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1.  Recent applications of chemosensitivity tests for colorectal cancer treatment 
World Journal of Gastroenterology : WJG  2014;20(44):16398-16408.
The evaluation of therapeutic efficacy is necessary to predict the outcome of patients with metastatic colorectal cancer (CRC). In these patients, there is a critical need for predictive chemosensitivity assays and biomarkers to optimize efficacy and minimize toxicity. The introduction of targeted agents has improved the progression-free survival and overall survival of patients with metastatic disease. However, approximately 50% of patients do not show a positive response to chemotherapy and the selection of patients likely to respond to a specific regimen remains challenging. Cell culture-based chemosensitivity tests use autologous viable tumor cells to evaluate susceptibility to specific agents in vitro and predict their direct effects. Adenosine triphosphate-based assays and methyl thiazolyl-diphenyl-tetrazolium bromide-based assays are used widely as sensitivity tests because of their short assay period, technical simplicity, and the requirement of small amount of specimen. Among protein- and gene-based chemosensitivity assays, assessment of KRAS mutation status predicts the response to epidermal growth factor receptor-targeted therapy in CRC patients. The validation of predictive and prognostic markers enables the selection of therapeutic regimens with optimal efficacy and minimal toxicity for each patient, which has been termed personalized treatment. This review summarizes currently available predictive and prognostic chemosensitivity tests for metastatic CRC.
PMCID: PMC4248183  PMID: 25469008
Colorectal adenocarcinomas; Colorectal cancer; Chemotherapy; In vitro assays; Molecular targeted therapy; Individualized therapy
2.  The Role of Diverting Stoma After an Ultra-low Anterior Resection for Rectal Cancer 
Annals of Coloproctology  2013;29(2):66-71.
A diverting stoma is known to reduce the consequences of distal anastomotic failure following colorectal surgery. The aim of this study was to evaluate the efficacy of a diverting stoma after an ultra-low anterior resection (uLAR) for rectal cancer.
Between 2000 and 2007, 836 patients who underwent an uLAR were divided into two groups, depending on the fecal diversion: 246 received fecal diversion, and 590 had no diversion. Patient- and disease-related variables were compared between the two groups.
Thirty-two of the 836 patients (3.8%) had immediate anastomosis-related complications and required reoperation. Anastomosis leakage comprised 72% of the complications (23/32). The overall immediate complication rate was significantly lower in patients with a diverting stoma (0.8%, 2/246) compared to those without a diverting stoma (5.1%, 30/590; P = 0.005). The fecal diversion group had lower tumor location, lower anastomosis level, and more preoperative chemo-radiation therapy (P < 0.001). In total, 12% of patients in the diverting stoma group had complications either in making or reversing the stoma (30/246).
The diverting stoma decreased the rate of immediate anastomosis-related complications. However, the rate of complications associated with the diverting stoma was non-negligible, so strict criteria should be applied when deciding whether to use a diverting stoma.
PMCID: PMC3659245  PMID: 23700573
Rectal neoplasms; Ileostomy; Colorectal surgery
3.  Risk factors for complications after bowel surgery in Korean patients with Crohn's disease 
To assess the incidence and factors predictive of early postoperative complications in Korean patients who undergo surgery for Crohn's disease (CD).
We retrospectively assessed 350 patients (246 males, 104 females; mean age, 30 ± 9 years) who underwent surgery for primary or recurrent CD at Asan Medical Center between January 1991 and May 2010. The incidence and predictive factors of early postoperative complications were analyzed by both univariate and multivariate analyses.
Of the 350 patients, 81 patients (23.1%) developed postoperative complications, the most common being septic complications (54 patients), including 19 cases of wound infection. Thirty patients (8.6%) required re-operations, and only one patient died. Multivariate analysis showed that four factors were independently associated with a high risk of early postoperative complications; preoperative moderate to severe anemia (hematocrit concentration <30%; odds ratio [OR], 3.1; 95% confidence interval [CI], 1.6 to 5.9), hypoalbuminemia (serum albumin level <3.0 g/dL; OR, 2.6; 95% CI, 1.4 to 4.7), emergency surgery (OR, 4.0; 95% CI, 1.5 to 10.6), and covering stoma (OR, 2.6; 95% CI, 1.3 to 5.4). Correction of preoperative moderate to severe anemia and hypoalbuminemia decreased the incidence of postoperative complications. Mean hospital stay was significantly longer in patients with than without postoperative complications (31.3 ± 27.2 days vs. 10.3 ± 3.8 days, P < 0.001).
Preoperative anemia, low albumin level, emergency surgery, and covering stoma significantly increased the risk of early postoperative complications in patients with CD. Correcting preoperatively deficient nutritional factors may reduce postoperative morbidities.
PMCID: PMC3433550  PMID: 22977760
Crohn disease; Surgery; Korea; Risk factors; Postoperative complications
4.  Characterization of biological responses of colorectal cancer cells to anticancer regimens 
Identification of subgroups of patients who differ in their response to treatment could help to establish which of the best available chemotherapeutic options are best, based on biological activity. In metastatic colorectal cancer (CRC), novel molecular-targeted agents that act on pathways that regulate cell growth, the cell cycle, apoptosis, angiogenesis, and invasion are being developed. Here, we employed an in vitro chemosensitivity assay to evaluate the biological efficacy of conventional monotherapies and combination chemotherapy with targeted drugs.
The chemosensitivities of 12 CRC cell lines to the established regimens FOLFOX (5-fluorouracil [5-FU] + leucovorin + oxaliplatin) and FOLFIRI (5-FU + leucovorin + irinotecan) and to therapy with these regimens in combination with the biologically targeted drugs bevacizumab or cetuximab were comparatively evaluated for their effects on apoptotic and autophagic cell death processes, angiogenesis, and invasion.
Each of the chemotherapeutic regimens promoted apoptotic cell death and invasion. All drug regimens caused significantly greater apoptotic cell death with activation of caspase-3 in SW480 cells compared to other cells, effects that were associated with a remarkable reduction in matrix metalloproteinase-9 activity. The FOLFOX regimen more effectively promoted apoptotic cell death, angiogenesis, and invasion than the FOLFIRI regimen. Combination therapy with FOLFOX/FOLFIRI regimen and bevacizumab produced a moderate angiogenesis-blocking effect in most cell lines.
The results validate our in vitro chemosensitivity assay, and suggest that it may be applied to help determine adequate regimens in individual CRC patients based on the biological characteristics of their tumors.
PMCID: PMC3392312  PMID: 22792530
Colorectal neoplasms; Chemotherapy; Pharmacological biomarkers
5.  Clinicopathologic Factors Affecting Recurrence after Curative Surgery for Stage I Colorectal Cancer 
The objective of the current study was to identify the clinicopathological risk factors affecting recurrence after a curative resection for stage I colorectal cancer.
We retrospectively studied 434 patients who underwent a curative resection for stage I colorectal cancer between January 1999 and December 2004. Postoperative oral chemotherapy was performed in 189 patients (45.3%). The following prognostic factors were correlated with recurrence: age, gender, preoperative carcinoembryonic antigen level, location of tumor, T stage, size of tumor, histologic differentiation, growth pattern, and lymphovascular invasion. The median follow-up duration was 65 months.
The overall recurrence rate was 4.6% (20/434). The median time to recurrence was 33 months. Two-thirds of the recurrence occurred more than two years after surgery. Risk factors associated with recurrence were rectal cancer (P = 0.009), T2 stage (P = 0.010), and infiltrative growth pattern (P = 0.020). A Cox proportional hazards regression analysis demonstrated that the infiltrative growth pattern was an independent predictor for recurrence. Tumor cell budding was observed in all pathologic reviews with recurrence.
Long-term follow-up is necessary for stage I colorectal patients with high risk factors like rectal cancer, T2 stage, and infiltrative growth pattern.
PMCID: PMC3296942  PMID: 22413082
Colorectal neoplasms; Recurrence; Risk factors
6.  Dual-Design Expandable Colorectal Stent for a Malignant Colorectal Obstruction: Preliminary Prospective Study Using New 20-mm Diameter Stents 
Korean Journal of Radiology  2011;13(1):66-72.
To evaluate the safety and effectiveness of a 20-mm diameter dual-design expandable colorectal stent for malignant colorectal obstruction.
Materials and Methods
The study series included 34 patients with malignant colorectal obstruction who underwent implantation of a 20-mm dual-design expandable colorectal stent in our department between March 2009 and June 2010. The 20-mm dual-design expandable colorectal stent was placed by using a 3.8-mm delivery system that had 28-mm diameter proximal and distal ends. Among the 34 patients, stent placement for palliation was performed in 20 patients, while stent placement for bridge to surgery was performed in 14 patients.
A 97% (33 of 34) success rate was achieved for the stent placement. The perforation rate in the bridge to surgery group was 7% (1 of 14), compared to 0% (0 of 19) in palliative group. Migration occurred in one of 33 patients (3%) at 30 days after stent placement.
The placement of a 20-mm diameter dual-design stent appears to be clinically safe and effective for the management of colorectal obstruction, with low perforation and migration rates.
PMCID: PMC3253405  PMID: 22247638
Colorectal cancer; Stent; Dual-design; Expandable
7.  Surgical Outcomes after Total Colectomy with Ileorectal Anastomosis in Patients with Medically Intractable Slow Transit Constipation 
The aim of this study was to evaluate outcomes of a total colectomy with ileorectal anastomosis in patients with slow transit constipation.
A retrospective review of 37 consecutive patients with slow transit constipation who underwent a total colectomy between 1994 and 2008 was undertaken. Preoperative and postoperative Wexner's constipation scores were collected and used to evaluate the outcomes after surgical treatment. Also patients' postoperative satisfaction scores were collected using a 4-point scale.
The 37 patients consisted of 31 women and 6 men, with a median age of 41 years (range, 17 to 71 years). Pre- and post-operative Wexner's scores were collected from 33 patients (89.1%), and the mean preoperative Wexner's score was 19.3 (range, 11 to 24), which decreased to an average post-operative score of 2.3 (range, 0 to 8). Neither intraoperative complications nor postoperative mortalities were noted. Five patients (13.5%) had early postoperative complications, and the most common complication was postoperative ileus (10.8%). Seven patients (18.9%) had late postoperative complications, and postoperative ileus (10.8%) was also the most common. Twenty seven of 33 patients were satisfied with their surgical outcome (81.8%).
A total colectomy with ileorectal anastomosis might be an effective surgical procedure with acceptable morbidity to treat medically intractable slow transit constipation.
PMCID: PMC3180598  PMID: 21980588
Colonic inertia; Colectomy; Treatment outcome; Postoperative complication
8.  Comparative analysis of radiofrequency ablation and surgical resection for colorectal liver metastases 
To evaluate the comparative therapeutic efficacy of radiofrequency ablation (RFA) and hepatic resection for the treatment of colorectal liver metastasis (CRLM).
Between 1996 and 2008, 177 patients underwent RFA, 278 underwent hepatic resection and 27 underwent combination therapy for CRLM. Comparative analysis of clinical outcomes was performed including number of liver metastases, tumor size, and time of CRLM.
Based on multivariate analysis, overall survival (OS) correlated with the number of liver metastases and the use of combined chemotherapy (P < 0.001, respectively). Disease-free survival (DFS) also correlated with the number of liver metastases (P < 0.001). In the 226 patients with solitary CRLM < 3 cm, OS and DFS rates did not differ between the RFA group and the resection group (P = 0.962 and P = 0.980). In the 70 patients with solitary CRLM ≥ 3 cm, DFS was significantly lower in the RFA group as compared with the resection group (P = 0.015).
The results indicate that RFA may be a safe alternative treatment for solitary CRLM less than 3 cm, with outcomes equivalent to those achieved with hepatic resection. A randomized controlled study comparing RFA and resection for patients with single small metastasis would help to determine the most efficient treatment modalities for CRLM.
PMCID: PMC3204557  PMID: 22066097
Radiofrequency ablation; Hepatectomy; Colorectal neoplasms; Liver metastasis
9.  Clinicopathological Characteristics of Colorectal Cancer with Family History: an Evaluation of Family History as a Predictive Factor for Microsatellite Instability 
Journal of Korean Medical Science  2007;22(Suppl):S91-S97.
To determine whether family history of cancer may be a risk factor for the mutator phenotype in colorectal cancer, we recruited 143 consecutive colorectal cancer patients with a family history of accompanying cancers not meeting the Amsterdam criteria. Microsatellite instability (MSI) at 5 markers, hMLH1-promoter methylation, and expression of mismatch repair (MMR) proteins (hMLH1, hMSH2, hMSH6, hMPS1, and hPMS2) were determined. Among the relatives of familial colorectal cancer patients, colorectal cancer was the most common tumor type. Of the proband colorectal cancers, 26 (18.2%) showed high-level MSI (MSI-H); 47 additional tumors with mutator phenotype (32.9%) were identified by hMLH1-promoter methylation and/or loss of MMR protein expression. Mutator phenotype was associated with right-sided colon cancer and the type of accompanying cancer. Family history, which was differentially quantified according to the degree of relatives and the type of accompanying cancers, effectively discriminated MSI-H from microsatellite stable (MSS) and low-level microsatellite instability (MSI-L) and mutator phenotypes. Our findings indicate that familial colorectal cancer may be associated with multiple occurrences of colorectal or accompanying cancers and that family history could be correlated with microsatellite instability.
PMCID: PMC2694396  PMID: 17923762
Familial Colorectal Cancer; Family History; Mutator Phenotype; Ncrosatellite Instability

Results 1-9 (9)