위암 치료에 대한 한의 임상 가이드라인

김효린,유화승,백동기,박인해,장철용,김효영,하예진,문구,Kim, Hyo-rin,Yoo, Hwa-seung,Baek, Dong-gi,Park, In-hae,Jang, Chul-yong,Kim, Hyo-young,Ha, Ye-jin,Moon, Goo 대한한방내과학회 2016 大韓韓方內科學會誌 Vol.37 No.1

Objectives: The purpose of this study was to present the clinical guidelines and traditional Korean medicines for gastric cancer.Results: Gastric cancer is the second most common cancer in Korea. Recent studies have reported that applying integrative Oriental and Western medicine can suppress the tumor, improve the survival, the immune system, and the quality of life in gastric cancer. However, there still is no unified protocol for gastric cancer treatment, which produces difficulty in clinical applications. In Korea, a “Synopsis on the Clinical Practice Guidelines of Gastric Cancer” was published by the Korean Journal of Gastroenterology in 2014. In China, Oriental medicine clinical practice guidelines were published for the first time in 2014. The present author proposed “Clinical Practice Guidelines of Korean Medicine for Gastric Cancer” in 2014, but there is a need for more advanced guidelines with reference to the aforementioned Oriental and Western guidelines. This study will be helpful for understanding and building systems for integrative gastric cancer treatment.Conclusions: Further studies on integrative gastric cancer treatment are needed to improve the survival of gastric cancer patients and build the clinical practice guidelines for gastric cancer.

위암의 발생부위 및 심달도에 따른 위전도검사(EGG)의 의의

박영숙,이광재,강한걸,김영수,함기백,김진홍,조성원,이상인,조용관,김명욱 아주대학교 의과학연구소 1996 아주의학 Vol.1 No.1

Gastric slow waves which reflect neuromuscular activity of stomach, are considered to originate from the circular muscle of the stomach or from the interstitial cells of Cajal on the greater curvature near the junction of the proximal and distal gastric corpus. Therefore, it is suggested that the gastric malignancy occurring at some region of the stomach may affect the gastric myoelectrical activity. Scarse information is available about the changes of myoelectrical activity in patients with gastric cancer. This study was aimed at investigaing the effect of gastric cancer on gastric myoelectrical activity according to the location and depth of invasion. Methods: Seventy patients(mean age: 54.9±12.9yr,M:F=44:26) with gastric cancer and seventy normal controls(mean age: 45.9±11.1yr, M:F=34:36) were included. Gastric myoelectrical activity was recorded via abdominal surface electrodes using an ambulatory electrogastrographic recorder (Digitrapper EGG, Syndics, Irving, TX). The record were analyzed based on running spectral analysis. Electrogastrography was recorded for at least 30-min during fasting and then 30-min after solid test meal(700 Cal, protein 32 gm, fat 15 g, carbohydrate 110 gm). Results: 1) The percentage of normal slow waves(2-4cpm) was 87.5±15.8% in early gastric cancer group(19), 95.4±18.9% in advanced gastric cancer group(81) and 91.3±9.9% in control group(70) in fasting state In postprandial state, the percentages were 85.9±12.7% 89.3±13.9% and 89.7±10.2% respectively. 2) In advanced gastric cancer, there was no statistical difference according to cancer location on gastric myoelectrical activity. 3) The power ratio defined as postprandial slow wave amplitude increment, was normal in most patients between early and advanced cancer group and control group. 4) In 11 patients with antral cancer and partial pyloric obstruction, the percentage of normal slow waves was 93.3±10.9% in fasting state and 92.8±11.2% in postprandial state and amplitude of slow waves in fasting state was significantly higher than in antral cancer without obstruction (p<0.05). Conclusions: There was no significant change in pattern of gastric myoelctrical activity in patients with gastric cancer according to the location and depth of invasion. However, the pyloric obstruction by cancer infiltration produced prominent increase of amplitude in slow waves similar to the effect of other benign obstruction.

분무부 위암의 임상적 특성과 예후인자 분석

이주호 인제대학교 2000 仁濟醫學 Vol.21 No.2

Background: Gastric cardia cancer has been rising in incidence and has relatively worse prognosis than that of other site gastric cancer. Materials and Methods: The clinicopathologic characteristics and prognosis were analyzed for 217 consecutive patients underwent operation for gastric cardia cancer at the Department of Surgery, Seoul National University Hospital from 1991 to 1995 and compared them to those of other site gastric cancer. Results: The mean age of cardia cancer patients was 54.3 years and male-to-female radio was 2.80 : 1. Gastric resection was performed in 189 patients and curative resection in 171 patients(87.1% resection rate, 78.8% curative resection rate) . Gastric cardia cancer was more advanced than other site gastric cancer. Gastric cardia cancer had worse prognosis than that of non-cardia cancer overall(45.8 % for cardia cancer, 61.2% for non-cardia canner). When we compare the survivals at same stage, survival of cardia cancer was worse than that of non-cardia cancer at stage I and II, but there was no significant difference at stage III and IV. Gross finding, size, depth of invasion, lymphatic invasion, lymph node metastasis, esophageal invasion, and length of proximal resection margin were significant in univariate analysis and in multivariate analysis, depth of invasion and lymph node metastasis were significant prognostic factors. In stave I and II, if the length of proximal resection margin was 3 cm or more, 5 year survival rate was 86.5%, but 61.4% if less than 3cm. However in stage III and IV, there was no survival difference according to the length of resection margin. Despite clear proximal resection margin in frozen biopsies, there were positive resection margin of 5.88% in cases with resection margin of less than 3cm and 1.15% in cases with resection margin more than 3cm(p〈 0.05). These results suggest that length of proximal resection margin should be more than 3cm at least. Conclusion: Gastric cardia cancer diagnosed at more advanced stage than other site gastric cancer. Poor prognosis of gastric cardia cancer was due to worse survival in stare I and II. To improve the survival of gastric cardia cancer, better means of early diagnosis should be developed and curative resection with more than 3cm resection margin should be performed.

위 상피 이형성의 전향적 연구

이영민(Young Min Lee),오경석(Kyung Seok Oh),조길현(Kil Hyeon Cho),장현정(Hyeon Jung Jang),이상혁(Sang Hyuk Lee),설상영(Sang Yong Seol),정정명(Jung Myung Chung),최하진(Ha Jin Choi),김찬환(Chan Hwan Kim) 대한내과학회 1996 대한내과학회지 Vol.50 No.3

Objectives: Gastric dysplasia is defined as a lesion characterized by cellular atypia, abnormal differentiation and disorganized architecture without showing malignant nature in histology. Even though it was known as a precursor of gastric cancer, there were few studies in clinical and biological aspect in practice. Because the early detection of gastric cancer is very important, we have evaluated the risk of gastric carcinoma following the gastric dysplasia in prevention of gastric cancer. Methods: The authors evaluated the clinical and histological findings of 27 cases of gastric dysplasia for at least 3-12 months among 38 cases of gastric dysplasia and which confirmed from January 1992 to June 1994. Results: The sex distribution of 38 cases with gastric dysplasia was that men were 29 cases and women were 9 cases. The Highest incidence was above 6th decades(30cases) in age. Twenty seven cases of gastric dysplasia could be followed prospectively. Each histologic findings were as follow, mild dysplasia 12 cases, moderate dysplasia 7 cases and severe dysplasia 8 cases respectively. The endoscopic findings showed erosion 6 cases(16%), flat lesion 8 cases(21%), ulcer 10 cases(26%), polypoid lesion 14 cases(37%) respectively, The evolution of dysplasia was regression 4 cases, persistence 4 cases, progression 3 cases, cancer 1 case(9%) in mild dysplasia and regression 2 cases, persistence 2 cases, progression 1 case, cancer 2 cases(29%) in moderate dysplasia. In eight severe dysplasia, 1 case of regression, 3 cases of persistence and 4 cases of cancer(50%) were developed. Polypectomy was performed in 12 cases and 1 case was regressed from severe dysplasia after mucosal resection. In 27 cases of gastric epithelial dysplasia, gastric cancers were developed in 7 cases(26%) and early gastric cancers were 4 cases(57%) among them and the most common lesion was ulcer(5 cases). Conclusion: Gastric dysplasia should be strictly followed up with repeated endoscopic examination as well as treated the adequate endoscopic procedure for the prevention of progression or the risk of developing cancer.

Borrmann 4형으로 진단된 진행성 위암환자의 임상적 검토

천영국,김영태,홍수진,김진오,조주영,이문성,심찬섭 순천향의학연구소 2001 Journal of Soonchunhyang Medical Science Vol.7 No.1

Background/Aim: It is difficult to dignosis of Borrmann type 4 gastric cancer at the early stage, because of its special morphology. Most of the cases have been detected at the advanced stage with poor survival rate. We reviewed patients with advanced gastric cancer, to define clinicopathologic characteristics of Borrmann type 4 gastric cancer comparing other types of gastric cancer. Methods: 1033 patients with advanced gastric cancer were divided into two groups, consisting of 50 patients with Borrmann type 4 gastric cancer, and the remaining 983 patients with all other types of gastric cancer, which were then compared clinicopatologically. Results: The proportion of Borrmann type 4 gastric cancer to advanced gastric cancer was 4.48%(50/1,033). The patients with Borrmann type 4 gastric cancer to advanced gastric cancer was 4.48%(50/1,033). The patients with Borrmann type 4 gastric cancer were composed 20 males and 30 males and revealed the highest frequency 3rd decade (24.0%) in age (range 26-78). In giant folds group (n=27), the number of poorly differentiated cell type, lymph node metastasis, peritoneal seeding were 20 (74.1%), 17 (63,0%), 12 (44.4%). In non-giant folds group (n=23), the number of poorly differentiated type, lymph node metastasis, peritoneal seeding were 17 (73.9%), 15 (65.2%), 6 (26.1%). Rate of tumor invasion in serosa and beyound serosa was 88.9% in giant fold group, 63.0% in non-giant fold group. Surgery was performed in only 32% as a modality of treatment (vs. 82.5%). Characteristics findings of Borrmann type 4 gastric cancer in EUS showed a thickening of the third (submucosa) and fourth (muscularis propria) layers in 72% of 50 patients, and a well preserved five-layered gastric wall structure in 33 patients. Conclusions: We concluded that Borrmann type 4 gastric cancer was diagnosed more in females, as a more advanced disease, early detection was needed. And endoscopic ultrasonography is useful for diagnosis of Borrmann type 4 gastric cancer in the cases of suspicious results of gastroscopy.

만성 Helicobacter pylori 감염에 의한 위암발생에서 위줄기세포의 역할

박무인,허정훈 대한상부위장관ㆍ헬리코박터학회 2015 Korean Journal of Helicobacter Upper Gastrointesti Vol.15 No.3

Gastric cancer is a disease with the second cancer-related mortality in the world. Helicobacter pylori infection that is one of major causes of gastric carcinogenesis induces a chronic inflammation in stomach. The epithelial-mesenchymal transition and/or the accumulation of genetic mutation occur during regenerating the injured gastric epithelial cells due to chronic inflammation by the infection of H. pylori. Normal gastric cells can be transformed into cancer stem cells by the epithelial-mesenchymal transition and/or the accumulation of genetic mutation that initiate the development of gastric cancer. Gastric epithelial cells, bone marrow-derived cells and gastric stem cells in gastric tissue might be the source of gastric cancer stem cells as the target cells that might be susceptible for epithelial-mesenchymal transition and/or the accumulation of genetic mutation. Normal stem cells in gastric tissue regenerating the injured gastric tissue also have the potential to be cancer stem cells known as the origin of cancer development when their ability for regulating differentiation and/or proliferation of normal stem cells is damaged by epithelial-mesenchymal transition and/or the accumulation of genetic mutation. Therefore if the mechanism regulating the transformation of normal stem cells to cancer stem cells is discovered, it might suggest the fundamental therapeutic strategy for preventing the development of gastric cancer by the chronic infection of H. pylori.

Tumor Size as a Prognostic Factor in Gastric Cancer Patient

임원진,권성준,김민규,하태경 대한위암학회 2012 Journal of gastric cancer Vol.12 No.3

Purpose: The purpose of this study is to investigate the prognostic significance of tumor size for 5-year survival rate in patients with gastric cancer. Materials and Methods: A total of 1,697 patients with gastric cancer, who underwent potentially curative gastrectomy, were evaluated. Patients were divided into 4 groups as follows, according to the median size of early and advanced gastric cancer, respectively: small early gastric cancer (tumor size ≤3 cm), large early gastric cancer (tumor size >3 cm), small advanced gastric cancer (tumor size ≤ 6cm), and large advanced gastric cancer (tumor size >6 cm). The prognostic value of tumor size for 5-year survival rate was investigated. Results: In a univariate analysis, tumor size is a significant prognostic factor in advanced gastric cancer, but not in early gastric cancer. Multivariate analysis showed that tumor size is an independent prognostic factor for 5-year survival rate in advanced gastric cancer (P=0.003, hazard ratio=1.372, 95% confidence interval=1.115~1.690). When advanced gastric cancer is subdivided into 2 groups,according to serosa invasion: Group 1; serosa negative (T2 and T3, 7th AJCC), and Group 2; serosa positive (T4a and T4b, 7th AJCC),tumor size is an independent prognostic factor in Group 1 (P=0.011, hazard ratio=1.810, 95% confidence interval=1.149~2.852)and in Group 2 (P=0.033, hazard ratio=1.288, 95% confidence interval=1.020~1.627), respectively. Conclusions: Tumor size

Differential MicroRNA Expression Between Gastric Cancer Tissue and Non-cancerous Gastric Mucosa According to Helicobacter pylori Status

이정원,김나영,박지현,김희지,장현,김정민,김진욱,이동호 대한암예방학회 2017 Journal of cancer prevention Vol.22 No.1

Background: MicroRNAs (miRNAs) are key post-translational mechanisms which can regulate gene expression in gastric carcinogenesis. To identify miRNAs responsible for gastric carcinogenesis, we compared expression levels of miRNAs between gastric cancer tissue and non-cancerous gastric mucosa according to Helicobacter pylori status. Methods: Total RNA was extracted from the cancerous regions of formalin-fixed, paraffin-embedded tissues of H. pylori-positive (n =8) or H. pylori-negative (n = 8) patients with an intestinal type of gastric cancer. RNA expression was analyzed using a 3,523 miRNA profiling microarray based on the Sanger miRBase. Validation analysis was performed using TaqMan miRNA assays for biopsy samples from 107 patients consisted of control and gastric cancer with or without H. pylori. And then, expression levels of miRNAs were compared according to subgroups. Results: A total of 156 miRNAs in the aberrant miRNA profiles across the miRNA microarray showed differential expression (at least a 2-fold change, P < 0.05) in cancer tissue, compared to noncancerous mucosa in both of H. pylori-negative and -positive samples. After 10 promising miRNAs were selected, validations by TaqMan miRNA assays confirmed that two miRNAs (hsa-miR-135b-5p and hsa-miR-196a-5p) were significantly increased and one miRNA (hsa-miR-145-5p) decreased in cancer tissue compared to non-cancerous gastric mucosa at H. pylori-negative group. For H. pylori-positive group, three miRNAs (hsa-miR-18a-5p, hsa-miR-135b-5p, and hsa-miR-196a-5p) were increased in cancer tissue. hsa-miR-135b-5p and hsa-miR-196a-5p were increased in gastric cancer in both of H. pylori-negative and -positive. Conclusions: miRNA expression of the gastric cancer implies that different but partially common gastric cancer carcinogenic mechanisms might exist according to H. pylori status.

Differential MicroRNA Expression Between Gastric Cancer Tissue and Non-cancerous Gastric Mucosa According to <i>Helicobacter pylori</i> Status

Lee, Jung Won,Kim, Nayoung,Park, Ji Hyun,Kim, Hee Jin,Chang, Hyun,Kim, Jung Min,Kim, Jin-Wook,Lee, Dong Ho Korean Society of Cancer Prevention 2017 Journal of cancer prevention Vol.12 No.2

<P><B>Background</B></P><P>MicroRNAs (miRNAs) are key post-translational mechanisms which can regulate gene expression in gastric carcinogenesis. To identify miRNAs responsible for gastric carcinogenesis, we compared expression levels of miRNAs between gastric cancer tissue and non-cancerous gastric mucosa according to <I>Helicobacter pylori</I> status.</P><P><B>Methods</B></P><P>Total RNA was extracted from the cancerous regions of formalin-fixed, paraffin-embedded tissues of <I>H. pylori</I>-positive (n = 8) or <I>H. pylori</I>-negative (n = 8) patients with an intestinal type of gastric cancer. RNA expression was analyzed using a 3,523 miRNA profiling microarray based on the Sanger miRBase. Validation analysis was performed using TaqMan miRNA assays for biopsy samples from 107 patients consisted of control and gastric cancer with or without <I>H. pylori</I>. And then, expression levels of miRNAs were compared according to subgroups.</P><P><B>Results</B></P><P>A total of 156 miRNAs in the aberrant miRNA profiles across the miRNA microarray showed differential expression (at least a 2-fold change, <I>P</I> < 0.05) in cancer tissue, compared to noncancerous mucosa in both of <I>H. pylori</I>-negative and -positive samples. After 10 promising miRNAs were selected, validations by TaqMan miRNA assays confirmed that two miRNAs (hsa-miR-135b-5p and hsa-miR-196a-5p) were significantly increased and one miRNA (hsa-miR-145-5p) decreased in cancer tissue compared to non-cancerous gastric mucosa at <I>H. pylori</I>-negative group. For <I>H. pylori</I>-positive group, three miRNAs (hsa-miR-18a-5p, hsa-miR-135b-5p, and hsa-miR-196a-5p) were increased in cancer tissue. hsa-miR-135b-5p and hsa-miR-196a-5p were increased in gastric cancer in both of <I>H. pylori</I>-negative and -positive.</P><P><B>Conclusions</B></P><P>miRNA expression of the gastric cancer implies that different but partially common gastric cancer carcinogenic mechanisms might exist according to <I>H. pylori</I> status.</P>

Hypermethylation and Clinicopathological Significance of RASAL1 Gene in Gastric Cancer

Chen, Hong,Pan, Ying,Cheng, Zheng-Yuan,Wang, Zhi,Liu, Yang,Zhao, Zhu-Jiang,Fan, Hong Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Background: Recent studies have suggested that expression of the RAS protein activator like-1 gene (RASAL1) is decreased in gastric carcinoma tissues and cell lines, indicated a role in tumorigenesis and development of gastric cancer. Reduced expression of RASAL1 could result in aberrant increase of activity of RAS signaling pathways in cancer cells. However, the exact mechanism which induces down-regulation of the RASAL1 gene remains unclear. This study aimed to determine the methylation status and regulation of RASAL1 in gastric cancer. Materials and Methods: Using the methylation-specific polymerase chain reaction (MSP), the methylation status of CpG islands in the RASAL1 promoter in gastric cancers and paired adjacent non-cancerous tissues from 40 patients was assessed and its clinicopathological significance was analyzed. The methylation status of RASAL1 in gastric cancer lines MKN-28, SGC-790l, BGC-823, as well as in normal gastric epithelial cell line GES-l was also determined after treatment with a DNA methyltransferase inhibitor, 5-aza-2'-doexycytidine (5-Aza-CdR). RAS activity (GAS-GTP) was assessed through a pull-down method, while protein levels of ERK1/2, a downstream molecule of RAS signaling pathways, were determined by Western blotting. Results: The frequencies of RASAL1 promoter methylation in gastric cancer and paired adjacent non-cancerous tissues were 70% (28/40) and 30% (12/40) respectively (P<0.05). There were significantly correlations between RASAL1 promoter methylation with tumor differentiation, tumor size, invasive depth and lymph node metastasis in patients with gastric cancer (all P<0.05), but no correlation was found for age or gender. Promoter hypermethylation of the RASAL1 gene was detected in MKN-28, SGC-790l and BGC-823 cancer cells, but not in the normal gastric epithelial cell line GES-1. Elevated expression of the RASAL1 protein, a decreased RAS-GTP and p-ERK1/2 protein were detected in three gastric cancer cell lines after treatment with 5-Aza-CdR. Conclusions: Aberrant hypermethylation of the RASAL1 gene promoter frequently occurs in gastric cancer tissues and cells. In addition, the demethylating agent 5-Aza-CdR can reverse the hypermethylation of RASAL1 gene and up-regulate the expression of RASAL1 significantly in gastric cancer cells in vivo. Our study suggests that RASAL1 promoter methylation may have a certain relationship with the reduced RASAL1 expression in gastric cancer.