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N K Kim

Publications and source records attributed to N K Kim.

At least 37 records · Page 2Linked to original sources
PubMed2001

Frameshift mutations at coding mononucleotide repeats of the hRAD50 gene in gastrointestinal carcinomas with microsatellite instability.

Microsatellite instability (MSI) and frameshift mutations in genes containing nucleotide repeats have been reported in a subset of colorectal and gastric carcinomas. This study describes the analysis of MSI-positive colorectal (39 cases) and gastric carcinomas (36 cases) for the presence of frameshift mutations of the six genes known to be involved in DNA repair and containing mononucleotide repeats in their coding region. Our mutational study of the 75 MSI-positive tumors revealed frequent mutations in hRAD50 (23 cases, 31%), BLM (16 cases, 21%), and hMSH6 (16 cases, 21%); rare mutations in BRCA1 (1 case, 1%) and ATM (3 cases, 4%); and no mutation in NBS1. In contrast, no frameshift mutation was found in 60 MSI-negative colorectal and gastric carcinomas. The mutation of hRAD50, a gene that is involved in the response to cellular DNA damage and forms a complex with hMRE11 and NBS1, has not been reported previously. Our results suggest that frameshift mutations of hRAD50, BLM, and hMSH6 are selected and play a role in the tumorigenesis of colorectal and gastric carcinomas with MSI. The MSI targeting of the hRAD50 and BLM genes represents an additional link between MSI and DNA repair because alteration of these genes could accelerate defective DNA repair.

Acid Anhydride Hydrolases↗
PubMed2001

Prognostic factors of Krukenberg's tumor.

OBJECTIVE: The aim of this study was to determine prognostic factors of metachronous Krukenberg's tumors of gastric origin, thereby helping to establish a therapeutic plan for this rare entity. METHODS: Thirty-four female patients who underwent curative resection of gastric carcinoma from 1987 through 1996 and subsequently developed Krukenberg's tumors were identified. The covariates used for survival analysis were patient age at the time of ovarian relapse (categorized as <50 years or >/=50 years), size of Krukenberg's tumor (categorized as </=5, 5-10, or >10 cm), initial AJCC stage of gastric carcinoma, relapse-free interval (categorized as <1, 1-2, or >/=2 years), extent of recurrent disease, and the presence of gross residual disease after treatment for Krukenberg's tumors. The influence of all covariates on the survival period was assessed using the Cox proportional hazards model. RESULTS: At a median follow-up of 32.3 months (range, 2.2-83.1), the median survival period of 34 study patients was estimated to be 7.7 months (95% confidence interval (CI), 5.8-9.6) after the diagnosis of metachronous Krukenberg's tumor. Cox-model-based survival analysis demonstrated that the absence of residual disease after treatment and limited disease extent were favorable prognostic factors. The median survival period of patients without gross residual disease was longer (10.9 months (95% CI, 4.6-17.1)) than that of patients with gross residual disease (7.5 months (95% CI, 6.6-8.3)) [P = 0.036]. Median survival periods according to the extent of metastasis were 10.9 months (95% CI, 0-23.0) for patients with disease confined to the ovaries, 13.1 months (95% CI, 5.9-20.3) for patients with disease confined to the pelvis, 7.5 months (95% CI, 6.8-8.1) for patients with intraabdominal disease, and 3.6 months (95% CI, 3.4-3.7) for patients with disease spread outside the abdomen and pelvis [P = 0.003]. In contrast, patient age, size of ovarian tumor, initial stage of gastric adenocarcinoma, and relapse-free interval were not prognostic indicators for survival after the development of ovarian metastases. CONCLUSION: The absence of residual disease after treatment and limited disease extent were favorable prognostic factors of metachronous Krukenberg's tumors of stomach origin. Our data suggest that resection might have a role in the management of Krukenberg's tumors of stomach origin if it could render patients free of gross residual disease.

Adult↗
PubMed2001

Ultralow anterior resection and coloanal anastomosis for distal rectal cancer: functional and oncological results.

We evaluated the functional and oncological outcome of ultralow anterior resection and coloanal anastomosis (CAA), which is a popular technique for preserving anal sphincter in patients with distal rectal cancer. Forty-eight patients were followed up for 6-100 months regarding fecal or gas incontinence, frequency of bowel movement, and local or systemic recurrence. The main operative techniques were total mesorectal excision with autonomic nerve preservation; the type of anastomosis was straight CAA, performed by the perianal hand sewn method in 38 cases and by the double-stapled method in 10. Postoperative complications included transient urinary retention (n=7), anastomotic stenosis (n=3), anastomotic leakage (n=3), rectovaginal fistula (n=2), and cancer positive margin (n=1; patient refused reoperation). Overall there were recurrences in seven patients (14.5%): one local and one systemic recurrence in stage B2; and one local, two systemic, and two combined local and systemic in C2. The mean frequency of bowel movements was 6.1 per day after 3 months, 4.4 after 1 year, and 3.1 after 2 years. The Kirwan grade for fecal incontinence was 2.7 after 3 months, 1.8 after 1 year, and 1.5 after 2 years. With careful selection of patients and good operative technique, CAA can be performed safely in distal rectal cancer. Normal continence and acceptable frequency of bowel movements can be obtained within 1 year after operation without compromising the rate of local recurrence.

Adult↗
PubMed2001

p53, BCL-2, and Ki-67 expression according to tumor response after concurrent chemoradiotherapy for advanced rectal cancer.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) for locally advanced rectal cancer is an important modality for curative resection, but tumors show wide spectrum response. The purpose of this study was to investigate any correlation among related genetic mutations, proliferative index, and tumor response after CCRT. METHODS: This study included 23 patients with rectal cancer, who were preoperatively staged as at least T3 N1 or T4 (determined by transrectal ultrasonography and MRI). Enrolled patients were given 5-FU 450 mg/m2/day and leucovorin 20 mg/m2/day intravenously for 5 days during weeks 1 and 5 of radiotherapy (45-54 Gy). Surgical resection was performed 4 weeks after completion of the scheduled treatment. Tumor response was classified as CR (complete response), PR (partial response: 50% diminution of tumor volume and downstaging), and NR (no response). Paraffin-embedded tissue obtained before chemoradiotherapy was studied by immunohistochemical staining for p53, BCL-2, and Ki-67. The extent of tumor response was correlated with proliferative activity and was measured by immunostaining Ki-67 proliferative antigen and the expression of p53 and BCL-2 oncoproteins. RESULTS: All patients were resectable. CR was obtained in 4 patients, PR in 10 patients, and NR in 9 patients. The p53 mutation was noted in 16 patients: NR in 5 patients, PR in 9 patients, and CR in 2 patients (P = .638). BCL-2 expression was noted in 11 patients: NR in 4 patients, PR in 3 patients, and CR in 4 patients (P = .799). The Ki-67 labeling index was NR: 615.4+/-47.2; PR: 663.2+/-20.4; and CR: 765.5+/-58.3 (CR + PR vs. NR, P = .029). CONCLUSIONS: Immunohistochemical expression of p53 and BCL-2 does not correlate with tumor response after CCRT, but Ki-67 labeling may be a useful parameter for radiosensitive tumors selected for CCRT.

Adenocarcinoma↗
PubMed2001

Cyclin E overexpression as an independent risk factor of visceral relapse in breast cancer.

AIM: Prognostic value of the cyclin E overexpression in breast cancer has not been clearly established, especially in relation to the pattern of recurrence. We investigated the implication of cyclin E overexpression for the pattern of recurrence in Korean breast cancer patients. METHODS: Using immunohistochemical methods, we retrospectively examined the cyclin E expression level in breast cancer specimens from 128 women who underwent curative breast surgery, and correlated the levels of expression with the pattern of relapse in patients. RESULTS: Cox model-based multivariate analysis indicated that distant relapse could be predicted by the number of positive axillary lymph nodes, high cyclin E expression, and the younger age (<35 years) of the patient. We tested further the association of cyclin E overexpression with the specific types of recurrence; multivariate analyses indicated that adjusted relative risks of bone and visceral relapse as the first events among high cyclin E group were 2.46 (95% confidence interval (CI), 0.86-7.02) (P=0.092), and 3.98 (95% CI, 1.23-12.94) (P=0.022), respectively. On the other hand, cyclin E overexpression was not associated with the risk of locoregional relapse. CONCLUSION: Our data suggest that cyclin E overexpression in primary breast carcinoma tissue could independently predict the risk of distant relapse, especially of visceral relapse, as the first failure after curative breast surgery.

Adult↗
PubMed2001

Three cases of fistulae arising from gastrointestinal tract treated with endoscopic injection of Histoacryl.

Treatment of gastrointestinal fistula usually consists of conservative management and surgery as definite therapeutic measure. Histoacryl can be used to treat gastrointestinal fistula with no response to conservative management in surgically high-risk patients. We report here three cases of gastrointestinal fistula successfully treated with endoscopic injection of Histoacryl through a catheter into the internal opening and fistulous tract.

Enbucrilate↗
PubMed2001

Intravenous 5-fluorouracil versus oral doxifluridine as preoperative concurrent chemoradiation for locally advanced rectal cancer: prospective randomized trials.

BACKGROUND: Preoperative radiation treatment with concomitant intravenous infusion of 5-fluorouracil (5-FU) is known to be effective in shrinking and downstaging of tumors. However, chemotherapy has often been limited by its toxicity and poor patient compliance. Oral 5-FU is known to have several advantages over conventional intravenous 5-FU infusion such as lower toxicity and higher quality of life without compromising the efficacy of the treatment. The aim of this study was to compare intravenous 5-FU with oral doxifluridine with respect to tumor response, toxicity and quality of life. METHODS: Twenty-eight patients with rectal cancer, staged as over T3N1 or T4 by transrectal ultrasonography between July 1997 and December 1998, were included in this study. Intravenous 5-FU (450 mg/m2) and leucovorin (20 mg/m2) were given for five consecutive days during the first and fifth weeks of radiation therapy (50.4 Gy) (n = 14). Oral doxifluridine (700 mg/m2/day) and leucovorin (20 mg/m2) were given daily during radiation treatment (n = 14). Quality of life was scored according to 22 activity items (good, >77; fair, >58; poor, <57). Surgical resection was performed 4 weeks after completion of concurrent chemoradiation treatment. Tumor response was classified into CR (complete remission), PR (partial response; 50% diminution of tumor volume or downstaging ) and NR (no response). RESULTS: Tumor response was CR 3/14 (21.4%), PR 7/14 (50%) and NR 4/14 (28.6%) in the IV arm versus CR 2/14 (14.2%), PR 6/14 (42.9%) and NR 6/14 (42.9%) in the Oral arm (p = 0.16, 0.23, 0.24), respectively. The quality of life was poor (36.4% versus 33.3%), fair and good (63.6% versus 66.7%) between the IV arm and Oral arm, respectively. Gastrointestinal toxicity was 2/14 (14.3%) in the IV arm versus 5/14 (35.7%) in the Oral arm, respectively. Stomatitis was only observed in the IV arm (1/14, 7.1%). Hematological toxicity was 3/14 (21.4%) in the IV arm versus 4/14 (28.5%) in the Oral arm, respectively. Systemic recurrence during the follow-up periods were 1/14 (7.1%) in the IV arm and 2/14 (14.3%) in the Oral arm, respectively (p = 0.307). One local recurrence was observed in the Oral arm. CONCLUSION: Even though the results were not entirely reliable owing to the small number of patients enrolled, oral doxifluridine-based chemotherapy as preoperative chemoradiation for advanced rectal cancer did not show any significant advantages over intravenous infusion.

Administration, Oral↗
PubMed2000

Adjuvant doxorubicin and cyclophosphamide versus cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy in premenopausal women with axillary lymph node positive breast carcinoma.

BACKGROUND: This randomized controlled trial was to determine whether a combination chemotherapy regimen that contains anthracycline (doxorubicin and cyclophosphamide [AC]) is superior to the conventional cyclophosphamide, methotrexate, and 5-fluorouracil [CMF] combination in premenopausal women with axillary lymph node positive Stage II breast carcinoma. METHODS: Premenopausal women with lymph node positive breast carcinoma were stratified according to age (younger than 35 or 35 years or older) and the number of positive axillary lymph nodes (1-3, 4-9, or >/= 10) and then randomly assigned to receive either doxorubicin 40 mg/m(2) and cyclophosphamide 600 mg/m(2) intravenously (i.v.) every 3 weeks or cyclophosphamide 100 mg/m(2) orally on Days 1 through 14, methotrexate 40 mg/m(2) and 5-fluorouracil 500 mg/m(2) i.v. on Days 1 and 8 every 4 weeks. Both arms were scheduled for six cycles. RESULTS: The median follow-up was 57 months. Eighteen of the 55 AC patients developed recurrence compared with 16 of the 69 CMF patients. The corresponding 5-year recurrence free survival rates were 64% and 78%, respectively (P = 0.12). The site of the first recurrence for AC patients was locoregional in 7%, distant in 22%, and combined in 4%. The corresponding data for the CMF arm were 4%, 16%, and 3%, respectively. Six AC patients died compared with 9 CMF patients. The corresponding 5-year survival rates were 90% and 86%, respectively (P = 0.96). More leukopenia (52%, mostly Grade 1-2) occurred in the CMF arm than in the AC arm (33%, P = 0.001), but no febrile episode was accompanied with leukopenia. CONCLUSIONS: This study showed no difference between AC and CMF with respect to both disease free and overall survival rates in premenopausal women with axillary lymph node positive breast carcinoma.

Adult↗
PubMed2000

Methylation of specific CpG sites in the promoter region could significantly down-regulate p16(INK4a) expression in gastric adenocarcinoma.

Silencing of p16(INK4a) by methylation of the CpG islands in the promoter region has been found to be an alternative mechanism of inactivation in several tumors. However, in gastric carcinoma, the relationship between methylation status and the transcriptional silencing of the p16 gene remains to be clarified. In this study, we investigated whether methylation of a few specific CpG sites in the promoter region could significantly down-regulate p16 activity in the tumorigenesis of gastric carcinoma. By Southern analysis and bisulfite-modified genomic sequencing of 9 gastric-carcinoma cell lines, we found that the 5 cell lines (55.5%) not expressing p16 mRNA had methylated CpG sites at the promoter region of p16. In addition, we analyzed the p16-protein expression of 28 primary gastric carcinomas and their normal counterparts by immunohistochemical staining (IHC) on paraffin sections. Loss of p16 expression was detected in 6 cases (22%). In 5 out of these 6 (83%), the actual p16 gene was inactivated by de novo methylation of the promoter sites. Taken together, these results suggest a strong correlation between de novo methylation of a few specific CpG sites and transcriptional silencing of the p16 gene in gastric carcinoma.

Adenocarcinoma↗
PubMed2000

Transcriptional inactivation of the tissue inhibitor of metalloproteinase-3 gene by dna hypermethylation of the 5'-CpG island in human gastric cancer cell lines.

The tissue inhibitor of metalloproteinase-3 (TIMP-3), a recently cloned member of TIMP gene family, has been implicated in the negative regulation of tumor cell invasion and tumor growth. Down-regulation of this gene has been shown to occur in a mouse carcinogenesis model, suggesting that it might play a role in the tumor progression of some cancers. In this study, we used human gastric cancer cell lines to investigate whether TIMP-3 gene expression is suppressed in human gastric cancer. We examined whether aberrant DNA methylation of the 5'-CpG island of the TIMP-3 gene is involved in this cancer. Nine of 10 human gastric cancer cell lines completely lost TIMP-3 gene expression compared with normal samples. Southern blot analysis and bisulfite genomic sequencing revealed aberrant hypermethylation near the transcription-start site of the TIMP-3 gene in all cell lines lacking TIMP-3 expression. Treatment of these cell lines with the demethylating agent 5-aza-2'-deoxycytidine restored TIMP-3 gene expression. Our results suggest that the TIMP-3 gene is another early target of tumor-associated aberrant DNA methylation in human gastric carcinogenesis. Consequently, genetic silencing of TIMP-3 may lead to a more malignant and invasive phenotype in these cancer cells.

Animals↗
PubMed2000

Clinical characteristics of Peutz-Jeghers syndrome in Korean polyposis patients.

Peutz-Jeghers syndrome is an autosomal dominant inherited disorder characterized by hamartomatous polyps in the small bowel and mucocutaneous pigmentation. Patients with Peutz-Jeghers syndrome often present as surgical emergencies with complications of the polyps, such as intussusception, bowel obstruction, and bleeding. Recently an increased risk of malignancies has also been reported. This study was initiated to determine the clinical features of Peutz-Jeghers syndrome in Korean patients, with special attention to the development of malignancies. Thirty patients with Peutz-Jeghers syndrome were investigated; their median age was 23.5 years, and symptoms appeared at a median age of 12.5 years. Family history was positive in one-half of cases, and mucocutaneous pigmentation was observed in almost all patients (93%). The jejunoileum was the most frequent site of the polyps, and there were generally 10-100 polyps. Multiple laparotomies were performed in a substantial portion of the patients, due mainly to polyp-induced bowel obstruction, and the surgical interventions were begun at a relatively young age (average 21.4 years). Four cases of small-bowel cancer and one case of breast cancer were detected in probands, at a relatively young age (mean 36 years). Cancers of the small bowel, stomach, colon, breast and cervix were diagnosed in the first relatives of the probands. Close follow-up from an early age should thus be performed in patients with Peutz-Jeghers syndrome as they are at high risk of surgical emergency and development of malignancy.

Adult↗
PubMed2000

A prospective randomized trial comparing intravenous 5-fluorouracil and oral doxifluridine as postoperative adjuvant treatment for advanced rectal cancer.

BACKGROUND: Postoperative adjuvant chemoradiation treatment after curative resection for rectal cancer was needed to reduce recurrence and improve a survival rate. Intravenous 5-fluorouracil (5-FU) and leucovorin has been a mainstay of chemotherapy, but oral 5-FU derivatives have been shown a comparable antitumor activity. Intravenous 5-FU and oral doxifluridine were compared with respect to therapeutic efficacy, drug toxicity, and quality of life. METHODS: A total of 166 patients were randomized to receive intravenous 5-FU (450 mg/m2/day) or oral doxifluridine (900 mg/m2/day) in combination with leucovorin (20 mg/m2/day) for depth of invasion, nodal status, metastasis (TNM) stage II and III patients between October 1997 and February 1999. Consecutive daily intravenous infusion for 5 days per every month for a total of 12 cycles (IV arm, n = 74) and oral doxifluridine daily for 3 weeks and 1 week rest for a total of 12 cycles (oral arm, n = 92). Drug toxicity and quality of life were observed. Quality of life was scored according to 22 daily activity items (good, > or =71; fair, < 70; poor, < 52). RESULTS: There was no difference of sex between two groups (IV arm: male/female = 45/29, oral arm: male/female = 59/33). The mean age was 52.3 vs. 59.5, respectively. There was also no difference of TNM stage distribution and type of operation between groups (P>.05). Mean numbers of chemotherapy cycles were 6.5+/-3.7 (IV arm) vs. 7.2+/-4.3 (oral arm), respectively. The rate of recurrence was 9/74 (12.1%) in the IV arm and 6/92 (6.5 %) in the oral arm, respectively (P = .937). Local recurrence was 2/74 (stage III; 2.7%) in the IV arm and 1/92 (stage II; 1.1%) in the oral arm, respectively. Systemic recurrence was 7/74 (stage III; 9.4%) in the IV arm and 5/92 (stage III; 5.4%) in the oral arm, respectively. The most common site of systemic recurrence was the liver. Toxicity profile was as follows: leukopenia (30/74 vs. 17/92) and alopecia (21/74 vs. 13/92) were statistically more common in the IV arm. Diarrhea was more common in the oral arm. Poor quality of life score between two groups was observed at 1 month (23.9% vs. 13%) and 2 months (15.8% vs. 3.7%) after chemotherapy. Good quality of life score was observed at 1 month (19.5% vs. 49%) and 2 months (47% vs. 72%), respectively (P<.05). CONCLUSIONS: Oral doxifluridine with leucovorin shows a comparable therapeutic efficacy to intravenous 5-FU regimen with high quality of life as postoperative adjuvant therapy. The oral regimen also can be safely given with appropriate toxicity and tolerability.

Adenocarcinoma↗
PubMed2000

Preoperative staging of rectal cancer with MRI: accuracy and clinical usefulness.

BACKGROUND: Preoperative staging is essential for planning of optimal therapy for patients with rectal cancer. Recently, magnetic resonance imaging (MRI) is used frequently because of its benefits of clear pelvic image are better than other diagnostic methods. The purpose of this study was to determine accuracy rates and clinical usefulness of MRI in preoperative staging of rectal cancer. METHODS: Between February, 1997, and December, 1999, 217 patients with histologically proven rectal cancer were staged preoperatively and had surgical resections performed. MRI criteria for depth of invasion was determined by the degree of disruption of the rectal wall. Metastatic perirectal lymph nodes were considered to be present if they showed heterogenous texture, irregular margin, and enlargement (>10 mm). RESULTS: The accuracy of the MRI for determining depth of invasion was 176/217 (81%) and regional lymph node invasion was 110/217 (63%). In the T stage, accuracy rate of T1 was 3/4 (75%), T2 was 20/37 (54%), T3 was 141/162 (87%), and T4 was 12/14 (86%), respectively. The specificity of lymph node invasion was 45/110 (41%) and the sensitivity was 91/107 (85%). The accuracy rate of regional lymph node involvement was 136/217 (63%). T1 and T2 were overstaged in 1/4 (25%) and 17/37 (46%), respectively, and T3 was understaged in 15/162 (9.2%). The accuracy rate to detect metastatic lateral pelvic lymph node was 4/14 (29%) after lateral pelvic lymph node dissection was done in 14 patients under MRI. The accuracy rate in assessing levator ani muscle tumor involvement was 8/11 (72%). CONCLUSIONS: MRI showed a good, comparable accuracy rate for determining depth of tumor invasion, compared with transrectal ultrasonography, which still has a low accuracy rate for detecting metastatic lymph node. MRI with endorectal coil may increase the accuracy rate of T1 and T2 lesions. In addition, clear sagittal and coronal sectional pelvic images can give a lot of information about adjacent organ invasion or any invasion of levator ani muscle. MRI can be useful for choosing an appropriate extent of lymph node dissection and type of surgery.

Adult↗
PubMed2000

Enhancement of adenoviral transduction with polycationic liposomes in vivo.

Although the high transfection efficiency with adenovirus in vitro is well documented, it is still not clear whether adenoviral vectors are effective in vivo in solid tumor models. In our preliminary experiment, transduction of tumor tissue was limited to just around the injection site after intratumoral injection of the adenoviral vector. To improve the transduction efficiency in vivo, we tried a combination of adenoviral vector and liposome in our animal model. Adenovirus carrying human placental alkaline phosphatase (AdALP) and Lipofectamine or 1,3-di-oleoyloxy-2-(6-carboxyspermyl)-propylamide were used as a marker gene and the cationic liposome, respectively. A >15-fold increase in the transfection efficiency was observed in CT26 tumor cell lines with the combination of AdALP adenovirus carrying murine granulocyte-macrophage colony-stimulating factor (AdmGM-CSF), and liposome compared with adenovirus alone, showing the feasibility of the combination treatment. In the animal model, with the combination of liposome and AdALP, deeper and wider distribution of the marker gene in the tumor mass was shown. We conclude that the limitations of direct application of adenoviral vectors in a solid tumor model could be overcome by the use of cationic liposomes. This approach will facilitate the more effective delivery of adenoviral vectors in a clinical trial setting.

Adenocarcinoma↗
PubMed2000

Ontogeny of natural killer cells and T cells by analysis of BCR-ABL rearrangement from patients with chronic myelogenous leukaemia.

Chronic myelogenous leukaemia (CML) is a haematological malignant disorder characterized by the Philadelphia chromosome (Ph) and BCR-ABL gene rearrangement. This abnormal fusion gene can be considered to serve as a marker for the transformed cell clone in CML and is found in all cells arising from the same malignant precursor cell. It has been detected in CML cells of the myeloid, monocytic, erythroid and B-lymphocytic lineages. However, it is still arguable as to whether T lymphocytes or natural killer (NK) cells carry this marker. Answering this question would clarify the ontogenic relationship between NK cells and T cells. We examined 12 CML patients and studied the expression of BCR-ABL rearrangement by fluorescence in situ hybridization (FISH) in both NK cells and T cells sorted by flow cytometry. The purity of T cells was 95.6-99.8% and that of NK cells was 95.3-99.3% after sorting. Neither NK cells nor T cells showed any positive BCR-ABL signal with the exception of one patient who recovered from a lymphoid blastic crisis. We speculate that T cells and NK cells originate from BCR-ABL-negative stem cells.

Adult↗
PubMed2000

Germline mutations of the STK11 gene in Korean Peutz-Jeghers syndrome patients.

Peutz-Jeghers syndrome (PJS) is an autosomal dominantly inherited disease characterized by hamartomatous gastrointestinal polyps and mucocutaneous pigmentation, with an increased risk for various neoplasms, including gastrointestinal cancer. Recently, the PJS gene encoding the serine/threonine kinase STK11 (also named LKB1) was mapped to chromosome 19p13.3, and germline mutations were identified in PJS patients. We screened a total of ten Korean PJS patients (nine sporadic cases and one familial case including two patients) to investigate the germline mutations of the STK11 gene. By polymerase chain reaction-single-strand conformation polymorphism and DNA sequencing analysis, three kinds of mis-sense mutation and a frame-shift mutation were identified: codon 232 (TCC to CCC) in exon 5, codon 256 (GAA to GCA) in exon 6, codon 324 (CCG to CTG) in exon 8, and a guanine insertion at codon 342 resulting in a premature stop codon in exon 8. These mis-sense variants were not detected in 100 control DNA samples. Furthermore, we found an intronic mutation at the dinucleotide sequence of a splice-acceptor site: a one base substitution from AG to CG in intron 1, which may cause aberrant splicing. Most reported germline mutations of the STK11 gene in PJS patients were frame-shift or non-sense mutations resulting in truncated proteins. Together, these findings indicate that germline mis-sense mutations of the STK11 gene are found in PJS patients in addition to truncating mutations. The effects of these mutations on protein function require further examination. In summary, we found germline mutations of the STK11 gene in five out of ten Korean PJS patients.

AMP-Activated Protein Kinase Kinases↗
PubMed2000

Restorative proctocolectomy: operative safety and functional outcomes.

Restorative proctocolectomy (total proctocolectomy and ileal J pouch anal anastomosis) has been accepted as the operation of choice in the setting of chronic ulcerative colitis and familial adenomatous polyposis. The purpose of this study was to assess operative safety and functional outcome after restorative proctocolectomy. A total of sixteen patients underwent surgery between January 1996 and December 1999. Hand sewn anastomosis with diverting ileostomy was performed in 9 patients and double stapled anastomosis in 7 patients. The underlying disease was ulcerative colitis in 9 cases and familial adenomatous polyposis in 7. Postoperative complications developed in 8 cases (50%), and intestinal obstruction was found in 4 cases (2 cases were operated upon). Anastomosis related complications were stenosis (n=2), leak (n=1) and perianal abscess (n=1). All patients were followed up at the outpatient clinic using questionnaires, with a mean follow up period of 19.9 months. The frequency of bowel movement was 8.2 per day in hand sewn anastomosis (HS), and 12 per day in double stapled anastomosis (DS) 3 months after surgery (period 1). This frequency decreased to 5.5 per day in HS, and 4.6 per day in DS after one year (period 2). Day and night continence was shown in 12/15, and 5/15, respectively in period 1, but improved to 10/11, and 10/11, respectively in period 2. Night time incontinence was noted in 10 of 15 patients in period 1 (seepage 3/15, soiling 7/15). The need to take anti-diarrheal medication, and to use a pad was noted in 2/15, and 10/15, respectively in period 1, but no patient took antidiarrheal medication or wore a protective pad in period 2. Postoperative urinary function was satisfactory in 13/14 patients. Postoperative sexual function was analyzed in a total of 8 patients, who showed good erection (5/5), ejaculation (5/5) and satisfactory sexual life (5/5). In females, 3 patients showed a satisfactory sexual life. In conclusion, restorative proctocolectomy for chronic ulcerative colitis and familial adenomatous polyposis can be performed safely with excellent functional outcomes, including bowel movement, urinary and sexual functions one year after surgery.

Adenomatous Polyposis Coli↗