Biomedical subjects

Jin Cheon Kim

Publications and source records attributed to Jin Cheon Kim.

At least 19 recordsLinked to original sources

PubMed2006

Optimal time interval between capecitabine intake and radiotherapy in preoperative chemoradiation for locally advanced rectal cancer.

PURPOSE: Capecitabine and its metabolites reach peak plasma concentrations 1 to 2 hours after a single oral administration, and concentrations rapidly decrease thereafter. We performed a retrospective analysis to find the optimal time interval between capecitabine administration and radiotherapy for rectal cancer. METHODS AND MATERIALS: The time interval between capecitabine intake and radiotherapy was measured in patients who were treated with preoperative radiotherapy and concurrent capecitabine for rectal cancer. Patients were classified into the following groups. Group A1 included patients who took capecitabine 1 hour before radiotherapy, and Group B1 included all other patients. Group B1 was then subdivided into Group A2 (patients who took capecitabine 2 hours before radiotherapy) and Group B2. Group B2 was further divided into Group A3 and Group B3 with the same method. Total mesorectal excision was performed 6 weeks after completion of chemoradiation and the pathologic response was evaluated. RESULTS: A total of 200 patients were enrolled in this study. Pathologic examination showed that Group A1 had higher rates of complete regression of primary tumors in the rectum (23.5% vs. 9.6%, p = 0.01), good response (44.7% vs. 25.2%, p = 0.006), and lower T stages (p = 0.021) compared with Group B1; however, Groups A2 and A3 did not show any improvement compared with Groups B2 and B3. Multivariate analysis showed that increases in primary tumors in the rectum and good response were only significant when capecitabine was administered 1 hour before radiotherapy. CONCLUSION: In preoperative chemoradiotherapy for rectal cancer, the pathologic response could be improved by administering capecitabine 1 hour before radiotherapy.

Adult↗

PubMed2006

A giant colonic hamartoma and multiple colonic hamartomatous polyps in a middle-aged man.

Colonic hamartomas are rare polypoid lesions. We report an unusual case of multiple colonic hamartomatous polyps, including a giant hamartoma, unrelated to hereditary or familial polyposis syndromes, in a 48-year-old man. The diameter of the largest polyp was 9.5 cm, and endoscopy revealed that the lesion caused colonic obstruction. The clinical, endoscopic and histological aspects of this case are discussed.

Colectomy↗

PubMed2006

[Clinicopathologic characteristics of colorectal neuroendocrine tumor].

BACKGROUND/AIMS: Colorectal neuroendocrine carcinoma is a rare neoplasm exhibiting fulminant progression and having poor prognosis. The purpose of this study is to verify the clinicopathologic characteristics of colorectal neuroendocrine carcinoma. METHODS: From June 1997 to December 2004 at Asan Medical Center, ten patients were originally identified as colorectal neuroendocrine carcinoma on the basis of H&E and immunohistochemical staining (IHC). Carcinoid tumors were excluded in this study. Medical records of thirteen patients were reviewed retrospectively. RESULTS: Ten patients (0.2%) with colorectal neuroendocrine tumors were identified from 4,512 patients with colorectal cancer; ten neuroendocrine carcinomas and three adenocarcinomas with neuroendocrine differentiation. Their median age was 60 (41-83) years. The subjects consisted of six males and seven females. Nine tumors were located in the rectum, two in the sigmoid, and each one in the transverse colon and cecum, respectively. Nine of ten neuroendocrine carcinomas expressed synaptophysin, but chromogranin A were expressed in four. All patients were advanced at the time of diagnosis, with AJCC TNM staging: stage IIIB (n=2), stage IIIC (n=3), and stage IV (n=8). The median survival for ten neuroendocrine carcinomas and three adenocarcinomas with neuroendocrine differentiation were 16.4 months and 30 months, respectively. Five patients who received chemotherapy showed median survival of 32 months (stage III) and 17.5 months (stage IV), whereas other five patients without chemotherapy died with a median survival of 6.2 months. CONCLUSIONS: Colorectal neuroendocrine tumors are extremely rare showing aggressive behavior biologically, i.e fulminant early distant metastasis. Nevertheless, improved survival may be achieved by aggressive multimodality therapy.

Adenocarcinoma↗

PubMed2005

Aberrant CpG island methylation in early-onset sporadic gastric carcinoma.

PURPOSE: Gastric carcinoma more commonly affects older patients, and it is thought that cases of early-onset gastric carcinoma may develop with a different molecular profile different from that of carcinoma occurring at a later age. We assayed the methylation status and genetic changes in genes associated with the APC-beta-catenin axis and the mismatch repair system in relatively early-onset gastric carcinoma samples to determine their association with gastric carcinogenesis. METHODS: Tumor and normal tissue DNA samples were obtained from 40 patients with early-onset (< 50 y) gastric carcinomas and assayed for APC and CTNNB1 mutations, microsatellite instability, and methylation of the promoters of the hMLH1, TIMP3, THBS1, DAP- K, GSTP1 , APC, and MINT2. RESULTS: Promoter methylation at these seven loci ranged from 12.5 to 62%, with 38/40 tumors (95%) showing promoter methylation at more than one locus. The CpG island methylation phenotype (CIMP) was classified as high in 16 tumors (40%), low in 22 tumors (55%), and negative in 2 tumors (5%). Two concurrent missense mutations (E1685G, R1763L) in the APC mutation cluster region were detected in two tumors, nine tumors showed loss of APC heterozygosity (LOH), and two showed both LOH and promoter methylation. CONCLUSIONS: Our results indicate that, unlike in colorectal carcinoma, APC and CTNNB1 mutations do not appear to be highly implicated in early-onset gastric carcinogenesis. In contrast, our data show that promoter methylation is a prevalent phenomenon in early-onset gastric carcinoma and may be related to gastric carcinogenesis.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Preoperative concurrent radiotherapy with capecitabine before total mesorectal excision in locally advanced rectal cancer.

PURPOSE: Capecitabine is an attractive radiosensitizer which can be tumor specific. This study was undertaken to evaluate the toxicity and efficacy of oral capecitabine when used with preoperative radiation therapy. METHODS AND MATERIALS: We conducted a prospective Phase II trial to assess the pathologic response, sphincter preservation effect, and acute toxicity of preoperative chemoradiation (CRT) in locally advanced (uT3-4/N +) but resectable adenocarcinoma of the lower two-thirds of the rectum. The radiation dose was 50 Gy over 5 weeks (46 Gy to whole pelvis + 4 Gy boost), and capecitabine was administered daily at a dose of 1650 mg/m(2) during the entire course of radiation therapy. Surgery was performed with standardized total mesorectal excision 4 to 6 weeks after completion of CRT and followed by four cycles of capecitabine (2500 mg/m(2)/day for 14 days). RESULTS: Ninety-five patients were entered into this study; their median age was 55 (range, 31-75 years). Ninety (95%) patients completed preoperative CRT as planned, and complete resection was achieved in 92 of 94 resected cases (98%). Downstaging rate was 71% (56/79) on endorectal ultrasonography, and it was 76% (71/94) on pathology finding. No tumor cell was observed in the specimens of 11 patients (12%). Among the 54 whose tumor was located within 5 cm from the anal verge, 40 patients (74%) underwent sphincter-preserving procedures. Elevation of the distal tumor margin from the anal verge by preoperative CRT was 0.8 +/- 1.3 cm. Grade 3 toxicities were rare (diarrhea in 3% and neutropenia in 1%). CONCLUSION: Preoperative CRT using capecitabine achieved encouraging rates of tumor downstaging and sphincter preservation with a low toxicity profile.

Adolescent↗

PubMed2005

Start codon polymorphisms in the vitamin D receptor and colorectal cancer risk.

The expression of the nuclear vitamin D receptor (VDR), which is involved in regulating cell growth and proliferation, may contribute to the development of colorectal cancer. Polymorphisms in the VDR gene (OMIM 601769) may influence the expression or function of the VDR protein. A population-based, case-control study of VDR start codon, intron, and exon polymorphisms, haplotypes for these polymorphisms, and the relationships between these polymorphisms and clinicopathological parameters in 190 colorectal cancer patients and 318 controls was conducted. The start codon variant VDR 27823*C/*C genotype was associated with an increased risk for colorectal cancer, while the 27823*T/*T genotype was associated with a decreased risk. In addition, the VDR 61888*G/*G genotype was associated with reduced colorectal cancer risk. The intron 8 60880G>A and exon 9 61968T>C polymorphisms were not associated with colorectal cancer risk. The VDR 27823*C-60890*G-61888*T-61968*T haplotype was associated with an increased risk of colorectal cancer, whereas the VDR 27823*T-60890*G-61888*G-61968*T haplotype was associated with a decreased risk of colorectal cancer. Moreover, the 27823*C/*C genotype was more frequently identified in patients with preoperative serum carcinoembryonic antigen (CEA) levels over 6ng/mL. These results suggest that the VDR start codon 27823*C allele may be linked to high risk for colorectal cancer, especially in a subset of colorectal cancers showing specific biological behaviors.

Adult↗

PubMed2005

Quality of life in colorectal cancer patients with colectomy and the validation of the Functional Assessment of Cancer Therapy-Colorectal (FACT-C), Version 4.

The purpose of this study was to determine whether the Functional Assessment of Cancer Therapy-Colorectal (the FACT-C), a disease-specific tool for the assessment of colorectal cancer patients' QOL, is a valid assessment tool for measuring QOL changes. Ninety-eight colorectal cancer patients performed the assessment at baseline and 52 of these patients completed the instrument at one month and six months after colectomy. In addition to the FACT-C, the shortened forms of the Profile of Mood States, the Eastern Cooperative Oncology Group Performance Status Rating, Neuroticism Scale in the Eysenck Personality Questionnaire, and Functional Living Index-Cancer were completed. We found convergent and divergent validity and good reliability of the FACT-C. Patients' overall QOL was lower at one month after colectomy and recovered to the pre-surgery level at six months after colectomy.

Colectomy↗

PubMed2005

CpG island methylation as an early event during adenoma progression in carcinogenesis of sporadic colorectal cancer.

BACKGROUND AND AIMS: CpG island methylation is present in various tumors, including colorectal carcinomas, and is thought to be an important mechanism in carcinogenesis. We evaluated the methylation status of primary colorectal tumors to determine its role in the adenoma to carcinoma sequence. METHODS: The methylation status of APC, THBS1, MGMT, hMLH1 and GSTP1, as determined by methylation specific PCR (MSP), and microsatellite instability (MSI) using three mononucleotide markers were assessed in 40 colorectal adenomas and 36 adenocarcinomas. The correlations of methylation status and MSI with the clinicopathologic parameters of the tumors were determined. RESULTS: Of the 40 adenomas, 24 (60%) were methylated at one or more loci, and 12 (30%) at two or more loci (CpG island methylation phenotype-high, CIMP-H). Of 36 carcinomas, 27 (75%) were methylated at one or more loci and 11 (30.5%) at two or more loci (CIMP-H). THBSI was the most frequently methylated locus in both adenomas (n = 19, 47.5%) and carcinomas (n = 16, 44.4%). Overall, methylation status of adenomas and carcinomas did not differ significantly (P = 0.53), nor did the methylation status of individual genes. For adenomas, size (P = 0.049) and histologic classification of the villous components (P = 0.018) were each associated with methylation status. For carcinomas, however, no clinicopathologic variable was related to methylation status. MSI was detected in three adenomas (7.5%) and five carcinomas (13.9%), and was closely correlated with hMLH1 methylation (P < 0.001). CONCLUSIONS: In colorectal tumors, CpG island methylation of tumor suppressor genes appears to be common and may be involved in the progression of adenomas.

Adenocarcinoma↗

PubMed2005

Cutoff values of preoperative s-CEA levels for predicting survivals after curative resection of colorectal cancer.

Serum carcinoembryonic antigen (s-CEA) is used to detect recurrence and predict prognosis in colorectal cancer. However, the cutoff values of s-CEA for prognosis have not been determined. We therefore tried to determine the preoperative s-CEA levels predictive of survivals in colorectal cancer patients. We retrospectively analyzed the medical records of 989 patients who underwent curative resection for colorectal cancer between July 1990 and December 1997, with a mean followup of 46 months (range, 3-129 months). When patients were divided into four subgroups with the cutoff values of s-CEA at 3,6, and 17 ng/mL, their 5-yr diseasefree survival rates were 85.3% (<3.0 ng/mL), 70.0% (3-6 ng/mL), 64.2% (6-17 ng/mL), and 55.2% (>17 ng/mL) (p<0.001). Multivariate analysis showed that factors predictive of survival included age (p=0.028), tumor stage (p<0.001), cell differentiation (p=0.016), and gross type (p=0.007), location (p=0.003) and preoperative s-CEA (p<0.001). Using the above-described cutoff levels, a significant difference in survival was observed only in patients with stage III tumors (p=0.007) when analyses were performed by stage. We can suggest the new cutoff values of s-CEA used in the present study.

Adult↗

PubMed2005

[The expression of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs) and angiogenesis in relation to the depth of tumor invasion and lymph node metastasis in submucosally invasive colorectal carcinoma].

BACKGROUND/AIMS: Lymph node (LN) metastasis occurs in approximately 10% of patients with submucosally invasive colorectal carcinoma. This study was performed to determine the role of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) production and microvessel formation on the LN metastasis in submucosally invasive colorectal carcinoma. METHODS: A total of forty-one subjects with surgically resected submucosally invasive colorectal carcinoma were included in this study. Immunohistochemical staining of MMP-2, MMP-9, TIMP-1, TIMP-2, and urokinase-type plasminogen activator were performed. Angiogenesis was evaluated by counting the number of microvessels in each pathologic specimen as identified by CD34 immunohistochemical staining. RESULTS: The depth of submucosal invasion was not significantly correlated with the expression of MMP-2, MMP-9, TIMP-1, TIMP-2, or urokinase-type plasminogen activator, but the microvessel count was significantly correlated with the absolute depth of invasion (r=0.312, p<0.05). Upregulation of TIMP-2 was positively correlated with adjacent lymphatic invasion (p<0.05) and increased TIMP-2 expression was correlated with LN metastasis in submucosally invasive colorectal carcinoma (p=0.088). CONCLUSIONS: These results suggest that the expression of TIMP-2 and the microvessel count may be useful parameters for considering additional surgery after endoscopic treatment of submucosally invasive colorectal carcinoma.

Adult↗

PubMed2005

[Analysis of pouchitis after restorative proctocolectomy].

BACKGROUND/AIMS: Pouchitis is one of the most common and debilitating complications of a restorative proctocolectomy. We aimed to analyze the features of pouchitis after restorative proctocolecomy and to determine the risk factors related to its development. METHODS: A study was undertaken in 169 patients who underwent total proctocolectomy with ileal pouch-anal anastomosis between July 1989 and December 2003. Pouchitis was defined as change of bowel habit, change in stool consistency, hematochezia or abdominal pain, febrile sensation and/or low-grade fever improved by metronidazole or ciprofloxacin without evidence of infectious disease and sphincter damage. RESULTS: Among the 169 patients, patients with ulcerative colitis were 64, familial and attenuated adenomatous polyposis 44, Crohn's disease 2, and synchronous or hereditary non-polyposis colorectal cancer were 59 cases. Overall, pouchitis occurred in 15.9% of the patients. The incidence was 37.5% in ulcerative colitis, 1% in non-ulcerative colitis, and 50% in Crohn's disease. In ulcerative colitis group, most of the pouchitis (60.9%) occurred within 6 months after the operation and the remainder experienced the first attack within 1 year after operation. Three patients progressed to chronic pouchitis. There was no association between pouchitis rate and sex, history of smoking, steroid use, temporary ileostomy construction, involvement of appendix or proximal colon, and evidence of indeterminate colitis. Only age was significantly related to the occurrence of pouchitis. CONCLUSIONS: Pouchitis developed exclusively in ulcerative colitis than other disease groups. Pouchitis occurred most frequently within 6 months after the operation, therefore, it is important to investigate carefully during one year after the operation in patients with ulcerative colitis.

Adenomatous Polyposis Coli↗

PubMed2005

[Colonoscopic surveillance after curative resection for colorectal cancer with synchronous adenoma].

BACKGROUND/AIMS: Guidelines for current postoperative colonoscopic surveillance are not specified in colorectal cancer (CRC) patients with synchronous adenoma (SA). We performed this retrospective study to determine the postoperative colonoscopic surveillance interval for the CRC patients with SA. METHODS: One hundred and twenty-four CRC patients with SA (SA-group) and the same number of patients without SA (NSA-group) were selected from our database. Two groups were matched by the stage of CRC. Median colonoscopic surveillance period was 55 (12-99) months. The colonoscopic surveillance frequency and interval were similar between the two groups. RESULTS: Mean age was higher and male was more frequent in SA-group than NSA-group (p= 0.0001). The incidence of missed adenoma, advanced missed adenoma and metachronous adenoma (MA) were higher in SA-group (30.8% vs. 5.8% at 1st yr., p=0.0001; 4.4% vs. 0%, p=0.0001; 31.1% vs. 9.1% at 2nd yr., p=0.016) during the first consecutive two years of surveillance. The MA- and advanced-MA-free survival rate were lower in SA-group (24.6% vs. 6.6%, p=0.0001; 4.1% vs. 0%, p=0.02) during three years after surgery. Dysplasia of the SA (p=0.04; OR, 110.3; 95% CI, 1.13-10742.6) and presence of missed adenoma (p=0.036; OR, 43.6; 95% CI, 1.28-1490.1) were risk factors for the advanced MA on a multivariate analysis in SA-group. CONCLUSIONS: Postoperative colonoscopic surveillance at first year after surgery is warranted in CRC patients with SA.

Adenoma↗

PubMed2004

Primary malignant melanoma of the rectum: CT findings in eight patients.

PURPOSE: To retrospectively evaluate computed tomographic (CT) findings in patients with pathologically proved primary malignant melanoma of the rectum. MATERIALS AND METHODS: CT scans of eight patients (three men and five women; age range, 38-74 years; mean age, 62 years) with histologically proved primary rectal malignant melanomas were retrospectively evaluated by two radiologists in consensus. Scans were evaluated for the involved site, approximate size and morphologic appearance of the primary mass, degree of perirectal infiltration, and presence or absence of lymphadenopathy, bowel obstruction, and distant metastases. RESULTS: All of the tumors were located in the distal rectum just above the anal verge. The approximate average sizes of the tumors were as follows: length, 4.8 cm (range, 3.8-6.9 cm); width, 3.8 cm (range, 2.8-5.2 cm); and mean diameter, 4.3 cm (range, 3.3-5.8 cm). Tumors usually appeared as polypoid or fungating intraluminal masses (n = 7). Perirectal infiltration commonly extended to the pelvic side wall or the presacral space (n = 5). All eight patients had lymphadenopathy, frequently larger than 3 cm in diameter (n = 3), which most commonly involved the perirectal lymph node station (n = 7). There was no evidence of bowel obstruction in any of the patients. Distant metastasis involving the liver was noted in one patient. CONCLUSION: On CT scans, primary rectal malignant melanomas appeared as bulky intraluminal fungating masses in the distal rectum, focally expanding and obscuring the lumen without causing obstruction, with perirectal infiltration and frequently enlarged lymph nodes.

Adult↗

PubMed2004

Small (<or= 2 cm) hepatic lesions in colorectal cancer patients: detection and characterization on mangafodipir trisodium-enhanced MRI.

OBJECTIVE: The purpose of this study was to evaluate whether mangafodipir trisodium (MnDPDP)-enhanced MRI improves the detection and characterization of small ( 2.0 cm). The differences between MnDPDP-enhanced MRI and helical CT with regard to the detection rates for hepatic lesions and metastases and with regard to the false-positive rates for hepatic metastases were analyzed using the McNemar test. The performances of MnDPDP-enhanced MRI and helical CT in indicating metastases of focal liver lesions were analyzed using receiver operating characteristic curves. RESULTS: No statistically significant differences were seen between MnDPDP-enhanced MRI and helical CT in the detection of all hepatic lesions (p = 0.383) and small lesions (p = 0.210). However, concerning the differentiation between benign and metastatic lesions, MnDPDP-enhanced MRI was superior to helical CT both for all hepatic lesions (p = 0.023) and for small lesions (p = 0.015), and remained better when the analyses were restricted to patients with histopathologic confirmation (p = 0.023 for both). MnDPDP-enhanced MRI changed the diagnosis of hepatic metastasis in nine (13.0%) of 69 patients. Of 12 metastases that were found on MnDPDP-enhanced MRI and missed on helical CT, 11 lesions (91.7%) were small. MnDPDP-enhanced MRI showed a significantly greater detection rate than helical CT for small hepatic metastases (p = 0.022). MnDPDP-enhanced MRI was better when the analyses were restricted to patients with histopathologic confirmation (p = 0.043). CONCLUSION: Although MnDPDP-enhanced MRI is equal to helical CT in detection of both all hepatic lesions and small lesions in patients with colorectal carcinoma, it is superior to CT in characterization of the lesions.

Adult↗

PubMed2004

[Should small bowel diverticula be removed?].

BACKGROUND/AIMS: Small bowel diverticulum is a rare disease that can be found incidentally during a surgical operation. Since reported complication rate is low, uncomplicated small bowel diverticula are generally recommended to be untreated. The aim of this study was to elucidate clinical features of this disease and to determine whether incidental small bowel diverticula should be removed for cure. METHODS: We reviewed the medical records of 80 patients with small bowel diverticular disease who underwent operation at Asan Medical Center between July 1989 and March 2003, retrospectively. RESULTS: Male to female ratio was 61:19, and the mean age was 44 (0-91) years. The most common diverticulum of small bowel is Meckel's diverticulum (63.8%), followed by duodenal diverticulum (15%), jejunal diverticulum (12.5%), and ileal diverticulum (8.7%). Of the 80 cases, 43 (53.7%) were symptomatic, and 37 (46.3%) were incidental. In the symptomatic patients, the most frequent symptom was abdominal pain (58.1%), followed by bleeding (44.2%). As for the treatments, segmental resection (53.7%) was performed more commonly than diverticulectomy (43.8%) in the symptomatic patients. Postoperative complications occurred more commonly in the symptomatic patients (25.6%) than the incidental patients (8.1%). Duodenal diverticula had a high morbidity and mortality rate. CONCLUSIONS: We should consider the diverticular disease of small bowel in patients with unexplained abdominal pain or gastrointestinal bleeding. As most small bowel diverticula, except for duodenal diverticula, are found incidentally and easily removed without postoperative morbidity or mortality, surgical resection appears to be recommended for the purpose of accurate diagnosis and treatment.

Adolescent↗

PubMed2003

Clinicopathologic features of ileocolonic malignant lymphoma: analysis according to colonoscopic classification.

BACKGROUND: The aims of this study were to classify primary ileocolonic lymphomas according to colonoscopic findings and to determine the clinicopathologic relationship according to classes. METHODS: Thirty-two patients (22 men, 10 women; age range 29 to 75 years) with primary malignant lymphoma of the terminal ileum and/or colorectum were studied. The clinicopathologic features were evaluated according to colonoscopic findings. RESULTS: Thirty-six lesions in 32 patients were endoscopically classified as follows: fungating (14, 39%), ulcerofungating (11, 31%), infiltrative (5, 14%), ulceroinfiltrative (4, 11%), and ulcerative (2, 6%). Location of the lesions was as follows: terminal ileum, 15 (42%); colorectum, 14 (39%); both regions, 7 (19%). The most common histopathologic types were diffuse large cell (22, 69%) and large cell immunoblastic (5, 16%). There was no relationship between the endoscopic findings and histologic types. In 9 patients (28%), the clinical manifestation was intussusception, and all were found endoscopically to have the fungating type lesion. CONCLUSIONS: Primary ileocolonic lymphomas can be classified endoscopically into fungating, ulcerative, infiltrative, ulcerofungating, and ulceroinfiltrative types. Among these, fungating and ulcerofungating are the most frequent. Intussusception is a common clinical finding in ileocolonic lymphomas, occurring mainly in patients with the fungating type of lesion.

Colon↗

PubMed2003

Oral doxifluridine plus leucovorin in metastatic colorectal cancer: randomized phase II trial with intravenous 5-fluorouracil plus leucovorin.

This phase II study was designed to evaluate the efficacy and toxicities of oral doxifluridine plus leucovorin as a randomized trial with those of intravenous 5-fluorouracil (5-FU) plus leucovorin in previously untreated metastatic colorectal cancer (CRC). Patients with metastatic CRC were randomized in either group A (oral doxifluridine 1,000 mg/m /d plus leucovorin 30 mg/d on days 1 to 7 and 15 to 21 of each cycle), or group B (intravenous 5-FU 400 mg/m /d plus leucovorin 20 mg/m /d on days 1-5 of each cycle), with the cycles repeated every 4 weeks. Between July 1998 and May 2000, 77 patients were enrolled (38 in group A and 39 in group B). Response rates were 23.7% (95% CI, 11-42%) in group A, and 15.4% (95% CI, 0-25%) in group B on an intent-to-treat analysis. The median response durations of the two groups were similar with 5.6 months in group A and 5.5 months in group B. Progression-free survival and overall survival were 5.4 months and 14.9 months in group A; 4.7 months and 19.5 months in group B. Toxicities in both groups were generally mild and reversible. This study shows that a combination of oral doxifluridine plus leucovorin can be active and safe as a first-line treatment for patients with metastatic CRC.

Adult↗

PubMed2003

Characterization of mutator pathway in younger-age-onset colorectal adenocarcinomas.

The high-frequency microsatellite instability (MSI-H) phenotype, frequently identified in hereditary nonpolyposis colorectal cancer (HNPCC), also accounts for approximately 15% of sporadic colorectal cancers. Microsatellite instability (MSI) occurs from the mutational inactivation of the DNA mismatch repair genes, i.e. hMSH2 and hMLH1 in HNPCC, as well as from epigenetic inactivation of hMLH1 in sporadic colorectal tumors. The mutator pathway including microsatellite instability, hMLH1 promoter methylation, and hMSH2 and hMLH1 mutation patterns were identified in 21 sporadic colorectal adenocarcinoma patients younger than 30 yr excluding HNPCC. More than half of tumors showed MSI, with five MSI-H and six MSI-L (low-frequency microsatellite instability). Three of six MSI-H tumors showed the hMLH1 promoter methylation and did not express the hMLH1 protein. On the other hand, all MSI-L and all MSS (microsatellite stable) tumors expressed both hMSH2 and hMLH1 proteins. Two novel mutations, i.e. a missense mutation in hMLH1 and a splice-site alteration in hMSH2, were identified in two patients respectively. Although mutator pathway was implicated in younger-age-onset colorectal carcinogenesis, many tumors appeared to evolve from different genetic events other than hMSH2 and hMLH1 mutations frequently identified in HNPCC.

Adaptor Proteins, Signal Transducing↗