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Seung-Yong Jeong

Publications and source records attributed to Seung-Yong Jeong.

At least 19 recordsLinked to original sources

Correlation between hypermethylation of the RASSF2A promoter and K-ras/BRAF mutations in microsatellite-stable colorectal cancers.

Recently, RASSF2A was identified as a potential tumor suppressor epigenetically inactivated in human cancers. Here, we evaluated the methylation status of RASSF2A in colorectal cancer (CRC) and analyzed its correlation with K-ras/BRAF mutations, microsatellite instability status and other clinicopathological features. Using methylation-specific PCR and bisulfite sequencing, we analyzed the methylation status in primary CRC, adenomas and corresponding normal tissues and then compared it with the presence of K-ras and BRAF mutations. We also examined the expression and methylation status of RASSF2A in CRC cell lines. We found that aberrant methylation of RASSF2A promoter regions is associated with gene silencing in CRC cell lines. In primary CRC, the frequency of RASSF2A methylation was 72.6%, and it was found in 16 of 16 (100%) adenomas. In addition, there was a positive correlation between K-ras/BRAF mutations and RASSF2A methylation in primary CRC. Furthermore, a significant positive correlation between K-ras/BRAF mutations and RASSF2A methylation was also observed in microsatellite-stable (p = 0.033) and distal CRC (p = 0.025). These results show that RASSF2A methylation is a frequent event in colorectal tumorigenesis and positively correlates with K-ras/BRAF mutation in microsatellite-stable or distal CRC.

Adenoma↗

Comparison of 5-fluorouracil/leucovorin and capecitabine in preoperative chemoradiotherapy for locally advanced rectal cancer.

PURPOSE: To describe our experience with a bolus injection of 5-fluorouracil and leucovorin (FL) vs. capecitabine in terms of radiologic and pathologic findings in preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. METHODS: The study enrolled 278 patients scheduled for preoperative CRT using two protocols with different chemotherapeutic regimens. Pelvic radiotherapy (50.4 Gy) was delivered concurrently with FL (n = 145) or capecitabine (n = 133). Surgery was performed 6 weeks after CRT completion. Tumor responses to CRT were measured using both radiologic and pathologic examination. Magnetic resonance volumetry was performed at the initial workup and just before surgery after completion of preoperative CRT. Post-CRT pathology tests were used to determine tumor stage and regression. RESULTS: Radiologic examination showed that tumor volume decreased by 68.2% +/- 20.5% in the FL group and 68.3% +/- 22.3% in the capecitabine group (p = 0.970). Postoperative pathologic T stage determination showed that downstaging occurred in 44.3% of FL and 49.9% of capecitabine patients (p = 0.571). The tumor regression grades after CRT were Grade 1 (minimal response) in 22.6% and 21.0%, Grade 2 (moderate response) in 53.2% and 50.0%, Grade 3 (near-complete response) in 12.9% and 12.9%, and Grade 4 (complete response) in 11.3% and 16.1% of the FL and capecitabine groups, respectively (p = 0.758). CONCLUSION: In the present study, the radiologic and pathologic findings did not reveal significant differences in short-term tumor responses between preoperative FL and capecitabine CRT for locally advanced rectal cancer. Long-term results and a prospective randomized trial are needed.

Adult↗

Analysis of microsatellite instability in stool DNA of patients with colorectal cancer using denaturing high performance liquid chromatography.

AIM: To evaluate the usefulness of denaturing high performance liquid chromatography (DHPLC) for analyzing microsatellite instability (MSI) status in stool DNA of patients with colorectal cancer. METHODS: A total of 80 cancer tissues from patients with primary sporadic colorectal tumor (proximal cancer: 27, distal cancer: 53) and matched stool (which were employed for comparison with the tissues) were analyzed for MSI status in BAT 26. DNA samples extracted from stool were evaluated by nested polymerase chain reaction (PCR) and DHPLC for MSI analysis. RESULTS: Six cases (7.5%) of MSI were identified in BAT 26 from 80 cancer tissues. All the stool DNA samples from patients whose cancer tissue showed MSI also displayed MSI in BAT 26. CONCLUSION: As MSI is one of the established fecal DNA markers to screen colorectal cancer, we propose to use DHPLC for the MSI analysis in fecal DNA.

Biomarkers, Tumor↗

Histopathological risk factors for lymph node metastasis in submucosal invasive colorectal carcinoma of pedunculated or semipedunculated type.

AIMS: To evaluate the histopathological risk factors for lymph node metastasis in cases of pedunculated or semipedunculated submucosal invasive colorectal carcinoma (SICC). METHODS: A total of 48 patients with non-sessile SICC who underwent systematic lymph node dissection were included. Tumour size, histological grade, angiolymphatic invasion, tumour budding, dedifferentiation, objective submucosal invasion depth from the identified muscularis mucosa, relative invasion depth of the submucosal layer, and depth of stalk invasion were investigated histopathologically. RESULTS: Lymph node metastasis was observed in seven cases (14.6%). Univariate analysis showed angiolymphatic invasion and tumour budding to be significantly associated with lymph node metastasis. Multivariate analysis showed that tumour budding was the only independent factor associated with lymph node metastasis in cases of non-sessile SICC. CONCLUSIONS: Results indicate that tumour budding is a useful risk factor for predicting lymph node metastasis in cases of pedunculated or semipedunculated SICC.

Adenocarcinoma↗

Preoperative chemoradiotherapy with concomitant small field boost irradiation for locally advanced rectal cancer: a multi-institutional phase II study (KROG 04-01).

PURPOSE: This study was designed to determine the effect of concomitant small field boost irradiation given during preoperative chemoradiotherapy for patients with locally advanced rectal cancer. METHODS: The study prospectively enrolled 38 patients scheduled for preoperative chemoradiotherapy. Pelvic radiotherapy of 43.2 Gy/24 fractions was delivered and boost radiotherapy of 7.2 Gy/12 fractions was concomitantly administered during the latter half of the pelvic radiotherapy treatment period. Two cycles of a bolus 5-fluorouracil and leucovorin injection in the first and fifth weeks of radiotherapy were administered. The median time to surgery after completion of chemoradiotherapy was six weeks. Tumor responses to chemoradiotherapy were assessed by using magnetic resonance volumetry and post-chemoradiotherapy pathology tests to determine tumor downstaging and tumor regression rate. RESULTS: Thirty-six of 38 patients (94.7 percent) underwent the scheduled surgery. The mean tumor volume reduction rate was 70.3 percent, and the clinical response rate was 66.7 percent. The downstaging rates were 41.7 percent for T classification, 85.2 percent for N classification, and 72.2 percent for stage. Tumor regression grades after preoperative chemoradiotherapy were Grade 1 in 5 patients (13.9 percent), Grade 2 in 24 patients (66.7 percent), Grade 3 in 3 patients (8.3 percent), and Grade 4 in 4 patients (11.1 percent). Ten patients (26.3 percent) experienced > or = Grade 3 acute toxicity. CONCLUSIONS: Our data suggest that concomitant boost irradiation does not improve clinical outcomes compared with other published preoperative chemoradiotherapy regimens. In addition, the clinicians choosing to use concomitant small field boost irradiation should be cautious to minimize the risk of unplanned sphincter ablation.

Adult↗

Surgical treatment of rectal cancer: radical resection.

Currently, surgery is the only potentially curative treatment modality for rectal cancer. The major goals of surgery for rectal cancer are to optimize oncologic outcome and maintain anorectal and genitourinary function. This article reviews the surgical management of primary rectal cancer and discusses major surgical considerations in the treatment of this disease.

Colectomy↗

Usefulness of magnetic resonance volumetric evaluation in predicting response to preoperative concurrent chemoradiotherapy in patients with resectable rectal cancer.

PURPOSE: We performed magnetic resonance (MR) volumetry before and after neoadjuvant chemoradiation for evaluating response to therapy in T3 and T4 rectal cancer. To investigate the utility of MR volumetry for predicting the response to neoadjuvant chemoradiation, we compared results from MR volumetry before chemoradiation with those after chemoradiation. METHODS AND MATERIALS: A total 112 patients with T3 or T4 rectal cancer who successfully underwent MR volumetry and completed neoadjuvant chemoradiation followed by radical resection for cure were identified. MR volumetries were performed before and after chemoradiation. We compared pre- and postchemoradiation tumor volume and % volume reduction rates of patients whose tumors were down-staged with those of patients that were not down-staged. The same analyses were also performed between those patients having a complete histologic regression and those with residual disease in the operative specimen. We assessed the difference of % volume reduction rate according to Dworak's rectal cancer regression grades. RESULTS: Fifty-seven patients (50.9%) demonstrated a tumor down-staging after chemoradiation therapy. Both pre- and posttreatment MR tumor volumes were significantly less in patients whose tumors were down-staged than in patients that were not down-staged (p = 0.04, 0.031), and % volume reduction rates were significantly higher in patients whose tumors were down-staged (p = 0.024). Sixteen patients (14.3%) showed pathologically complete tumor regression. The differences of MR tumor volumes before and after chemoradiation and % volume reduction rates were not significantly different between patients having a complete histologic regression and those with residual disease (p = 0.688, 0.451, and 0.480). The differences of % volume reduction rates according to Dworak's grades were statistically significant (p = 0.03). CONCLUSION: The MR volumetric examinations before and after chemoradiation demonstrated the significant difference of tumor volume and % volume reduction rate between patients whose tumors were down-staged and those that were not down-staged. The volume reduction rates were significantly different among groups according to Dworak's grades. However, the MR volumetric evaluation could not identify any differences between those patients having a complete histologic regression and those with residual disease.

Adult↗

Comparison of the belly board device method and the distended bladder method for reducing irradiated small bowel volumes in preoperative radiotherapy of rectal cancer patients.

PURPOSE: To determine the most effective method to reduce the irradiated small bowel volume when using a belly board device (BBD), a distended bladder (DB), or both in patients with rectal cancer undergoing preoperative pelvic radiotherapy (RT). METHODS AND MATERIALS: The study involved 20 patients with rectal cancer who were scheduled to receive preoperative pelvic RT. Patients were asked to empty their bladders and then drink 300 mL of water 2 h before the treatment planning computed tomographic (CT) scan. To identify the small bowel, an oral contrast solution (450 mL) was given 1 h before the CT scan. Two sets of transverse images were taken at 1-cm-thickness intervals with patients in the prone position with or without the BBD. After voiding, two additional sets of CT scans were obtained in prone positions with or without BBD. The conventional three-field treatment plan, composed of a 6-MV photon posterior-anterior field and 15-MV photon opposed lateral fields with wedges of 45 degrees, was made using a three-dimensional treatment planning system. The beam weights of the three-field plan were equal. The volume of irradiated small bowel was calculated for doses between 10% and 100% of the prescribed dose at 10% intervals. For each 10% dose increment, the effect of the BBD and the DB on the irradiated volume was analyzed using Kruskal-Wallis, Wilcoxon signed rank, and Wilcoxon rank-sum tests. RESULTS: All patients underwent four sets of CT scan under the conditions of four different methods as follows: Group I = empty bladder without the use of belly board; Group II = empty bladder with the use of belly board; Group III = distended bladder without the use of belly board; Group IV = distended bladder with the use of belly board. We found that the volume of irradiated small bowel decreased in the order of Group I, Group II, Group III, and Group IV at all dose levels (p < 0.05). Compared with Group I, the mean volume reduction rate (reduced volume) of irradiated small bowel in Group II varied between 14.5% and 65.4% (15.5-80.4 cm(3)), in Group III it varied between 48.1% and 82.0% (21.6-163.1 cm(3)), and in Group IV between 51.4% and 96.4% (28.6-167.1 cm(3)). CONCLUSIONS: The DB was more effective than the BBD for reducing the volume of irradiated small bowel in rectal cancer patients receiving pelvic RT. The combination of the BBD and DB showed an additive effect and was the most effective method for reducing the irradiated small bowel volume.

Adult↗

Colonic J-pouch anal anastomosis after ultralow anterior resection with upper sphincter excision for low-lying rectal cancer.

AIM: There is some evidence of functional superiority of colonic J-pouch over straight coloanal anastomosis (CAA) in ultralow anterior resection (ULAR) or intersphincteric resection. On the assumption that colonic J-pouch anal anastomosis is superior to straight CAA in ULAR with upper sphincter excision (USE: excision of the upper part of the internal sphincter) for low-lying rectal cancer, we compare functional outcome of colonic J-pouch vs the straight CAA. METHODS: Fifty patients of one hundred and thirty-three rectal cancer patients in whom lower margin of the tumors were located between 3 and 5 cm from the anal verge received ULAR including USE from September 1998 to January 2002. Patients were randomized for reconstruction using either a straight (n = 26) or a colonic J-pouch anastomosis (n = 24) with a temporary diverting-loop ileostomy. All patients were followed-up prospectively by a standardized questionnaire (Fecal Incontinence Severity Index (FISI) scores and Fecal Incontinence Quality of Life (FIQL) scales). RESULTS: We found that, compared to straight anastomosis patients, the frequency of defecation was significantly lower in J-pouch anastomosis patients for 10 mo after ileostomy takedown. The FISI scores and FIQL scales were significantly better in J-pouch patients than in straight patients at both 3 and 12 mo after ileostomy takedown. Furthermore, we found that FISI scores highly correlated with FIQL scales. CONCLUSION: This study indicates that colonic J-pouch anal anastomosis decreases the severity of fecal incontinence and improves the quality of life for 10 mo after ileostomy takedown in patients undergoing ULAR with USE for low-lying rectal cancer.

Adult↗

Metabotropic glutamate receptor 4 expression in colorectal carcinoma and its prognostic significance.

PURPOSE: Metabotropic glutamate receptors (mGluR) play a variety of roles in both neuronal and nonneuronal cells. Recently, we reported that mGluR4 mediates 5-fluorouracil resistance in a human colon cancer cell line. In this study, we evaluated the nonneural expression of mGluR4 and clarified the existence of mGluR4 in normal colon epithelium and colorectal carcinomas. We also investigated the association of mGluR4 expression levels with various clinicopathologic parameters. EXPERIMENTAL DESIGN: mGluR4 expression was investigated in 21 normal and 312 malignant tissues from various organs using immunohistochemistry. In addition, 241 cases of colorectal carcinomas were examined and correlations between mGluR4 expression and various clinicopathologic parameters were then statistically analyzed. RESULTS: Expression of mGluR4 was identified in the normal epithelia of the upper respiratory tract, gastrointestinal tracts, breast, uterine cervix, urinary bladder, and skin, whereas it was not detected in the thyroid, lung alveoli, liver, testis, or prostate. In the corresponding malignant tissues, mGluR4 expression was frequently identified in colorectal carcinoma (68%), followed by malignant melanoma, laryngeal carcinoma, and breast carcinomas. Expression of mGluR4 was detected in 131 (54%) of 241 colorectal carcinomas and 12 (5%) cases among them showed overexpression in their cytoplasms. Loss of mGluR4 expression was negatively associated with tumor differentiation (P = 0.028), whereas overexpression of mGluR4 was positively associated with recurrence (P = 0.034) and poor disease-free survival (P = 0.017) in multivariate analyses. CONCLUSIONS: Our results suggest that mGluR4 signaling may play a role in colorectal carcinomas and that overexpression of mGluR4 is associated with poor prognosis.

Aminobutyrates↗

Comparative analysis of the effects of belly board and bladder distension in postoperative radiotherapy of rectal cancer patients.

PURPOSE: To compare the effect of reducing the irradiated small-bowel volume with the use of belly board, bladder distension or both methods combined, in patients with rectal cancer undergoing postoperative pelvic radiotherapy. PATIENTS AND METHODS: This study enrolled 20 consecutive patients with rectal cancer who were scheduled to receive postoperative pelvic radiotherapy. All patients underwent four sets of CT scans under four different methods as follows: group I: empty bladder without the use of a belly board; group II: empty bladder with the use of a belly board; group III: bladder distension without the use of a belly board; group IV: bladder distension with the use of a belly board. The conventional three-field treatment plan was made using a three-dimensional treatment planning system. The irradiated small-bowel volume was calculated at 10% intervals from 10% to 100% of the prescribed dose. RESULTS: The volume of the irradiated small bowel decreased in the order of group I, group II, group III, and group IV at all dose levels (p < 0.001). In comparison to group I, the mean absolute volume reductions (relative volume reduction) of the irradiated small bowel were 41.5 +/- 20.1 cm(3) (33.9 +/- 12.9%) in group II, 76.6 +/- 30.5 cm(3) (55.1 +/- 17.8%) in group III, and 98.5 +/- 36.7 cm(3) (70.7 +/- 14.5%) in group IV. CONCLUSION: Bladder distension was a more effective method than the belly board for reducing the irradiated small-bowel volume in postoperative pelvic radiotherapy of rectal cancer patients. The combination of the belly board and bladder distension showed an additive effect and was the most effective method for reducing the irradiated small-bowel volume.

Adenocarcinoma↗

Bax, a predictive marker for therapeutic response to preoperative chemoradiotherapy in patients with rectal carcinoma.

In an attempt to improve local control and survival in patients with advanced rectal carcinoma, neoadjuvant chemoradiation therapy (CRT) has been increasingly used in patient management. However, a significant proportion of patients shows poor response to adjuvant CRT. Thus, the ability to predict CRT responsiveness in patients with rectal cancer would benefit effective management. Several molecular markers related to regulation of cell cycle, apoptosis, or DNA repair have been proposed as candidate predictors of therapeutic response to CRT, but, to date, none has been definitively proven to be predictive of CRT response. To evaluate the use of various molecular markers as predictors of the response to CRT in rectal carcinoma, we investigated immunohistochemical expressions of p53, p21 WAF1/CIP1 , Bcl-2, Bax, Ki-67, Ku-70, and 2 new candidate markers (histone deacetylase 1 and metabotropic glutamate receptor 4) in pretreatment biopsy samples of 130 rectal carcinomas. We further compared the expressions of these molecular markers with the pathological responses of the tumors after therapy. We found that Bax expression, among the markers studied, was exclusively related to tumor regression. Its expression was significantly higher in the complete response group as compared with the partial response group (54% versus 29%, P = .017). This result confirms that apoptosis plays an important role in tumor response to CRT and provides evidence that Bax may serve as a predictable molecular marker for chemoradiosensitivity in rectal carcinoma.

Adult↗

Contemporary applications of transanal endoscopic microsurgery: technical innovations and limitations.

PURPOSE: Transanal endoscopic microsurgery (TEM) is a minimally invasive procedure used to transanally excise select benign and malignant tumors of the rectum. In properly selected patients, TEM can provide for decreased postoperative morbidity without compromising oncologic outcome. This report summarizes the recent literature concerning TEM, comprehensively analyzes the authors' experience with TEM, and describes recent technical innovations and indications. PATIENTS AND METHODS: Thirty-two consecutive patients scheduled for TEM were identified from our prospectively maintained colorectal service database. Clinicopathologic factors, postoperative complications, and oncologic outcomes were analyzed for all patients. In addition, a PubMed literature search was performed with use of the key words "transanal endoscopic microsurgery," "TEM," "rectal tumor," and "rectal cancer." RESULTS: Transanal endoscopic microsurgery was performed for rectal adenocarcinoma (n = 17; 53%), adenoma (n = 12; 38%), and carcinoid tumors (n = 3; 9%). Median tumor location was 9 cm from the anal verge (range, 3-15 cm). Of the 32 attempted TEM procedures, 27 (84%) were completed. Reasons for inability to complete TEM included narrow rectal lumen or contour of bony pelvis prohibiting passage of the operating proctoscope into the upper rectum and inability to maintain the proctoscope in the rectal lumen with carbon dioxide insufflation because of the distal location of the tumor. Innovations used in the excision of rectal tumors via TEM included the use of the harmonic scalpel, closure of the rectal defect with an extracorporeal slip knot, and a hybrid approach incorporating TEM and traditional transanal techniques. CONCLUSION: Transanal endoscopic microsurgery provides for low morbidity and does not appear to impair oncologic outcome in properly selected patients.

Adenocarcinoma↗

Granular cell tumor of colon: report of a case and review of literature.

Granular cell tumor (GCT) is uncommon in the colon and rectum. Here we report a case of GCT in the transverse colon. A 48-year-old male patient underwent a screening colonoscopy. A yellowish sessile lesion, about 4 mm in diameter, was found in the transverse colon. An endoscopic snare resection was performed without complication. Histological examination revealed the tumor consisted of plump neoplastic cells with abundant granular eosinophilic cytoplasm containing acidophilic periodic acid Schiff-positive, diastase-resistant granules. Immunohistochemical analysis showed the tumor cells expressed S-100 protein and neuron-specific enolase. Thus, the resected tumor was diagnosed as a GCT. Since GCTs are usually benign, endoscopic resection constitutes an easy and safe treatment. Colonoscopists should consider the possibility of GCT in the differential diagnosis of submucosal tumors of the colon.

Adenocarcinoma↗

A functional polymorphism (-347 G-->GA) in the E-cadherin gene is associated with colorectal cancer.

E-cadherin, the main adhesion molecule of epithelial cells, has been implicated in carcinogenesis because its expression is frequently lost in human epithelial cancers. E-cadherin protein expression is significantly reduced in sporadic colorectal cancers (CRC), but apparently not as a consequence of allele loss or somatic mutation. We reported recently that a single nucleotide polymorphism (-347 G-->GA) in the E-cadherin promoter suppressed E-cadherin expression and was associated with familial gastric cancer. Here we sought to investigate whether the functional polymorphisms of E-cadherin might affect CRC. We genotyped 407 individuals (260 CRC patients and 147 normal controls) for the -347 G-->GA promoter polymorphism of E-cadherin using denaturing high-performance liquid chromatography and direct sequencing. We also measured the activity of promoters harboring the polymorphism by dual luciferase reporter assay in several CRC cell lines. We found that the E-cadherin GA genotype (G/GA heterozygous and GA homozygous) was more common in CRC patients than in normal controls (P = 0.011). Subjects with the E-cadherin GA genotype had an overall 1.75-fold increased risk of CRC. We also observed an increased risk association between the E-cadherin GA genotype and both proximal colon (P = 0.019) and distal CRC (P = 0.036). Interestingly, the GA allele decreased transcriptional efficiency by 12-, 9- and 10-fold compared with the G allele in SNU-C4, SNU-C5 and SNU-1033 cell lines, respectively. Additionally, we examined whether there was a correlation between the E-cadherin promoter polymorphism and microsatellite instability status, and found no such correlation. Taken together, our results suggest that the E-cadherin -347 G-->GA polymorphism may be associated with CRC.

Adenine↗

Prognostic significance of microsatellite instability in sporadic colorectal cancer.

BACKGROUND AND AIMS: Colorectal cancers exhibiting microsatellite instability (MSI) appear to have unique biological behavior. The influence of MSI on the prognosis of sporadic colorectal cancers is controversial and requires further investigation. The aim of this study was to analyze the association between MSI status and clinicopathological features and prognosis in sporadic colorectal cancer patients. PATIENTS AND METHODS: Of the 322 consecutive colorectal cancer patients operated upon at the Seoul National University Hospital between January and December 1998, we examined the clinicopathological features and prognosis of 248 patients with sporadic primary colorectal cancer. The MSI status of these 248 patients has been reported in a previous study. Of the 248 patients, 23 (9.3%) had MSI+ tumors. The patients' clinicopathological parameters were obtained from their medical records, and follow-up and survival data were obtained from medical records and phone calls. RESULTS: MSI+ sporadic colorectal cancers were found predominantly in the proximal colon ( p<0.001) and were associated with poor differentiation ( p=0.030), a lower preoperative serum carcinoembryonic antigen (CEA) level ( p=0.012), and less frequent systemic metastasis ( p=0.034) than MSI- tumors. Low tumor grade ( p=0.022), low tumor T-stage ( p=0.002), no lymph node metastasis ( p<0.001), no systemic metastasis ( p<0.001), adjuvant chemotherapy ( p<0.001) and MSI+ status ( p=0.038) were independent favorable prognostic factors for survival in sporadic colorectal cancer patients. CONCLUSION: MSI status was an independent favorable prognostic factor for survival in sporadic primary colorectal cancer patients.

Adult↗