ORIGINAL ARTICLE J Surg Ultrasound 2017;4:35-40 JSU Journal of Surgical Ultrasound 초음파유도하인도시아닌그린주사후근적외선형광카메라를사용한관내유두종병변의절제술 서남대학교의과대학명지병원유방갑상선센터외과학교실 최현정, 김완성, 신혁재 Segmentectomy of Intraductal Papillary Lesion Using Ultrasonography Guided Near-infrared Indocyanine Green Fluorescence Hyun Jung Choi, Wan Sung Kim, Hyuk Jai Shin Department of Surgery, Breast and Thyroid Care Center, Myongji Hospital, Seonam University College of Medicine, Goyang, Korea Received May 15, 2017 Revised August 12, 2017 Accepted August 23, 2017 Correspondence to: Hyuk Jai Shin Department of Surgery, Breast & Thyroid Care Center, Myongji Hospital, 697-24 Hwajung-dong, Deokyang-gu, Goyang 10475, Korea Tel: +82-31-810-6890 Fax: +82-31-810-6163 E-mail: drgsshj@gmail.com *2017년대한외과초음파학회춘계학술대회우수구연상수상 Purpose: An intraductal papillary lesion is a nonpalpable lesion for which surgical resection is difficult; therefore, a method of resection using a wire is commonly used. However, this method is not accurate for mass resection. Indocyanine green is commonly employed in breast cancer surgery when finding sentinel lymph nodes using a near-infrared indocyanine green fluorescence. The present study was conducted to demonstrate the usefulness of a method of mass excision of the intraductal papillary lesion using a near-infrared fluorescent camera by injecting indocyanine green into the lesion under ultrasound guidance. Methods: From October 2014 to May 2015, 10 women who were diagnosed with intraductal papilloma by ultrasonography and biopsy at our hospital were operated on by a single surgeon. Indocyanine green was injected into the lesion under ultrasound guidance. After injection, mass excision was performed using a near-infrared camera. The size of the resected lesion and the operation time were reviewed. Results: The mean size of the specimen was 6.00 3.71 1.81 cm and the operation time was 36.5 minutes. Conclusion: It is useful for the surgeon and the patient to conduct mass excision of the papilloma lesion using a near-infrared fluorescent camera by injecting indocyanine green into the lesion under ultrasound guidance. However, we studied just 10 cases to date and also there was no comparative group. Therefore, Further studies are needed. Keywords: Indocyanine green, Intraductal papilloma, Ultrasound, Breast 서론 관내유두종은환자에게있어혈행성유두분비물의증상을유발하여불편감을줄수도있으며유방암이나상피내암등의발생률이높고수술시암을동반하고있는경우 도있는종양이며비정형세포의과증식을동반하기도하는수술적절제가필요한병변이다.(1,2) 그러나잘만져지지않는병변으로수술적절제에있어어려움이있다. 통상적으로관내유두종은유두근처인중앙에위치하는경우가많아 wire cannula를이용하여유관을찾아유관 Journal of Surgical Ultrasound is an Open Access Journal. All articles are distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright c 2017 by The Korean Surgical Ultrasound Society ISSN 2288-9140
J Surg Ultrasound Vol. 4, No. 2, 2017 을점차적으로넓히면서병변을찾아절제하는것이이상적이나 (microdochectomy) 이러한방법은병변에확실하게접근할수없으며수술후병변이확실하게절제되었는지육안으로확인할수없어정확도가떨어진다. 따라서광범위하게유방절제술을시행하게되므로불필요하게정상조직까지제거하게되고유방의모양변형, 장액종이발생하여환자에게통증을유발하게하는등의문제가생기게된다. 이방법이외에도메틸렌블루등을사용하기도하나메틸렌블루는유방실질조직으로들어가게되면시야가확실하게보이지않으며메틸렌블루로인해병변주위가흐려져서경계가분명하지않게되어정확도가떨어지게되며이방법또한광범위하게유방절제술을시행할수밖에없게된다.(3-7) 인도시아닌그린은유방암수술에있어감시림프절생검술에사용하고있다.(8-10) 인도시아닌그린을주사용수와희석하여근적외선형광카메라로비추면형광색으로빛나는성질이있어화면을통해볼수있으며 (Fig. 1) 따라서감시림프절이형광색으로빛나면서화면을보면서감시림프절생검술을편리하게할수있다 (Fig. 2). 따라서본연구에서는이러한인도시아닌그린의특성을이용하였으며초음파가이드하에인도시아닌그린을병변에주사하여근적외선형광카메라를사용하여관내유두 종을절제하는방법이유용함을보여주고자하였다. 방법 2014년 10월부터 2015년 5월까지본센터에서유방초음파를시행한후이상소견으로초음파유도하총생검조직검사를시행하여관내유두종으로진단된여자환자 10 명을대상으로하였으며단일술자를통하여수술을시행하였다. 본연구는명지병원임상시험위원회 (IRB) 의승인을받았다. 이후승인된동의서를사용하여수술전환자에게수술방법에대한설명과함께환자의동의하에본연구를시행하였다 (IRB No. MJH 14-013). 생리식염수 10 cc와인도시아닌그린 1 cc를혼합하면 Fig. 3과같이육안으로는옅은녹색을띠게된다 (Fig. 3). 수술실에서전신마취하에먼저인도시아닌그린을상기방법으로혼합하고이렇게혼합한인도시아닌그린과식염수혼합용액 0.5 cc를초음파유도하에관내유두종이보이는병변내로주입하였다 (Fig. 4A). 다발성병변인경우에는하나의병변당 0.5 cc씩주입하였다. 이렇게초음파유도하에병변내로주입하면유관이늘어나는모습이보이면서정확하게병변에들어갔는지여부를초음파화면으로직접실시간으로확인할수있다 (Fig. 4B). 초음파 Fig. 1. (A) is Indocyanine Green, (B) color is green under naked eye, (C) color is Bright white under Near Infrared Fluorescent Camera. Fig. 2. When we do sentinel node biopsy, We use not only radio isotope with gamma probe, but also ICG and Near-Infrared fluorescent Camera. 36
Hyun Jung Choi, et al.: Semectomy of Intraductal Papillary Lesion Using USG Guided Localization with ICG and NIRF System 를이용하여병변에인도시아닌그린식염수혼합용액을주입한후모니터로연결된근적외선형광카메라 (Fig. 5) 를사용하여병변에비추어보면피부주위및유방병변에밝게빛나는형광색의모습을화면을통해볼수있다 (Fig. 6). 피부절개를가하여절개창을열게되면병변이밝은형광색으로보이게되며 (Fig.6A) 유방병변을밝은형광색으로염색된부위를따라절제를시행하였다 (Fig.6B). 절제한병변조직에근적외선형광카메라를사용하여비추어보면유관을따라병변이염색된것을확인할수있었으며따라서실시간으로육안으로직접절제연을확인할수있었다 (Fig. 6C). 대조군으로는 2013년 2월부터 2013년 12월까지본센터에서유방초음파를시행한후이상소견으로초음파유도하총생검조직검사를시행하여관내유두종으로진단 된여자환자 10명을대상으로하였으며단일술자를통하여수술을시행하였다. 수술 1일전초음파로관내유두종으로진단된병변의피부에마킹을하여표시하여놓았으며수술중표시된부위를따라병변을절제하였다. 결과 환자의임상적특징에대해서살펴보면 10건의환자의평균연령은 47.7 세였으며병변은단일성병변이 6건, 다발성병변이 4건이었다. 평균수술시간은 36.5분이었으며 (20-75 분 ) 평균절제된병변의크기는 5.99 3.71 1.81 cm이었다 (Table 1). 초음파유도하에인도시아닌그린과생리식염수혼합용액을주입시에정확하게병변에 10건의수술에서모두 Fig. 3. This Picture is ICG with Saline 1:100 mixture under naked eye. Fig. 5. (A) is Near Infrared Fluorescent Camera. (B) is the Body of Near Infrared Fluorescent Camera Monitor system. Fig. 4. (A) is that we target the intraductal lesion with needle under Ultrasonography. (B) is the dilated intraductal lesion after ICG 0.5 cc injection under Ultrasonography. 37
J Surg Ultrasound Vol. 4, No. 2, 2017 Fig. 6. (A) is that the lesion is bright fluorescent color thought the open window under NIRF Camera. (B) is that we exactly excise the fluorescent white lesion under NIRF Camera. (C) is that we confirm that the lesion after excision under NIRF Camera. Table 1. Patients Characteristics and Postoperative Data (ICG Group) Case no Age Mass single or multiple Operation time (min) Resected specimen size (cm) 1 47 Single 40 3.7 2.3 1.2 2 58 Single 75 7.0 5.0 2.0 3 45 Single 30 5.5 3.0 1.5 4 45 Single 30 6.0 4.0 1.7 5 62 Multiple (2) 35 5.5 3.0 1.2 6 52 Multiple (2) 45 5.0 3.0 1.2 7 45 Single 25 6.0 7.3 2.0 8 45 Multiple (2) 40 8.0 3.0 2.0 9 44 Multiple (2) 20 7.2 4.0 2.0 10 34 Single 25 6.0 2.5 2.5 Median 47.7 36.5 5.99 3.71 1.81 성공적으로주입되었으며따라서주입성공률은모두 100% 이었다. 그리고이후최종적으로수술한절제조직의병리결과에서 10건의수술에서모두완전절제된결과를확인하였고병리결과모두관내유두종이었으며다른추가병리결과는발견되지않았다. 대조군의결과를살펴보면 10건의환자의평균연령은 42.7 세였으며병변은 10건모두단일성병변이었다. 평균수술시간은 39.5 분이었으며 (25-55 분 ) 평균절제된병변의크기는 6.45 3.67 1.98 cm이었다 (Table 2). 고찰 관내유두종은환자에게있어혈행성유두분비물의증상을유발하여불편감을줄수도있으며유방암이나상피 38
Hyun Jung Choi, et al.: Semectomy of Intraductal Papillary Lesion Using USG Guided Localization with ICG and NIRF System Table 2. Patients Characteristics and Postoperative Data (Skin Marking Group) Case no Age Mass single or multiple Operation time (min) Resected specimen size (cm) 1 42 Single 35 6.0 2.5 2.5 2 48 Single 55 15.0 7.0 2.5 3 30 Single 45 8.0 4.0 2.5 4 41 Single 30 5.0 3.2 2.0 5 51 Single 45 7.0 5.0 2.0 6 43 Single 30 5.5 2.5 2.0 7 23 Single 25 2.5 1.5 0.8 8 51 Single 40 3.0 2.5 1.5 9 54 Single 35 5.5 2.5 2.0 10 44 Single 55 7.0 6.0 2.0 Median 42.7 39.5 6.45 3.67 1.98 내암등의발생률이높고수술시암을동반하고있는경우도있는종양이며비정형세포의과증식을동반하기도하기때문에수술적절제가필요한것으로알려져있다. (1,2) 그러나이병변은보통크기가크지않고잘만져지지않기때문에수술적절제에있어병변을찾아절제하는것은쉽지않다. 따라서수술전에 MRI를사용하여병변을확인하는방법이있으나비용적인면에서효율성이없으며수술중정확도가떨어지는단점이있다.(11,12) 통상쓰는와이어를이용한 ductoscope 로유관내병변을찾아보는방법은유관으로 scope 을넣고와이어를넣어병변을넓게하면서병변을찾아절제하는것이이상적이나이러한방법은병변에확실하게접근할수없으며수술후병변이확실하게절제되었는지육안으로확인할수없다. 이에따라광범위하게유방절제술을시행할수밖에없게된다. 또한 ductoscope 를사용하는데익숙한숙련된술자가아니면어려운수술방법이기도하다.(3,4) 이방법이외에도메틸렌블루등을사용하기도하나메틸렌블루는유방실질조직으로들어가게되면수술하고있는유방조직이메틸렌블루로인하여염색되어병변주위가흐려지고경계가분명하지않아시야가뿌옇게되어정확하게병변을알수없고결국완전절제연을확보하기위해무리하게광범위한유방절제술을시행할수밖에없게된다.(5-7) 초음파유도하에 hook wire를사용하여 localization 을시행하는방법은수술실에서한다면시간을줄일수있으나수술중절개창을열고시야확보를위해움직이다보면 wire가빠지거나위치가움직여지면서변동이생기 게될수있는경우가있어병변에정확하게접근하기어려울수있다. 본연구방법을이용하면수술중에도 hook wire 처럼위치가바뀌거나병변이벗어나게된다던지빠진다든지하는경우가없이수술도중에계속해서형광카메라를비추면서확인가능하기때문에정확도가떨어지지않는다. 또한 ductoscope 를사용하여와이어를넣는방법도수술시간이외에수술실에하든, 수술실들어오기전에하든준비시간이꽤필요하다는단점이동반된다.(5,6) 그러나본연구방법을사용하면환자가불편하거나통증을느끼는불편감을없앨수있어고통을줄일수있다. 또한술자도수술전에시간을들여병변을찾는시간을줄일수있으며이에따라수술시간및수술전준비시간그리고환자가준비하는데사용하는시간을절약할수있는장점이있다. 메텔렌블루는비용적인면에서는유용하지만염증반응등을일으켜유방조직이나피부병변에이물질을만들거나괴사를만드는부작용이동반될수있다.(13) 그러나메틸렌블루와같은단점이인도시아닌그린에서는없다. 인도시아닌그린과생리식염수를혼합한용액은인체에반응을일으키지않고부작용을일으키지않는물질로이러한부작용이적은물질이며 FDA 의승인을받았으며본센터에서도승인을받아사용하였으며환자에게도상기염증반응으로인한부작용은없었다.(9,10) 초음파유도하에병변으로인도시아닌그린과생리식염수를혼합한용액을주입하는것은 targeting 하는시간이길게걸리지않는다. 그렇기때문에단시간에수술할수있으며수술시간이매우단축되어본연구에서는평균 36.5분밖에걸리지않았다. 또한수술실에서환자에게통증이나불편감을주지않고도사용할수있으며바로초음파화면을통하여유관이늘어나면서병변에정확하게용액이들어갔는지를실시간으로확인할수있으며본연구에서도 10건에서모두 100% 의정확도를보였다. 본연구방법은수술하는도중에도병변의절제연을확인하면서술자가수술할수있는것이큰장점이다. 다른방법과달리수술에서의수술시야를흐리거나방해하지않으면서도근적외선형광카메라를비추면바로염색된곳이보이기때문에수술중정확한병변확인이가능하며절제면을확실히확인하여절제조직을최소화할수있다. 또한정확하게절제되어절제연이확실히확보되었는지 39
J Surg Ultrasound Vol. 4, No. 2, 2017 를절제조직에근적외선형광카메라를직접절제조직에비추어한번더확인할수있다 (Fig. 6C). 본연구방법은절제면이적어지게되어유방의모양변형을막을수있고수술후생기는통증그리고장액종등의부작용을줄일수있어환자의불편감을줄여줄수있으며, hook wire을사용한 localization에비하여술자에게도쉽게수술중정확하면서도간편하게그리고필요한만큼절제연을최소화하여수술시간을단축시킬수있음을알수있으므로매우의미가크다고하겠다. 그러나본연구는 10건을대상으로하여사례가많지않고비교군또한사례가적어좀더많은사례를모아추가적인연구를진행하는것이필요하겠다. 결 론 초음파유도하에병변에인도시아닌그린용액을주입하고근적외선형광카메라를이용하는방법으로관내유두종병변을절제하는것은환자와술자에게매우유용하다고하겠다. 다만증례가많지않고비교군도적어이에대한추가적인연구가필요하다. REFERENCES 1. Foulkes RE, Heard G, Boyce T, Skyrme R, Holland PA, Gateley CA. Duct excision is still necessary to rule out breast cancer in patients presenting with spontaneous bloodstained nipple discharge. Int J Breast Cancer 2011;2011:495315. 2. Locker AP, Galea MH, Ellis IO, Holliday HW, Elston CW, Blamey RW. Microdochectomy for single-duct discharge from the nipple. Br J Surg 1988;75:700-1. 3. Ma XP, Wang W, Kong Y, Ren Y, Liu SJ, Gao J, et al. A novel light-emitting wire enhances the marking and visualization of pathologic mammary ducts during selective microdochectomy. Ann Surg Oncol 2016;23: 796-800. 4. Ohno T, Inoue K, Nagayoshi S, Fukuda T, Irie J. A novel duct-lobular segmentectomy for breast tumors with nipple discharge using near-infrared indocyanine green fluorescence imaging. Asian J Surg 2013;36:170-3. 5. Simpson JS, Connolly EM, Leong WL, Escallon J, McCready D, Reedijk M, et al. Mammary ductoscopy in the evaluation and treatment of pathologic nipple discharge: a Canadian experience. Can J Surg 2009; 52:E245-8. 6. Hahn M, Fehm T, Solomayer EF, Siegmann KC, Hengstmann AS, Wallwiener D, et al. Selective microdochectomy after ductoscopic wire marking in women with pathological nipple discharge. BMC Cancer 2009;9:151. 7. Youn HJ, Kang SY, Jung SH. Usefulness of intraoperative ultrasound in breast and thyroid surgery. J Surg Ultrasound 2016;3:1-6. 8. Aoyama K, Kamio T, Ohchi T, Nishizawa M, Kameoka S. Sentinel lymph node biopsy for breast cancer patients using fluorescence navigation with indocyanine green. World J Surg Oncol 2011;9:157. 9. Tafra L, Lannin DR, Swanson MS, Van Eyk JJ, Verbanac KM, Chua AN, et al. Multicenter trial of sentinel node biopsy for breast cancer using both technetium sulfur colloid and isosulfan blue dye. Ann Surg 2001;233:51-9. 10. Kern KA. Concordance and validation study of sentinel lymph node biopsy for breast cancer using subareolar injection of blue dye and technetium 99m sulfur colloid. J Am Coll Surg 2002;195:467-75. 11. Lorenzon M, Zuiani C, Linda A, Londero V, Girometti R, Bazzocchi M. Magnetic resonance imaging in patients with nipple discharge: should we recommend it? Eur Radiol 2011;21:899-907. 12. Ballesio L, Maggi C, Savelli S, Angeletti M, De Felice C, Meggiorini ML, et al. Role of breast magnetic resonance imaging (MRI) in patients with unilateral nipple discharge: preliminary study. Radiol Med 2008; 113:249-64. 13. Bleicher RJ, Kloth DD, Robinson D, Axelrod P. Inflammatory cutaneous adverse effects of methylene blue dye injection for lymphatic mapping/sentinel lymphadenectomy. J Surg Oncol 2009;99:356-60. 40