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Biomedical subjects

Seok-Byung Lim

Publications and source records attributed to Seok-Byung Lim.

At least 19 recordsLinked to original sources

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↗

Germ line mutations of mismatch repair genes in hereditary nonpolyposis colorectal cancer patients with small bowel cancer: International Society for Gastrointestinal Hereditary Tumours Collaborative Study.

PURPOSE: The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC). EXPERIMENTAL DESIGN: A questionnaire was mailed to 55 members of the International Society for Gastrointestinal Hereditary Tumours, requesting information regarding patients with HNPCC-associated SBC and germ line mismatch repair gene mutations. RESULTS: The study population consisted of 85 HNPCC patients with identified mismatch repair gene mutations and SBCs. SBC was the first HNPCC-associated malignancy in 14 of 41 (34.1%) patients for whom a personal history of HNPCC-associated cancers was available. The study population harbored 69 different germ line mismatch repair gene mutations, including 31 mutations in MLH1, 34 in MSH2, 3 in MSH6, and 1 in PMS2. We compared the distribution of the mismatch repair mutations in our study population with that in a control group, including all pathogenic mismatch repair mutations of the International Society for Gastrointestinal Hereditary Tumours database (excluding those in our study population). In patients with MSH2 mutations, patients with HNPCC-associated SBCs had fewer mutations in the MutL homologue interaction domain (2.9% versus 19.9%, P = 0.019) but an increased frequency of mutations in codons 626 to 733, a domain that has not previously been associated with a known function, versus the control group (26.5% versus 2.8%, P < 0.001). CONCLUSIONS: In HNPCC patients, SBC can be the first and only cancer and may develop as soon as the early teens. The distribution of MSH2 mutations found in patients with HNPCC-associated SBCs significantly differed from that found in the control group (P < 0.001).

Adaptor Proteins, Signal Transducing↗

Is T classification still correlated with lymph node status after preoperative chemoradiotherapy for rectal cancer?

BACKGROUND: It is well known that the risk of lymph node involvement increases according to pathologic T classification in rectal cancers, but to the authors' knowledge, the correlation between risk of lymph node involvement and ypT classification in rectal cancers treated with preoperative chemoradiotherapy (CRT) remains unclear. The current study investigated the correlation between tumor involvement in regional lymph nodes and rectal mural tumor status in patients who underwent preoperative CRT for rectal cancer. METHODS: Between October 2001 and February 2005, 282 patients underwent preoperative CRT followed by proctectomy for locally advanced rectal adenocarcinoma. Correlations between lymph node status and ypT classification, Dworak regression grade, and magnetic resonance (MR) volumetry findings were explored. RESULTS: Lymph nodes harboring tumors were found in 87 of 282 (30.9%) patients. The rate of lymph node involvement was found to be correlated with ypT-classification (P < .001); positive lymph nodes were detected in 1 of 45 (2.2%) ypT0 patients, 1 of 13 (7.7%) ypT1 patients, 13 of 77 (16.9%) ypT2 patients, 69 of 140 (49.3%) ypT3 patients, and 3 of 7 (42.9%) ypT4 patients. The rate of lymph node involvement decreased as Dworak regression grade increased (P < .001); tumor-harboring lymph nodes were found in 62.3% of Grade 1 patients, 31.4% of Grade 2 patients, 16.1% of Grade 3 patients, and 2.2% of Grade 4 patients. There were no differences noted with regard to MR volumetry findings, including mean volume of pre- or post-CRT tumor and the tumor volume reduction rate between lymph node-negative and lymph node-positive patients. CONCLUSIONS: Pathologic T classification is still the most reliable predictor of lymph node metastasis in rectal cancer patients who have undergone preoperative CRT. The risk of lymph node metastasis was found to be 3.4% in rectal cancer that had regressed to ypT0 or ypT1.

Adenocarcinoma↗

Isolated tumor cells in lymph nodes are not a prognostic marker for patients with stage I and stage II colorectal cancer.

BACKGROUND AND OBJECTIVES: Lymph node metastasis is an important prognostic factor for colorectal cancer (CRC). The relationship between isolated tumor cells (ITC) in lymph nodes and the prognosis is controversial. The aim of this study is to evaluate the prognostic importance of ITC in lymph nodes from patients with stage I and II CRC. METHODS: We examined all the lymph nodes obtained during surgery from 121 consecutive patients with stage I and II CRC after a curative resection in 1999 by using monoclonal antibody against cytokeratin (MNF116). Clinicopathologic data and follow-up information were obtained from all patients. The mean follow up duration was 57 months. RESULTS: ITC were found in 50% (60/121) of the patients. The mean number of examined lymph node was 19.3 +/- 9.4. The presence of ITC was not related to clinicopathologic factors such as age, sex, location of tumor, tumor size, tumor depth, differentiation, lymphovascular invasion, and the preoperative CEA level, except for the tumor gross type (P = 0.002). There were no statistically significant differences for the recurrence rate (10/60 = 16.7% and 9/61 = 14.8%, respectively), and disease-free survival (P = 0.809) between the ITC positive group and ITC negative group. CONCLUSIONS: The presence of ITC detected by immunohistochemical staining does not have an influence on the prognosis of patients with stage I and II CRC.

Adult↗

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↗

The effect of belly board location in rectal cancer patients treated with preoperative radiotherapy.

AIMS: To evaluate the effect of the belly board aperture location on the irradiated small bowel volume in rectal cancer patients treated with preoperative pelvic radiotherapy. MATERIALS AND METHODS: Twenty patients with rectal cancer scheduled to receive preoperative pelvic radiotherapy were evaluated prospectively. Each patient underwent computed tomography with the belly board aperture lower border at three different locations relative to patient anatomy: the lumbosacral junction (location I), the lower end of the sacroiliac joint (location II) and the upper end of the symphysis pubis (location III). The irradiated small bowel volume was calculated for doses between 10 and 100% of the prescribed dose at 10% intervals. For each 10% dose increment, the effect of the belly board aperture at the three different locations on the irradiated small bowel volume was analysed using Wilcoxon signed rank and Wilcoxon rank sum tests. RESULTS: At 10-20% dose levels, the irradiated small bowel volume increased in the order of locations I, II and III, and the differences between each location were significant. At > or = 30% dose levels, the irradiated small bowel volume increased in the order of locations III, II and I, and the differences between locations I and II were significant, but the differences between locations II and III were not significant. CONCLUSION: The belly board aperture location can influence the irradiated small bowel volume differently at each dose level. When considering the use of a belly board in routine clinical practice, we recommend that the clinician take into account the patterns of irradiated small bowel volume according to belly board aperture location.

Adult↗

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↗

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↗

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↗

Mutational analysis of BRAF and K-ras in gastric cancers: absence of BRAF mutations in gastric cancers.

Recently, BRAF mutations were found in a variety of human cancers. Interestingly, the most common of BRAF mutation (V599E) has not been identified in tumors with K-ras mutations. Whereas the majority of human cancer types has been screened for BRAF mutations, no detailed studies on gastric cancers have been investigated. Thus, we decided to investigate the incidence of BRAF mutations in gastric cancers, and the relationship between BRAF and K-ras mutations in such cancers. Three non-pathogenic BRAF polymorphisms and seven K-ras missense mutations were found in 66 gastric cancers and 16 gastric cancer cell lines. Although only 9% of our gastric cancer panels had K-ras mutations, the incidence of BRAF mutations was not high. Thus, BRAF mutations, which are present in a variety of other human cancers, do not seem to be involved in gastric cancer development.

Base Sequence↗

Robust microsatellite instability (MSI) analysis by denaturing high-performance liquid chromatography (DHPLC).

Microsatellite instability (MSI) plays an important biological role in various types of cancers, and especially in colorectal cancers. This study aimed to develop a simple, efficient, new method for robust MSI analysis. DNA was extracted from 175 (105 proximal colon and 70 distal colorectal) cancer samples and matched normal tissues, and five Bethesda microsatellite markers (BAT-25, BAT-26, D5S346, D2S123, and D17S250) were examined for MSI by denaturing high-performance liquid chromatography (DHPLC) analysis at a temperature of 50 degrees C and a flow rate of 0.9 ml/min. It took just 9 min per PCR product to determine MSI or microsatellite stability (MSS) using the new protocol. The DHPLC results were confirmed with conventional gel-based electrophoresis and capillary-based sequencing method. Of 175 samples, 45 (26%) showed high microsatellite instability (MSI-H), 12 (7%) showed low microsatellite instability (MSI-L), and 118 (67%) showed MSS. All MSI samples were deletion mutants and all 12 MSI-L cases had MSI in dinucleotide markers (D5S346, D2S123, and D17S250). MSI was significantly associated with proximal colon cancers ( p<0.0001), as previously reported. The MSI-H tumors were also associated with tumor node metastasis (TNM) I/II stages ( p=0.05) and high-grade tumors ( p<0.01). Here, we propose a DHPLC-based method as an alternative for MSI analysis.

Chemistry Techniques, Analytical↗