-4 silencing increases cell proliferation and, concomitantly, activates NF-κB and STAT3 signaling along with IL-6 up-regulation. In addition, we found that shRNA-mediated galectin-4 silencing promotes the expression of NF-κB target genes and other cancer-related genes and, concomitantly, enhances the in vivo growth of xenografts.ConclusionsWe show that abrogation of galectin-4 expression promotes cancer cell proliferation and, for the first time, provide evidence that down-regulation of galectin-4 elicits tumor promotion in vitro and in vivo through activation of IL-6/NF-κB/STAT3 signaling.

Risk Factors for Treatment Failure and Recurrence after Metronidazole Treatment for Clostridium difficile-associated Diarrhea

BACKGROUND/AIMS The incidence of treatment failure or recurrence of Clostridium difficile-associated diarrhea (CDAD) following metronidazole treatment has increased recently. We studied the treatment failure, recurrence rate, and risk factors predictive of treatment failure and recurrence after metronidazole treatment for CDAD. METHODS We retrospectively identified consecutive patients who were admitted and treated for CDAD at a single tertiary institution in Korea over a recent 10-year period (i.e., 1998-2008). RESULTS Metronidazole was administered as the initial treatment to 111 of 117 patients (94.9%) with CDAD. Fourteen patients (12.6%) had no clinical response to the metronidazole treatment, and in 13 patients (13.4%) CDAD recurred after successful metronidazole treatment. Diabetes mellitus (p=0.014) and sepsis (p=0.002) were independent risk factors for metronidazole treatment failure. Patients who had received surgery within 1 month before CDAD developed were more likely to experience a recurrence after metronidazole treatment (p=0.032). Vancomycin exhibited a higher response rate after treatment failure, and metronidazole showed a reasonable response rate in the treatment of recurrence. Treatment failure and recurrence rates increased with time after metronidazole treatment for CDAD over the 10-year study period. CONCLUSIONS Our data suggest that diabetes mellitus and sepsis are independent risk factors for metronidazole treatment failure, and that operation history within 1 month of development of CDAD is a predictor of a recurrence after metronidazole treatment.

Metformin use is associated with a decreased incidence of colorectal adenomas in diabetic patients with previous colorectal cancer

BACKGROUND Metformin use has been associated with decreased cancer risk and mortality. However, the effects of metformin on the development of colorectal adenomas, the precursors of colorectal cancers, are not defined. AIMS This study aimed to evaluate the potential effect of metformin on the incidence of colorectal adenomas in diabetic patients with previous colorectal cancer. METHODS Among 488 consecutive diabetic patients who underwent colonoscopic surveillance after curative resection of colorectal cancer between 1998 and 2008, 240 patients were enrolled in this study and were compared in two groups: 114 patients taking metformin and 126 patients not taking metformin. Patient demographics, clinical characteristics, and colorectal adenoma incidence rate were analysed. RESULTS After a median follow-up of 58 months, a total of 33 patients (28.9%) exhibited adenomatous colorectal polyps among the 114 patients who used metformin, compared with 58 (46.0%) patients with colorectal adenomas among the 126 patients who did not use metformin (odds ratio = 0.48, 95% confidence interval = 0.280-0.816, P = 0.008). After adjustment for clinically relevant factors, metformin use was found to be associated with a decreased incidence of colorectal adenomas (odds ratio = 0.27, 95% confidence interval = 0.100-0.758, P = 0.012) in diabetic patients with previous colorectal cancer. Metformin use in diabetic patients with previous colorectal cancer is associated with a lower risk of colorectal adenoma.

Clinical characteristics and prognosis of hepatocellular carcinoma with different sets of serum AFP and PIVKA-II levels.

Objective &agr;-Fetoprotein (AFP) and prothrombin induced by the absence of vitamin K or antagonist-II (PIVKA-II) are useful tumor markers for hepatocellular carcinoma (HCC). However, little is known about the clinical characteristics and prognosis of HCC with different levels of AFP and PIVKA-II. Methods Consecutive 1447 HCC patients were assigned to four groups according to the cutoff values of AFP (400 ng/ml) and PIVKA-II (100 mAU/ml): both values high (AP), one of the values high (Ap and aP), and both values low (ap). The clinical characteristics and the prognosis of group ap were compared with those of the other groups. Results HCC patients in group ap were more asymptomatic at diagnosis, and had smaller size, fewer numbers, and earlier stages of HCC, and more preserved liver functions (all, P<0.001). The survival rate of group ap was significantly higher than those of the other groups (P<0.001). In multivariate analysis, the combined status of AFP and PIVKA-II values were independent predictors for survival (P<0.001), together with tumor size, number, portal vein thrombosis, Child–Pugh class, and treatment modality. Conclusion HCC patients with low values of both AFP and PIVKA-II had more favorable clinical characteristics and showed a better prognosis than those with elevated levels of AFP or PIVKA-II.

Clinical outcomes and factors related to resectability and curability of EMR for early colorectal cancer.

BACKGROUND EMR has emerged as an alternative therapeutic option for selected cases of early colorectal cancer (ECC). However, the factors associated with resectability and curability of EMR for ECC remain unknown. OBJECTIVE To investigate clinical outcomes and factors related to resectability and curability in ECC cases treated with EMR. DESIGN Retrospective study. SETTING Tertiary-care academic medical center. PATIENTS This study involved all patients in whom EMR was performed for ECC at Severance Hospital between March 1997 and August 2007. A total of 236 cases of ECC occurring in 231 patients (66.2% men) were enrolled. INTERVENTION EMR. Curative surgical resection and lymph node dissection were used in cases that were incompletely cured by EMR. MAIN OUTCOME MEASUREMENTS Resectability, curability, and recurrence. RESULTS Complete cure was achieved for 162 lesions (68.6%). Of the remaining 74 cases (31.4%), 69 (29.2%) were incompletely cured, and the other 5 (2.1%) had an undetermined resection status and ultimately required supplementary surgical resection for curative treatment. Location on the right side of the colon, piecemeal resection, and submucosal carcinoma were independently associated with incomplete resection, whereas depressed tumor type was independently related to incomplete cure. Among the ECC cases completely cured by EMR and followed for more than a year (n = 118), local recurrence was observed in one case (0.8%) during the median follow-up period of 39.4 months (range 12.4-123.1 months). LIMITATIONS Single-center, retrospective study. CONCLUSION Our data show that EMR is feasible and could be an effective option for treatment of ECC if the technique is applied with the appropriate indications.

Expression of a soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) correlates with clinical disease activity in intestinal Behcet's disease

Background: No serological marker currently exists to assess disease activity in patients with intestinal Behcets disease (BD). We conducted this study to determine if the expression level of serum soluble triggering receptor expressed on myeloid cells‐1 (sTREM‐1) can be used as a biological marker to assess disease activity in intestinal BD. Methods: A total of 88 patients with intestinal BD were enrolled prospectively. We assessed their clinical disease activities using the disease activity index for intestinal BD (DAIBD). At the time that the DAIBD was assessed, serum erythrocyte sedimentation rate (ESR) as well as levels of TREM‐1, C‐reactive protein (CRP), and tumor necrosis factor‐&agr; (TNF‐&agr;) were measured. Results: The mean ESR and mean levels of sTREM‐1, CRP, and TNF‐&agr; in patients with intestinal BD were significantly higher than those in healthy controls. Levels of sTREM‐1 were the most highly correlated with disease activity (r = 0.762 for the DAIBD score), followed by CRP levels (r = 0.383 for the DAIBD score) and ESR (r = 0.236 for the DAIBD score). However, serum levels of TNF‐&agr; level were not correlated with disease activity (r = −0.017 for the DAIBD score). Conclusions: Serum sTREM‐1 levels were more highly correlated with disease activity than were CRP levels or ESR in patients with intestinal BD, suggesting that serum sTREM‐1 level could be a potential marker for the assessment of disease activity of intestinal BD. (Inflamm Bowel Dis 2011;)

Inhibitory effect of metformin therapy on the incidence of colorectal advanced adenomas in patients with diabetes.

Background/Aims Metformin use has been associated with decreased colorectal cancer risk and mortality among diabetic patients. Recent research suggests that metformin use may decrease the incidence of colorectal adenomas in diabetic patients with previous colorectal cancer. This study aimed to assess the clinical effect of metformin use on the development of colorectal adenomas in diabetic patients without previous colorectal cancer. Methods Among 604 consecutive diabetic patients who underwent colonoscopic surveillance after initial colonoscopy between January 2002 and June 2012, 240 patients without previous colorectal cancer were enrolled in this study and were divided in two groups: 151 patients receiving metformin and 89 patients not receiving metformin. Patient demographics and clinical characteristics as well as the colorectal adenoma incidence rate were retrospectively analyzed. Results The incidence rate of total colorectal adenomas was not different according to metformin use (P=0.349). However, the advanced adenoma incidence rate was significantly lower in the metformin group compared with the non-metformin group (relative risk [RR], 0.09; P=0.011). Metformin use was independently associated with a decreased incidence of advanced colorectal adenomas after adjustment for clinically relevant factors (RR, 0.072; P=0.016). In addition, the cumulative development rate of advanced adenomas during follow-up was significantly lower in the metformin group compared with the non-metformin group (P=0.007). Conclusions Metformin use in diabetic patients without previous colorectal cancer is associated with a lower risk of advanced colorectal adenomas.

Feasibility of salvage endoscopic mucosal resection by using a cap for remnant rectal carcinoids after primary EMR

BACKGROUND Secondary endoscopic treatment for remnant lesions of rectal carcinoid tumors after primary EMR or polypectomy is technically difficult because of fibrosis of residual tissues. EMR by using a cap (EMR-C), a method to resect the submucosal layer by suction by using a transparent cap, may be feasible as a salvage treatment. OBJECTIVE To assess the feasibility of salvage EMR-C. DESIGN Retrospective analysis. SETTING Tertiary academic health care system. PATIENTS Thirty-one patients who were referred for salvage treatment of a failed en bloc excision of rectal carcinoid tumors after primary EMR or polypectomy between January 2007 and December 2009. INTERVENTIONS Salvage EMR-C for remnant carcinoid tumors in the rectum. MAIN OUTCOME MEASUREMENTS Rate of complete resection, complications, length of procedure, and recurrence rate. RESULTS The mean age of the patients was 52.0±11.8 years (range 30-78 years). The mean tumor size was 8.9±3.2 mm (range 5.0-13.0 mm). The mean procedure time was 9.1±3.7 minutes, and clear resection margins were pathologically confirmed in all 31 patients. The most common complication of salvage EMR-C was bleeding (7 patients, 22.6%), which was successfully treated by hemoclipping in all cases. The 1-year follow-up colonoscopy and CT results for all patients were negative for recurrence. LIMITATIONS Retrospective design and limited cases at a single center. CONCLUSIONS EMR-C is a feasible salvage therapeutic option for failed en bloc excision after primary endoscopic treatment of rectal carcinoid tumors.