전(全)복강경하 원위부 위절제술의 초기 경험

김진조,송교영,진형민,김욱,전해명,박조현,박승만,임근우,박우배,김승남,Kim Jin Jo,Song Gyo Young,Chin Hyung Min,Kim Wook,Jeon Hae Myoung,Park Cho Hyun,Park Seung Man,Lim Keun Woo,Park Woo Bae,Kim Seung Nam 대한위암학회 2005 대한위암학회지 Vol.5 No.1

목적:최근 조기위암환자를 대상으로 복강경보조하 원위부 위적제술이 활발히 시행되고 있으나 전복강경하 원위부 위절제술은 복강 내 위장관 문합의 어려움 때문에 아직까지 활성화되어 있지 않다. 이에 저자들은 복강경용 선형 자동 문합기를 이용한 복강 내 위십이지장 문합술을 통한 전복강경하 원위부 위절제술의 초기 경험을 통하여 그 유용성을 알아보고자 하였다. 대상 및 방법: 2004년 6월부터 9월까지 가톨릭대학교 의과대학 성모자애병원 외과에서 조기위암으로 진단되어 전복강경하 원위부 위절제술을 시행받은 환자 8명을 대상으로 하였으며 복강 내 위십이지장 문합에는 복강경용 선형 자동 문합기를 이용한 델타형 문합 밥법을 이용하였다. 대상 환자에 대한 수술 관련 사항(수술 및 문합에 소요된 시간), 수술의 경과와 임상병리학적인 결과를 통한 근치도를 조사하였다. 결과: 수술 시간은 $369.4\pm62.5$분, 문합에 소요된 시간은 $45.1\pm14.4$분이었으며 증례의 증가에 따라 점차 단축되었다. 문합에 사용한 자동 문합기의 수은 $7.1\pm0.6$개였다. 절제 림프절은 $31.9\pm13.1$개였으며 개복 수술로 전환한 예는 없었다. 수술 후 첫 가스 배출은 $2.8\pm0.5$일, 첫 유동식 섭취는 $4.1\pm0.8$일, 재원 기간은 $10.3\pm4.1$일이었다. 수술과 관련된 합병증은 없었다. 결론: 델타형 위십이지장 문합을 이용한 전복강경하 원위부 위절제술은 기술적으로 용이하였고 조기위암환자에서 복강경 수술의 장점을 최대화할 수 있는 최소침습수술의 하나라고 생각된다.0\%$), 위 중부 20예($21\%$), 위 상부 18예($9\%$)였다. 위암 환자 중 흡연력이 있는 경우는 56명, 없는 경우는 40명이었고, 음주력이 있는 경우는 45명, 없는 경우는 51명이었다. 환자군에서 MTHFR의 유전자 다형성은 C/C 18($19\%$), C/T 59($61\%$), T/T 19($20\%$)였고, 대조군에서는 C/C 116($40\%$), C/T 103$40\%$), T/T 68($24\%$)이었다(P=0.045). 암의 위치에 따른 MTHFR유전자형의 분포는 위 하부에서 C/C 16($28\%$), C/T & T/T 42($77\%$)이었고, 위 중부 및 상부에서 C/C 2($5\%$), C/T & T/T 36($75\%$) 이었다(P=0.006). 환자군 내에서 흡연력 유무에 따른 MTHFR유전 자형의 분포는 흡연력이 있을 때 C/C 13($23\%$), C/T & T/T 43($77\%$)이었고, 흡연력이 없을 때 C/C 5($12\%$), C/T & T/T 35 ($88\%$)였다(P=0.189). 환자군 내에서 음주력 유무에 따른 MTHFR유전자형의 분포는 음주력이 있을 때 C/C 12($26\%$), C/T & T/T 33($74\%$)이었고, 음주력이 없을 때 C/C 6($12\%$), Purpose: In Korea, the number of laparoscopy-assisted distal gastrectomies for early gastric cancer patients has been increasing lately. Although minimally invasive surgery is more beneficial, no reported case of a totally laparoscopic distal gastrectomy has been reported because of difficulty with intracorporeal anastomosis. This study attempts, through our experiences, to determine the feasibility of a totally laparoscopic distal gastrectomy using an intracorporeal gastroduodenostomy in treating early gastric carcinoma. Materials and Methods: We investigated surgical results and clinicopatholgic characteristics of eight(8) patients with an early gastric carcinoma who underwent a totally laparoscopic distal gastrectomy at the Department of Surgery, Our Lady of Mercy Hospital, The Catholic University of Korea, between June 2004 and September 2004. The intracorporeal gastroduodenostomy was performed with a delta-shaped ananstomosis by using only laparoscopic linear staplers (Endocutter 45mm; Ethicon Endosurgery, OH, USA). Results: The operative time was $369.4\pm62.5$ minutes (range $275\∼465$ minutes), and the anastomotic time was 45.1\pm14.4$ minutes (range $32\∼70$ minutes). The anastomotic time was shortened as surgical experience was gained. The number of laparoscopic linear staplers for an operation was $7.1\pm0.6$. The number of lymph nodes harvested was $31.9\pm13.1$. There was 1 case of transfusion and no case of conversion to an open procedure. The time to the first flatus was 2.8$\pm$0.5 days, and the time to the first food intake was $4.1\pm0.8$ days. There were no early postoperative complications, and the postoperative hospital stay was $10.0\pm3.9$ days. Conclusion: A totally laparoscopic distal gastrectomy using an intracorporeal gastroduodenostomy with a delta-shaped anastomosis is technically feasible and can maximize the benefit of laparoscopic surgery for early gastric cancer.

위암에서 조직학적 특징에 따른 혈청 E-cadherin의 농도

허훈,송교영,김진조,진형민,김욱,박조현,박승만,임근우,박우배,김승남,전해명,Hur, Hoon,Song-Gyo-Young,Kim, Jin-Jo,Chin-Hyung-Min,Kim, Wook,Park, Cho-Hyun,Park, Seung-Man,Lim-Keun-Woo,Park, Woo-Bae,Kim, Seung-Nam,Jeon, Hae-Myoung 대한위암학회 2004 대한위암학회지 Vol.4 No.3

Purpose: While E-cadherin in normal cells induces calciumdependent cell-cell adhesion, in malignant cell, it plays a role in invasion and metastasis with a reduction of adhesion. Serum soluble E-cadherin is a result of the reduction of the cellular E-cadherin molecule and is found in the circulation of normal individuals, but it is particularly known to be increased in patients with malignancies. Accordingly, through checking the level of serum soluble E-cadherin in patients with gastric cancer and analyzing it in the view of clinicopathology, we investigated whether serum soluble E-cadherin could be translated into a clinicopathologic esult and used as a tumor marker. Materials and Methods: The investigation targeted 88 patients who had been diagnosed as having gastric cancer by the Department of Surgery, St. Mary's Hospital, from October 1, 2002, to July 30, 2003, and who had under gone performed surgery. We measured the level of preoperative serum E-cadherin in the 88 patients by unsing ELISA. Among them, we collected gastric cancer tissues from 54 patients and executed immunohistochemistry for E-cadherin. The samples were compared with normal tissues in terms of both serum E-cadherin level and immunohistochemistry level, as well as with other clinicopathologic factors. Result: The mean serum E-cadherin level of the 88 patients was 4368.7 ng/ml and was significantly higher than the level in 12 normal control patients, 3335.5 ng/ml (P=0.016). In terms of clinicopathology, the serum level of E-cadherin was significantly correlated with increasing age (P=0.0006) and was higher in positive venous invasion patients (P=0.0005). When the E-cadherin immunohistochemical stain was compared with the serum E-cadherin level in 54 patients, no significant statistically meaningful result was obtained (P=0.2881). However, 4 patients with serum E-cadherin levels about 6000 ng/ml were classified into the lower expression group ($<80\%$ of E-cadherin immunohistochemicals stain. In the analysis for 36 patients who were early gastric cancer patients, the serum E-cadherin level in lymph-node-metastatic patients was higher than it was in the other patients (P=0.0442). Conclusion: The serum E-cadherin level in gastric cancer patients was higher than the level in normal control patients. In advanced gastric cancer patients, that the difference was increased. Also, since the E-cadherin level correlated with the serum E-cadherin level with venous invasion, it can be used as an effective tumor marker for gastric cancer. Particularly, in that the serum E-cadherin level correlated with lymph node metastasis in early gastic cancer, it can be used when a therapeutic method for early gastric cancer is selected.

위암에서 P16 및 hMLH1 유전자의 메틸화

성기영,전경화,송교영,김진조,진형민,김욱,박조현,박승만,임근우,박우배,김승남,전해명,Sung, Gi-Young,Chun, Kyung-Hwa,Song, Gyo-Yeong,Kim, Jin-Jo,Chin, Hyung-Min,Kim, Wook,Park, Cho-Hyun,Park, Seung-Man,Lim, Keun-Woo,Park, Woo-Bae,Kim, Seun 대한위암학회 2005 대한위암학회지 Vol.5 No.4

목적: 위암조직에서 P16과 hMLH1 유전자의 메틸화상태를 검사하여 위암의 발생과정에서의 작용과 유전자의 발현에 미치는 영향과 Helicobacter paylori균 감염여부 및 임상병리학적인자와의 연관성을 알아보고자 하였다. 대상 및 방법: 위암 신선 동결 절편조직 100예를 대상으로 유전자의 단백질 발현상태는 면역조직화학 염색을 시행하여 확인하였고. 메틸화 상태는 methylation-specific PCR(MSP)과 염기서열분석을 시행하였다. 결과: P16유전자의 메틸화는 19예(19%)에서 관찰되었고 이 중 18예(94.7%)에서 P16유전자의 단백질 발현 소실이 있어, P16 유전자의 단백질 발현 소실이 P16유전자의 메틸화와 연관이 있음을 알 수 있었다(kappa 계수=0.317, P=.0011). hMLH1 유전자의 메틸화는 27예(27%)에서 관찰되었고, 이 중 24예(8.8%)에서 hMLH1 단백의 소실이 hMLH1유전자의 메틸화와 연관이 있음을 보여주었다(kappa계수=0.675, p<0.0001). hMLH1 유전자의 메틸화는 나이, 암종의 크기, Lauren 분류와 연관성이 있었다. P16 유전자와 hMLH1 유전자 메틸화 모두 Helicobacter paylori균 감염여부와는 연관성이 없었다. 결론: 위암에서 P16 및 hMLH1 유전자의 불활성화에는 DNA 메틸화가 작용을 함을 알 수 있었고, hMLH1유전자의 메틸화는 나이, 암종의 크기, Lauren 분류와 연관이 있음을 알 수 있었다. Purpose: We investigated the impacts of the methylation states of the P16 and the hMLH1 genes on pathogenesis and genetic expression of stomach cancer and their relationships with Helicobater pylori infection, and with other clinico-pathologic factors. Material and Methods: In our study, to detect protein expression and methylation status of the P16 and the hMLH1 genes in 100 advanced gastric adenocarcinomas, used immunohistochemical staining and methylation-specific PCR (MSP) and direct automatic genetic sequencing analysis. Results: Methylation of the P16 gene was observed in 19 out of 100 cases (19%) and in the 18 of those cases (94.7%) loss of protein expression was seen. We were sble to show that loss of P16 gene expression was related to methylation of the P16 gene (kappa coefficient=0.317, p=0.0011). Methylation of the hMLH1 gene was observed in 27 cases (27%), and in 24 cases of those 27 cases (88.8%), loss of protein expression was seen, which suggested that loss of protein expression in the hMLH1 gene is related to methylation of hMLH1 gene (kappa coefficient=0.675, P<0.0001). Also methylation of the hMLH1 gene was related to age, size of the mass, and lauren's classification. Conclusion: We found that methylation of DNA plays an important role in inactivation of the P16 and the hMLH1 genes. The methylation of the hMLH1 genes is significantly related to age, size of the mass, and lauren's classification.

위암에서의 p14<SUP>ARF</SUP>, p16<SUP>INK4a</SUP>, p53, pRb 단백 발현

채병주(Byung Joo Chae),송교영(Gyo Young Song),김진조(Jin Jo Kim),진형민(Hyung Min Chin),김욱(Wook Kim),박조현(Cho Hyun Park),전해명(Hae Myung Jeon),박승만(Seung Man Park),임근우(Keun Woo Lim),김응국(Eung Kook Kim),김승남(Seung Nam K 대한외과학회 2004 Annals of Surgical Treatment and Research(ASRT) Vol.67 No.2

위암에서의 $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ 단백 발현

김신선,박용근,전경화,정헌,송교영,김진조,진현민,김욱,박조현,박승만,임근우,김승남,전해명,Kim, Sin-Sun,Park, Yong-Geun,Jun, Kyong-Hwa,Jung, Hun,Song, Gyo-Young,Kim, Jin-Joo,Chin, Hyung-Min,Kim, Wook,Park, Cho-Hyun,Park, Seung-Man,Lim, Keun- 대한위암학회 2006 대한위암학회지 Vol.6 No.1

목적: 암의 발생과 진행에 있어서 비정상적인 세포주기로 인하여 조절이 불가능한 세포성장과 분열이 중요한 기전으로 관여한다. 세포주기는 cyclin, CDK와 cyclin의 복합체는 CDKI에 의해 억제된다. 세포주기를 억제하는 인자는 종양 세포에서도 종양억제인자로 작용한다. 세포 주기 조절인자 CDKI는 INK family, CIP/KIP family로 구분된다. 본 연구는 CIP/KIP family인 $p21^{Waf1/Cip1}\;27^{kip1}$ 단백질의 발현유무에 따른 위암의 임상조직학적인 특성 및 예후와 연관성에 대해 조사하였다. 대상 및 방법: 1993년부터 1997년까지 위암으로 진단받고 수술적 치료를 받은 환자들 중에 추적 조사가 가능하고 파라핀 포매 조직상태가 좋은 192명의 환자를 대상으로 하였다. $p21^{Waf1/Cip1}$과$p27^{kip1}$에 대해 면역조직화학염색을 시행하였고, 종양세포의 핵에 염색되는 세포를 양성 판정하였다. 통계학적 분석은 임상조직학적인 특성과 생존율의 차이에 대하여 시행하였다. 결과: $p21^{Waf1/Cip1}$은 15.6% (30/192), $p27^{kip1}$은 28.1% (54/192)의 발현율을 보였다. $p21^{Waf1/Cip1}$은 양성에서는 T1-2 (80.0%), 음성에서는 T3-4 (50.6%)가 차지하는 비율이 높았으며(P<0.05) 다른 인자에서는 통계적인 유의성이 없었다. $p27^{kip1}$에서는 T-stage에서 $p21^{Waf1/Cip1}$과 비슷한 결과(77.8%, 55.1%)를 보였으며, Lauren 분류에서는 장형(62.7%)보다 미만형(91.3%)에서 음성을 보이는 비율이 높았다.(P<0.05)$p27^{kip1}$도 다른 인자에서는 통계적인 유의성이 없었다. 의 상관관계는 $p21^{Waf1/Cip1}(+)$과 $p27^{kip1}$의 상관관계는 $p21^{Waf1/Cip1}(+)/p27^{kip1}(+)$ 보이는 경우(53.3%)와, $p21^{Waf1/Cip1}(-)/p27^{kip1}(-)$ 보이는 경우(76.5%)가 많았다(P<0.05). $p21^{Waf1/Cip1}$과 $p27^{kip1}$ 복합 검사에서는 $p21^{Waf1/Cip1}(+)/p27^{kip1}(+)$인 경우에 T1-2 (87.5%)가 많았고 $p21^{Waf1/Cip1}(-)/p27^{kip1}(-)$인 경우에는 T3-4(58.1%)가 많았다(P<0.05). 또한 Lauren 분류에서는 $p21^{Waf1/Cip1}(+)/p27^{kip1}$인 경우가 장형 (100%)에서만 나타났으며(P<0.05), $p21^{Waf1/Cip1}(-)/p27^{kip1}(-)$인 경우는 미만형인 경우(87.0%)가 장형(54.9%)의 경우보다 많은 비율을 차지하였다(P<0.05). 5년 장기 생존율에 있어서는 각각의 $p21^{Waf1/Cip1}$과$p27^{kip1}$의 발현 유무에 따른 통계적인 유의성은 없었고 복합 검사에서도 $p21^{Waf1/Cip1}(+)/p27^{kip1}(+)$의 경우에 생존율이 높았지만 통계적인 유의성은 없었다. 결론: 저자들의 경우에는 $p21^{Waf1/Cip1}$과$p27^{kip1}$은 서로 비슷한 발현 형태를 나타내고 $p21^{Waf1/Cip1}$과$p27^{kip1}$의 발현은 침윤 정도에 영향을 주며, $p27^{kip1}$의 경우에는 Lauren분류와 관련성이 있었다. 또한, $p21^{Waf1/Cip1}$과$p27^{kip1}$ 복합 검사는 침윤 정도와 Lauren 분류와 연관성이 있다고 할 수 있다. 하지만, $p21^{Waf1/Cip1}$과$p27^{kip1}$의 발현에 따른 생존율의 차이가 유의성을 보이지 않아, 예후 예측인자로의 적용은 한계가 있다고 생각한다. Purpose: The $p21^{Waf1/Cip1}$ protein Inhibits the cell cycle by Inhibiting the phosphorylation at the $G1{\rightarrow}S$ check point, and the $p27^{kip1}$ protein similarly performs the suppressor function by controlling the p27-mediated G1 arrest. In this study, we analysed the clinical status and survival rates in correlations with p21 and p27 expression patterns in gastric cancer. Materials and Methods: Between 1993 and 1997, 192 patients who underwent surgeries in Catholic Medical Center were analysed retrospectively in this study. Immunohistochemical staining was performed and if the nuclei of the tumor cells were stained, we assumed those as positive results. Statistical analysis was based on clinicopathological findings and differences in survival rates. Results: The expression rate of p27 was 28.1% and 15.6% in p21 each. The ratio of T1-2(80.0%) was significantly high in p21 (+), but the ratio of T3-4 (50.6%) was slightly high in p21 (-). There was no statistical significance regarding other factors. The results in p27 was not much different from expression rate of p21 in T-stage. In addition, p27 expression in diffuse type (91.3%) was higher than in intestinal type (62.7%) by Lauren's classification (P<0.05). Also, there was no statistical significance in other factors. In the correlation of p21 and p27, p27 was positive when p21 was positive (53.5%). Conversely, p27 was negative when p21 was negative (76.5%, p<0.05). In the p21 and p27 combination test, there was higher rate of T1-2 (87.5%) in p21 (+)/p27 (+), and higher rate of T3-4 (58.1%) in p21 (-)/p27 (-) (P<0.05). Results showed higher rate of intestinal type (100%) in p21 (+)/p27 (+), and diffuse type (87.0%) was dominant in p21 (-)/p27 (-) (P<0.05) by Lauren's classification. Moreover, there was no statistical significance in the 5-year survival rate in the expression of p21 and p27, and the 5-year survival rate was highest in the case of p21 (+)/p27 (+) without statistical significance. Conclusion: In our study, $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ expressed similar patterns. The expression of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ affected the degree of invasiveness of the tumor, and. Combined examination result revealed the correlation of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ with Lauren's classification and depth of invasion of the tumor. However, we assumed that little difference between the survival rates depending on expression of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ has limited their value as predictable prognostic indicators.