PURPOSE: Few studies have reported ovarian cancer risks in Korean patients with the BRCA1/2 mutation. We investigated the prevalence of ovarian cancer in Korean women at high risk for hereditary breast-ovarian cancer (HBOC) syndrome and reviewed the clinicopathological factors of ovarian cancer. METHODS: Female subjects who were enrolled in the Korean Hereditary Breast Cancer study were included. The questionnaire included a personal and family history of cancer. The BRCA1/2 mutation and CA-125 level were tested at the time of enrollment. A transvaginal ultrasonogram (TVUS) was recommended for subjects with an elevated CA-125 level. RESULTS: A total of 1,689 patients were included. No ovarian cancer was newly diagnosed by CA-125 level or TVUS during the enrollment. The prevalence of ovarian cancer was 1.71% in BRCA1/2 mutation carriers and 0.39% in non-carriers. Among 11 patients with ovarian cancer, five had the BRCA1 mutation and one had the BRCA2 mutation. The most common histopathological type was serous cystadenocarcinoma. No difference in clinicopathological findings between BRCA1/2 mutation carriers and non-carriers was observed. CONCLUSION: The prevalence of ovarian cancer was 58-fold elevated in women at high-risk for HBOC syndrome and 146-fold elevated in the BRCA1 subgroup, compared with the Korean general population. Further investigation with a long-term follow-up is required to evaluate BRCA1/2 gene penetrance.
Female ; Humans ; Breast Neoplasms ; Ovarian Neoplasms

PURPOSE: The vein graft was considered as a useful conduit for nerve defect. But the problem is that it might be collapsed in long vein graft state. A new experimental model using vein graft filled with hyaluronic acid was considered. METHODS: Thirty rats were used for the experimental animal. In group I, one side of the femoral nerve was exposed and a segment was removed about 15mm. The neural gap was connected with nerve graft. In group II, the nerve gap was connected with vein graft only. In group III, the nerve gap was connected with vein graft filled with hyaluronic acid. A walking track analysis was made periodically for 2 months and NCV(nerve conduction velocity) was executed at the end of the experiment. And morphologic studies were also done for all groups RESULTS: In a walking track analysis, the toe-spread was widen and the foot-length was lengthened. The recovery of the toe-spread and foot length was checked 2 weeks interval, periodically for two months. The SFI (sciatic function index) was -52.5+/-8.2 in group I, -68.1+/-4 in group II, -55.3+/-7.9 in group III. In electrophysiological study, NCV(nerve conduction velocity) was 26.71+/-3.11m/s in group I, 17.94+/-4.35 m/s in group II, 25.69+/-2.81m/s in group III. The functional recovery in group I and III was superior to that the group II statistically(p<0.05) Under electromicroscopic study, the number of the myelinated axons were 1419.1+/-240 in group I, 921.7+/-176.8 in group II, 1322.2+/-318 in group III. The number of the myelinated axons were much more in group I and III than group II statistically (p<0.05). CONCLUSION: This study suggested that the vein graft filled with hyaluronic acid is more effective than vein graft only for the conduit of the nerve gap. It was thought that the technique could be used in clinical cases with nerve defects as an alternative method to classical nerve grafts.
Animals ; Axons ; Femoral Nerve ; Foot ; Hyaluronic Acid* ; Models, Animal* ; Models, Theoretical ; Myelin Sheath ; Nerve Regeneration* ; Rats* ; Transplants* ; Veins* ; Walking

PURPOSE: The vein graft was considered as a useful conduit for nerve defect. But the problem is that it might be collapsed in long vein graft state. A new experimental model using vein graft filled with hyaluronic acid was considered. METHODS: Thirty rats were used for the experimental animal. In group I, one side of the femoral nerve was exposed and a segment was removed about 15mm. The neural gap was connected with nerve graft. In group II, the nerve gap was connected with vein graft only. In group III, the nerve gap was connected with vein graft filled with hyaluronic acid. A walking track analysis was made periodically for 2 months and NCV(nerve conduction velocity) was executed at the end of the experiment. And morphologic studies were also done for all groups RESULTS: In a walking track analysis, the toe-spread was widen and the foot-length was lengthened. The recovery of the toe-spread and foot length was checked 2 weeks interval, periodically for two months. The SFI (sciatic function index) was -52.5+/-8.2 in group I, -68.1+/-4 in group II, -55.3+/-7.9 in group III. In electrophysiological study, NCV(nerve conduction velocity) was 26.71+/-3.11m/s in group I, 17.94+/-4.35 m/s in group II, 25.69+/-2.81m/s in group III. The functional recovery in group I and III was superior to that the group II statistically(p<0.05) Under electromicroscopic study, the number of the myelinated axons were 1419.1+/-240 in group I, 921.7+/-176.8 in group II, 1322.2+/-318 in group III. The number of the myelinated axons were much more in group I and III than group II statistically (p<0.05). CONCLUSION: This study suggested that the vein graft filled with hyaluronic acid is more effective than vein graft only for the conduit of the nerve gap. It was thought that the technique could be used in clinical cases with nerve defects as an alternative method to classical nerve grafts.
Animals ; Axons ; Femoral Nerve ; Foot ; Hyaluronic Acid* ; Models, Animal* ; Models, Theoretical ; Myelin Sheath ; Nerve Regeneration* ; Rats* ; Transplants* ; Veins* ; Walking

PURPOSE: To report of a series of successful reconstruction of soft tissue defect on distal leg with extensor digitorum brevis myo-cutaneous flap. METHODS: Between April 2002 to December 2004, 7 patients with soft tissue defect on distal leg were operated with Extensor Digiotorum Brevis myocutaneous flap. 6 of these patients had osteomyelitis. RESULTS: Extensor Digiotorum Brevis myocutaneous flap were used in 6 patients and reverse flow flap was used in one patient. Average follow up was 19 months. All flap were survived 100% without any complication and osteomyelitis were controled in all cases. Aesthetic and functional out come were excellent on both recipient and donor sites. CONCLUSION: The advantages of this flap are effectively control of local wound infection, constant and reliable anatomical structures, adequately thin flap. Technical easiness for raising flap and wide arch of rotation. Extensor Digitorum Brevis myo-cutaneous flap is one of ideal option for the reconstruction of distal leg and foot defects.
Follow-Up Studies ; Foot ; Humans ; Leg* ; Myocutaneous Flap ; Osteomyelitis ; Tissue Donors ; Wound Infection

We investigated the expression of membrane type-1 (MT1)-MMP, MMP2, MMP9 and TIMP2 mRNAs and their roles in ductal carcinoma in situ (DCIS) and T1 and T2 invasive ductal carcinoma of the breast. We further compared these two types of carcinomas for differences in microvessel density, and expression of angiogenic factors and CD44std. MT1-MMP, MMP2, MMP9 and TIMP2 mRNA were expressed in both DCIS and invasive ductal carcinomas. Expression rates of MT1-MMP, MMP2, MMP9 and TIMP2 mRNAs were not statistically different between DCIS and invasive ductal carcinomas, nor did they differ statistically when grouped by tumor size, histologic grade or nuclear grade of invasive ductal carcinoma. Microvessel density and expression of VEGF and TGF-beta were not statistically different between DCIS and invasive ductal carcinoma. CD44std expression was significantly increased in DCIS compared to invasive ductal carcinoma (p < 0.05) and it was also significantly increased in lower clinical stage, histologic grade and nuclear grade of invasive ductal carcinoma (p < 0.05). Axillary node metastasis was significantly correlated with MT1-MMP mRNA, VEGF and TGF-beta expression (p < 0.05) and MT1-MMP mRNA was positively correlated with VEGF expression and TIMP2 mRNA (p < 0.05). In summary, patterns of MMP mRNA expression in DCIS and invasive ductal carcinoma suggest that the invasive potential of breast carcinoma is already achieved before morphologically overt invasive growth is observed. As MT1-MMP mRNA expression is significantly correlated with axillary nodal metastasis, it may be useful as a prognostic indicator of invasive ductal carcinoma. Considering the positive correlation of MT1-MMP mRNA and TIMP2mRNA expression, our finding supports a role for TIMP2 in tumor growth, as well as the utility of CD44std as a prognostic indicator of breast cancer.
Tissue Inhibitor of Metalloproteinase-2/genetics ; RNA, Messenger/metabolism ; Matrix Metalloproteinases, Membrane-Associated ; Matrix Metalloproteinases/*genetics ; Matrix Metalloproteinase 9/genetics ; Matrix Metalloproteinase 2/genetics ; Matrix Metalloproteinase 1/genetics ; Humans ; Gene Expression Regulation, Neoplastic ; Gene Expression Regulation, Enzymologic ; Female ; Carcinoma, Ductal, Breast/genetics/*physiopathology ; Carcinoma in Situ/genetics/*physiopathology ; Breast Neoplasms/genetics/*physiopathology

We investigated the expression of membrane type-1 (MT1)-MMP, MMP2, MMP9 and TIMP2 mRNAs and their roles in ductal carcinoma in situ (DCIS) and T1 and T2 invasive ductal carcinoma of the breast. We further compared these two types of carcinomas for differences in microvessel density, and expression of angiogenic factors and CD44std. MT1-MMP, MMP2, MMP9 and TIMP2 mRNA were expressed in both DCIS and invasive ductal carcinomas. Expression rates of MT1-MMP, MMP2, MMP9 and TIMP2 mRNAs were not statistically different between DCIS and invasive ductal carcinomas, nor did they differ statistically when grouped by tumor size, histologic grade or nuclear grade of invasive ductal carcinoma. Microvessel density and expression of VEGF and TGF-beta were not statistically different between DCIS and invasive ductal carcinoma. CD44std expression was significantly increased in DCIS compared to invasive ductal carcinoma (p < 0.05) and it was also significantly increased in lower clinical stage, histologic grade and nuclear grade of invasive ductal carcinoma (p < 0.05). Axillary node metastasis was significantly correlated with MT1-MMP mRNA, VEGF and TGF-beta expression (p < 0.05) and MT1-MMP mRNA was positively correlated with VEGF expression and TIMP2 mRNA (p < 0.05). In summary, patterns of MMP mRNA expression in DCIS and invasive ductal carcinoma suggest that the invasive potential of breast carcinoma is already achieved before morphologically overt invasive growth is observed. As MT1-MMP mRNA expression is significantly correlated with axillary nodal metastasis, it may be useful as a prognostic indicator of invasive ductal carcinoma. Considering the positive correlation of MT1-MMP mRNA and TIMP2mRNA expression, our finding supports a role for TIMP2 in tumor growth, as well as the utility of CD44std as a prognostic indicator of breast cancer.
Tissue Inhibitor of Metalloproteinase-2/genetics ; RNA, Messenger/metabolism ; Matrix Metalloproteinases, Membrane-Associated ; Matrix Metalloproteinases/*genetics ; Matrix Metalloproteinase 9/genetics ; Matrix Metalloproteinase 2/genetics ; Matrix Metalloproteinase 1/genetics ; Humans ; Gene Expression Regulation, Neoplastic ; Gene Expression Regulation, Enzymologic ; Female ; Carcinoma, Ductal, Breast/genetics/*physiopathology ; Carcinoma in Situ/genetics/*physiopathology ; Breast Neoplasms/genetics/*physiopathology

Clinical application of the cartilage formed by tissue engineering is of no practical use due to the failure of long-term structural integrity maintenance. One of the important factors for integrity maintenance is the biomaterial for a scaffold. The purpose of this study is to evaluate the difference between polylactic-co-glycolic acids (PLGA) and chitosan as scaffolds. Human auricular chondrocytes were isolated, cultured, and seeded on the scaffolds, which were implanted in the back of nude mice. Eight animals were sacrificed at 4, 8, 12, 16, and 24 weeks after implantation respectively. In gross examination and histological findings, the volume of chondrocyte-PLGA complexes was decreased rapidly. The volume of chondrocyte-chitosan complexes was well maintained with a slow decrease rate. The expression of type II collagen protein detected by immunohistochemistry and western blots became weaker with time in the chondrocyte-PLGA complexes. However, the expression in the chondrocyte-chitosan complexes was strong for the whole period. Collagen type II gene expressions using RT-PCR showed a similar pattern. In conclusion, these results suggest that chitosan is a superior scaffold in cartilage tissue engineering in terms of structural integrity maintenance. It is expected that chitosan scaffold may become one of the most useful scaffolds for cartilage tissue engineering.
Animals ; Blotting, Western ; Cartilage* ; Chitosan* ; Chondrocytes ; Collagen Type II ; Gene Expression ; Humans ; Immunohistochemistry ; Mice ; Mice, Nude ; Tissue Engineering*

PURPOSE: Sentinel lymph node (SLN) biopsy is considered a highly accurate and very economic method of assessing the axillary nodal status in breast cancer patients. Recently immunohistochemical (IHC) staining and reverse transcriptase polymerase chain reaction (RT-PCR) are commonly used to evaluate micrometastasis in the sentinel lymph node. However, most of the RT-PCR studies have been performed using fresh tissue. This study was conducted to assess micrometastasis in clinically node-negative breast cancer by using RT-PCR technique on the paraffin embedded sentinel lymph nodes. METHODS: Sixty patients who undergone SLN biopsy followed by axillary lymph node dissection due to breast carcinoma were evaluated from February 2000 to January 2001 at the Breast Cancer Center, Department of Surgery, Yongdong Severance Hospital. Serial sections were made from all sentinel lymph nodes for the H&E staining and for the IHC staining with monoclonal anti-cytokeratin antibody. RNA was extracted from the paraffin embedded sentinel lymph nodes and RT-PCR was performed using cytokeratin 19 mRNA, MUC-1 mRNA, and MAGE-A3 mRNA. RESULTS: In 32 out of 60 cases, beta-actin mRNA was detected after RT-PCR, and the 28 cases which had no product after RT-PCR for beta-actin were excluded from this study. Twenty five cases showed as being metastasis positive and 7 cases showed as being metastasis negative by serial section (SS) H&E staining. Three out of 25 negative cases tested for by SS H&E staining were found to be positive by IHC. Ten, six and, eight cases out of the 25 negative cases tested for by SS H&E were found to be positive by RT-PCR for cytokeratin 19, MUC-1, and MAGE-A3, respectively. Among the 22 cases that were found to be negative by both SS H&E staining and IHC staining, 9, 4, and 6 cases were converted to positive by RT-PCR for cytokeratin 19, MUC-1, and MAGE-A3, respectively. Using the combination of two or three markers for performing RT-PCR was more sensitive than any single marker to detect micrometastasis (p < 0.05). CONCLUSION: Even though we failed to extract RNA in 46% of the paraffin embedded tissues, it may be possible to detect micrometastasis by using RT-PCR with the paraffin embedded tissue. RT-PCR is far more sensitive than IHC for detecting microme tastasis, and when we combine multiple markers, the detection rate is higher than for any one marker.
Actins ; Biopsy ; Breast Neoplasms* ; Breast* ; Humans ; Keratin-19 ; Lymph Node Excision ; Lymph Nodes* ; Neoplasm Metastasis ; Neoplasm Micrometastasis* ; Paraffin ; Reverse Transcriptase Polymerase Chain Reaction ; RNA ; RNA, Messenger

PURPOSE: Sentinel lymph node (SLN) biopsy is considered a highly accurate and very economic method of assessing the axillary nodal status in breast cancer patients. Recently immunohistochemical (IHC) staining and reverse transcriptase polymerase chain reaction (RT-PCR) are commonly used to evaluate micrometastasis in the sentinel lymph node. However, most of the RT-PCR studies have been performed using fresh tissue. This study was conducted to assess micrometastasis in clinically node-negative breast cancer by using RT-PCR technique on the paraffin embedded sentinel lymph nodes. METHODS: Sixty patients who undergone SLN biopsy followed by axillary lymph node dissection due to breast carcinoma were evaluated from February 2000 to January 2001 at the Breast Cancer Center, Department of Surgery, Yongdong Severance Hospital. Serial sections were made from all sentinel lymph nodes for the H&E staining and for the IHC staining with monoclonal anti-cytokeratin antibody. RNA was extracted from the paraffin embedded sentinel lymph nodes and RT-PCR was performed using cytokeratin 19 mRNA, MUC-1 mRNA, and MAGE-A3 mRNA. RESULTS: In 32 out of 60 cases, beta-actin mRNA was detected after RT-PCR, and the 28 cases which had no product after RT-PCR for beta-actin were excluded from this study. Twenty five cases showed as being metastasis positive and 7 cases showed as being metastasis negative by serial section (SS) H&E staining. Three out of 25 negative cases tested for by SS H&E staining were found to be positive by IHC. Ten, six and, eight cases out of the 25 negative cases tested for by SS H&E were found to be positive by RT-PCR for cytokeratin 19, MUC-1, and MAGE-A3, respectively. Among the 22 cases that were found to be negative by both SS H&E staining and IHC staining, 9, 4, and 6 cases were converted to positive by RT-PCR for cytokeratin 19, MUC-1, and MAGE-A3, respectively. Using the combination of two or three markers for performing RT-PCR was more sensitive than any single marker to detect micrometastasis (p < 0.05). CONCLUSION: Even though we failed to extract RNA in 46% of the paraffin embedded tissues, it may be possible to detect micrometastasis by using RT-PCR with the paraffin embedded tissue. RT-PCR is far more sensitive than IHC for detecting microme tastasis, and when we combine multiple markers, the detection rate is higher than for any one marker.
Actins ; Biopsy ; Breast Neoplasms* ; Breast* ; Humans ; Keratin-19 ; Lymph Node Excision ; Lymph Nodes* ; Neoplasm Metastasis ; Neoplasm Micrometastasis* ; Paraffin ; Reverse Transcriptase Polymerase Chain Reaction ; RNA ; RNA, Messenger

PURPOSE: Sentinel lymph node (SLN) biopsy has become a new standard procedure in the treatment of patients with early breast cancer. Furthermore, many institutions have begun offering the sentinel lymph node biopsy without simultaneous axillary dissection as a possible standard procedure when the SLN was free from tumors. For appropriate intraoperative decision making on the presence of cancer cells in axillary lymph nodes, a fast and accurate method to assess the SLN is required. The authors performed a prospective investigation of the relative merits of rapid cytokeratin immunohistochemical (IHC) staining of the SLN removed during the operations of breast cancer patients. METHODS: Between December 2002 and August 2003, 38 patients with T1and T2 breast cancer were enrolled after undergoing successful sentinel lymph node biopsy. A total of 60 sentinel lymph nodes (mean number, 1.58) were biopsied and first examined by hematoxylin-eosin (H&E) staining. All the tumor free sentinel lymph nodes by H&E stained section were immunostained for cytokeratin using a rapid immunohistochemical assay (Cytokeratin (PAN), 1:50, Newcastle, UK) during the operation. Finally, the sentinel lymph nodes were submitted for paraffin embedding and serial section after surgery. Both H&E stained and cytokeratin immunostained sections were also performed. RESULTS: This technique has a turnaround time of less than 20 minutes during the operation. Rapid IHC staining revealed 4 positive sentinel lymph nodes that were negative for metastasis by H&E staining. Among these false negative 4 cases, two cases had problems with the frozen section of H&E staining and the other 2 cases had problems due to micrometastasis. This study showed a sensitivity of 88.89%, a specificity of 100%, an accuracy of 98.33%, and a negative predictive value of 98.08%. The false-negative case (1 of 52), which was negative on H&E staining and rapid IHC staining during the operation, was disclosed as positive only after a serial permanent section examination with IHC stain. CONCLUSION: The introperative examination of sentinel lymph nodes is a highly accurate and effective way of predicting the axillary lymph node status of patients with breast cancers. This may be a promising technique in deciding whether to spare axillary lymph node dissection for the patient in the operating room.
Biopsy ; Breast Neoplasms* ; Breast* ; Decision Making ; Frozen Sections ; Humans ; Keratins* ; Lymph Node Excision ; Lymph Nodes* ; Neoplasm Metastasis ; Neoplasm Micrometastasis ; Operating Rooms ; Paraffin Embedding ; Prospective Studies ; Sensitivity and Specificity ; Sentinel Lymph Node Biopsy