EndoFest Korea(제4회)-편집.hwp

Size: px
Start display at page:

Download "EndoFest Korea(제4회)-편집.hwp"

Transcription

1 B-II. Intestinal Neuroendocrine Tumors: A to Z Room B 광범위장신경내분비종양의치료 동아대학교의과대학내과학교실 Jonghoon Lee Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea 서론 고자한다. 신경내분비종양 (Neuroendocrine tumors; NETs) 은인체의전체에걸쳐다양한장소에퍼져서발생할수있다. 다양한장소에서발생한 NETs는그조직학적인특징에따라분류되는데, 용어와 grading에다양한차이를보이지만, 일반적으로진행이느리고, 잘분화된종양 (well-differentiated tumor) 과좀더공격적인행태를보이는분화가나쁜암 (poorlydifferentiated carcinoma) 으로나눌수있다. 카르시노이드 (carcinoid) 라는용어는일반적으로소화기계, 폐, 신장이나난소와같은드문원발병소등에서발생한 NETs에사용되어진다. 통상 카르시노이드 라함은조직학적으로고분화의특징을가진종양에사용되지만, 때로드문저분화도의종양에사용되기도한다. 분화도가낮은신경내분비암은임상적으로빠른진행을보이며, 반면분화도가좋은경우의 NETs는훨씬좋은예후를보인다. Mitotic count와 Ki67 labeling index에의해평가하는 proliferative rate은종양의병기에무관하게예후평가의중요한지표가된다. WHO 분류에서는고분화도의위장관췌장 NETs를 proliferative rate에따라 low-grade (G1) 와 intermediate grade (G2) 로분류하고, 그외저분화 NETs 를 high-grade (G3) 신경내분비암으로분류하였다 1 (Table 1). 여기에서는위장관 NETs 치료중내시경적인치료가적용되는경우외, 그리고고분화도의전이성 (metastatic) 위장관 NETs의국소적인치료옵션과함께저분화도의진행성 (advanced) 또는전이성 NETs에서의종양성장억제와호르몬과분비에의한증상억제를위한전신성치료에대해논하 본론 1. Treatment options for non-metastatic gastrointestinal NETs 1) Stomach 위장의 NETs는생물학적인행태와예후에따라다음세가지로분류한다. Type 1: 전체위장 NETs의 70~80% 에이른다. 만성위축성위염과관계가있는데, 이럴경우위장의무산증에의해혈중가스트린농도가상승하게되고, 이에의해위장에서의신경내분비세포의증식과다발성의용종양 NETs 발생을촉진하게된다. 대개이분류의 NETs 는임상적으로느린진행양상을보인다. Type 2: 전체위장 NETs의약 5% 정도로, 역시상승된혈중가스트린농도에의해다발성의용종양 NETs의형태를보인다. 이분류의위장 NETs의기저원인은췌장또는십이지장의가스트린분비종양 (Zollinger-Ellison syndrome) 이고, 역시임상적으로는느린진행양상을보인다. Type 3 : Sporadic carcinoids 위축성위염이나 Zollinger-Ellison syndrome 없이발생하는위장 NETs로, 전체위장 NETs 중약 20% 이며, 위장 NETs 중가장공격적인양상을보인다. 위장의부분또는전절제를시행한환자들중국소전이또는간전이를보이는경우가 65% 에이른다. 산발성의 3형위장 NETs는부분또는전위절제술과함께국소임파절절제술을시행한다. 2 임파절전이의위험성은종 제 4 회 EndoFest Korea 119

2 Table 1. ENETS/WHO Nomenclature and Classification for Neuroendocrine Tumors Differentiation Grade Mitotic count* Ki-67 index Traditional ENETS, WHO Well differentiated Low grade (G1) <2 per 10 HPF <3 percent Carcinoid, islet cell, pancreatic (neuro) endocrine tumor Neuroendocrine tumor, Grade 1 Intermediate grade (G2) 2-20 per 10 HPF 3-20 percent Cacinoid, atypical carcinoid 4, islet cell, pancreatic (neuro) endocrine tumor Neuroendocrine tumor, Grade 2 Poorly differentiated High grade (G3) >20 per 10 HPF >20 percent Small cell carcinoma Neuroendocrine carcinoma Grade 3, small cell Large cell neuroendocrine carcinoma Neuroendocrine carcinoma, Grade 3, large cell ENETS: European Neuroendocrine Tumor Society; WHO: World Health Organization. *Counted in 10 high power fields (HPF). 10 HPF -2 mm 2, at least 40 fields (at400x magnification) evaluated in areas of highest mitotic density. Cut-offs per American Joint Commission on Cancer Staging Manual, 7th edition. Ki-67 index as assessed by MIBI antibody staining: percent positive after count of 2000 cells in area of highest nuclear labeling. Cut-offs per American Joint Commission on Cancer Staging Manual, 7th edition. The term atypical carcinoid only applies to intermediate grade NETs of the lung. Table 2. TNM Staging Carcinoid Tumors of the Stomach Primary tumor (T) TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ/dysplasia (tumor size less than 0.5 mm), confined to mucosa T1 Tumor invades lamina propria or submucosa and 1 cm or less in size T2 Tumor invades muscularis propria or more than 1 cm in size T3 Tumor penetrates subserosa T4 Tumor invades visceral peritoneum (serosal) or other organs or adjacent structures For any T, add (m) for multiple tumors Regional lymph nodes (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis Distant metastases (M) M0 No distant metastasis M1 Distant metastasis Anatomic stage/prognostic groups Stage 0 Tis N0 M0 Stage I T1 N0 M0 Stage IIA T2 N0 M0 Stage IIB T3 N0 M0 Stage IIIA T4 N0 M0 Stage IIIB Any T N1 M0 Stage IV Any T Any N M1 양의크기과침범깊이에따라다르다. 일부에서는상피내의종양이 2 cm 이하이거나, 점막하층에국한된 1cm 이하크기의경우에는내시경적절제술만으로도적당한치료가될수있다고하지만, 3 표준치료방침은아니다. 1형이나 2형의위장 NETs 중 1~2 cm 이하크기의경우는내시경적절제술이적절한치료이다. 4 이런경우제거후에도지속적인가스트린레벨의증가로인해 enterochromaffin-like cells (ECL) 의증식과점막변화가계속될수있으므로 6~12개월간격의내시경추적검사가계속필요하다. 크기가작은경우악성으로의진행이나질병과관련된사망은드물고, 5 2 cm 이하크기의종양중전이는 10% 미만에서발생한다. 6 1형의위장 NETs에서그수가매우많으면서종양의크기가커지는경우유문방절제술 (antrectomy) 이적절한치료가될 120 The Korean Society of Gastrointestinal Endoscopy

3 Table 3. Incidence of Metastases Related to the Size of the Primary Carcinoid Tumor location and size, cm Total patient numbers Nodal metastases, number of patients (percent) Distant metastases, number of patients (percent) Small intestine (12) 2 (5) (70) 16 (19) (85) 28 (47) Appendix (7.5) 2 (4) (33) 4 (12) Colon < (62) 17 (40) Table 4. TNM Staging Carcinoid Tumors of the Small Bowel and Ampulla of Vater Primary tumor (T) TX Primary tumor cannot be assessed T0 No evidence of primary tumor T1 Tumor invades lamina propria or submucosa and size 1 cm or less* (small intestinal tumors); tumor 1 cm or less (ampullary tumors) T2 Tumor invades muscularis propria or size >1 cm (small intestinal tumors); tumor >1 cm (ampullary tumors) T3 Tumor invades through the muscularis propria into subserosal tissue without penetration of overlying serosa (jejunal or ileal tumors) or invades pancreas or retroperitoneum (ampullary or duodenal tumors) or into non-peritonealized tissues T4 Tumor invades visceral peritoneum (serosa) or invades other organs For any T, add (m) for multiple tumors Regional lymph nodes (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis Distant metastases (M) M0 No distant metastasis M1 Distant metastasis Anatomic stage/prognostic groups Stage I T1 N0 M0 Stage IIA T2 N0 M0 Stage IIB T3 N0 M0 Stage IIIA T4 N0 M0 Stage IIIB Any T N1 M0 Stage IV Any T Any N M1 *Tumor limited to ampulla of Vater for ampullary gangliocytic paraganglioma. 수있다. 유문방절제술로써가스트린생성세포가감소하여혈중가스트린농도가감소하고, 대부분의경우에서종양의퇴행을보인다. 4,7 2) Small intestine 대부분의소장 NETs는회장, 특히회맹판의 60 cm 이내에서발견된다. 소장 NETs는크기에상관없이전이의가능성을가지고있다 (Table 3). 전이가없는경우원발부위의소장과장간막을절제해준다. 약 26% 에서다발성의 NETs를보이므로, 수술과동시에절 제하지않는부분도검사하여야한다. 8 아직정확한결론을내리지는못하고있지만, 소장의 NETs가원격전이를보이는경우에도장폐쇄, 출혈, 원발병소로인한복통등의가능성을줄이기위해원발병소에대한수술이권유되기도한다. 예후는병기에따라다르게나타나지만, 보고에따라 5년생존율이 40~85%, 10년생존율이 40~60% 로보고되었다. 9,10 3) Appendix 충수돌기 NETs의예후는크기와밀접한관계가있다. 대부분의 2 cm 이하크기의충수돌기 NETs는진단당시에전이를 제 4 회 EndoFest Korea 121

4 Table 5. TNM Staging of Appendiceal Carcinoid Primary tumor (T)* TX Primary tumor cannot be assessed T0 No evidence of primary tumor T1 Tumor 2 cm or less in greatest dimension T1a Tumor 1 cm or less in greatest dimension T1b Tumor more than 1 cm but not more than 2 cm T2 Tumor more than 2 cm but not more than 4 cm or with extension to the cecum T3 Tumor more than 4 cm or with extension to the ileum T4 Tumor directly invades other adjacent organs or structures, eg, abdominal wall and skeletal muscle Regional lymph nodes (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis Distant metastases (M) M0 No distant metastasis M1 Distant metastasis pn0. Histological examination of a regional lymphadenectomy specimen will ordinarily include 12 or more lymph nodes. If the lymph nodes are negative, but the number ordinarily examined is not met, classify as pn0. Anatomic stage/prognostic groups Stage I T1 N0 M0 Stage II T2, T3 N0 M0 Stage III T4 N0 M0 Any T N1 M0 Stage IV Any T Any N M1 *Tumor that is adherent to other organs or structures, grossly, is classified ct4. However, if no tumor is present in the adhesion, microscopically, the classification should be classified pt1-3 depending on the anatomical depth of wall invasion. Penetration of the mesoappendix does not seem to be as important a prognostic factor as the size of the primary tumor and is not separately categorized. 가지는경우가드물다. 반면, 2 cm 이상크기의약 30% 가진단당시에전이를보이며, 대부분국소임파절전이이다. 충수돌기 NETs의 TNM 병기는다른위장관 NETs와다르게분류된다 (Table 5). 충수돌기 NETs의적절한수술적치료에대해서는다소이견이있다. 대부분의경우다른이유로복부의수술을진행하면서동시에시행하는충수돌기절제술에서우연히발견되기때문에이후우측대장절제술을다시시행해줄것인지결정해야한다. 크기와예후의밀접한연관성으로인해 2 cm 이상큰경우우측대장절제술이시행되어져왔다. 하지만, 크기가 2 cm 보다작은경우에대한근거가부족하여우측대장절제술의시행여부는아직명확하지않다. 크기가 1 cm 이하인경우는일반적으로단순한충수돌기절제술만시행한다. 4) Colon 대장의 NETs는직장의경우보다그임상양상이더공격적인경우가많다. 직장의경우 5년생존율이 88% 인데비해대장은 62% 로보고되었다. 11 대장의 NETs는우측대장에서더흔히관찰되고, 국소적진행을보일때까지는모르는경우가대부분이다. 대장 NETs의 2/3 정도는진단당시에임파절또는 원격전이를가진다고한다. 12 전이가없는대부분의경우는대장의선암과마찬가지로부분대장절제술과함께국소임파절절제술을시행하여야한다. 예후는병기에따라다르게나타난다 (Table 6). 5) Rectum 대부분의직장 NETs는작고, 국소적이며점막또는점막하층에위치하며, 13 내시경초음파검사가진단에유용한도구로사용된다. TNM 병기체계는대장과같다 (Table 6). 점막또는점막하층에국한된 1 cm 이하크기의경우는내시경적절제로치료할수있다. 13,14 병기가 1기인경우거의재발이없고, 13 5 년생존율은 97% 로보고되었다. 15 크기가 1~2 cm인경우의적절한치료방침은아직논란이있다. 16 점막하층에국한된 1~2 cm 크기의종양은 transanal excision 이치료의한가지방법이될수있다. 13 고유근층을침범한경우 (T2) 에서도임파절전이가없다면 transanal excision 으로치료할수있다는보고가있다. 17 이런경우 transanal endoscopic microsurgery (TEM) 가또다른옵션으로이용될수있는데, 제거하기어려운위치에있거나절제단면에서잔존종양이양성인경우도움이된다 The Korean Society of Gastrointestinal Endoscopy

5 Table 6. TNM Staging Carcinoid Tumors of the Colon and Rectum Primary tumor (T) TX Primary tumor cannot be assessed T0 No evidence of primary tumor T1 Tumor invades lamina propria or submucosa and size 2 cm or less T1a Tumor size less than 1 cm in greatest dimension T1b Tumor size 1-2 cm in greatest dimension T2 Tumor invades muscularis propria or size more than 2 cm with invasion of lamina propria or submucosa T3 Tumor invades through the muscularis propria into the subserosa, or into non-peritonealized pericolic or perirectal tissues T4 Tumor invades peritoneum or other organs For any T, add (m) for multiple tumors Regional lymph nodes (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis Distant metastases (M) M0 No distant metastasis M1 Distant metastasis Anatomic stage/prognostic groups Stage 0 Tis N0 M0 Stage I T1 N0 M0 Stage IIA T2 N0 M0 Stage IIB T3 N0 M0 Stage IIIA T4 N0 M0 Stage IIIB Any T N1 M0 Stage IV Any T Any N M1 크기가 2 cm 이상이고, 고유근층또는그너머로침범한경우또는임파절전이가있는경우는 low anterior resection (LAR) 또는 abdominoperineal resection (APR) 을시행한다. APR은일반적으로항문피부선 (anal verge) 에가까운하부의종양인경우시행하게된다. 11 예후는주로종양의크기와침범깊이에따라달라지는데, 9 localized, regional, distant 각각의병태에따른 5년생존율은 90, 49, 26% 로보고되었다 Local treatment options for well-differentiated metastatic gastrointestinal NETs 고분화도의위장관 NETs는일반적으로진행이느린종양이지만, low 또는 intermediate grade의조직학적특성을보이는전이성암의경우에서도환자의생존율은매우다양하게나타난다. 진행성의 NETs에서도생존율은원발병소에따라다양하여, 비교적예후가좋은공장, 회장, 맹장등에서 55-65개월의중앙생존값을보이는반면, 가장예후가나쁜폐, 대장등의원발병소를가지는경우에는 7-17개월의중앙생존값을보인다. 이러한큰차이로인해각각의치료의이점을단순히비교하여평가하기는어렵다. 전이병소를보이는위장관췌장 NETs의증상은대개종양의물리적인크기에의한증상보다는호르몬과분비에의한증상을보이는경우가많다. 특히이러한호르몬과분비에의한증상은기능성의췌장 NETs에서흔하게보인다. 환자들에서세로토닌과같은 vasoactive substances 가전신순환계에들어가게되면카르시노이드증후군을유발하게된다. 기능성 NETs의호르몬과분비에의한증상은옥트레오타이드와같은소마토스타틴유사체로비교적잘조절될수있다. 그러나, 이러한약제로도종양의크기를줄이는것은제한이있다. 전통적으로사용되어오던세포독성제제, 분자생물학적표적치료제등은진행성의위장관 NETs보다는췌장 NETs에서훨씬좋은치료성적을보인다. 진행성의위장관췌장 NETs의대부분은간전이소견을보인다. 절제의가능성이있는환자에서는절제가가장적합한치료옵션이고, 좀더오랫동안증상을조절하고, 종양성장을억제할수있다. 그러나완전절제를시행한경우를포함하여간전이병소절제를시행받은많은환자에서재발을보인다. 절제가불가능한전이병소를가진환자에서증상을조절하기위한치료옵션으로소마토스타틴유사체, 종양의부피를줄이기위한수술, 비수술적인 liver-directed therapy, 전신적인항암 제 4 회 EndoFest Korea 123

6 치료등이있다. 1) Surgical Options (1) Hepatic predominant metastatic disease 1 Resection 간전이병소의절제는, 미만성의양엽침범, 간기능의저하, 간외전이등이없는위장관 NETs 환자에서완치에목적을두고시행해볼수있다. 완전절제를시행받은환자들의장기무병생존율은 20% 에이르는것으로보고되었다. 19,20 간전이병소절제는또오랫동안증상없이지내는것을가능하게해주기도한다. 19,21,22 간전이병소의절제를시행받은전이성 NETs 환자백칠십명의연구에따르면 90% 의환자에서증상의호전을보고하였지만, 전체적인재발률은 84% 였고, 5년과 10년각각의생존율은각각 61, 35% 였다. 2 대상을잘선정하여시행한간전이병소 debulking 수술을받은환자군에서, 비록전체병소를제거하지못하였다고하여도, 수술을받지않았던환자군에비해삶의질호전과더긴생존을보였다는후향성연구에의한보고들이있다. 23,24 하지만, 종양의부피를줄이기위한 debulking 수술이도움이될수있는군은매우한정적이며, 신뢰할만한무작위연구보고도아직없어서, 일반적인경우에서의 debulking 수술의적용은아직의문이다. 2 Management of the primary site in patients with metastases 대부분의악성종양치료와마찬가지로, 넓게퍼져있으면서, 전이병소의완전절제가불가능한경우에원발병소를절제하는것은적절하지못하다. 그러나, 원발병소에의해증상을야기하거나, 또는원발병소와간전이병소모두근치적인절제의가능성이있다면 NETs 환자에서원발병소의절제를고려해볼만하다. 25 소장의 NETs 종양은종종간헐적인장폐쇄와일부에서소장허혈을보일수있다. 장폐쇄와원발병소와관련된복부증상이심할경우에는전이병소가있다하더라도원발병소의절제가고려되어야하지만, 26 무증상의소장원발병소를가진환자에서일률적인원발병소의절제는의문이다. 3 Liver transplantation 간에국한된전이병소를가진환자에서간이식을시행한보고의수는많지않고, 전이성병소를가진 NETs 환자에서의간이식의효과는아직명확하지않다. 27 한다기관연구에서는간이식을시행한환자의 5년생존율이 69% 에이른다고보고하였다. 28 하지만, 간이식을시행받은대부분의환자는결국재발을보였다. 28,29 (2) Solitary brain metastases 고분화도를가진 NETs에서의뇌전이는드물다. 보고가매우적지만, 후향적연구에서전이병소의절제와함께방사선 치료를하여생존을연장시켰다는보고들이있다. 30,31 (3) Valve replacement for carcinoid heart disease 카르시노이드심질환은카르시노이드증후군을가진환자의약 2/3에서나타난다. 거의모든경우에서삼첨판폐쇄부전소견을보이고, 삼첨판협착, 폐동맥판폐쇄부전, 폐동맥판협착등도같이나타날수있다. 이런과정을거쳐우심부전을보이게되면임상적인예후는좋지못하다. 좌심의질환은약 10% 에서보이게되는데, 거의모두심실 right-to-left shunt와연관이있다. 세로토닌이풍부한혈액이폐모세혈관계를거치지못하고바로전신순환계로들어가게되어혈중세로토닌농도가높아지게된다. 전이성 NETs의느린진행과카르시노이드증후군증상에대한효과적인치료로인해, 적절하게선택된환자군에서는판막치환술을통해임상적으로의미있는증상의호전을보인다. 2) Nonsurgical Liver-Directed Therapy (1) Hepatic artery embolization 간동맥색전술은수술의대상이되지못하는간전이성 NETs 환자에서시행할수있는완화성의치료로자주이용된다. Gel foam powder만을이용하는 bland embolization, doxorubicin, cisplatin 등의항암제와같이이용하는 chemoembolization, 방사성동위원소와같이색전하는 radioembolization 등이이용된다. 호르몬분비, 증상의호전, 방사선학적인종양크기감소등의면에서간동맥색전술의치료반응은 50% 를상회하는것으로보고되었다 무작위임상연구보고가없는상황에서세가지색전술모두간전이가있으면서수술적치료의적응이되지않는 NETs 환자에서시도해볼만한치료법이다. 세가지색전술의효용성은비슷할것으로여겨진다. 색전술의방법과무관하게, 치료대상군을잘선정하는것이치료와관련된또병과관련된부작용들을최소화하는데중요하다. 카르시노이드증후군을가진환자에서는색전술시행전카르시노이드 crisis에대한대비가필요하다. 35 (2) RFA and cryoablation 간전이에대한다른치료법으로 radiofrequency ablation (RFA) 과 cryoablation 이있는데, RFA를많이이용한다. 이들치료법들은간전이병소절제나간동맥색전술에비해경피적또는복강경의경로를이용하므로이용하기는좀더편한면이있지만, 상대적으로작은병소에만적용이가능하다. RFA에대한대부분의보고들은적은수의환자들을대상으로한증례연구들 이다. 작은간전이병소를가진환자들, 특히수술의적응이될수있는환자들에서 RFA의치료적인역할은아직분명하지않다. 124 The Korean Society of Gastrointestinal Endoscopy

7 3) Prevention and Management of Carcinoid Crisis 카르시노이드 crisis는종양에대한접촉이나마취에의해유발될수있는, 카르시노이드증후군의치명적인병태이다. 항암치료, 간동맥색전증또는방사성동위원소에의한치료도 입이후로는다소보고가줄어들고있으며, 대개매우큰종양덩어리를가진경우에서발생한다. 카르시노이드 crisis는종양으로부터과량의생물학적활성성분이배출되어발생하는데 (Table 7), 혈역학적불안정성외에도홍조, 설사, 빈맥, 부정 Table 7. Produccts of Carcinoid Tumors Amines Serotonin, 5-Hydroxytryptophan, Norepinephrine, Dopamine, Histamine Polypeptides Kallikrein, Pancreatic polypeptide, Bradykinin, Motilin, Somatostatin, Vasoactive intestinal peptide, Neuropeptide K, Substance P, Neurokinin A, Neurokinin B, Corticotropin (ACTH), Gastrin, Growth hormone, Peptide YY, Glucagon, Beta-endorphin, Neurotensin, Chromogranin A Prostaglandins Table 8. Efficacy of Somatostatin Analogs and Interferon-alpha in Advanced Neuroendocrine Tumors Agent(s) Patients N Biochemical response rate, percent Tumor response rate, percent Author, year Somatostatin analogs Octreotide kvols, L; kvols, L; Oberg, K; NR 0 Salts, L; Janson, E; NR 0 Amold, R; Dibartolomeo, M; 1996 Lanreotide Eriksson, B; Ruszniewski, P;1996 Lanreotide-SR 18 NR 0 Tomassetti, P; 1998 Interferon-alpha IFN-alfa Moertel, C; Hanssen, C; Oberg, K; Creutzfeldt, W; Oberg, K; Schober, C; Joensuu, H; Biesma, B; Janson, E; Bajetta, E; DiBartolomeo, M; Doberauer, C; 1987 Somatostatin analogs plus interferon-alpha Uncontrolled series Janson, E; Frank, M; 1999 Randomized studies Lanreotide 27 NR 4 Faiss, S; 2003 INF 28 NR 3.7 Lanreotide+IFN-alfa 29 NR 7.1 NR, not reported. 제 4 회 EndoFest Korea 125

8 맥, 기관지경련, 의식의혼탁등이포함된다. 수술적처치중에는필요할경우빨리옥트레오타이드를사용할수있도록준비해두고, 술전에 300 mg의옥트레오타이드를피하주사함으로써카르시노이드 crisis의빈도를낮출수있다. 카르시노이드 crisis의치료는수술중의다른급성저혈압에대한치료와달라서, 칼슘이나카테콜아민등의주사는종양덩어리로부터매개체의분비를야기하여상황을악화시킬수있다. 카르시노이드 crisis가일어났을경우에는플라즈마보충또는옥트레오타이드 300 mg을즉시정주하여야한다. 이후추가적인옥트레오타이드의지속적인정맥주입이필요할수도있다. 카르시노이드 crisis의위험성이높은환자에서는술전에미리옥트레오타이드지속주입을시작할수있다. 3. Systemic therapy options to control tumor growth and symptoms of hormone hypersecretion 1) SOMATOSTATIN ANALOGS 전술한바와같이전이성의위장관 NETs 환자의증상은대개종양덩어리자체보다는종양에서과분비되는호르몬에의해발생한다. 카르시노이드증후군은세로토닌과같은 vasoactive substances 가전신순환혈류계에들어감으로써발생하게된다. (1) Octreotide and other somatostatin analogs 소마토스타틴은 14개의아미노산으로구성된펩타이드로, 다양한호르몬들의분비를광범위하게저해한다. 소마토스타틴은대부분의 NETs에서표현되는소마토스타틴수용체에부착하여작용한다. 39 소마토스타틴수용체의여부는소마토스타틴유사체인옥트레오타이드에방사성동위원소를표지하여이용하는검사로알수있다. 옥트레오타이드와같은소마토스타틴유사체는 NETs, VIPoma, glucagonoma 등에서발생하는다양한증상을조절하는데매우효과적이다 (Table 8). 증상을보이는환자들에서처음의치료는대개짧은작용시간을가지는제제를먼저시작하여빠른시간안에작용시간이긴제제로바꾸어주고, 증상을조절하는데적당한용량으로조절하여준다. 약물이긴시간에걸쳐천천히작용하는 depot 형태를이용하게되면매일주사를맞아야하는번거로움을피할수있다. 대개짧은기간동안작용시간이짧은제제를먼저시작하여본후, 20 mg을월 1회근육주사하는것으로치료를시작하며, 적절한증상조절을위한용량으로점차올리게된다. 40 돌발적으로발생하는증상의조절을위해짧은작용시간을가지는제제를추가적으로사용할수있다. 옥트레오타이드는비교적환자의순응도가좋으며부작용은대개심하지않다. 41,42 1/3 정도의환자에서치료첫주에약한정도의오심, 복부불편감, 팽만감, 무른변, 지방흡수부전등 을보일수있지만, 대개그시기가지나면사라진다. 췌장효소제제를사용하여췌장기능부전으로인한증상을없앨수있다. 일시적인인슐린분비저해로약한정도의내당능저하를보일수있다. 옥트레오타이드는식후의담낭수축을떨어뜨려담낭이완전히비워지는것을늦춘다. 약 25% 의환자에서치료 18개월안에무증상의담석을보인다. 42 (2) 무증상환자에서의옥트레오타이드사용병의진행이느린경우환자의증상이없다면, 소마토스타틴유사체치료를시작할적절한시기를정하는것은아직분명하지않다. 소마토스타틴유사체치료가비기능적인위장관췌장 NETs 환자에서 progression-free survival 기간을증가시킬수있는가에대한무작위연구들이진행중이다. 2) Interferon Interferon α (IFNa) 는과거수십년간진행성의 NETs 치료에사용되어져왔다. IFNa는 T-cell 기능촉진, 종양산물의분비조절등의효과로인해카르시노이드증후군환자에게초치료로사용되었다. 43 IFNa는 T-cell 기능촉진, 세포주기의정지유도, 혈관신생저해등을통해항종양효과를나타낼수있다. 44 대규모의후향적연구에서저용량의 IFNa 단독치료를통해위장관췌장 NETs 환자의 40~50% 에서호르몬과분비로인한증상의호전을보였고, 20~40% 에서종양의안정화가유도되었다. 종양의크기감소를보인경우는 15% 이하로흔하지않았다. 43,45 (Table 8) 임상보고들에서사용된 IFNa은 3~9 백만단위를피하주사로사용하였고, 주 3~7회주사하였다. IFNa는어느정도의골수억제를보이므로, 대개백혈구수를 3000 /ml 정도로맞추도록개별적으로용량을조절하도록한다. IFNa의부작용에는피로, 우울증, 골수억제, 갑상선기능의변화등이있는데, 이들부작용때문에전이성 NETs의치료에좀더폭넓게이용되지못하고있다. 46 현재로서는소마토스타틴유사체를이용한치료에도불구하고병이진행하거나, 증상의악화를보이는진행성 NETs에서 IFNa 치료가많이시도되어진다. 3) Cytotoxic Chemotherapy (1) 위장관 NETs 췌장 NETs와다르게진행성의위장관 NETs에서의화학요법에대한반응은분명하지않다. 5-fluorouracil (5-FU), streptozocin, doxorubicin의단독화학요법은전이성의위장관 NETs에서높지않은반응률을보였다. 47 Capecitabine (1000 mg/m2 twice daily for 14 days, every three weeks) 단독요법을이용한 2상임상에서는 19명의 NETs 환자 ( 위장관 12명, 난소 1명, 모름 6명 ) 중 13명에서 stable disease를보였으며, 이중 4명에서는 12개월이상 stable disease 를보였다. 126 The Korean Society of Gastrointestinal Endoscopy

9 Table 9. Selected Chemotherapy Trials in Metastatic Carcinoid Tumors Phase II trials Regimen Number of patients* Tumor response Median overall rate, percent survival, months Reference Dacarbazine Bukowski, R; 1994 Dacarbazine (second-line) Sun, W; 2005 Etoposide NR Kelsen, D; 1987 Paclitaxel Ansell, S; 2001 Docetaxel Kulke, M; 2004 Gemcitabine Kulke, M; 2004 Streptozocin + fluorouracil + doxorubicin + cyclophosphamide Bukowski, R; 1994 Streptozocin + fluorouracil + cyclophosphamide 9 22 Streptozocin + fluorouracil + cisplatin Tumer, N; 2010 Temozolomide + thalidomide 15 7 NR Kulke, M; 2006 Gemcitabine + oxaliplatin 18 (previously treated ) Cassier, P; 2009 Randomized trials Regimen Number of patients* Tumor response Median overall rate, percent survival, months Reference Streptozocin + cyclophosphamide VS * 12.5 Moertel, C; 1979 Streptozocin + fluorouracil 42 33* 11.2 Doxorubicin VS Engstrom, p; 1984 Streptozocin + fluorouracil Doxorubicin + flurouracil VS Sun, W; 2005 Streptozocin + fluorouracil (p=0.03) NR, not reported. *Response rates included both radiographic tumor regression and reduction urinary 5-HIAA levels. Patients also received granulocyte-colony-stimulating factor. Indludes patients with carcinoid (n=14), pancreatic islet cell (n=9) and anaplastic (n=1) neuroendocrine tumors. Indludes patients with carcinoid (n=9), pancreatic islet cell (n=7) and pheochromoctyoma (n=2) neuroendocrine tumors. Response rates is for non-pancreatic neuroendocrine tumors in a combined series with 47 pancreatic nueroendocrine tumors. Median survival is for the entire group. Includes patients with well differntiated neuroendocrine carcinoma, not otherwise specified. Taxanes, topotecan, gemcitabine 같은항암제들은단독요법에서반응률이낮았다 Streptozocin combinations (Table 9) 췌장을제외한진행성 NETs 환자에서 streptozocin 을포함한화학요법에대한반응률은높지않고, 또한동반되는독성들때문에드물게이용되고있다. 2 Dacarbazine and temozolomide 전이성 NETs 환자 56명에게 dacarbazine 을단독투여한 SWOG 연구에서전체적인반응률은 16% 를보인반면, 88% 의환자에서오심, 구토의부작용을보고하였다. 49 Streptozocin/5-FU 또는 doxorubicin/5-fu 치료에이은 second-line으로 dacarbazine 을단독투여한다른연구에서도반응률은 8% 에불과하였다. 50 Temozolomide를포함한화학요법을 44명의 NETs 환자를대상으로시행한연구에서반응률은단 2% 에그쳤다. 이연구에포함된대부분의대상환자는위장관 NETs 환자였다. 3 Oxaliplatin-based regimens Oxaliplatin 을포함한화학요법의예비보고에서항암효과가 일부있을것으로보고하였으나, 대상군의수가매우적었다. 11 명의진행성 NETs 환자를대상으로 FOLFOX + bevacizumab 을사용한 2상임상연구의예비보고에서 5명의환자에서반응을보였는데, 1명에서 partial response 를, 4명에서 stable disease 를보였다. 51 진행성 NETs 환자 31명을대상으로 capecitabine, oxaliplatin, bevacizumab 을투여한또다른 2상임상연구의예비보고에서 23% 의 partial response, 71% 의 stable disease 반응을보였다. 52 이조합의화학요법이 NETs에대한반응을나타내었지만, 결론을도출하기에는데이터가너무제한적이다. (2) Poorly differentiated tumors 저분화위장관췌장 NETs는좀더전형적인고분화종양에비해세포독성항암치료의반응률이좀더높은것으로생각되고있다. 플래티늄제제를포함한화학요법이저분화 NETs에비교적반응을보인다. 흔히소세포폐암에사용되는 cisplatin+etoposide 조합은저분화암과같은것으로추정하는 anaplastic NETs 환자 18 제 4 회 EndoFest Korea 127

10 Table 10. Nonrandomized Trials of Novel Targeted Therapies in Neuroendocrine Tumors Agent Molecular target(s) Patients* Tumor type Objective tumor response rate, percent Median TTP or PFS Reference VEGF pathway inhibitors Bevacizumab VEGF 22 Carcinoid weeks Yao J; 2008 Sunitinib VEGFR-1,-2,-3; PDGFR-α,-β; KIT; 41 Carcinoid months (TTP) Kulke M; 2008 RET; CSF-1F; FLT3 66 Pancreatic NET months (TTP) Sorafenib VEGFR-2, PDGFR, FGFR-1, BRAF 50 Carcinoid months Hobday T; Pancreatic NET months Pazopanib VEGFR-1,-2,-3; PDGFR-α,-β; KIT 22 Carcinoid months Phan AT; Pancreatic NET months mtor inhibitors Everolimus mtor 115 Pancreatic NET months Yao J; 2008 Everolimus mtor 30 Carcinoid weeks Yao J; Pancreatic NET weeks Everolimus mtor 115 Carcinoid months Yao J; Pancreatic NET months Everolimus mtor 21 Carcinoid months Duran I; Pancreatic NET months CSF-1R, colony-stimulating factor receptor; EGFR, epidermal growth factor receptor; KIT, stem cell factor receptor; mtor, mammalian target of rapamycin; PDGFR, platelet-derived growth factor receptor; RET, rearranged during transfection or glial cell-line derived neurotrophic factor; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor; NET, neuroendocrine tumor; PFS, progession-free survival; TTP, time to tumor progression; NR, not reported. *Number of patients evaluable for efficacy endpoints. Patients also received treatment with octreotide. Confirmed. After failure of octreotide. Concurrent with octreotide. Table 11. Randomized Trials of Novel Agents in Advanced Neuroendocrine Tumors Agent Carcinoid tumor Everolimus + Octreotide LAR versus Placebo + Octreotide LAR Octreotide + Bevacizumab versus Octreotide + Placebo Pancreatic neuroendocrine tumor Sunitinib versus Placebo Everolimus versus Placebo Everolimus versus Everolimus + Bevacizumab Number of patients* NR, not reported; PFS, progression-free survaivla; TTP, time to progression. Tumor response rate (percent) 2 Median TTP or PFS, months SWOG S0518/North American Intergroup, ongoing CALGB 80701, ongoing Reference Pavel et al Raymond et al Yao et al. 2001(RADIANT-3) 명에서 67% 의반응률을보였지만, 고분화종양환자군에서는거의효과를보이지않았다. 53 진행성 NETs 환자 36명을대상 으로한후속연구에서 cisplatin+etoposide 조합은 36% 의반응률과 19개월의중앙생존값을보였다. 54 이연구에서도대상 128 The Korean Society of Gastrointestinal Endoscopy

11 군모두는저분화암이거나임상적으로빠른진행을보이는환자들이었다. 같은조합의화학요법을이용한다른후향적연구에서도 41명의저분화 NETs 환자군에서는 42% 의반응률, 15 개월의중앙생존값을보였지만, 11명의고분화 NETs 환자군에서는단지 1명만반응을보였다. 4) Molecularly Targeted Therapy 많은연구들에서 vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), platelet-derived growth factor (PDGF), PDGF receptor (PDGFR), stem cell factor receptor (KIT) 등을포함한다양한 cellular growth factor 들과그수용체의표현이위장관췌장 NETs에서증가되어있음을보고하였다. 이들수용체들중많은경우가 tyrosine kinases (TKs) 로기능한다. 전임상시험에서이들 signaling pathway들의차단이신경내분비세포의성장을저해하였다. 이러한점에근거하여 sunitinib, sorafenib, pazopanib과같은 small molecule TK inhibitor들과 anti-vegf MoAb bevacizumab과같은 growth factor signaling을타깃으로하는 monoclonal antibodies (MoAbs) 를이용하여진행성 NETs를대상으로한많은임상시험이이루어졌다. Mammalian Target of Rapamycin (mtor) 은 VEGF와 IGF signaling pathways 를포함하는, 신경내분비종양의성장에관계하는많은경로들의 downstream signaling 을중개하는 threonine kinase이다. 55 또한, mtor는 hypoxia inducible factor의생성조절을통하여 angiogenesis를조절한다. 세포독성항암치료에서처럼이들제제들도위장관 NETs보다췌장 NETs에서좀더효과가좋은것으로나타났다.(Table 10) 아래의기술들은췌장 NETs의성적 (Table 10, 11에포함 ) 을제외한부분에서의성적이다. (1) Small molecule TK inhibitors Sunitinib, sorafenib, pazopanib을이용한진행성의 NETs 대상군의 2상임상연구들에서 stable disease 반응을보이는경우가많았고, PFS가늘어날가능성을보였으나, 치료에대한반응률은낮았다 (Table 10). 무작위연구가없는상태에서진행성 NETs 에대한 TK inhibitors 의역할은아직분명하지않다. (2) Everolimus 다양한연구들의결과를보면 everolimus는진행성의 NETs 에일정정도의치료효과를가지는것으로보이지만, 구내염 (62%), 발진 (37%), 피로 (31%), 설사 (27%) 등의부작용도많았다 (Table 11). 56 Everolimus는카르시노이드증상을보이는진행성의질환을가진환자가옥트레오타이드를이용한증상의조절에실패한경우, 부작용을받아들인다면, PFS의증가를위해시도해볼수있는치료옵션이다. (3) Bevacizumab 진행성또는전이성의 NETs 환자를대상으로 bevacizumab 을이용하여시행한 2상임상연구에서옥트레오타이드 +IFNa 을사용한군에서보인 68% 의 progression-free rate에비해옥트레오타이드 +bevacizumab을사용한군에서는 95% 의 progression-free rate을보였다. 57 이연구결과에근거해진행성의 NETs을대상으로 SWOG에서대규모의무작위연구를진행중이다. 58 결론 신경내분비종양은인체의전체에걸쳐다양한장소에퍼져서발생할수있고, 다양한조직학적형태를보이며, 이에따른병의임상경과도다양하여, 일률적인치료의적용이어렵다. 또한신경내분비종양중에서도위장관의 NETs과췌장 NETs 는같은치료에대한반응도다르게나타나는경우가많고, 분화도에따른치료의반응도다르게나타날수있다. 따라서, 각각의환자에따른철저한개별적인치료가적용되어야할것으로생각된다. 과거의전통적인치료에비해, 최근많이연구되고있거나이미결과가나온다양한분자생물학적표적치료제의도입으로신경내분비종양의치료성적은과거에비해매우발전할것이다. 향후적절한치료옵션은계속변해가면서점점발전할것으로생각된다. 따라서계속적인치료옵션에대한업데이트를통해적절한치료옵션을이용하여환자개개인에맞는최적의치료성적을얻을수있도록노력해야하겠다. 참고문헌 1. Rindi G, Arnold R, Bosman FT, et al. Nomenclature and classification of neuroendocrine neoplasms of the digestive system. In: WHO Classification of Tumours of the Digestive System, 4th ed, Bosman TF, Carneiro F, Hruban RH, Theise ND. eds. International Agency for Research on cancer (IARC), Lyon p Plöckinger U, Rindi G, Arnold R, et al. Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumours. A consensus statement on behalf of the European Neuroendocrine Tumour Society (ENETS). Neuroendocrinology 2004;80: Saund MS, Al Natour RH, Sharma AM, et al. Tumor size and depth predict rate of lymph node metastasis and utilization of lymph node sampling in surgically managed gastric carcinoids. Ann Surg Oncol 2011;18: Borch K, Ahrén B, Ahlman H, et al. Gastric carcinoids: biologic behavior and prognosis after differentiated treatment in relation to type. Ann Surg 2005;242:64. 제 4 회 EndoFest Korea 129

12 5. Schindl M, Kaserer K, Niederle B. Treatment of gastric neuroendocrine tumors: the necessity of a type-adapted treatment. Arch Surg 2001;136: Soga J. Early-stage carcinoids of the gastrointestinal tract: an analysis of 1914 reported cases. Cancer 2005;103: Ozao-Choy J, Buch K, Strauchen JA, et al. Laparoscopic antrectomy for the treatment of type I gastric carcinoid tumors. J Surg Res 2010;162: Yantiss RK, Odze RD, Farraye FA, Rosenberg AE. Solitary versus multiple carcinoid tumors of the ileum: a clinical and pathologic review of 68 cases. Am J Surg Pathol 2003;27: Jann H, Roll S, Couvelard A, et al. Neuroendocrine tumors of midgut and hindgut origin: tumor-node-metastasis classification determines clinical outcome. Cancer 2011;117: Landerholm K, Zar N, Andersson RE, et al. Survival and prognostic factors in patients with small bowel carcinoid tumour. Br J Surg 2011;98: Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer 2003;97: Ballantyne GH, Savoca PE, Flannery JT, et al. Incidence and mortality of carcinoids of the colon. Data from the Connecticut Tumor Registry. Cancer 1992;69: Kwaan MR, Goldberg JE, Bleday R. Rectal carcinoid tumors: review of results after endoscopic and surgical therapy. Arch Surg 2008;143: Mani S, Modlin IM, Ballantyne G, et al. Carcinoids of the rectum. J Am Coll Surg 1994;179: Landry CS, Brock G, Scoggins CR, et al. A proposed staging system for rectal carcinoid tumors based on an analysis of 4701 patients. Surgery 2008;144: Naunheim KS, Zeitels J, Kaplan EL, et al. Rectal carcinoid tumors--treatment and prognosis. Surgery 1983;94: Schindl M, Niederle B, Häfner M, et al. Stage-dependent therapy of rectal carcinoid tumors. World J Surg 1998;22: Tsai BM, Finne CO, Nordenstam JF, et al. Transanal endoscopic microsurgery resection of rectal tumors: outcomes and recommendations. Dis Colon Rectum 2010;53: Sarmiento JM, Heywood G, Rubin J, et al. Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival. J Am Coll Surg 2003;197: Cho CS, Labow DM, Tang L, et al. Histologic grade is correlated with outcome after resection of hepatic neuroendocrine neoplasms. Cancer 2008;113: Dousset B, Saint-Marc O, Pitre J, et al. Metastatic endocrine tumors: medical treatment, surgical resection, or liver transplantation. World J Surg 1996;20: Mayo SC, de Jong MC, Pulitano C, et al. Surgical management of hepatic neuroendocrine tumor metastasis: results from an international multi-institutional analysis. Ann Surg Oncol 2010; 17: Landry CS, Scoggins CR, McMasters KM, Martin RC 2nd. Management of hepatic metastasis of gastrointestinal carcinoid tumors. J Surg Oncol 2008;97: Givi B, Pommier SJ, Thompson AK, et al. Operative resection of primary carcinoid neoplasms in patients with liver metastases yields significantly better survival. Surgery 2006;140: National Comprehensive Cancer Network (NCCN) guidelines. Available at: (Accessed on October 13, 2011). 26. Gulec SA, Mountcastle TS, Frey D, et al. Cytoreductive surgery in patients with advanced-stage carcinoid tumors. Am Surg 2002;68: Olausson M, Friman S, Herlenius G, et al. Orthotopic liver or multivisceral transplantation as treatment of metastatic neuroendocrine tumors. Liver Transpl 2007;13: Le Treut YP, Delpero JR, Dousset B, et al. Results of liver transplantation in the treatment of metastatic neuroendocrine tumors. A 31-case French multicentric report. Ann Surg 1997; 225: Florman S, Toure B, Kim L, et al. Liver transplantation for neuroendocrine tumors. J Gastrointest Surg 2004;8: Hlatky R, Suki D, Sawaya R. Carcinoid metastasis to the brain. Cancer 2004;101: Maiuri F, Cappabianca P, Del Basso De Caro M, Esposito F. Single brain metastases of carcinoid tumors. J Neurooncol 2004;66: Swärd C, Johanson V, Nieveen van Dijkum E, et al. Prolonged survival after hepatic artery embolization in patients with midgut carcinoid syndrome. Br J Surg 2009;96: Christante D, Pommier S, Givi B, Pommier R. Hepatic artery chemoinfusion with chemoembolization for neuroendocrine cancer with progressive hepatic metastases despite octreotide therapy. Surgery 2008;144: Gaur SK, Friese JL, Sadow CA, et al. Hepatic arterial chemoembolization using drug-eluting beads in gastrointestinal neuroendocrine tumor metastatic to the liver. Cardiovasc Intervent Radiol 2011;34: Gates J, Hartnell GG, Stuart KE, Clouse ME. Chemoembolization of hepatic neoplasms: safety, complications, and when to worry. Radiographics 1999;19: Gillams A, Cassoni A, Conway G, Lees W. Radiofrequency ablation of neuroendocrine liver metastases: the Middlesex experience. Abdom Imaging 2005;30: Hellman P, Ladjevardi S, Skogseid B, et al. Radiofrequency tissue ablation using cooled tip for liver metastases of endocrine tumors. World J Surg 2002;26: Mazzaglia PJ, Berber E, Siperstein AE. Radiofrequency thermal ablation of metastatic neuroendocrine tumors in the liver. Curr Treat Options Oncol 2007;8: Reubi JC, Kvols LK, Waser B, et al. Detection of somatostatin receptors in surgical and percutaneous needle biopsy samples of carcinoids and islet cell carcinomas. Cancer Res 1990; 50: Rubin J, Ajani J, Schirmer W, et al. Octreotide acetate long-acting formulation versus open-label subcutaneous octreotide acetate in malignant carcinoid syndrome. J Clin Oncol 1999; 17: Lamberts SW, van der Lely AJ, de Herder WW, Hofland LJ. Octreotide. N Engl J Med 1996;334: Newman CB, Melmed S, Snyder PJ, et al. Safety and efficacy of long-term octreotide therapy of acromegaly: results of a 130 The Korean Society of Gastrointestinal Endoscopy

13 multicenter trial in 103 patients--a clinical research center study. J Clin Endocrinol Metab 1995;80: Oberg K, Funa K, Alm G. Effects of leukocyte interferon on clinical symptoms and hormone levels in patients with mid-gut carcinoid tumors and carcinoid syndrome. N Engl J Med 1983;309: Detjen KM, Welzel M, Farwig K, et al. Molecular mechanism of interferon alfa-mediated growth inhibition in human neuroendocrine tumor cells. Gastroenterology 2000;118: di Bartolomeo M, Bajetta E, Buzzoni R, et al. Clinical efficacy of octreotide in the treatment of metastatic neuroendocrine tumors. A study by the Italian Trials in Medical Oncology Group. Cancer 1996;77: Välimäki M, Järvinen H, Salmela P, et al. Is the treatment of metastatic carcinoid tumor with interferon not as successful as suggested? Cancer 1991;67: Bergsland EK, Ko AH, Tempero M, et al. Phase II trial of FOLFOX plus bevacizumab in advanced, progressive neuroendocrine tumors (abstract 216). Data presented at the 2008 ASCO Gastrointestinal Cancers Symposium, Orlando, FL, January 25-27, 2008, Abstracts?&vmview=abst_detail_view&confID=53&abstractID =10380 (Accessed on February 10, 2011). 48. Kunz PL, Kuo T, Zahn JM, et al. A phase II study of capecitabine, oxaliplatin, and bevacizumab for metastatic or unresectable neuroendocrine tumors (abstract 4104). J Clin Oncol 2010;28:326s. Abstract available online at asco.org/ascov2/meetings/abstracts?&vmview=abst_detail_view&confid=74&abstractid=54381 (Accessed on February 10, 2011). 49.Kulke MH, Mayer RJ. Carcinoid tumors. N Engl J Med 1999; 340: Kulke MH, Kim H, Stuart K, et al. A phase II study of docetaxel in patients with metastatic carcinoid tumors. Cancer Invest 2004;22: Bukowski RM, Tangen CM, Peterson RF, et al. Phase II trial of dimethyltriazenoimidazole carboxamide in patients with metastatic carcinoid. A Southwest Oncology Group study. Cancer 1994;73: Sun W, Lipsitz S, Catalano P, et al. Phase II/III study of doxorubicin with fluorouracil compared with streptozocin with fluorouracil or dacarbazine in the treatment of advanced carcinoid tumors: Eastern Cooperative Oncology Group Study E1281. J Clin Oncol 2005;23: Moertel CG, Kvols LK, O'Connell MJ, Rubin J. Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin. Evidence of major therapeutic activity in the anaplastic variants of these neoplasms. Cancer 1991;68: Fjällskog ML, Granberg DP, Welin SL, et al. Treatment with cisplatin and etoposide in patients with neuroendocrine tumors. Cancer 2001;92: Missiaglia E, Dalai I, Barbi S, et al. Pancreatic endocrine tumors: expression profiling evidences a role for AKT-mTOR pathway. J Clin Oncol 2010;28: Pavel, M, Hainsworth, JD, Baudin, E, et al.a randomized, double-blind, placebo-controlled, multicenter phase III trial of everolimus + octreotide LAR VS placebo + Octreotide LAR in patients with advanced neuroendocrine tumors (NET) (Radiant-2) (abstract LBA8). Data presented at the 35th ESMO Congress, Milan Italy, October 5-12, Abstract available online at NP.full.pdf+html (Accessed on October 22, 2010). 57. Yao JC, Phan A, Hoff PM, et al. Targeting vascular endothelial growth factor in advanced carcinoid tumor: a random assignment phase II study of depot octreotide with bevacizumab and pegylated interferon alpha-2b. J Clin Oncol 2008;26: Trial information available online at gov/ct2/show/nct ?term=carcinoid+and+bevacizumab&rank=6 (Accessed on February 11, 2011). 제 4 회 EndoFest Korea 131

김범수

김범수 Analysis of Outcomes after Resection of Sarcomatous Hepatocellular Carcinoma Purpose: Sarcomatous hepatocellular carcinoma (HCC) is rare. Therefore, the clinicopathologic characteristics and prognosis

More information

( )Jkstro011.hwp

( )Jkstro011.hwp 비인강암의방사선치료결과및생존율에관한예후인자분석 2005 2 1 2005 3 28. :, Tel: 053)250-7665, Fax: 053)250-7984 E-mail: jhkim@dsmc.or.kr 정영연외 2 인 : 비인강암의예후인자분석 정영연외 2 인 : 비인강암의예후인자분석 Carcinoma of the nasopharynx treated by radiotherapy

More information

황지웅

황지웅 Comparison of Laparoscopy and Exploration in the Distal Pancreatectomy BACKGROUND: To determine the benefits of laparoscopic surgery compared with exploration, the clinical outcomes of open and laparoscopic

More information

레이아웃 1

레이아웃 1 대한위장관기질종양연구회 01 GIST 06 02 11 03 Imatinib 14 04 05 06 07 Sunitinib 32 40 44 48 GIST 6 01 7 GIST Guide book GIST 8 01 9 GIST Guide book GIST (CT) MRI FDG-PET 10 02 11 GIST Guide book 12 02 (Imatinib)

More information

untitled

untitled Systemic Treatment of Pancreatic Neuroendocrine Tumors 장흥문 울산대학교의과대학서울아산병원종양내과학교실 췌장에생기는신경내분비종양 (pancreatic neuroendocrine tumor: PNET) 은매우드문종양으로주로췌장의 islets of Langerhans 에서발생하므로 islet cell tumor라고도부른다.

More information

기관고유연구사업결과보고

기관고유연구사업결과보고 기관고유연구사업결과보고 작성요령 2001 ~ 2004 2005 ~ 2007 2008 ~ 2010 2001 ~ 2004 2005 ~ 2007 2008 ~ 2010 1 2/3 2 1 0 2 3 52 0 31 83 12 6 3 21 593 404 304 1,301 4 3 1 8 159 191 116 466 6 11 (`1: (1: 16 33 44 106

More information

내시경 conference

내시경 conference 부울경소화기내시경학회 6월집담회 고신대학교복음병원소화기내과전임의서광일 F/63 CASE C.C) epigastric pain for 2 wks P. I) 2014.04.16 EGD at LMC adm via OPD for further evaluation. P. Hx) CASE HTN/DM/Hepatitis/Tbc (+/+/-/-) S. Hx) N-S ROS)

More information

연하곤란

연하곤란 2015.03.04 부울경소화기내시경지회 Intramucosal gastric cancer: The rate of lymph node metastasis in signet ring cell carcinoma was as low as that in welldifferentiated adenocarcinoma 인제대부산백병원 소화기내과 지삼룡 Signet ring

More information

노영남

노영남 Purpose: Delayed massive hemorrhages from pseudoaneurysm rupture of the peripancreatic large arteries, after pancreaticoduodenectomy, are fatal. We reviewed the clinical course and outcome of bleeding

More information

120304강신용

120304강신용 Clinical Features and Prognostic Factors Influencing Long-term Survival in pt2 Gallbladder Carcinoma Patients Purpose: The prognosis of gallbladder carcinoma is unfavorable, and the depth of invasion,

More information

Minimally invasive parathyroidectomy

Minimally invasive parathyroidectomy 2013. 2. 2 대한간암연구학회 7차 심포지움 및 학술대회 Indication and Clinical Outcomes of Metachronous HCC Metastasectomy Shin Hwang Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan

More information

Very low-risk Low-risk Intermediate-risk High-risk Appendiceal mucinous tumours Mucinous adenoma Mucinou

Very low-risk Low-risk Intermediate-risk High-risk Appendiceal mucinous tumours Mucinous adenoma Mucinou I. Workshop 결과에대한설문조사결과 A. 종양의행태 (behavior) 코드부여에이견이있는소화기계암에대한설문조사결과 Organ or Subject Stomach Colon Diagnosis 응답자수 ( 총 240 명 ) Low grade adenoma/dysplasia 230 10 0 1 2 3 6 무응답 High grade adenoma/dysplasia

More information

Kjhps016( ).hwp

Kjhps016( ).hwp Surgical Extent and Types in Pancreatic Cancer Song Cheol Kim, M.D. Department of Surgery, Ulsan University College of Medicine & Asan Medical Center, Seoul, Korea Pancreatic cancer continues to pose a

More information

A 617

A 617 Special Issue Diabetic Retinopathy Won Ki Lee, M.D. Department of Ophthalmology The Catholic University of Korea College of Medicine Kangnam St. Mary s Hospital E mail : wklee@catholic.ac.kr Abstract R

More information

Jkbcs016(92-97).hwp

Jkbcs016(92-97).hwp Expression of bcl-2 and Apoptosis and Its Relationship to Clinicopathological Prognostic Factors in Breast Cancer - A Study with Long Term Follow-up correlated with the survival rate.(journal of Korean

More information

Jkbcs032.hwp

Jkbcs032.hwp Clinical Correlation of HER-2/neu Overexpression in Patients with Breast Cancer Sung Yong Kim, Tae Yoon Kim, Jae Jun Kim, Chang Ho Kim, Ok Pyung Song, Min Hyuk Lee, Eui Han Kim 1, and Moo Sik Cho Departments

More information

<B0E6C8F1B4EBB3BBB0FA20C0D3BBF3B0ADC1C E687770>

<B0E6C8F1B4EBB3BBB0FA20C0D3BBF3B0ADC1C E687770> 2012 개원의와함께하는임상강좌 경희대학교의과대학종양혈액내과학교실 백선경 한국인사망원인 평균수명까지생존시암발생확률 길라잡이 : 개정된가이드라인을중심으로 History of anti-cancer chemotherapy Chabner BA & Roberts TG Jr. Nat Rev 2005 Use standard therapies 2012 개원의와함께하는임상강좌

More information

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee University College of Medicine & Hospital E mail : ycell2@yahoo.co.kr Abstract

More information

Kaes010.hwp

Kaes010.hwp 갑상선자극호르몬이갑상선암세포의 VEGF, 신생혈관형성, 성장, 침윤및전이에미치는영향 Effects of TSH on the Production of VEGF, Angiogenesis, Growth, Invasion and Metastasis in Thyroid Cancer Cells Euy Young Soh, M.D., Hee Boong Park, M.D.,

More information

EndoFest Korea(제4회)-편집.hwp

EndoFest Korea(제4회)-편집.hwp B-II. Intestinal Neuroendocrine Tumors: A to Z Room B 대장신경내분비종양의위험도평가와전략적인접근 국립암센터 Risk Stratification and Strategic Approach for Colorectal Neuroendocrine Tumor Byung Chang Kim National Cancer Center,

More information

02 KJG (조창민)-124.hwp

02 KJG (조창민)-124.hwp Korean J Gastroenterol Vol. 73 No. 3, 124-131 https://doi.org/10.4166/kjg.2019.73.3.124 pissn 1598-9992 eissn 2233-6869 REVIEW ARTICLE 진행성췌장신경내분비종양치료의최신지견 조창민 1,2 경북대학교의과대학내과학교실 1, 칠곡경북대학교병원담도췌장암센터 2 Recent

More information

김범수

김범수 Gastrointestinal stromal tumors (GISTs) are rare tumers of the alimentary tract, and these tumors arise from primitive mesenchymal cells. Duodenal GISTs comprise 4-5% of all GISTs. In this article, we

More information

May 10~ Hotel Inter-Burgo Exco, Daegu Plenary lectures From metabolic syndrome to diabetes Meta-inflammation responsible for the progression fr

May 10~ Hotel Inter-Burgo Exco, Daegu Plenary lectures From metabolic syndrome to diabetes Meta-inflammation responsible for the progression fr May 10~12 2012 Hotel Inter-Burgo Exco, Daegu Plenary lectures From metabolic syndrome to diabetes Meta-inflammation responsible for the progression from obesity to metabolic syndrome originates in the

More information

<C7EFB8AEC4DA5F B3E25FC3E1B0E8BDC9C6F7C1F6BEF65FB1B3C0E72E687770>

<C7EFB8AEC4DA5F B3E25FC3E1B0E8BDC9C6F7C1F6BEF65FB1B3C0E72E687770> 009 년대한 Helicobacter 및상부위장관연구학회춘계심포지엄 Symposium I Carcinoid tumor 성균관대학교의과대학내과학교실 이준행 김정하 1. 왜카르시노이드가문제인가 국내에서위암의검진을위한상부위장관내시경검사가광범위하게진행되면서조기위암뿐만아니라위나십이지장의카르시노이드종양의진단예가증가하고있다. 카르시노이드는신경내분비분화를보이는악성의가능성을가진저도상피종양

More information

지원연구분야 ( 코드 ) LC0202 과제번호 창의과제프로그램공개가능여부과제성격 ( 기초, 응용, 개발 ) 응용실용화대상여부실용화공개 ( 공개, 비공개 ) ( 국문 ) 연구과제명 과제책임자 세부과제 ( 영문 ) 구분 소속위암연구과직위책임연구원

지원연구분야 ( 코드 ) LC0202 과제번호 창의과제프로그램공개가능여부과제성격 ( 기초, 응용, 개발 ) 응용실용화대상여부실용화공개 ( 공개, 비공개 ) ( 국문 ) 연구과제명 과제책임자 세부과제 ( 영문 ) 구분 소속위암연구과직위책임연구원 지원연구분야 ( 코드 ) LC0202 과제번호 1110550 창의과제프로그램공개가능여부과제성격 ( 기초, 응용, 개발 ) 응용실용화대상여부실용화공개 ( 공개, 비공개 ) ( 국문 ) 연구과제명 과제책임자 세부과제 ( 영문 ) 구분 1 2 3 소속위암연구과직위책임연구원 성명류근원전공외과 세부과제명 세부과제책임자 성명 소속 ( 직위 ) 전공 총연구기간 2011

More information

조기 위암 집담회 부산대학교 병원 CASE

조기 위암 집담회   부산대학교 병원 CASE 부산대학교병원 CASE PRESENTATION 전임의이현정 2013.10.02 CASE PRESENTATION F/79 C.C) Epigastric soreness P.I) 2011년 4월외부병원시행한 EGD 상병변보여본원의뢰됨 P.Hx) HT / DM / Hepa / Tbc - / - / - / - S.Hx) smoking (-), alcohol (-) F.Hx)

More information

Treatment and Role of Hormaonal Replaement Therapy

Treatment and Role of Hormaonal Replaement Therapy Treatment and Role of Hormone Replacement Therapy Chung-Ang University Hospital Chee Jeong Kim 7.2 5.3 6.4 5.6 7.3 5.5 1 1 2 3 4 10 11 7 34 49 122 123 1.0 - - 10. 2001 1998 1998 Improvement of postmenopausal

More information

한약치료와표적항암요법 ( 아피니토 ) 을병행하여부분관해된신세포암간전이환자 1 례 Abstract Sung-Hwan Chang 1, Ji-Hye Park 1,2, Hwa Seung Yoo,2*

한약치료와표적항암요법 ( 아피니토 ) 을병행하여부분관해된신세포암간전이환자 1 례 Abstract Sung-Hwan Chang 1, Ji-Hye Park 1,2, Hwa Seung Yoo,2* https://doi.org/10.15432/jkto.2017.22.2.013 한약치료와표적항암요법 ( 아피니토 ) 을병행하여부분관해된신세포암간전이환자 1 례 Abstract Sung-Hwan Chang 1, Ji-Hye Park 1,2, Hwa Seung Yoo,2* 1 JangDeuk Integrative Medical Center, Korean Medicine

More information

Kaes017.hwp

Kaes017.hwp 갑상선의 Poorly Differentiated (Insular) Carcinoma Insular Carcinoma: An Aggressive Subtype of Differentiated Thyroid Neoplasms Seok-Jin Nam, M.D., Sang-Dal Lee, M.D., Hal-lin Park, M.D., Young-Ryun Oh, M.D.

More information

388 The Korean Journal of Hepatology : Vol. 6. No COMMENT 1. (dysplastic nodule) (adenomatous hyperplasia, AH), (macroregenerative nodule, MR

388 The Korean Journal of Hepatology : Vol. 6. No COMMENT 1. (dysplastic nodule) (adenomatous hyperplasia, AH), (macroregenerative nodule, MR 6 3 2000 ; 387-392 (3) Dysplastic Nodule Young Nyun Park, M.D., Chanil Park, M.D. Department of Pathology, Yonsei University College of Medicine BRIEF HISTORY 56. AST/ALT 72/73 IU/L, total bilirubin 0.7

More information

Lumbar spine

Lumbar spine Lumbar spine CT 32 111 DOI : 10.3831/KPI.2010.13.2.111 Lumbar Spine CT 32 Received : 10. 05. 23 Revised : 10. 06. 04 Accepted : 10. 06. 11 Key Words: Disc herniation, CT scan, Clinical analysis The Clinical

More information

Jksvs019(8-15).hwp

Jksvs019(8-15).hwp Grade I Grade II Grade III 12 대한혈관외과학회지 : 제 20 권 제 1 호 2004 Control Group A Group B Fig. 4. Microscopic findings of vein wall in control, group A and group B on the day of 7 after venous occlusion. The

More information

00약제부봄호c03逞풚

00약제부봄호c03逞풚 경희대학교 동서신의학병원 약품 정보지 2 0 0 7. S P R I N G. V O L. 0 1 신약 소개 02 Journal Review 03 Special Subject 04 복약 지도 06 의약품 안전성 정보 07 약제부 알림 07 약제부 업무 소개 08 E A S T - W E S T N E O M E D I C A L C E N T E R 본 약품

More information

7.ƯÁýb71ÎÀ¯È« š

7.ƯÁýb71ÎÀ¯È« š J KMA Special Issue Myelodysplastic Syndrome June Won Cheong, MD Yoo Hong Min, MD Department of Internal Medicine, Yonsei University College of Medicine E mail : jwcheong70@yumc.yonsei.ac.kr minbrmmd@yumc.yonsei.ac.kr

More information

Novartis Sample Deck for Externals

Novartis Sample Deck for Externals 항암약물치료 Recent Clinical Data Review -Gastric Cancer (Anticancer Systemic Treatment) Do-Youn Oh, MD., PhD. Medical Oncology, Seoul National University Hospital Cancer Research Institute, Seoul National University

More information

550호(01-09)

550호(01-09) T H E K O R E A N D O C T O R S W E E K L Y www.docdocdoc.co.kr I N S I D E 38 3 5 6 8 11 13 24 25 27 29 31 38 41 42 2 Advertisement Government & Medicine 3 Government & Medicine 4 Government & Medicine

More information

Sok Kyun Hong, et al : A case of carcinoid tumor of ampulla of vater presenting as asthmatic symptoms :, 57 : : kg. :, 1998 l. :. :, 110/70 mmh

Sok Kyun Hong, et al : A case of carcinoid tumor of ampulla of vater presenting as asthmatic symptoms :, 57 : : kg. :, 1998 l. :. :, 110/70 mmh : 59 2 2000 Carcinoid 1, *, * = A bs tra c t= A cas e of carcinoid tumor of ampulla of v ater pres enting as as thmatic s y mptoms Sok Kyun Hong, M.D., Im Hw an Roe, M.D., Myung In Lee, M.D., Sang Hyun

More information

Intest Res 2013;11(1):14-22 나, 과거에는비교적드문질환이고병에대한정확한이해가부족하여명확하게분류되지못했다 년세계보건기구 (World Health Organizati

Intest Res 2013;11(1):14-22 나, 과거에는비교적드문질환이고병에대한정확한이해가부족하여명확하게분류되지못했다 년세계보건기구 (World Health Organizati REVIEW ISSN 1598-9100 http://dx.doi.org/10.5217/ir.2013.11.1.14 Intest Res 2013;11(1):14-22 Variable Clinical Classifications and Diagnostic Coding Systems of Colorectal Neuroendocrine Tumor Byung Chang

More information

Kaes025.hwp

Kaes025.hwp 고위험군유두상갑상선암환자에대한방사성옥소최대허용선량측정법및치료법의검증 Verification of Measurement Methods and Therapeutic Efficacy of Maximum Permissible Dose of I-131 in High Risk Patients with Differentiated Papillary Thyroid Cancer

More information

ECG & EP CASES Young-Keun On, MD, PhD Division of Cardiology, Department of Medicine Cardiac & Vascular Center, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea A case of

More information

(49-54)Kjhps004.hwp

(49-54)Kjhps004.hwp Biliary Cystadenoma and Cystadenocarcinoma of the Liver Jae Hoon Lee, M.D., Dong Ho Choi, M.D. 1, Kyeong Geun Lee, M.D., Hwon Kyum Park M.D. and Kwang Soo Lee, M.D. Department of Surgery, College of Medicine,

More information

<C1A63530C8B820BCBCB9CCB3AA2DC6EDC1FD2E687770>

<C1A63530C8B820BCBCB9CCB3AA2DC6EDC1FD2E687770> B-III. 대장점막암및유암종의진단코드 : C 또는 D, 어느것이적절한가? Room B 인하대학교의과대학부속병원병리과 A Pathologist's View Joon Mee Kim Department of Pathology, Inha University School of Medicine, Incheon, Korea 서론서구화된식습관과내시경술기의발달로조기대장암의빈도가증가하고있다.

More information

- i - - ii - - iii - - iv - - v - - vi - - 1 - - 2 - - 3 - 1) 통계청고시제 2010-150 호 (2010.7.6 개정, 2011.1.1 시행 ) - 4 - 요양급여의적용기준및방법에관한세부사항에따른골밀도검사기준 (2007 년 11 월 1 일시행 ) - 5 - - 6 - - 7 - - 8 - - 9 - - 10 -

More information

암센터뉴스레터1

암센터뉴스레터1 CANCER HOSPITAL News News Letter For Yonsei University Gangnam Severance Hospital http://gs.iseverance.com 2012.06.21 2012.08.16 2012.09.19 2012.10.04 2012.10.25 CONTENTS 2012.07.27 2012.10.06 2012.11.06

More information

Microsoft PowerPoint - 김미영

Microsoft PowerPoint - 김미영 암세포의위험한여행 한국과학기술원 김미영 강의개요 전이란무엇인가? 전이는어떤과정을통해진행될까? 전이예측방법은어떤것들이있을까? Cancer ( 악성종양 ) US South Korea 질병사망률질병사망률 1. 심장병 26% 1. Cancer 26.7% 2. Cancer 23% 2. 뇌출혈 12.7% 3. 뇌출혈 5.6% 3. 심장병 7.9% >20,000 환자가악성종양에의해매일사망함

More information

386-390.hwp

386-390.hwp 386 HANYANG MEDICAL REVIEWS Vol. 29 No. 4, 2009 우리나라 미숙아의 통계와 의료비용 Statistics and Medical Cost of Preterm in Korea 윤혜선 을지대학교 노원을지병원 소아청소년과학교실 Hye Sun Yoon, M.D., Ph.D., Department of Pediatrics, Nowon

More information

<4D F736F F F696E74202D DBFACBCF6B0ADC1C22DC7A5C0FBC4A1B7E12DC0CCB1D9BFED2DBFF8B0ED2E BC8A3C8AF20B8F0B5E55D>

<4D F736F F F696E74202D DBFACBCF6B0ADC1C22DC7A5C0FBC4A1B7E12DC0CCB1D9BFED2DBFF8B0ED2E BC8A3C8AF20B8F0B5E55D> 2008.8.31. 내과연수강좌 표적치료제의 허와실 - 항암치료의최신동향- 분당서울대학교병원혈액종양내과이근욱 Treatment of Cancer 1890-1980s 1990s 2000s Surgery Radiotherapy Chemotherapy Biologic therapy Gene therapy? Target-based Therapy Most Anticancer

More information

<32302DC1F5B7CA BCDBC0BAB9CC2E687770>

<32302DC1F5B7CA BCDBC0BAB9CC2E687770> 대한내과학회지 : 제 80 권제 2 호 2011 부신피질자극호르몬을분비하는췌장의악성신경내분비종양 1 예 이화여자대학교의과대학 1 내과학교실, 2 병리학교실, 3 인제대학교의과대학내과학교실 송은미 1 이경은 1 조정연 1 구혜수 2 최문영 3 성주명 1 이순남 1 An Adrenocorticotropic Hormone-secreting Malignant Pancreatic

More information

untitled

untitled Gallbladder, Perihilar Bile Ducts & Distal Bile Duct 연세대학교의과대학세브란스병원외과학교실 김경식 서론암의병기결정은 1977년 1판 AJCC cancer staging 이나온이래 6 8년의주기로개정작업이시행되어왔다. 2002년개정된 6판은간문부암에대한병기가세분되어있지않았고담낭암및담도암에있어서림프절침범유무에만구분하였으나

More information

한국성인에서초기황반변성질환과 연관된위험요인연구

한국성인에서초기황반변성질환과 연관된위험요인연구 한국성인에서초기황반변성질환과 연관된위험요인연구 한국성인에서초기황반변성질환과 연관된위험요인연구 - - i - - i - - ii - - iii - - iv - χ - v - - vi - - 1 - - 2 - - 3 - - 4 - 그림 1. 연구대상자선정도표 - 5 - - 6 - - 7 - - 8 - 그림 2. 연구의틀 χ - 9 - - 10 - - 11 -

More information

<30352DB1E8C0AFC1A42DC6EDC1FD2DBDBD2E687770>

<30352DB1E8C0AFC1A42DC6EDC1FD2DBDBD2E687770> Introduction to Medical Oncology and Molecularly Targeted Therapy 서울대학교의과대학내과학교실분당서울대학교병원혈액종양내과 김유정 연도별성별암발생자수추이 70 분당서울대학교병원 제 8 회분당서울대학교병원내과연수강좌 2012 평균수명까지생존시암발생확률, 2009 주요암종발생분율, 2009 분당서울대학교병원 71

More information

The Window of Multiple Sclerosis

The Window of Multiple Sclerosis THE WINDOW OF MULTIPLE SCLEROSIS Vol.2 No.1 MAR 2009 Topic Review Article Review 01. 02. 03. 04. Case Review The Window of Multiple Sclerosis THE WINDOW OF MULTIPLE SCLEROSIS The Window of Multiple Sclerosis

More information

석사논문.PDF

석사논문.PDF ABO Rh A study on the importance of ABO and Rh blood groups information in Public Health 2000 2 1 ABO Rh A study on the importance of ABO and Rh blood groups information in Public Health 2000 2 2 ABO Rh

More information

<30332EBABBB9AE2E687770>

<30332EBABBB9AE2E687770> 간세포암에서의표적치료 울산대학교의과대학서울아산병원내과 이한주 Targeted therapy in hepatocellular carcinoma Han Chu Lee, M.D. Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

More information

( )Kju269.hwp

( )Kju269.hwp 만성세균성전립선염모델흰쥐에서 의항염효과 Anti-inflammatory Effect of Lycopene on Chronic Bacterial Prostatitis Rat Model Cho Hwan Yang, Dong Wan Sohn, Yong-Hyun Cho From the Department of Urology, The Catholic University

More information

<B0E6C8F1B4EBB3BBB0FA20C0D3BBF3B0ADC1C E687770>

<B0E6C8F1B4EBB3BBB0FA20C0D3BBF3B0ADC1C E687770> 심전도연수강좌 : 처음시작하는사람들을위한심전도 연세대학교원주의과대학순환기내과학교실 안민수 Cardiac Electrophysiology I : Automaticity : 60-100 회 /min, His bundle : 40-60 회 /min Bundle branch : 20-40 회 /min Purkinje fiber : 20 회 /min Cardiac Electrophysiology

More information

歯1.PDF

歯1.PDF 200176 .,.,.,. 5... 1/2. /. / 2. . 293.33 (54.32%), 65.54(12.13%), / 53.80(9.96%), 25.60(4.74%), 5.22(0.97%). / 3 S (1997)14.59% (1971) 10%, (1977).5%~11.5%, (1986)

More information

<313020BFF8C0FA203030373320B1E8BACEB0E62E687770>

<313020BFF8C0FA203030373320B1E8BACEB0E62E687770> 대한내과학회지: 제 80 권 제 6 호 0 진행성 위암에 대한 차 요법으로 Docetaxel, Cisplatin, 5-FU 복합화학요법의 효과와 안전성 고신대학교 의과대학 내과학교실 김부경 박무인 박선자 김규종 문 원 정수현 김혜수 남성진 Docetaxel, Cisplatin, 5-FU Combination Chemotherapy as a First-Line

More information

1..

1.. Volume 12, Number 1, 6~16, Factors influencing consultation time and waiting time of ambulatory patients in a tertiary teaching hospital Jee-In Hwang College of Nursing Science, Kyung Hee University :

More information

페링야간뇨소책자-내지-16

페링야간뇨소책자-내지-16 야간뇨의진단과치료 - 실제적접근 - Reference 1. Choo MS, Ku JH, Park CH et al. Prevalence of Nocturia in a Korean Population Aged 40 to 89 Years. Neurourol Urodyn 2008; 27:60-64. 2. Weiss JP. Prevalence

More information

( )Jksc057.hwp

( )Jksc057.hwp 직장암환자의전직장간막절제술의 예측인자분석 : 불완전절제와절제시간에영향을미치는인자에관한연구 Analysis of Factors Affecting the Degree of Difficulty in Total Mesorectal Excision for Rectal Cancer: Investigation of the Factors Affecting Incomplete

More information

달생산이 초산모 분만시간에 미치는 영향 Ⅰ. 서 론 Ⅱ. 연구대상 및 방법 達 은 23) 의 丹 溪 에 최초로 기 재된 처방으로, 에 복용하면 한 다하여 난산의 예방과 및, 등에 널리 활용되어 왔다. 達 은 이 毒 하고 는 甘 苦 하여 氣, 氣 寬,, 結 의 효능이 있

달생산이 초산모 분만시간에 미치는 영향 Ⅰ. 서 론 Ⅱ. 연구대상 및 방법 達 은 23) 의 丹 溪 에 최초로 기 재된 처방으로, 에 복용하면 한 다하여 난산의 예방과 및, 등에 널리 활용되어 왔다. 達 은 이 毒 하고 는 甘 苦 하여 氣, 氣 寬,, 結 의 효능이 있 대한한방부인과학회지 THE JOURNAL OF ORIENTAL OBSTETRICS & GYNECOLOGY VOL.17, NO.2 : 115-122 (2004) 달생산이 초산모 분만시간에 미치는 영향 * 북경한의원, ** 윤산부인과의원, *** 최은림산부인과의원, 상지대학교 한의과대학 부인과학교실 ****, 경희대학교 동서의학대학원 김성준 *****, 윤왕준

More information

12È«±â¼±¿Ü339~370

12È«±â¼±¿Ü339~370 http://www.kbc.go.kr/ k Si 2 i= 1 Abstract A Study on Establishment of Fair Trade Order in Terrestrial Broadcasting Ki - Sun Hong (Professor, Dept. of Journalism & Mass Communication,

More information

untitled

untitled 간암치료에서 Molecular Target Agents 의역할 최종영 가톨릭대학교의과대학서울성모병원소화기내과 요약 Sorafenib은 RAF, VEGF, PDGF, Flt-3, c-kit receptor typrosine kinase inhibitor로서간암세포증식과신혈관생성을억제하는기능을가지고있어 2007년에미국 FDA에서간암, 신장암에서그효과가인정되었다.

More information

DBPIA-NURIMEDIA

DBPIA-NURIMEDIA 27(2), 2007, 96-121 S ij k i POP j a i SEXR j i AGER j i BEDDAT j ij i j S ij S ij POP j SEXR j AGER j BEDDAT j k i a i i i L ij = S ij - S ij ---------- S ij S ij = k i POP j a i SEXR j i AGER j i BEDDAT

More information

°Ç°�°úÁúº´6-2È£

°Ç°�°úÁúº´6-2È£ K O R E A C E N T E R S F O R D I S E A S E C O N T R O L & P R E V E N T I O N PHWR Vol. 6 No. 2 www.cdc.go.kr 2013 1 11 6 2 ISSN:2005-811X Flavivirus surveillance in mosquitoes collected from the quarantine

More information

untitled

untitled Case Report : Asan Medical Center Cardiac Rehabilitation AACVPR (http://www.aacvpr.org/) KACVPR (http://www.kacvpr.com/) Backgrounds PCI 2,395 consecutive patients in Minnesota (Mayo Clinic) Between1994

More information

DBPIA-NURIMEDIA

DBPIA-NURIMEDIA The e-business Studies Volume 17, Number 6, December, 30, 2016:275~289 Received: 2016/12/02, Accepted: 2016/12/22 Revised: 2016/12/20, Published: 2016/12/30 [ABSTRACT] SNS is used in various fields. Although

More information

K O R E A C E N T E R S F O R D I S E A S E C O N T R O L & P R E V E N T I O N PHWR Vol. 5 No. 41 www.cdc.go.kr/phwr 2012 10 12 5 41 ISSN:2005-811X Comparison of drug-susceptibility test to the anti-tuberculosis

More information

권유진

권유진 Malignant Peripheral Nerve Sheath Tumor of the Pancreas: A Case Report Malignant peripheral nerve sheath tumor (MPNST) is rare, soft tissue, spindle cell sarcoma of an ectomesenchymal origin. MPNSTs frequently

More information

Table 1. Distribution by site and stage of laryngeal cancer Supraglottic Glottic Transglottic Total Stage Total 20

Table 1. Distribution by site and stage of laryngeal cancer Supraglottic Glottic Transglottic Total Stage Total 20 KISEP Head and Neck Korean J Otolaryngol 1999;42:1284-9 후두암수술환자에대한치료성적 송달원 김희준 정현수 김영한 안재현 이복수 박선호 Treatment Result in Laryngeal Cancer Patients Submitted to Surgical Treatment Dal Won Song, MD, Hee Jun

More information

- iii - - i - - ii - - iii - 국문요약 종합병원남자간호사가지각하는조직공정성 사회정체성과 조직시민행동과의관계 - iv - - v - - 1 - - 2 - - 3 - - 4 - - 5 - - 6 - - 7 - - 8 - - 9 - - 10 - - 11 - - 12 - - 13 - - 14 - α α α α - 15 - α α α α α α

More information

012임수진

012임수진 Received : 2012. 11. 27 Reviewed : 2012. 12. 10 Accepted : 2012. 12. 12 A Clinical Study on Effect of Electro-acupuncture Treatment for Low Back Pain and Radicular Pain in Patients Diagnosed with Lumbar

More information

l l l l l l l l l Lee, Geon Kook None This project was designed to establish the Tumor Bank of National Cancer Center in 2000. From the first tumor sample in 2000, the total of tumor and tumor-related

More information

(

( 317 318 319 320 1 3 5 5 5 5 2 321 : 1.,,,,, 06 2. X-ray beam penetration (density) (contrast) 03 3. patch coating, precipitation, flaking 03 4. centering 03 5. Esophagus, cardia, fundus, body, angle, antrum,

More information

°Ç°�°úÁúº´5-44È£ÃÖÁ¾

°Ç°�°úÁúº´5-44È£ÃÖÁ¾ K O R E A C E N T E R S F O R D I S E A S E C O N T R O L & P R E V E N T I O N PHWR Vol. 5 No. 44 www.cdc.go.kr/phwr 2012 11 2 5 44 ISSN:2005-811X Vector surveillance after elimination of lymphatic filariasis

More information

OvCa guideline ( )

OvCa guideline ( ) Practice Guideline for Gynecologic Cancer v 2.0, 2010 Ovarian Cancer Guideline Tae Joong, Kim Department of OB/GYN Samsung Medical Center Sungkyunkwan Univ. School of Medicine : : :,,,, :,,,,,,,,,, :,,,,

More information

Sheu HM, et al., British J Dermatol 1997; 136: Kao JS, et al., J Invest Dermatol 2003; 120:

Sheu HM, et al., British J Dermatol 1997; 136: Kao JS, et al., J Invest Dermatol 2003; 120: Sheu HM, et al., British J Dermatol 1997; 136:884-890 Kao JS, et al., J Invest Dermatol 03; 1:446-464 1 10 0 3 Day Normal MLE Lotion Lotion MLE Cream Cream 80 7 70 6 3 Day Normal MLE Lotion Lotion MLE

More information

A Study on the Relationships between Self-Differentiation and Adaptability Factors for Senior Dementia Patients Care Givers Department of Social Welfare, Seoul Welfare Graduate University Full-time Lecturer

More information

서론 34 2

서론 34 2 34 2 Journal of the Korean Society of Health Information and Health Statistics Volume 34, Number 2, 2009, pp. 165 176 165 진은희 A Study on Health related Action Rates of Dietary Guidelines and Pattern of

More information

충북의대학술지 Chungbuk Med. J. Vol. 27. No. 1. 1~ Charcot-Marie-Tooth Disease 환자의마취 : 증례보고 신일동 1, 이진희 1, 박상희 1,2 * 책임저자 : 박상희, 충북청주시서원구충대로 1 번지, 충북대학교

충북의대학술지 Chungbuk Med. J. Vol. 27. No. 1. 1~ Charcot-Marie-Tooth Disease 환자의마취 : 증례보고 신일동 1, 이진희 1, 박상희 1,2 * 책임저자 : 박상희, 충북청주시서원구충대로 1 번지, 충북대학교 충북의대학술지 Chungbuk Med. J. Vol. 27. No. 1. 1~5 2017 Charcot-Marie-Tooth Disease 환자의마취 : 증례보고 신일동 1, 이진희 1, 박상희 1,2 * 책임저자 : 박상희, 충북청주시서원구충대로 1 번지, 충북대학교의과대학마취통증의학교실, 의학연구소 (28644), happycat19@hanmail.net

More information

Can032.hwp

Can032.hwp Chromosomal Alterations in Hepatocellular Carcinoma Cell Lines Detected by Comparative Genomic Hybridization Sang Jin Park 1, Mahn Joon Ha, Ph.D. 1, Hugh Chul Kim, M.D. 2 and Hyon Ju Kim, M.D. 1 1 Laboratory

More information

untitled

untitled The Korean Journal of Gastrointestinal Endoscopy Case Report 내시경점막절제술로치료한십이지장유암종 최종학ㆍ송인도ㆍ오인수ㆍ김범진ㆍ오형철ㆍ김정욱ㆍ김재규 중앙대학교의과대학내과학교실 Tumor Treated by Endoscopic Mucosal Resection Jong Hak Choi, M.D., In Do Song,

More information

12이문규

12이문규 Review on Conservative Treatment of Spinal Scoliosis Moon-kyu Lee, O.M.D., Gil-jae Lee, O.M.D., Yun-kyung Song, O.M.D., Hyung-ho Lim, O.M.D. Dept. of Oriental Rehabilitation Medicine College of Oriental

More information

원위부요척골관절질환에서의초음파 유도하스테로이드주사치료의효과 - 후향적 1 년경과관찰연구 - 연세대학교대학원 의학과 남상현

원위부요척골관절질환에서의초음파 유도하스테로이드주사치료의효과 - 후향적 1 년경과관찰연구 - 연세대학교대학원 의학과 남상현 원위부요척골관절질환에서의초음파 유도하스테로이드주사치료의효과 - 후향적 1 년경과관찰연구 - 연세대학교대학원 의학과 남상현 원위부요척골관절질환에서의초음파 유도하스테로이드주사치료의효과 - 후향적 1 년경과관찰연구 - 연세대학교대학원 의학과 남상현 원위부요척골관절질환에서의초음파 유도하스테로이드주사치료의효과 - 후향적 1 년경과관찰연구 - 지도김석원교수 이논문을석사학위논문으로제출함

More information

전립선암발생률추정과관련요인분석 : The Korean Cancer Prevention Study-II (KCPS-II)

전립선암발생률추정과관련요인분석 : The Korean Cancer Prevention Study-II (KCPS-II) 전립선암발생률추정과관련요인분석 : The Korean Cancer Prevention Study-II (KCPS-II) 전립선암발생률추정과관련요인분석 : The Korean Cancer Prevention Study-II (KCPS-II) - i - - ii - - iii - - iv - - v - - vi - - vii - - viii - - ix - -

More information

2 1896 2 26 ( ) 2 7-20 2) 1897 1898 ( )3) 6 1902 8 1904 10 10 (19 05-1914 ) ( ) ( ) 4) 1915 ( ) ( ) 1917 2) 3) 4) 285

2 1896 2 26 ( ) 2 7-20 2) 1897 1898 ( )3) 6 1902 8 1904 10 10 (19 05-1914 ) ( ) ( ) 4) 1915 ( ) ( ) 1917 2) 3) 4) 285 13 2 ( 25 ) 2004 12 Korean J Med Hist 13 284 296 Dec 2004 ISSN 1225 505X 1) * ** ** 1 1920 1930 40 ( 1896-1973) 80 * ** 1) 2003 284 2 1896 2 26 ( ) 2 7-20 2) 1897 1898 ( )3) 6 1902 8 1904 10 10 (19 05-1914

More information

The Clinicopathologic Characteristics of Cases with Negative Pathologic Diagnosis after Endoscopic Submucosal Dissection

The Clinicopathologic Characteristics of Cases with Negative Pathologic Diagnosis after Endoscopic Submucosal Dissection CASE PRESENTATION 2014.06.11 전임의윤종민 M/59 C.C.: SMT on stomach, duodenum P.I.: 2013. 12월외부병원검진위내시경상 cardia 및 2 nd portion of duodenum의 SMT 관찰되어 EUS 등 F/E 위해내원 HISTORY P.Hx) HT / DM / Hepa / Tbc - / - /

More information

DBPIA-NURIMEDIA

DBPIA-NURIMEDIA The e-business Studies Volume 17, Number 4, August, 30, 2016:319~332 Received: 2016/07/28, Accepted: 2016/08/28 Revised: 2016/08/27, Published: 2016/08/30 [ABSTRACT] This paper examined what determina

More information

2016 학년도약학대학면접문제해설 문제 2 아래의질문에 3-4분이내로답하시오. 표피성장인자수용체 (epidermal growth factor receptor, EGFR) 는수용체티로신인산화효소군 (receptor tyrosine kinases, RTKs) 의일종으로서세

2016 학년도약학대학면접문제해설 문제 2 아래의질문에 3-4분이내로답하시오. 표피성장인자수용체 (epidermal growth factor receptor, EGFR) 는수용체티로신인산화효소군 (receptor tyrosine kinases, RTKs) 의일종으로서세 본문제에대한지적소유권은동국대학교에있습니다. 본교의서면허락없이무단으로출판, 게재, 사용할수없습니다. 문제 2 2016 학년도약학대학면접문제 아래의질문에 3-4 분이내로답하시오. 표피성장인자수용체 (epidermal growth factor receptor, EGFR) 는수용체티로신 인산화효소군 (receptor tyrosine kinases, RTKs) 의일종으로서세포의생존과증식

More information

untitled

untitled DOI: 10.3857/JKSTRO.2008.26.2.113 노령의 피부암에서 방사선치료 계명대학교 의과대학 동산의료원 방사선종양학교실 김 진 희 목 적: 노령의 피부암에서 방사선치료 후 국소 제어률, 생존율, 실패양상, 부작용을 알아보기 위해 이 연구를 시행 하였다. 대상 및 방법: 1990년 1월부터 2002년 10월까지 계명대학교 동산의료원 방사선종양학과에서

More information

Journal of Educational Innovation Research 2017, Vol. 27, No. 2, pp DOI: : Researc

Journal of Educational Innovation Research 2017, Vol. 27, No. 2, pp DOI:   : Researc Journal of Educational Innovation Research 2017, Vol. 27, No. 2, pp.251-273 DOI: http://dx.doi.org/10.21024/pnuedi.27.2.201706.251 : 1997 2005 Research Trend Analysis on the Korean Alternative Education

More information

Jkbcs042.hwp

Jkbcs042.hwp Invasive Ductal Carcinoma Arising from Axillary Accessory Breast Tae Wan Kim, Sang Wook Kang, Ji Young Park 2, Seung Sang Ko 1, Min Hee Hur 1, Hae Kyung Lee 1, Sung Soo Kang 1, and Jee Hyun Lee 1 Department

More information

PowerPoint 프레젠테이션

PowerPoint 프레젠테이션 Gastro intestinal lymphomas R3. 정세진 정의 GI lymphoma introduction 위장관및이와관련된배액부위림프절에국한, 간이나비장및기타림프절침범이없고, 단순흉부촬영상이정상, 말초혈액검사의백혈구가정상인경우. Extranodal lymphoma 69.6% GI lymphoma 29.22% Kim JM, WHO Classification

More information

untitled

untitled J Korean Surg Soc 2011;80:23-28 DOI: 10.4174/jkss.2011.80.1.23 원 저 위암에서새로운 TNM 병기체계에따른예후의평가 영남대학교의과대학외과학교실 배정민ㆍ김세원ㆍ김상운ㆍ송선교 Evaluation of Prognostic Values according to the New TNM Classification in Gastric

More information

슬라이드 1

슬라이드 1 Proposed Korean guideline for the diagnosis of BPH Hyun Woo Kim The Catholic University of Korea BPH Guideline AHCPR guideline on BPH (1994) AUA guideline on BPH (2003) EAU guideline on BPH (2004) International

More information

이준규 (tryptophan, Tryp), (parietal cell)., (vagal nerve) gastrin releasing peptide (GRP), Ca ++ (epinephrine)., (trophic action),. ph 3.0 G D. gastric

이준규 (tryptophan, Tryp), (parietal cell)., (vagal nerve) gastrin releasing peptide (GRP), Ca ++ (epinephrine)., (trophic action),. ph 3.0 G D. gastric SESSION IV The Korean Journal of Pancreas and Biliary Tract 2014;19(Suppl. 1) 위장관호르몬과소화 동국대학교의과대학동국대학교일산병원내과 이준규 Gastrointestinal Hormones and Digestion Jun Kyu Lee Department of Internal Medicine, Dongguk

More information

Abstract Background : Most hospitalized children will experience physical pain as well as psychological distress. Painful procedure can increase anxie

Abstract Background : Most hospitalized children will experience physical pain as well as psychological distress. Painful procedure can increase anxie Volume 12, Number 1, 92~102, An Intervention Study of Pain Reduction during IV Therapy in Hospitalized Children Myo-Jin Kim 1), Joung-Hae Bak 1), Won-Seok Seo 2) Mi-Young Kim 3), Sun-Kyoung Park 3), Jai-Soung

More information

(01) hwp

(01) hwp Journal of Life Science 2013 Vol. 23. No. 2. 157~166 ISSN (Print) 1225-9918 ISSN (Online) 2287-3406 DOI : http://dx.doi.org/10.5352/jls.2013.23.2.157 α μ δ κ 158 생명과학회지 2013, Vol. 23. No. 2 Journal of

More information

..........5-45..

..........5-45.. K O R E A C E N T E R S F O R D I S E A S E C O N T R O L & P R E V E N T I O N PHWR Vol. 5 No. 45 www.cdc.go.kr 2012 11 9 5 45 ISSN:2005-811X Monitoring of antimicrobial resistance on non-tertiary hospitals

More information