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3 INVITATION 안녕하십니까? 자연의싱그러움과생명의경이로움을느끼는여름이시작되었습니다. 여러가지업무로바쁘신가운데 6월을맞이하여여러선생님들의건승을기원합니다. 만성골반통에대한선생님들의뜨거운관심에힘입어 6월 23일 ( 일 ) 제3차만성골반통학회학술대회및연수강좌를개최하게되었음을알려드립니다. 만성골반통이많은관심을받고는있지만여전히그원인규명에괄목할만한성과가부족하여여성들의건강과삶의질에상당히심각한영향을끼치고있고그원인에대한감별진단과치료에아직도많은시간과노력이필요한상황입니다. 금번학술대회및연수강좌를통해서만성골반통교과서소개와더불어외래에서할수있는만성골반통의감별진단및치료, 그리고만성골반통의극복을위한다학제적인접근에대한최신지견들을접할수있는기회를마련하였습니다. 또한지난수십년간의만성골반통환자에대한경험과자궁내막증에대한 Know-how 를여러선생님들과함께공유하는자리를갖고자합니다. 이번학술대회를통해서만성골반통및자궁내막증환자들을진료할때느꼈을애로사항과궁금증들이많은부분해소가될것으로기대합니다. 만성골반통에관심이있으신여러선생님들께는금번학술대회및연수강좌가활발한지식교류와친목도모를넘어대학과개원가가함께상생할수있는매우뜻깊은자리가될것이라확신하며바쁘신와중에도금번의학술대회및연수강좌에참석하셔서만성골반통분야의미래를위한고견을주시기를진심으로희망합니다. 그동안학술대회준비를노고를아끼지않으신여러관계자여러분들께깊은감사의말씀을드리며여러분가정에주님의은혜가늘함께하시기를기도드립니다. 감사합니다 년 6 월 대한만성골반통학회회장허주엽

4 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 P R O G R A M 08:30-08:50 Registration 사회이은주 ( 중앙의대 ) 08:50-09:00 Opening Ceremony & Introduction of Korea CPP Society 회장허주엽 ( 경희의대 ) I. CPP 진단 TIP 좌장 : 김흥열 ( 고신의대 ), 김동호 ( 중앙의대 ) 09:00-09:15 1. CPP 진단의최신경향 나용진 ( 부산의대 ) / 3 09:15-09:30 2. 만성골반통환자의감별진단및꼭필요한검사 박은주 ( 을지의대 ) / 13 09:30-09:40 Q and A II. Office Based Treatment I 좌장 : 홍서유 ( 을지의대 ), 김홍배 ( 한림의대 ) 09:40-09:55 1. The Recent Trend in Treatment of Chronic Pelvic Pain 최영준 ( 경희의대 ) / 29 09:55-10:10 2. 미혼여성의효과적생리통관리 고석봉 ( 대구가톨릭의대 ) / 40 10:10-10:25 3. 만성골반통환자의효과적약물치료선택과부작용 지용일 ( 인제의대 ) / 51 10:25-10:35 Q and A 10:35-10:55 Coffee Break III. PRESIDENT s SYMPOSIUM Meet the Expert 좌장 : 장윤석 ( 마리아병원명예원장, 서울의대명예교수 ) 10:55-11:30 만성골반통클리닉 - 환자의진단및치료 Know-How 허주엽 ( 경희의대 ) / 61 11:30-11:35 Q and A 11:35-12:15 IV. 일반연제좌장 : 배동한 ( 순천향의대 ) LUNCH SYMPOSIUM 좌장 : 조삼현 ( 한양의대 ) 12:15-12:25 1. 만성골반통교과서어떤내용들이있나? 박형무 ( 중앙의대 ) / 77 12:25-12:40 2. CPP 진료후효과적인의료보험청구 전호용 ( 다나산부인과 ) / 85 12:40-13:20 LUNCH

5 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 사회주종길 ( 부산의대 ) V. Office Based Treatment II 좌장 : 백원영 ( 경상의대 ), 정혜원 ( 이화여대 ) 13:20-13:35 1. 만성골반통으로인한성교통과음문통의진단과치료는? 김탁 ( 고려의대 ) /101 13:35-13:50 2. Treatment of Unexplained Chronic Pelvic Pain 정혁 ( 조선의대 ) /108 13:50-14:05 3. CPP 치료의 Medical and Surgical Treatment 실패시무엇을해야하나? 이철민 ( 인제의대 ) /123 14:05-14:15 Q and A VI. Office Based Treatment III: Perfect Master of CPP Control 좌장 : 이규섭 ( 부산의대 ), 오한진 ( 관동의대 ) 14:15-14:30 1. 개원가에서할수있는다양한 TPI의 Perfect Master 조창식 ( 닥터조의원 ) /135 14:30-14:45 2. 통증치료의임상적용 Case 보고 강민아 ( 누리여성의원 ) / :45-14:55 Q and A 14:55-15:15 Coffee Break VII. Special Lecture 좌장 : 김정구 ( 서울의대 ), 조진호 ( 차의과대학 ) 15:15-15:30 1. Visanne : A New Vision for Endometriosis Treatment 이은주 ( 중앙의대 ) /153 15:30-15:45 2. Current Management of Bladder Pain Syndrome (BPS) / Interstitial Cystitis (IC) 이형래 ( 경희의대 ) /168 15:45-15:55 Q and A VIII. State-of-the-Art SYMPOSIUM 좌장 : 김장흡 ( 가톨릭의대 ) 15:55-16:20 내가경험한자궁내막증환자의진단및치료의 Knowhow 오성택 ( 전남의대 ) /185 16:20-16:30 Q and A 16:30-16:40 시상식회장허주엽 ( 경희의대 ), 오성택 ( 전남의대 ) 16:40 Closing 회장허주엽 ( 경희의대 )

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7 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 I. CPP 진단 TIP 좌장 : 김흥열 ( 고신의대 ), 김동호 ( 중앙의대 )

8 2013 년대한만성골반통학회 제 3 차학술대회및연수강좌

9 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 CPP 진단의최신경향 나용진 부산대학교의과대학 Chronic Pelvic Pain (CPP) Noncyclic pain that lasts 6 months or more Localized to pelvis (below umbilicus or buttock) Enough to cause functional disability or require treatment Reiter RC, Clin Obstet Gynecol 1990 Referrals to gynecologist : 10% Indication of all hysterectomies for benign disease : 20% Gynecologic diagnostic laparoscopy : over 40% Farquhar CM, Obstet Gynceol 2002; Howard FM, Obstet Gynecol Surv 1993 Woman with CPP usually want to - receive personalized care from their physicians - be taken seriously - receive an explanations for their condition (more so than a cure) -be reassured 3 major points in CPP evaluation - Complete history - Physical examination - Counseling 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 3

10 I. CPP 진단 TIP Evaluation of CPP History Physical examination Diagnostic tests History Characteristics of pain quality, duration, modifying factors, association with menses, sexual activity, urination, defecation Should ask sexual or physical abuse Red flag symptoms unexplained weight loss, hematochezia, perimenopausal irregular bleeding, postmenopausal vaginal bleeding, postcoital bleeding prompt investigation to rule out malignancy or serious systemic disease Ortiz DD, Am Famil Physis 2008 IPPS Pelvic pain assessment form Extensive review of systems Reproductive Urological Gastrointestinal Screening questionnaire for sexual and physical abuse, somatization Pelvic pain quantification and mapping 년대한만성골반통학회제 3 차학술대회및연수강좌

11 나용진 :CPP 진단의최신경향 Characteristics of pain first occurrence, location, intensity, quality, duration, temporal pattern, precipitating and alleviating factors, relationship to urination and defecation, and patterns of radiation Record of pain intensity visual analog or numerical rating system Effect of pain on patients life work, school, social activities, relationships, exercise, sleep Pain history can help in differential diagnosis Dull and diffuse : visceral Specific location : somatic Cyclic pelvic pain : endometriosis, adenomyosis Pain before menarche : non-gynecologic cause Hot or burning pain, paresthesia : nerve entrapment Aggravated by the urge or need to void : interstitial cystitis Abdominal pain with weight loss : malignancy Reproductive history Pregnancy and childbirth : traumatic events to the musculoskeletal system especially pelvis and back may lead to CPP Difficult delivery, large infant, use of vacuum or forceps : relevant diagnostic hints if CPP begun in the postpartum period periparum pelvic pain syndrome 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 5

12 I. CPP 진단 TIP Pain map Can be helpful for localized pain Evaluation of CPP History Physical examination Diagnostic tests Physical examination It is important to proceed gently and with patience. Abdomen examination identifying areas of localized or generalized tenderness, surgical scars, hernias, and the presence of masses Pelvic examination careful evaluation of the shape, size, and mobility of the pelvic organs, as well as any areas of tenderness The goal is to identify tender areas correlate these areas with the patient's pain map determine whether the pain produced on examination represents her CPP 년대한만성골반통학회제 3 차학술대회및연수강좌

13 나용진 :CPP 진단의최신경향 Pelvic examination should begin with a single-digit, one-handed examination. Bimanual examination should be performed after singledigit examination nodularity, point tenderness, cervical motion tenderness, mobility of the uterus A moistened cotton swab should be used to elicit point tenderness in the vulva and vagina. Sharma JB, Arch Gynecol Obstet 2011 Carnett s sign Placing a finger on the painful, tender area of the patient s abdomen and having the patient raise both legs off the table while lying in the supine position Positive test = pain increases during maneuver Myofascial cause of pain : within the abdominal wall (fibromyalgia or trigger point) Ortiz DD, Am Fam Physician 2008 History Evaluation of CPP Physical examination Diagnostic tests 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 7

14 I. CPP 진단 TIP Diagnostic evaluation Laboratory CBC with differential count and ESR UA with urine culture Vaginal swabs for chlamydia and gonorrhea Pregnancy test Diagnostic evaluation Imaging study Pelvic ultrasound Identifying pelvic mass/cyst Determine origin of mass Less reliable for distinguishing between benign and malignancy MRI Better define an abnormality suspected by sonography Diagnostic for adenomyosis Cody RF, Baillieres Best Pract Res Clin Obstet Gynaecol 2000 Laparoscopy The role of laparoscopy for CPP : uncertain Absence of visible pathology is not synonymous with -no disease - no physical basis for her pain Several common disorders can be visualized Endometriosis adnexal mass Adhesions Some uterine abnormalities PID Howard FM, J Am Assoc Gynecol Laparosc 년대한만성골반통학회제 3 차학술대회및연수강좌

15 나용진 :CPP 진단의최신경향 Use of laparoscopy should be individualized adhesiolysis is not necessarily effective for relief of CPP adnexal masses and uterine abnormalities can be diagnosed noninvasively by ultrasound A negative laparoscopy by a highly experienced clinician very reliable for excluding endometriosis but, occult microscopic implants may be present submesothelially in normal appearing peritoneum Swank DJ, Lancet 2003 Laparoscopic pain mapping Conscious laparoscopic pain mapping under local anesthesia A technique that has been described in the literature for more than a decade, can be a particularly helpful tool to assist with pelvic pain diagnosis and treatment decisions Etiology may be suggested if the pain induced Ideally, this information would allow a targeted approach But, the role of conscious laparoscopicy is unclear No data from controlled study Yunker A, J Minim invasive Gynecol 2010 Ortiz DD, Am Fam Physician 년대한만성골반통학회제 3 차학술대회및연수강좌 9

16 I. CPP 진단 TIP Ortiz DD, Am Fam Physician 2008 Useful diagnostic test (I) Symptoms, findings, suspected diagnosis Potentially useful tests Adenomyosis Chronic urethral syndrome Compression neuropathy Constipation Depression Diarrhea Diverticular disease Dyspareunia USG, HSG, MRI Urodynamic testing Nerve conduction velocities, needle EMG Anorectal balloon manometry, colonic transit time TFT, CBC, RFT, LFT, electrolyte, rapid plasma regin Stool exam: parasite, RBC, WBC, culture, Cl. toxin, Barium enema, colonoscopy, UGI series, CT Barium enema Gonorrhea, chlamydia culture, Chlamydia PCR, vaginal culture, urine culture, Wet prep. vaginal ph Vercellini, Chronic pelvic pain, 1st ed. 2011; Benjamin-Pratt AR, Minerva Gynecol 2010 Useful diagnostic test (II) Symptoms, findings, suspected diagnosis Potentially useful tests Endometriosis Hernias Interstitial cystitis Ovarian remnant syndrome Pelvic congestion syndrome Pelvic tuberculosis Urethral diverticulum CA-125, USG, Barium enema, HSG, CT, MRI Abdominal wall USG, CT, Herniography Cystoscopy, KCL bladder challenge test, urine culture, cytology, urodynamic test, bladder biopsy FSH, E2, GnRH agonist stimulation test, USG ± Clomiphen stimulation, Barium enema, CT USG ± Doppler, Pelvic venography Chest X-ray, PPD skin test USG, MRI, voiding cystourethrography, double balloon cysoturethrography Vercellini, Chronic pelvic pain, 1st ed. 2011; Benjamin-Pratt AR, Minerva Gynecol 년대한만성골반통학회제 3 차학술대회및연수강좌

17 나용진 :CPP 진단의최신경향 Ortiz DD, Am Fam Physician 2008 Ortiz DD, Am Fam Physician 2008 Summary A complete history and physical examination related to the possible causes are the most valuable tool in the evaluation of CPP. Further investigations should be based on the history and physical examination findings. Evaluation must include reproductive, GI tract urologic, neurologic, musculoskeletal systems as well as psychologic factors 년대한만성골반통학회제 3 차학술대회및연수강좌 11

18 I. CPP 진단 TIP General guideline for evaluation of CPP Take a thorough history Pain mapping examination Laboratory and imaging studies should be obtained specifically to confirm or refute pain-related diagnoses derived from the history and physical examination Laparoscopy has a limited role as a diagnostic studies Those diagnoses with level A evidence of association with CPP should always be considered first 년대한만성골반통학회제 3 차학술대회및연수강좌

19 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 만성골반통환자의감별진단및꼭필요한검사 박은주 을지대학교의과대학산부인과학교실 만성골반통은하나의질환이아닌다양한원인에의해발생할수있는복합적인질환이다. 증상도중첩되고다양하여세밀한문진과진찰을통해가장가능성있는질환을예측하고이때, 증상이있는경우그질환에대해정밀검사하고, 만약없다면만성골반통증후군으로간주한다. 이러한만성골반통증후군에서, 특정기관의이상을나타내는증상이없다면바로통증관리를시작할수있다. 다학체적인골반통관리팀에의뢰하여정신과적인약물과물리치료및통증치료등을시작할수있다. 만성골반통증후군에서특정기관의이상을나타내는증상이있다면그기관에해당되는정밀검사및치료적접근을고려하면되겠다. 이러한기관특이적인증상들에는산부인과적인증상, 비뇨기과적인증상, 소화기과적인증상, 신경계, 성생활과관련된증상, 근골격계, 골반저의이상과관련된증상들이있을수있다. 골반통의임상적평가인문진과진찰을통해감별진단을어느정도예측할수있다. 문진시환자에게 Pre-wrritten pelvic pain questionnaire(available online from the international Pelvic Pain Society) 를작성하게하고이를분석한다. 병력청취로는주로통증의위치, 정도, 빈도, 완화또는악화인자, 발생당시의양상, 특성, 이에따른환자의감정적인반응과정신적인측면들로이루어져있다. 이학적검사로는시진과함께한손가락진찰및양손진찰, 직장진찰과근골격계진찰등이있다. 병력청취와이학적검사를통해다음단계의진단을위한검사를결정한다. 일차진료기관에서산부인과적인원인과비산부인과적인특히소화기계, 비뇨기과적인원인을감별해내는것이중요하다 (20% vs 37% and 31%). 실제비산부인과적인원인이더흔하기때문이다. 또한, 만성골반통의 50% 가중복되어일어날수있으므로생물학적인, 정신과적인, 사회적인요인들을고려한다학제적인접근이필요하다. 만성골반통과관련된질환은크게여섯가지질환군으로감별을요한다. 산부인과적인원인질환과비산부인과적인것을감별하고후자는비뇨기과적인질환, 위장관계질환, 근골격계질환, 신경학적인질환, 정신사회학적인질환들이있다. 산부인과적으로는 Endometriosis Chronic PID, Adhesions, Pelvic congestion syndrome, Adnexal pathology, Gynaecological malignancies 등을감별진단하고후자는 Interstitial cystitis, Irritable bowel syndrome, Pelvic floor dysfunction 등의대표적인질환들을염두에두고감별해야한다. 일차진료에서기본검사및진단검사를시행후에더정밀검사가필요하다판단되면이차진료기관으로의의뢰를한다. 일차진료에서먼저시행하는꼭필요한검사로는기본비침습적인검사에골반염증선별검사, 소변검사및소변배양검사, 통증유발점확인검사, 소변혈액클라미디아검사, 혈청 CA 125 등이있으며, 방사선과적인검사로골반초음파및혈류검사를시행한다 년대한만성골반통학회제 3 차학술대회및연수강좌 13

20 I. CPP 진단 TIP 이차진료기관으로의뢰되면일차진료에서의기본비침습적인검사는기본으로시행하고 Porphyrias 를검사하기위한소변 porphyrobilinogen 검사와 imaginig 검사로골반초음파및도플러검사, CT,MRI, Retrograde ovarian venography, transuterine pelvic venography, Intravenous urography 등을필요에따라시행하고, 침습적인방법으로진단복강경과 Concious laparoscopic pain mapping 등을시행할수있으며, 특별검사가필요하다고판단되면방광경과 KCL sensitivity tests, Barium meal, sigmoidoscopy, colonoscopy, anorectal balloon manometry, colonic transit time 등을시행할수있겠다 The European Association of Urology (EAU) Guidelines Working Group for Chronic Pelvic Pain 에서는만성골반통환자를평가하고치료하는데있어서상식적인, 단계적인가이드라인을제시하고있다. 1. 처음인지된증상들과관련된기관들의질환들을먼저고려한다. 2. 흔한질환 ( 예를들면방광염 ) 의진단을먼저시작하고진단되면이를먼저지침에따라치료한다. 3. 치료가통증에효과가없으면더정밀검사즉방광경, 초음파등이시행되어야한다. 4. 위와같은검사에어떤이상이나타나면적절하게치료한다. 5. 치료가효과가없으면통증팀으로의뢰한다. 6. 질환이진단되지않거나이상소견이검사상나타나지않으며통증팀으로의뢰한다 년대한만성골반통학회제 3 차학술대회및연수강좌

21 박은주 : 만성골반통환자의감별진단및꼭필요한검사 Contents CPP and CPPS(CPP syndrome) Algorithm for diagnosing CPP CPP 의임상적평가병력청취이학적검사 by use of Pelvic pain assessment form CPP 의원인질환의감별진단 CPP 의치료에꼭필요한검사일차진료시이차진료시 Conclusion CPP & CPPS Chronic pelvic pain (CPP) Prevalent condition which can present a major challenge to health care providers due to its complex aetiology and poor response to therapy Multifactorial condition and therefore, quite often, poorly managed Management requires knowledge of all pelvic organ systems and their association with other systems and conditions, including musculoskeletal, neurologic, urologic, gynaecologic and psychological aspects, promoting a multidisciplinary approach Chronic pelvic pain syndrome (CPPS) a subdivision of CPP the occurrence of CPP when there is no proven infection or other obvious local pathology that may account for the pain. often associated with negative cognitive, behavioural, sexual or emotional consequences, as well as with symptoms suggestive of lower urinary tract, sexual, bowel or gynaecological dysfunction Algorithm for diagnosing CPP The European Association of Urology (EAU) Guidelines Working Group for Chronic Pelvic Pain 년대한만성골반통학회제 3 차학술대회및연수강좌 15

22 I. CPP 진단 TIP Algorithm for diagnosing CPP The EAU algorithms introduce the concept of the minimum investigations required to exclude a well-defined condition -The European Association of Urology (EAU) Guidelines Working Group for Chronic Pelvic Pain 2013 Algorithms of diagnosis and treatment of CPP or CPPS Algorithms of diagnosis and treatment of CPP or CPPS 년대한만성골반통학회제 3 차학술대회및연수강좌

23 박은주 : 만성골반통환자의감별진단및꼭필요한검사 CPP 의임상적평가 History taking and physical examination Use of Pelvic pain assessment form -International pelvic pain society 2008 version History taking form Pain history, characteristics and location Family background Surgical and obstetrical history Medication and treatment history Menstrual patterns, gastrointestinal urinary symptoms Eating and exercise habits Coping mechanisms, abuse history Physical examination form Inspection Single digit and bimanual exam Rectal and musculoskeletal exam Pelvic pain assessment form pain scoring 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 17

24 I. CPP 진단 TIP pelvic pain assessment form pain mapping pelvic pain assessment form menstrual and G_-I History pelvic pain assessment urological History 년대한만성골반통학회제 3 차학술대회및연수강좌

25 박은주 : 만성골반통환자의감별진단및꼭필요한검사 pelvic pain assessment form Bladder function and symptoms CPP 의임상적평가 - 통증에대한병력청취 History GI Musculo -skeletal Endometriosis Gynecological Urological Psychitrical Site of pain Pelvis Pelvis Abdomen/ pelvis Suprapubic / flanks Back, pelvis Abdomen, others* Nature of pain Onset with menses Suppressed with COC Obvious precipitants Dull ache Dull ache Colicky Ache Sharp Mixed + +/ / /- Menses None Diet, stress UTI Bending/l ifting None Comparisons between visceral and somatic pain 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 19

26 I. CPP 진단 TIP CPP 의임상적평가 - 산부인과적인병력청취 History Endometriosis Gynecological GI urological Musculoskeletal Psychitrical Gynaecology Dysmenorrhoea, dyspareunia Menstrual disturbances Vaginal discharge Symptoms of PMS + + +/ / / (PID only) / CPP 의임상적평가 - 위장관계및비뇨기과적병력청취 History Endometriosis Gynecological GI urological Musculoskeletal Psychitrical Bowel Bloating +/ /- Intermittent constipation/ diarrhoea Relieved by defecation +/ /- Urological Dysuria, frequency, nocturia, urgency CPP 의임상적평가 - 근골격계, 정신사회학적청취 History +/ /- Endometriosis Gynecological Musculoskeletal Lumbosacral pain Prior back surgery GI urological Musculoskeletal Psychitrical Psychological Physical or sexual abuse - - +/ Social Domestic violence Alcohol and drug abuse 년대한만성골반통학회제 3 차학술대회및연수강좌

27 박은주 : 만성골반통환자의감별진단및꼭필요한검사 History (previous) CPP 의임상적평가 - 이전과거력 Gynec o- logical GI Endometriosis Urological Musculoskeletal Psychitrical Successful drug or diet therapy + (with COC) - +(with diet and Laxatives) Adhesions, pelvic surgery, PID Known endometriosis / Appendectomy - + +/ - + +/ /- ---+/- Urinary tract infections pelvic pain assessment form Physical Examination pelvic pain assessment form Physical Examination Total 18 points If above 11 points, positive 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 21

28 I. CPP 진단 TIP pelvic pain assessment form Physical Examination Moistened cotton swab should be used to elicit point tenderness in the vulva and vagina. Begin at the thighs and then move to the vestibule. Assessing for pain at 2,4,6,8,10,12 o`clock. while asking the patient to quantify the pain as mild, moderate or severe. Haefner et al, 2005 pelvic pain assessment form Physical Examination pelvic pain assessment form Physical Examination 년대한만성골반통학회제 3 차학술대회및연수강좌

29 박은주 : 만성골반통환자의감별진단및꼭필요한검사 CPP 의임상적평가 - 이학적검사 CPP 의임상적평가 - 이학적검사 CPP 의임상적평가 - 이학적검사 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 23

30 I. CPP 진단 TIP Gynecological disease CPP 의원인질환의감별진단 Non gynecological disease Endometriosis Chronic PID Adhesions Pelvic congestion Adnexal pathology Gynaecological malignancies Bowel IBS Inflammatory bowel disease Adhesions Constipation GI malignancies urological Interstitial cystitis Urethral syndrome Urological malignancies musculoskeletal Musculoskeletal Disc degeneration Nerve entrapment Myofascial syndromes Pelvic floor dysfunction Psychosocial factors CPP 의원인질환의감별진단 - 가장흔한질환, 굵은글씨체 CPP 의치료에꼭필요한검사 -primary care 1, persistent haematuria may indicate urological malignancy, calculi, glomerulonephritis and infection, and mandates further investigation of the kidneys and renal tract 년대한만성골반통학회제 3 차학술대회및연수강좌

31 박은주 : 만성골반통환자의감별진단및꼭필요한검사 CPP 의치료에꼭필요한검사 -secondary care laparoscopy Most important diagnostic study in the evaluation of chronic pelvic pain Over 40% of diagnostic laparoscopies are carried out For chronic pelvic pain, endometriosis and adhesions account for around 55% of cases No visible pathology can be identified in 35% of cases Treatment possibilities for chronic pelvic pain 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 25

32 I. CPP 진단 TIP Conclusions 1. Start by considering the organ system in which the symptoms appear to be primarily perceived. 2. Well-defined conditions, such as cystitis, should be diagnosed and treated according to national or international guidelines. 3. When treatment has no effect on the pain, additional tests, such as cystoscopy or ultrasonography, should be performed. 4. If these tests reveal any pathology, it should be treated appropriately. 5. If treatment has no effect, the patient should be referred to a pain team. 6. In the case in which no well-defined condition is present, or if no pathology is found by additional testing, the patient should also be referred to a pain team 년대한만성골반통학회제 3 차학술대회및연수강좌

33 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 II. Office Based Treatment I 좌장 : 홍서유 ( 을지의대 ), 김홍배 ( 한림의대 )

34 2013 년대한만성골반통학회 제 3 차학술대회및연수강좌

35 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 The Recent Trend in Treatment of Chronic Pelvic Pain Young-Joon Choi Kyung-Hee University College of Medicine, Department of Obstetrics & Gynecology Guidelines for CPP How about nowadays? 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 29

36 II. Office Based Treatment I Guidelines for CPP Summary of Recommendation ACOG PRACTICE BULLETIN CLINICAL MANAGEMENT GUIDELINES FOR OBSTETRICIAN & GYNECOLOGISTS NUMBER 51, MARCH 2004 Guidelines for CPP Summary of Recommendation Level A 1. Combined oral contraceptives - Should be considered as a treatment option to decrease pain from primary dysmenorrhea. 2. GnRH agonists - Effective in relieving pelvic pain associated with endometriosis and irritable bowel syndrome, as well as in women with symptoms consistent with endometriosis who do not have endometriosis. - Thus, empiric treatment with GnRH agonists without laparoscopy should be considered as an acceptable approach to treatment. 3. NSAIDs, including COX-2 inhibitors - Should be considered for moderate pain and are particularly effective for dysmenorrhea. Guidelines for CPP Summary of Recommendation Level A 4. Progestins in daily, high doses - Should be considered as an effective treatment of chronic pelvic pain associated with endometriosis and pelvic congestion syndrome. 5. Laparoscopic surgical destruction of endometriosis lesions - Should be considered to decrease pelvic pain associated with stages I III endometriosis. 6. Adding psychotherapy to medical treatment of CPP - Appears to improve response over that of medical treatment alone and should be considered 년대한만성골반통학회제 3 차학술대회및연수강좌

37 최영준 :The Recent Trend in Treatment of Chronic Pelvic Pain Guidelines for CPP Summary of Recommendation Level A 7. Presacral neurectomy - May be considered for treatment of centrally located dysmenorrhea but has limited efficacy for chronic pelvic pain or pain that is not central in its location. 8. LUNA - Also can be considered for centrally located dysmenorrhea, but it appears to be less effective than presacral neurectomy. 9. Combining LUNA or presacral neurectomy with surgical treatment of endometriosis - Does not further improve overall pain relief. Guidelines for CPP Summary of Recommendation Level B 1. GnRH agonists - Should be considered as a treatment option for chronic pelvic pain because they have been shown to relieve endometriosis-associated pelvic pain. 2. Surgical adhesiolysis - Should be considered to decrease pain in women with dense adhesions involving the bowel, but it is unclear if lysis of other types of adhesions is effective. 3. Hysterectomy - An effective treatment for CPP asw reproductive tract symptoms that results in pain relief in 75 95% of women and should be considered. Guidelines for CPP Summary of Recommendation Level B 4. Sacral nerve stimulation - May decrease pain in up to 60% of women with CPP and should be considered as a treatment option. 5. Various physical therapy modalities - Appear to be helpful in the treatment of CPP and should be considered as a treatment option. 6. Nutritional supplementation with vitamin B1 or magnesium - May be recommended to decrease pain of dysmenorrhea 년대한만성골반통학회제 3 차학술대회및연수강좌 31

38 II. Office Based Treatment I Guidelines for CPP Summary of Recommendation Level B 7. Injection of trigger points of the abdominal wall, vagina, and sacrum with local anesthetic - May provide temporary or prolonged relief of CPP and should be considered. 8. Treatment of abdominal trigger points by the application of magnets to the trigger points - May be recommended to improve disability and reduce pain. 9. Acupuncture, acupressure, and TNS therapies - Should be considered to decrease pain of primary dysmenorrhea. Guidelines for CPP Summary of Recommendation Level C 1. A detailed history and physical examination - The basis for differential diagnosis of CPP and should be used to determine appropriate diagnostic studies. 2. Antidepressants - May be helpful in the treatment of CPP 3. Opioid analgesics - can be used to provide effective relief of severe pain with a low risk of addiction but do not necessarily improve functional or psychologic status and are not well studied in patients with CPP Cochrane Review for CPP 년대한만성골반통학회제 3 차학술대회및연수강좌

39 최영준 :The Recent Trend in Treatment of Chronic Pelvic Pain The Recent Trends in CPP Tx. Medication - 1 Non-narcotic analgesics (level III) - NSAIDs, Acetaminophen, Acetylsalicylic acid - 1 st line Tx. for pain relief Hormonal Methods - OCS (level III) - Continuous progestins (level I) - GnRH agonist (level I) Growing trend to treat CPP with GnRH agonists without doing a laparoscopy first The theory ; any pelvic condition that varies with menstrual cycles will respond to suppression of the HPO axis. Endometriosis, IC, IBS, PCS, ovarian retention syndrome, and ovarian remnant syndrome The duration can be extended over 6 mos d/t add back therapy (level I) TCA (level III), Serotonin-norepinephrine reuptake inhibitor (level II), opioids (level III) The Recent Trends in CPP Tx. Medication - 2 The Recent Trends in CPP Tx. Medication 년대한만성골반통학회제 3 차학술대회및연수강좌 33

40 II. Office Based Treatment I The Recent Trends in CPP Tx. Medication - 4 The Recent Trends in CPP Tx. Surgery - 1 The Recent Trends in CPP Tx. Surgery 년대한만성골반통학회제 3 차학술대회및연수강좌

41 최영준 :The Recent Trend in Treatment of Chronic Pelvic Pain The Recent Trends in CPP Tx. Surgery - 3 The Recent Trends in CPP Tx. Surgery - 4 The Recent Trends in CPP Tx. Intervention / CAM 년대한만성골반통학회제 3 차학술대회및연수강좌 35

42 II. Office Based Treatment I The Recent Trends in CPP Tx. Intervention / CAM 년대한만성골반통학회제 3 차학술대회및연수강좌

43 최영준 :The Recent Trend in Treatment of Chronic Pelvic Pain The Recent Trends in CPP Tx. Intervention / CAM - 3 Thiamine (Vitamin B1) - Gokhale (1996) - Thiamine 100mg/d for 2 months - Disappearance of dysmenorrhea in 87% The Recent Trends in CPP Tx. Intervention / CAM - 4 Magnesium - Seifert (1989) Small RCT studies : improve Sx Variable dosage & duration in every study 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 37

44 II. Office Based Treatment I The Recent Trends in CPP Tx. Intervention / CAM 년대한만성골반통학회제 3 차학술대회및연수강좌

45 최영준 :The Recent Trend in Treatment of Chronic Pelvic Pain The Recent Trends in CPP Tx. Intervention / CAM Brown (2002) The Recent Trends in CPP Tx. Future Study 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 39

46 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 미혼여성의효과적생리통관리 고석봉 대구가톨릭병원산부인과 Dysmenorhea(painful menstruation) Acute pain : intense & sudden onset, sharp rise, short course ; anatomic reflex response Cyclic pain : definite ass. to mens period Def : most common cyclic pain Primary, secondary dysmenorrhea : asso. anatomic pathology Chronic pelvic pain(cpp) : continuous or intermittent pain in the lower abdomen, lasting for at least 6 months and not exclusively related to menstrual period or sexual intercourse. Up-regulation of normally non-painful stimuli Primary dysmenorrhea 정의 : mens. pain without pelvic pathology 특징 : within 1 to 2 yrs of menarche, ovulation cycle are established, younger women-40s 원인 : endometrial prostaglandin 생성의증가 기전 : 황체기후반에 progesterone level -> lytic enzymatic action -> phospholipids release -> arachidonic action & COX activation -> prostanoids 합성이증가 -> 자궁수축이증가 -> 생리통유발 증상 : 생리시작몇시간전부터 2-3 일지속. 진통과유사, suprapubic cramping, lumbosacral backpain, radiating ant. thigh, nausea, vomiting, diarrhea, syncopal episodes, colicky nature 년대한만성골반통학회제 3 차학술대회및연수강좌

47 고석봉 : 미혼여성의효과적생리통관리 Secondary dysmenorrhea 정의 : cyclic mens. pain with underlying pelvic pathology 특징 : years after menarche and anovulatory cycles, 1 to 2 wks before mens. flow a few days after the cessation of bleeding 원인 : endometriosis, adenomyosis, PID, IUD. 증상 : 치료 : Tx of the underlying disorder Prevalence of primary dysmenorrhea rates of 43 93% but usually above 60-70% in adolescence adult women are generally lower; for women in the US it has been estimated at 40% a major cause of school and work absence for adolescent girls estimated that 600 million working hours are lost annually in the US as a result of absenteeism due to primary dysmenorrhea Prevalence of dysmenorrhea in adolescents 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 41

48 II. Office Based Treatment I Symtoms & signs of primary dysmenorrhea 생리시작몇시간전혹은직후부터 2-3일지속 진통과유사 suprapubic cramping, lumbosacral backpain radiating ant. Thigh, nausea, vomiting Diarrhea, syncopal episodes, colicky nature V/S, bowel sound : normal Suprapubic region ; tender to palpation No upper abd. tenderness, & R/T Bimanual exam. : uterine tenderness, not occur with movement of the cervix or palpation of the adnexal structures 년대한만성골반통학회제 3 차학술대회및연수강좌

49 고석봉 : 미혼여성의효과적생리통관리 Pathophysiology of primary dysmenorrhea not been fully elucidated but prostaglandins appear to play an important role. 황체기후반에 progesterone level -> lytic enzymatic action - > phospholipids release -> arachidonic action & COX pathway activation -> prostanoids 합성이증가 -> 자궁수축이증가 -> 생리통유발 during endometrial sloughing, the disintegrating endometrial cells release prostaglandin as menstruation begins The elevated levels of prostaglandins are thought to increase myometrial contractions->uterine hypercontraction leading to uterine ischemia and sensitization of nerve endings -> peripheral nerve hypersensitivity Elevated vasopressin levels are also thought to have a role -> decreased uterine blood flow Diagnosis of primary dysmenorrhea Clinically R/O underlying pelvic pathology Pelvic exam. CBC & ESR help R/O endometritis & PID Pelvic USG Laparoscopy is not necessary at this point 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 43

50 II. Office Based Treatment I Management options for dysmenorrhea Nonsteroidal anti-inflammatory drugs (NSAIDs) : Prostaglandin synthase inhibitors, COX enzyme inhibitors Hormonal treatment : Oral contraceptives (OCs), MPA, Dienogest (Visanne), Gestrione, GnRH agonists, Danazol Surgery : Laparoscopic uterine nerve ablation (LUNA), laparoscopic presacral neurectomy (PSN) Complementary therapies : herbal preparations, acupuncture, acupressure, transcutaneous nerve stimulation (TENS ), topical heat, Vitamin B1 and B6, magnesium, low-fat vegetarian diet, omega-3 Behavioral interventions : relaxation, biofeedback, pain management & coping skills, exercise NSAIDs(PG inhibitors) 70-90% 환자에서효과 Should be taken up to 1 to 3 days before menses, continously every 6 to 8 hours to prevent reformation of PG Should be taken before or onset of pain & then continuosly (first few days), 4-6 months course of therapy Changes in dosages & types of NSAIDs Proprionic acid 유도체 : Naproxen, Ibuprofen, Ketoprofen Fenamate 유도체 : mefenamic acid, tolfenamic acid, flufenamic acid, meclofenamic acid COX-2 inhibitor : celecoxib, Cerebrex NSAIDs Drug Brand Names Recommended doses Ibprofen Brufen tab mg q6-8h Naproxen Naxen F mg q6-8h Naproxen Naxen F CR 1000 mg q24h Mefenamic acid Pontal cap, tab mg q6-8h Nafroxen sodium Anaprox, mg q6-8h El-Minawi AM and Howard FM, 2000 KIMS, 3 rd Edi., 년대한만성골반통학회제 3 차학술대회및연수강좌

51 고석봉 : 미혼여성의효과적생리통관리 NSAIDs (PG synthase inhibitors) Two serious drawbacks 1. Ceiling effects (upper limit of pain relief) Once that upper limit or ceiling is reached, taking additional medication will not provide any further pain relief. 2. Side effects mild GI systems(nausea, dyspepsia), liver, kidney, fatigue Hormonal contraceptives Indicated for primary dysmenorrhea unresponsive to NSAIDs, no contraindications to hormonal contraceptives, desire contraception Agents : combined estrogen & progestin, progesterone only Ocs (cyclic or continuous regimens), transdermal patch, vaginal ring, injectable progestin preparations, levonorgestrel-releasing IUDs directly by limiting endometrial growth and reducing the amount of endometrial tissue available for PG and LT production indirectly by inhibiting ovulation and subsequent progesterone secretion Method of Oral contraceptives (OCs) Continuous administration : 12주연속 Cyclic administration Conventionally (35 g ethinylestradiol) low-dose oral contraceptive (20 g ethinylestradiol) can statistically and clinically significantly reduce the incidence and severity of dysmenorrhea If not repond, hydrocodone or codeine may be added for 2 to 3days per month 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 45

52 II. Office Based Treatment I Aromatase inhibitors Aromatase inhibitors might be reasonable as a second-line medical treatment, but more research is required (weak) : γ Aromatase inhibitor는국소에스트로겐합성을감소시킴. Aromatase P 자궁내막증, adenomyosis, leiomyoma 환자의자궁내막에서발견. 2. 정상여성의자궁내막에서는발견되지않음. Farquhar C, 2006 Surgery for dysmenorrhea The addition of LUNA to laparoscopic removal of endometriosis does not improve pain relief (strong) : β Although PSN might benefit a small number of women, the benefits are likely to be outweighed by the potential for harmful effects (strong) : γ Level of Consensus α : > 80% agreed without caveat & < 5% disagreed β : < 80% agreed without caveat & < 5% disagreed γ : 50 ~ 80% agreed δ : < 50% agreed with or without caveat Australasian CREI Consensus Expert Panel on Trial evidence Group of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) 년대한만성골반통학회제 3 차학술대회및연수강좌

53 고석봉 : 미혼여성의효과적생리통관리 Complementary therapies for dysmenorrhea Aim : increase physical, psychological, or emotional well-being in a complementary fashion to standard medical therapy Herbal preparations, acupuncture, acupressure, transcutaneous nerve stimulation (TENS), topical heat, Vitamin B1 and B6, magnesium, low-fat vegetarian diet, omega-3 Behavioral interventions : relaxation, biofeedback, pain management & coping skills, exercise Vitamin B1 and B6 Vitamin B1, Vitamin B6, Vitamin E. Mechanism of action : Vit. B1 protects from muscle cramps and various pains. Vit. B6 related to prostaglandin E2 production, assists with myometrial relaxation and utilisation of magnesium. Vit. E has analgesic and anti-inflammatory properties. Vitamin B1 and B6 can be used to relieve pain for women with dysmenorrhea but there is limited evidence of effectiveness and there are safety concerns with vitamin B6 at higher doses (weak) : γ Magnesium Mechanism of action : Possible role in pain reduction by inhibiting calcium entry into the cell. There is some evidence of effectiveness of magnesium in reduction of pain for women with dysmenorrhea (weak) : γ 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 47

54 II. Office Based Treatment I Transcutaneous electrical nerve stimulation (TENS) Mechanism of action : Alteration of the body s ability to receive or perceive pain signals Stimulation of the skin using electrical currents at various pulse rates Adverse effects : minor There is evidence of effectiveness of TENS for short-term pain management for women with dysmenorrhea (weak) : γ- Proctor et al., 2002 Farquhar C, 2006 Acupuncture Insertion of a needle into the skin and underlying tissues in special sites, known as points, for therapeutic or preventive purposes. Mechanism of action : Possible modulation of endogenous opioids such as β-endorphins, serotonin and dopamine. There is some evidence of effectiveness of acupuncture, but it requires repeated treatments and effects are unlikely to be long lasting (weak) : γ 년대한만성골반통학회제 3 차학술대회및연수강좌

55 고석봉 : 미혼여성의효과적생리통관리 Topical heat Superficial heat such as hot water bottles, heated stones, soft heated packs filled with grain, heat pads, and infra-red heat lamps Mechanism of action : Superficial heat elevates the temperature of tissues and provides the greatest effect at 0.5cm or less from the surface of the skin Adverse effects : Mild pink tinge of skin. There is no evidence of effectiveness for topical heat (weak) : γ Behavioral interventions relaxation, biofeedback, pain management & coping skills, exercise Mechanism of action : The behavioural approach assumes that psychological and environmental factors interact with, and influence, physiological processes. There is insufficient evidence to support behavioral interventions (weak) : γ 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 49

56 II. Office Based Treatment I Conclusions Clinically R/O underlying pelvic pathology History taking & P/E are crucial 1 st line therapy : NSAIDs, Hormonal treatment Multidisciplinary 년대한만성골반통학회제 3 차학술대회및연수강좌

57 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 만성골반통환자의효과적약물치료선택과부작용 지용일 인제대학교해운대백병원산부인과학교실 만성통증은급성통증과는다른통증이므로접근방법을달리하여야한다. 급성통증은몸의방어기전으로서중요한역할이며조직이회복되면통증도완화된다. 그러나만성통증은이러한역할없이조직회복후에도통증이지속되므로진단된다. 급성통증과는달리만성통증에서는염증없이통증이지속되는경우가대부분이기에소염작용이있는약물을투여할필요가없을경우가많다. 만성통증은스트레스상태나정신과적인문제에의해좀더증폭되는신호를중심신경조직으로보내게되어나타나기때문에여러분야의전문가들의도움이필요하다. 1 만성통증조절을위한약물치료의단일원칙은없지만, 약물치료의과거력과내과적질환에대한조사가먼저이루어져야겠다. 약물은환자의나이, 과거력 ( 특히, 약물이나알코올의존성 ), 약물알레르기및다른약물부작용등을고려하여선택하고, 약물섭취전에약물의효능및부작용, 상호작용, 사용기간및이유등에대하여환자가충분히숙지하도록하여야한다. 환자는현재선택된약물이모든통증을해결할수있는것이아니다라는인식이있어야하며, 첫번째약물선택은통증의경감과함께일상생활기능을향상시키는목적으로시작한다. 2 약물치료는특정한통증에선택되는것은없으며, 약물치료가시작되면반드시주의감시하여야한다. 약물은같은효과라면좀더안정하고, 저렴한약물이좋다. 또한약물을선택하는데중요한요소로는효능이부작용에비해높아야하며추적감시가가능할수있는약물이좋다. 만성골반통환자의약물치료의선택은먼저환자의증세확인과치료의목적에따라적절한진단과정이선행되어야한다. 각각의증세에따른약물치료는사회생활로의복귀나가임력보전또한고려할대상이다. 약물치료의선택에서위장관이나비뇨기계의증세에따른내과적치료에반응할수있는정확한진단이있어야하며, 신경병증성증세에따른것이지도확인되어야할것이다. 약물요법의종류에는먼저경도에따른진통제의선택이있고, 신경병증성통증에관한약물치료가있다. 그리고, 호르몬변화를유도할수있는약물이있으며골반의긴장을완화시킬수있는약물들이있다. 약물치료의선택에있어서치료효과에따른적절한약물선택은필수적이지만, 약물치료로인한부작용도함께고려해야할대상이다 (Table 1). 약물치료의효과가극대화되어증세를정확하게조절하거나일상생활의질을높이기위해서는정신과적인요소, 특히통증에관한공포, 우울, 및공황같은증세를감별하고조절해주는것이도움이될것이다. 이러한이유로진단과치료의영역에서필요한협력이약물치료의선택에서도다학제간협진이필수적인요소이다. 그래서의료진은만성통증을호소하는환자의표현에귀를기울여일상적이지않을수있는통증의표현들을찾아내어환자의통증이어떤종류의통증인지적절하게구분할수있어야하며, 적절한약물을선택할수있어야할것이다. 만성골반통환자를관례적인 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 51

58 II. Office Based Treatment I Table 1. Commonly available drugs in chronic pelvic pain Drug Caution Non-opioid analgesics aspirin Warfarin interaction, bleeding acetaminophen Hepatic failure celecoxib CV side effect diclofenac GI,CV, renal side effect ibuprofen GI,CV, renal side effect naproxen GI,CV, renal side effect Mefenamic acid GI,CV, renal side effect Opioid analgesics Morphine Renal failure meperidine Metabolites ; renal toxic Fentanyl Available as transdermal codeine More nausea and constipation tramandol Less constipation, not to severe pain Anti-depressants amitriptyline Anticholinergic effect, arrythmia duloxetine Nausea, dry mouth, constipation nortriptyline Fewer anticholinergic effect venlafaxine Headache, seating, sedation, seizure Anticonvulsants carbamazepine Hyponatremia, allergic rash, ataxia gabapentine Renal failure, dizziness, edema pregabalin Renal failure, dizziness, edema Benxodiazepine clonazepam Sedation, memory impair Steroids prednisolone Edema, CV side effect 방법으로진단하고치료약물을선택하여치료한후에일차적으로치료를실패하게되면환자의치료에대한기대나방향은정확하지않은또는다른방향으로향하게되어점점치료가어렵게진행될수있다. 그러므로만성통증은아직까지논란의여지는있지만다양한전문가들의복합적진단과치료가추천되고있다. 비록처음에다학제적접근방법을시도하지않았지만치료의방향이잘못되었을경우에는다시한번진단및치료의방향을설정하고, 환자에게서다른방향의치료를받아들일수있는준비가된다면통증의정도가아닌적절한시간간격에따라치료관리를하여야겠다. 또한지속적인치료의관리도중요한요소중하나이며다른기관이나의사에게환자가갈경우라도지속성이보장되어야할것이다. 약물치료중에도다른전문의의진료가필요할때에는즉각적으로협진을하고, 수술적처치가필요할경우에도바로판단할수있어야겠다 (Fig. 1.). 3 Fig. 1. Management of chronic pelvic pain 년대한만성골반통학회제 3 차학술대회및연수강좌

59 지용일 : 만성골반통환자의효과적약물치료선택과부작용 만성골반통환자에서약물치료의선택 폐경후여성에서만성골반통의감소는호르몬치료를통한난소기능을비특이적으로억제함으로써골반통증을줄일수있는좋은정보가되었다. 정신과적인분석또한통증경감에많은도움과정보를줄수있으므로통증으로인한공포감이나스트레스상태를정확히알아보는것이중요하다. 몇몇환자들은내재되어있는통증에대한염려와진통제를사용하면중요한병의진단을놓칠수있다는걱정으로약물치료를거부하는경우도있다. 환자들은약물요법으로사용하는약물들의서로다른기전과효과에대해잘알지못한다. 그러므로간단하고단순한약물을사용하더라도환자에게약물의효과와부작용에관한자세한설명이필요하고, 적절한상담이이루어져야한다. 약물요법과더불어지지치료를동반함으로효과를극대화할수도있다. 약물치료를선택하기전에가장중요한것은수술이필요한사항이지감별하는것이다. 자궁내막증이있는경우증세조절을위해서수술이선행되어야할경우가있다. 악물치료의선택은주의깊은진단검사와환자의증세를잘이해하는것에서출발하여야하며, 진통제선택에있어서신경병증성통증에관한약물을추가할지에대한고찰이반드시필요하다. 만성골반통의약물치료선택과부작용 1. 만성골반통에서호르몬치료만성골반통에서호르몬약물치료에관한무작위실험에관한보고들이있는데, 프로제스토겐 (Progestogen; medroxyprogesteroneacetate) 을 4개월간사용하였을때통증점수가감소하였고, 프로제스토겐과정신과적인지지치료를하였을때에는좀더효과가좋았다는보고가있다. 4 프로제스토겐과비교하여생식샘자극호르몬방출호르몬작용제 (GnRH; goserelin) 을사용하였을때는치료후에도골반정맥촬영이나증세등의호전이지속되는것을볼수있었다 만성골반통에서일반적약물치료 1) 비마약성진통제만성골반통분야에서이약물에대한임상시험은많지않은것이사실이다. 경도의통증에서아세트아미노펜 (acetaminophen) 을우선적으로고려해야한다는보고는있다. 6 또한생리통에서약물을선택하는데있어서비스테로이드성항염제 (NSAID: nonsteroidal anti-inflammatory drugs) 나선택적 COX2 길항제 (COX2 selective drugs) 는효과적이라는것이이미증명된바있다. 6 이약제는습관성과의존성이없고비교적투약초기에부작용이마약성진통제에비해적으며, 용량증가에비해효과가늘지않는천정효과 (ceiling effect) 가있지만, 신기능, 간기능을악화시키거나치명적인위장관부작용을나타낼수도있다. 통증이염증을동반한경우라면, 비선택적인낮은효능의비스테로이드성항염제 (NSAID) 를먼저선택한다. 말초통증에주로작용하는약물그룹에는아스피린 (aspirin), 아세트아미노펜 (acetaminophen), 비스테로이드성항염제 (NSAID) 등이포함되는데, 이약물은사이클로옥시게나제회로 (cyclooxygenase) 를억제하여프로스타글란딘 (prostaglandin) 의합성을저지시킴으로써진통효과를가져온다. 통증이있을때환자들이가장먼저찾게되고, 의사들도우선적으로처방하게되는약물이지만심각한부작용을고려하여만성통증환자에게장기적으로투여하는것은일반적으로추천되지않는다. 통증조절에따라서점차높은효능의비스테로이드성항염제 (NSAID) 를먼저선택하 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 53

60 II. Office Based Treatment I 고, 65세이상으로오랫동안치료를받았거나, 다른복합적인약물로인하여위장관출혈의위험성이있는경우에는선택적 COX2 길항제를고려한다. 만성통증환자에게사용할경우에는일정기간만투여하는것이좋으며, 장기간투여할경우에는신기능과간기능을검사해봐야한다. 비스테로이드성항염제 (NSAID) 를선택하면음식물과섭취를권하거나, 위장보호제를함께처방하는것을고려한다. 비스테로이드성항염제 (NSAID) 를남용하지않고적절히이용한다면그부작용에비해더튼효과를볼수있다. 그러나, 출혈성위장질환이나궤양, 신장질환, 천식등을악화시킬수있어, 강한진통효과가필요한경우에는마약성진통제를같이사용하는것을고려하여야한다. 7 아스피린은강력한소염작용을가지고있으며경도및중증도의통증에효과가있다. 위에서흡수된지 2시간지나서혈중농도가최고에달하며복부불쾌감, 구역, 구토, 위장관출혈등을일으킬수있다. 아세트아미노펜은아스피린과유사한진통효과가있으나중추의프로스타글란딘합성을강하게억제시키며소염작용은없다. 최대투여용량은하루 4 g이며 650 mg 서방형제제를 2정씩 8시간간격으로투여할수있다. 최대용량초과시신장과간에무리를줄수있고, 특히간부전을초래할수있으므로간기능이상이나만성알코올남용의병력이있으면 50-75% 감량하여사용하고장기간사용시주기적인간기능검사가필요하다. 비스테로이드성항염제 (NSAID) 는염증의매개물들을억제하여진통효과를나타내는데아세트아미노펜에비하여부작용의위험성이크고신기능에이상이있을시는사용상에주의를요한다. 인도메타신 (Indomethacin) 은두통을, 메페남산 (mefenamic acid:pontal R ) 은설사를악화시킬수있다. 케토로락 (Ketorolac) 제제는위장관출혈증가로인해 5일이상투여는제한하고있으므로만성통증에사용하기에는부적합하다. 8 강력한항염효과와함께진통효과를가진스테로이드가있다. 포스포리파아제A2(Phospholipase A2) 의작용을방해하여아라키돈산 (arachidonic acid) 의분비를억제함으로써통증의매개체인프로스타글란딘 (prostaglandin) 과류코트리엔 (leukotriene) 의합성을줄임으로써진통효과를나타낸다. 진통효과뿐만아니라식욕을촉진하고기분을좋게하는작용들도도움이될수있으나장기투여시심각한부작용들의발생가능성을염두에두어야한다. 2) 마약성진통제아편유사약물 (Opioids) 은만성통증에분명히효과는있지만, 비뇨생식기계통에서유발되는통증에관여하는연구는많지않은것이현실이다. 다른진통제들과달리천장효과가없어용량을올릴수록더큰진통효과를기대할수있으나, 마약성진통제에대한의존성이발생하는것은이약물을선택하는어려움과동시에만성치료시전문가들의꾸준한추적관찰및감시가필요한이유이다. 흔한부작용으로는졸림, 가면, 변비, 발한, 소양증등이있으며, 장기간투여할경우에는신체의존성이발생하게되어갑자기약물을끊으면금단증세를나타내게되며때로는도취감을얻기위해약물을찾는정신적의존성이발생할수있는데최근에서방형제재는의존성발생이적은것으로알려져있다. 대사물질로인한영향도주의하여야하는데대사물질들의일부는소변으로배설되어모르핀 (morphine) 같이대사물질자체가효력이있거나메페리딘 (meperidine) 과같이대사물질이독성을가지고있어신기능장애가있는경우신중하게약물을선택하여야한다. 모르핀 (morphine) 은대표적인마약성진통제로서체내에서느리게분비되는형태의약물이다. 또한, Mu 아편유사수용체에서신경뉴우론의노르에피네프린 (norepinephrine) 과세로토닌 (serotonin) 의재흡수를억제하여진통효과를가져오는트라마돌 (tramadol) 이있다. 트라마돌은중추에작용하는마약성진통제로 80% 이상이간에서활성을띤대사물질로변환되고 90% 가신장으로배설된다. 간기능이나신기능이저하된환자에서트라마돌의반감기는두배로증가하기도하므로투약간격을늘려야한다. 펜타닐은주로경피흡수패치로사용되는강력한마약성진통제로 72시간동안혈중에고르게분포한다. 간에서사이토크롬 P-450 효소에 년대한만성골반통학회제 3 차학술대회및연수강좌

61 지용일 : 만성골반통환자의효과적약물치료선택과부작용 의해비활성, 비독성대사물질의형태로대사되어신장으로배설된다. 경구약물섭취가불가능하거나신기능이감소된환자에서비교적안전하게사용할수있다. 9,10 신경병증성통증 신경손상으로인하여뇌에서통증에관한감작이발생하여통증이발생될때에는삼환계항우울제 (tricyclic antidepressants) 또는항경련제 (anticonvulsants) 등의약물을사용함으로써신경병증성통증에대한효과를증대시킬수있다. 신경병증성통증에서세로토닌재흡수억제제 (Serotonin reuptake inhibitors) 도사용할수있는데그효과는항우울제 (antidepressants) 보다낮은것으로알려져있다. 11 gabapentin 은만성신경병증성통증에많이사용되는약물로삼환계항우울제보다오히려저녁에숙면을도와주는역할이있는데, 이전에사용되던항경련제들이심각한부작용을일으킬수있는데반해비교적심각한부작용이없다는장점도가지고있다. 부작용으로졸림, 어지러움, 운동실조등이있다. 11 카르바마제핀 (carbamazepine) 은신경병증성통증에서가장많이사용되었지만진정, 현기증, 운동실조등의부작용과골수억제작용, 간기능저하등의부작용에대한우려로잘사용되지않고있다. N-methyl-D-aspartate (NMDA) receptor complex 는만성통증의발생과유발의중요한경로인데, 이경로의길항작용을하는약물인케타민 (ketamine) 은만성신경병증성통증에유용하다. 12 또한케타민은마약성진통제로효과가없거나약물치료에잘반응하지않는만성골반통에사용할수있는약물이다. 13 섬망과혈압상승, 타액분비과다등의부작용이있는데섬망은벤조디아제핀 (benzodiazepine) 계통의약물을미리투여하여줄일수있다. 또한케타민은강한의존성이있는약물로각별한주의가필요한약물이다. 13 리도케인 (lidocaine) 같은 sodium channel blocker은낮은혈중농도만으로신경병증성통증에유용할수있다. 통증수용체에영향없이한번주입으로몇달효과를볼수있지만이약물은숙련된전문가들이사용하고유지하여야한다. 경구제로는멕시틸 (mexiletine) 이같은환경에서도움이될수있는약물이다. 14,15 만성신경병증성통증이있는경우우선적으로삼환계항우울제 (TCA) 를선택하는데, 저용량으로시작하여도 30~50% 정도의효과를볼수있다. 만성통증환자들에게서우울증이동반되는경우가흔하고우울증이동반된환자들은통증에대하여더민감하다. 항우울제는통증에대한역치 (threshold) 를올리는데진통효과는투여후주로 1주일정도지나야나타난다. 가장흔한부작용은졸림이므로주로잠들기전에복용하도록하며이런부작용은통증과불면증이동반된환자들에게는도움을줄수도있다. 다른부작용으로는항콜린작용에의해입마름, 변비, 시력불선명, 심계항진등이나타날수있으며, 심장에서전도장애를일으킬수도있다. 삼환계항우울제의용량은각개인마다커다란차이가있어소량으로시작하여수일간에걸쳐진통효과가나타날때까지용량을서서히올린다. Fluoxetine 이나 paroxetine 같은선택적세로토닌재흡수억제제 (SSRI: selective serotonin reuptake inhibitor) 들은삼환계항우울제의부작용이없는장점이있지만통증에는효과가적다. 16,17 1차약물이잘듣지않는경우에는이차적으로 gabapentin 나 pregabalin 을사용한다. 3차약물로는 serotonin norepinephrine reuptake inhibitors (SNRIs) 를사용할수있으며삼환계항우울제 (tricyclic antidepressant) 보다는선택적으로좋은효과를보인다. 또한삼환계항우울제와는달리졸음을초래하지않아잠들기전에복용할필요는없지만오심이흔하게나타나는부작용이다. 마지막단계로마약성진통제, tramadol and tapentadol 등을사용한다. 그밖에 Baclofen, cyclobenzaprine, diazepam, methocarbamol 등과같이통증의원인중일부가불수의적인근육수축에의한것으로판단되면근이완제들이도움이될수있다. 졸림, 근력약화, 시력불선명등의부작 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 55

62 II. Office Based Treatment I 용이발생할수있고일부약물은갑자기사용을중단할때에는발작을일으킬수도있다. 항불안효과뿐만아니라근이완, 항경련, 수면을유발하는작용들을가지고있어흔히처방되는벤조디아제핀 (benzodiazepine) 계의약물이있다. 일정기간지나면용량을올려야하는문제점이따르게된다. 장기복용하면신체적의존성에의해금단증상이나타날수있다. 의존성이나타나지않는 diphenhydramine 이나 hydroxyzine 과같은항히스타민제를대체사용할수있다. 결론 만성통증은그원인이복합적이어서환자의인지기능, 일상생활수행능력, 동반질환등을모두고려하여원인에따른치료가함께이루어져야한다. 치료약물의선택은환자의신장기능이나간기능등을고려하여선택하고부작용에대한검토가반드시필요하며개별화된통증평가방법을선택하여주기적으로통증을재평가하여야한다. REFERENCES 1. Kim JH, Choi YS. Chronic Pain Assessment and treatment inthe elderly. Korean J Clin Geri 2008; 9: Park HJ, Moon DE. Pharmacologic management of chronicpain. Korean J Pain 2010; 23: Selfe SA, Matthews Z, Stones RW. Factors influencing outcome inconsultations for chronic pelvic pain. J Womens Health 1998; 7: Farquhar CM, Rogers V, Franks S, Pearce S, Wadsworth J, Beard RW.A randomized controlled trial of medroxyprogesterone acetate andpsychotherapy for the treatment of pelvic congestion. Br J ObstetGynaecol 1989; 96: Soysal ME, Soysal S, Vicdan K, Ozer S. A randomized controlled trialof goserelin and medroxyprogesterone acetate in the treatment ofpelvic congestion. Hum Reprod 2001; 6: Zhang WY, Li Wan Po A. Efficacy of minor analgesics in primarydysmenorrhoea: a systematic review. Br J ObstetGynaecol 1998;105: Furniss LD. Nonsteroidal anti-inflammatory agents in the treatment ofprimary dysmenorrhea. Clin Pharm 1982;1: Milsom I, Andersch B. Effect of ibuprofen, naproxen sodium andparacetamol on intrauterine pressure and menstrual pain in dysmenorrhoea.br J ObstetGynaecol 1984;91: Trescot AM, Helm S, Hansen H, Benyamin R, Glaser SE,Adlaka R, Patel S, Manchikanti L. Opioids in the managementof chronic noncancer pain: an update of American Socisety ofthe Interventional Pain Physicians (ASIPP) Guidelines, PainPhysician 2008;11:S5-S McQuay H. Opioids in pain management. Lancet 1999;353: Rowbotham M, Harden N, Stacey B, Bernstein P, Magnus-Miller L.Gabapentin for the treatment of postherpetic neuralgia: a randomizedcontrolled trial. JAMA 1998;280: 년대한만성골반통학회제 3 차학술대회및연수강좌

63 지용일 : 만성골반통환자의효과적약물치료선택과부작용 12. Graven-Nielsen T, Aspegren Kendall S, Henriksson KG, Bengtsson M,Sorensen J, Johnson A, et al. Ketamine reduces muscle pain, temporalsummation, and referred pain in fibromyalgia patients. Pain 2000;85: Sorensen J, Bengtsson A, Backman E, Henriksson KG, Bengtsson M.Pain analysis in patients with fibromyalgia. Effects of intravenousmorphine, lidocaine, and ketamine. Scand J Rheumatol 1995;24: Galer BS, Harle J, Rowbotham MC. Response to intravenous lidocaineinfusion predicts subsequent response to oral mexiletine: a prospectivestudy. J Pain Symptom Manage 1996;12: Boas RA, Covino BG, Shahnarian A. Analgesic responses to i.v.lignocaine. Br J Anaesth 1982;54: Chen H, Lamer TJ, Rho RH, Marshall KA, Sitzman BT, GhaziSM, Brewer RP. Contemporary management of neuropathicpain for the primary care physician. Mayo ClinProc 2004; 79: Argoff CE, Backonja MM, Belgrade MJ, Bennett GJ, ClarkMR, Cole BE, Fishbain DA, Irving GA, McCarberg BH,McLean MJ. Consensus guidelines: treatment planning andoptions. Mayo ClinProc 2006; 81:S12-S 년대한만성골반통학회제 3 차학술대회및연수강좌 57

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65 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 III. PRESIDENT s SYMPOSIUM Meet the Expert 좌장 : 장윤석 ( 마리아병원명예원장, 서울의대명예교수 )

66 2013 년대한만성골반통학회 제 3 차학술대회및연수강좌

67 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 만성골반통클리닉 - 환자의진단및치료 Know-How 허주엽 경희대학교의과대학산부인과학교실 만성골반통의시작 만성골반통학회창립 2005년 7월만성골반통모임결성및교류시작 2005년 12월만성골반통연구회발족 2006년 9월제1차만성골반통연수강좌 2008년 1월제1회만성골반통 Expert Meeting 2009년 5월만성골반통환우회모임결성및환자가이드북발간 ( 현재 3차개정판발행 ) 2010년 11월대한만성골반통학회창립발기인모임 2011년 7월제1차대한만성골반통학회학술대회및연수강좌 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 61

68 III. PRESIDENT s SYMPOSIUM (Meet the Expert) 언론홍보및무료검진 년대한만성골반통학회제 3 차학술대회및연수강좌

69 허주엽 : 만성골반통클리닉 - 환자의진단및치료 Know-How 방송을통한만성골반통의저변확대 만성골반통소개 CPP is a Significant and Common Disorder in Women Need medical Care Not symptom, Disease Entity CPP accounts for 10% of referrals for OB/GYN visits over 40% of laparoscopies 18% of hysterectomies Reiter RC. A profile of women with chronic pelvic pain. Clin Obstet Gynecol Patients with CPP have significantly lower general health scores compared with patients without CPP 만성골반통진료의애로사항 An unpleasant sensory and emotional experience associated with actual or potential tissue damage Why is Chronic Pelvic Pain so Different / Difficult / Unsatisfactory Difficult to diagnose. Difficult to treat. Difficult to cure 년대한만성골반통학회제 3 차학술대회및연수강좌 63

70 III. PRESIDENT s SYMPOSIUM (Meet the Expert) Copyright IASP(International Association for the Study of Pain), September 2007 www. Iasp-pain.org 만성골반통의진단 문진 질병의양상과정도, 병력, 스트레스와우울증 부인과진찰 자궁부속기및자궁경부, 질회음부상태를파악 일반검사 혈액검사, 갑상선검사, 방사선검사 정밀검사 스트레스에대한면역검사, 자율신경검사 Screening 정밀초음파 CT angio, MRI 혈관조영술 진단복강경 증례초음파 년대한만성골반통학회제 3 차학술대회및연수강좌

71 허주엽 : 만성골반통클리닉 - 환자의진단및치료 Know-How 증례 CT angio 증례 MRI Adenomyosis vs. Myometrial contraction 감별진단 Gynecologic Endometriosis Primary Dysmenorrhea Leiomyomas Dyspareunia Vaginismus Adenomyosis Infectious causes Pelvic congestion syndrome Pelvic organ immobility Cancer 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 65

72 III. PRESIDENT s SYMPOSIUM (Meet the Expert) 자궁내막증과의연관관계 A Fauconnier et al. Human Reproduction Update 2005 자궁내막증병변 스트레스의평가 Chronic stress & Acute stress Pituitary Gland, Hypothalamus and Amygdala Adrenal glands ; Secrete hormones Epinephrine / Cortisol/ Glucocorticoids Increased glucocorticosteroids weaken immune system reduce bone mass reproductive suppression memory problems Anxiety, Depression, Tension, Sleeping problems 년대한만성골반통학회제 3 차학술대회및연수강좌

73 허주엽 : 만성골반통클리닉 - 환자의진단및치료 Know-How 골반장기의반응 Vagina Uterus Cervix Tube Ovarian Ligament Ovary Endocrine glands brain Vaginismus prevent coitus Changing uterine blood flow Changing uterine motility, Uterine contraction Congested, cyanotic or violet color Uterotubal spasm Contraction of ovarian ligament Excessive stress may even lead to complete suppression of the menstrual cycle In less severe cases, it could cause anovulation or irregular menstrual cycles. the pituitary gland produces increased amounts of prolactin, and elevated levels of prolactin could cause irregular ovulation brain produces special molecules called neuropeptides, in response to emotions, and these can interact with every cell of the body, including those of the immune system lack of sexual desire Visceral Pain Pain that is caused by activation of pain receptors from infiltration, compression, extension or stretching of the thoracic, abdominal or pelvic viscera (chest, stomach and pelvic areas). IN RESPONSE TO: distention, stretching, chemical irritation, hypoxia, inflammation Referred Pain Noxious stimulus from an internal organ perceived as radiating from more superficial region Ovary T10 umbilical area Uterus T12 lower abdominal wall Vagina L1 skin over groin 통증의표현 고동치는통증 끊임없이갉는통증 Ballard et al. Fertil Steril 년대한만성골반통학회제 3 차학술대회및연수강좌 67

74 III. PRESIDENT s SYMPOSIUM (Meet the Expert) 통증의표현 Ballard et al. Fertil Steril 2009 만성골반통의발생 Functional Symptoms Somatic presentation among patients with depression or anxiety Organic Causes 병력청취 Psychological Causes; Level A Depression Somatization Personality disorder History of abuse (verbal/ physical/ sexual)? Diagnosis of psychiatric disease? Association with life stressors? Exacerbated by life stressors? Family/ spousal support? 년대한만성골반통학회제 3 차학술대회및연수강좌

75 허주엽 : 만성골반통클리닉 - 환자의진단및치료 Know-How 내과적치료 Oral analgesics Tri-cyclic antidepressants Anxiolytics Anticonvulsants Medroxyprogesterone Acetate Gonadotropin releasing hormone analogue Marital / Partner Counseling (or Education) 복강경수술 Standardized & thorough manner routine part of evaluation of CPP diagnosis or r/o endometriosis and adhesions General Survey of the Pelvis Scarring Area that correlate with pelvic tenderness Pelvic sidewall Post. Broad ligament 복강경수술의장점 patient reassurance differentiation between gyn and non-gyn etiology r/o serious or malignant disease increased accuracy of diagnosis immediate surgical treatment is often possible 년대한만성골반통학회제 3 차학술대회및연수강좌 69

76 III. PRESIDENT s SYMPOSIUM (Meet the Expert) 복강경소견 no visible pathology - 35% ; Occult somatic pathology - 47% in CPP and negative laparoscopic finding Endometriosis - 33% pelvic adhesion 24% chronic PID 5% ovarian cyst 3% pelvic varicosities - <1% Myomas - <1% Others - 4% 수술적치료 Resection/ablation of lesions Lysis of adhesions Interruption of neural pathways: LUNA (laparoscopic uterine nerve ablation) presacral neurectomy : resection of superior hypogastric plexus Hysterectomy with BSO Surgical management of non-gynecologic causes. 복강경시음성소견의환자 Hysterectomy More marked improvement in symptoms and quality of life than non-surgical therapy. Pain after hysterectomy Intrinsic vaginal apex pain laparoscopic vaginal apex revision. Residual ovary surgical removal Ovarian remnant syndrome laparoscopic dissection. Postoperative adhesion laparoscopic lysis Occult somatic pathology unrelated to the female reproductive organs 년대한만성골반통학회제 3 차학술대회및연수강좌

77 허주엽 : 만성골반통클리닉 - 환자의진단및치료 Know-How 국소질내주사요법 Topical effect Steroid Mistletoe Lidocaine 2 주간격시행 수술후약물요법 면역강화제 Oral analgesics Prokinetics & Visceral analgesics Anxiolytics 미슬토치료 ABNOBA viscum Helixor 면역증강작용을하는미슬토를이용한주사로서독일의의학자 Rudolf Steiner 에의해창안되어주로유럽지역 ( 독일, 영국, 오스트리아, 스위스 ) 중심으로발전되어온전통면역치료방법 종양치료와완화의학의중요한부분으로인식 면역기능의향상이요구되는많은질환에적용 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 71

78 III. PRESIDENT s SYMPOSIUM (Meet the Expert) Conclusion 1. 환자의문진을통해서병력과현재의통증의정도를파악하는것이중요하다. 2. 환자와의관계형성을통해신뢰관계를구축한다. 3. 정확한진단방법을적용하여잠재질환을놓치지않도록한다. ( 부인과정밀초음파, 골반 MRI, 면역유세포검사등 ) 4. 명확한진단이힘들경우다학제적인접근을통해서최대한환자의삶의질을향상시키도록한다. 5. 약물치료시가능한한마약성진통제는피하도록한다. 6. 환자의병을함께치료한다는개념으로환자의질병에대한자세와치료에대한지식을교육하고자세한상담을시행한다. 7. 수술적치료시유착된부위는상복부에서하복부까지가능한한모두제거하고필요한경우조직검사를시행한다. 8. 폐경이되지않았을경우가능한한난소를보존하도록한다. 9. 수술적치료만으로질병이모두호전되는것은아니므로수술후약물치료에대한설명을통해환자가치료에잘순응하도록한다 년대한만성골반통학회제 3 차학술대회및연수강좌

79 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 IV. 일반연제 좌장 : 배동한 ( 순천향의대 )

80 2013 년대한만성골반통학회 제 3 차학술대회및연수강좌

81 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 LUNCH SYMPOSIUM 좌장 : 조삼현 ( 한양의대 )

82 2013 년대한만성골반통학회 제 3 차학술대회및연수강좌

83 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 만성골반통교과서어떤내용들이있나? 박형무 중앙대학교의과대학 / 대한만성골반통학회편집위원장 만성골반통 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 77

84 Lunch Symposium 대한만성골반통학회만성골반통의출간 2005 년 7 월첫모임을시작으로 12 월연구회발족 2010 년 11 월정식으로대한만성골반통학회출범 2012 년 7 월만성골반통출간을위한원고작업시작 2012 년 11 월만성골반통출간을위한편집회의 2013 년 2 월 28 일만성골반통출간 발간사 년대한만성골반통학회제 3 차학술대회및연수강좌

85 박형무 : 만성골반통교과서어떤내용들이있나? 추천사 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 79

86 Lunch Symposium 년대한만성골반통학회제 3 차학술대회및연수강좌

87 박형무 : 만성골반통교과서어떤내용들이있나? 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 81

88 Lunch Symposium 만성골반통의특성 1 기초연구와최신치료방법들을포괄하여정리 년대한만성골반통학회제 3 차학술대회및연수강좌

89 박형무 : 만성골반통교과서어떤내용들이있나? 만성골반통의특성 2 산부인과뿐만아닌한의학과영상의학등각분야의선생님들께서원고를집필 만성골반통의특성 3 일반치료의접근과더불어특수상황에서의치료적접근법 만성골반통의특성 4 만성골반통의연구방향까지제시 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 83

90 Lunch Symposium 만성골반통의특성 5 < 부록 > 만성골반통환자진료의실제 손때묻은사랑받는교과서 되기를바랍니다 년대한만성골반통학회제 3 차학술대회및연수강좌

91 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 CPP 진료후효과적인의료보험청구 전호용 다나산부인과 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 85

92 Lunch Symposium 년대한만성골반통학회제 3 차학술대회및연수강좌

93 전호용 :CPP 진료후효과적인의료보험청구 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 87

94 Lunch Symposium 년대한만성골반통학회제 3 차학술대회및연수강좌

95 전호용 :CPP 진료후효과적인의료보험청구 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 89

96 Lunch Symposium 년대한만성골반통학회제 3 차학술대회및연수강좌

97 전호용 :CPP 진료후효과적인의료보험청구 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 91

98 Lunch Symposium 년대한만성골반통학회제 3 차학술대회및연수강좌

99 전호용 :CPP 진료후효과적인의료보험청구 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 93

100 Lunch Symposium 년대한만성골반통학회제 3 차학술대회및연수강좌

101 전호용 :CPP 진료후효과적인의료보험청구 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 95

102 Lunch Symposium 년대한만성골반통학회제 3 차학술대회및연수강좌

103 전호용 :CPP 진료후효과적인의료보험청구 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 97

104 Lunch Symposium 년대한만성골반통학회제 3 차학술대회및연수강좌

105 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 V. Office Based Treatment II 좌장 : 백원영 ( 경상의대 ), 정혜원 ( 이화여대 )

106 2013 년대한만성골반통학회 제 3 차학술대회및연수강좌

107 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 만성골반통으로인한성교통과음문통의진단과치료는? 김 탁 고려대학교의과대학 Terminology - Dyspareunia ( 성교통 ): a recurrent or persistent genital pain associated with sexual intercourse, which causes distress or interpersonal difficulty. (not caused exclusively by vaginismus or lack of lubrication, not accounted for by another Axis disorder, and not due to direct physiological effects of a substance or general medical condition) - Vaginismus ( 질경련 ): recurrent or persistent involuntary spasm of the musculature of the outer third of the vagina that interferes with sexual intercourse. - Vulvodynia ( 음문통 ): vulvar discomfort, most often described as burning pain, occurring in the absence of relevant visible findings or a specific, clinically identifiable, neurologic disorder. Vulvodynia 1. Definition - vulvar discomfort, most often described as burning pain, occurring in the absence of relevant visible findings or a specific, clinically identifiable, neurologic disorder [2] - It is not caused by commonly identified infection (eg, candidiasis, human papillomavirus, herpes), inflammation (eg, lichen planus, immunobullous disorder), neoplasia (eg, Paget s disease, squamous cell carcinoma), or a neurologic disorder (eg, herpes neuralgia, spinal nerve compression). - It is defined by the International Society for the Study of Vulvovaginal disease (ISSVD) 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 101

108 V. Office Based Treatment II 2. Causes - embryologic abnormalities - increased urinary oxalates - genetic or immune factors - hormonal factors - inflammation - infection - neuropathic changes Most likely, there is not a single cause. 3. Diagnosis and Evaluation - Vulvodynia is a diagnosis of exclusion, a pain syndrome with no other identified cause. - A thorough history should identify the patient s duration of pain, previous treatments, allergies, medical and surgical history, and sexual history. 1) Cotton swab testing (Fig. 1) - to identify areas of localized pain - to classify the areas where there is mild, moderate, or severe pain. - A diagram of pain locations may be helpful in assessing the pain over time. Fig. 1. Cotton swab testing for vestibulodynia. The vestibule is tested at the 2-, 4-, 6-, 8-, and 10-o clockpositions. When pain is present, the patient is asked to quantify it as mild, moderate, or severe. 5 2) The vagina should be examined and tests - wet mount, vaginal ph, fungal culture, and Gram stain should be performed as indicated. - Fungal culture may identify resistant strains, but sensitivity testing usually is not required. - Testing for human papillomavirus infection is unnecessary. 4. Treatment Multiple treatments have been used for vulvodynia (Fig. 2.) 년대한만성골반통학회제 3 차학술대회및연수강좌

109 김탁 : 만성골반통으로인한성교통과음문통의진단과치료는? - vulvar care measures - topical, oral, and injectable medications - biofeedback; physical therapy - low-oxalate diet and calcium citrate supplementation - surgery - newer treatments (acupuncture, hypnotherapy, nitroglycerin and botulinum toxin) Fig. 2. Vulvodynia treatment algorithm. 1 1) Vulvar Care Measures Gentle care of the vulva is advised. The following vulvar care measures can minimize vulvar irritation: Wearing 100% cotton underwear (no underwear at night) Avoiding vulvar irritants (perfumes, dyes, shampoos, detergents) and douching Using mild soaps for bathing, with none applied to the vulva Cleaning the vulva with water only Avoiding the use of hair dryers on the vulvar area Patting the area dry after bathing, and applying a preservative-free emollient (such as vegetable oil 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 103

110 V. Office Based Treatment II or plain petrolatum) topically to hold moisture in the skin and improve the barrier function Switching to 100% cotton menstrual pads (if regular pads are irritating) Using adequate lubrication for intercourse Applying cool gel packs to the vulvar area Rinsing and patting dry the vulva after urination 2) Topical Therapies The commonly prescribed topical medication (Table 1 1 ) 1 Local anesthetics - lidocaine ointment 5% (Xylocaine jelly 2% or ointment 5%) applied as required for symptoms and 30 minutes before sexual activity. - Emla (eutectic mixture of local anesthesia, comprised of lidocaine 2.5% and prilocaine 2.5%) - ELA-Max (lidocaine 4% and 5%) L-M-X 4 (formerly ELA-Max 4% cream [lidocaine 4%]; and L-M-X 5 (formerly ELA-Max Anorectal 5% cream [lidocaine 5%] Table 1. Topical Medications Used to Treat Vulvodynia 년대한만성골반통학회제 3 차학술대회및연수강좌

111 김탁 : 만성골반통으로인한성교통과음문통의진단과치료는? These may cause stinging or sensitization. Male sexual partners may experience penile numbness and should avoid oral contact. 2 Plain petrolatum (Vaseline): Some patients benefit symptomatically from the application of Vaseline 3 Estrogen cream, and the intravaginal estrogen ring 4 Capsaicin: available to treat neuropathic pain 5 Estrogen cream, and tricyclic antidepressants compounded into topical form. 3) Oral Medications - Antidepressants and anticonvulsants can be used. - When first prescribing drugs, clinicians should avoid polypharmacy. - One drug should be prescribed at a time. 1 Antidepressants - Tricyclic antidepressants: amitriptyline, nortriptyline and desipramine Causion Alcohol should be limited to one drink daily. Contraception should be provided in the reproductive age group. This medication should not be used in patients with abnormal heart rates (for example, tachycardia) or in patients taking monoamine oxidase inhibitors. - The SSRI(selective serotonin reuptake inhibitors), SNRI(serotonin-norepinephrine reuptake inhibitors) 6 2 Anticonvulsants: Gabapentin, carbamazepine 4) Biofeedback and Physical Therapy - internal (vaginal and rectal), external soft tissue mobilization, myofascial release - trigger-point pressure - visceral, urogenital, and joint manipulation - electrical stimulation - therapeutic exercises - active pelvic floor retraining - biofeedback - bladder and bowel retraining - instruction in dietary revisions - therapeutic ultrasonography - home vaginal dilation. 5) Intralesional Injections Although topical steroids generally do not help patients with vulvodynia, trigger-point injections of a combination of steroid and bupivacaine have been successful for some patients with localized vulvodynia. 3 6) Surgical Excision - Local Excision 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 105

112 V. Office Based Treatment II - Total Vestibulectomy - Perineoplasty - Surgery for Pudendal Nerve Entrapment Fig. 3. Sharp dissection (15-blade knife) is used to remove the area of pain on the vestibule. 5 7) Low-Oxalate Diet with Calcium Citrate Supplementation Oxalate is an irritant and has been suggested that vulvar burning may be associated with elevated levels of oxalates in the urine 5. SUMMARY - Vulvar pain is a complex disorder that frequently is frustrating to both practitioner and patient. - Many treatments for vulvodynia(generalized and localized) have been discussed. - Improvement in pain may take weeks to months. - No single treatment is successful in all women. - Concurrent emotional and psychological support can be invaluable. 6. References 1. Haefner HK, Collins ME, Davis GD, Edwards L, Foster DC, Hartmann EH, et al. The vulvodynia guideline. J Low Genit Tract Dis 2005;9: Moyal-Barracco M, Lynch PJ ISSVD terminology and classification of vulvodynia: a historical perspective. J Reprod Med 2004;49: Segal D, Tifheret H, Lazer S. Submucous infiltration of betamethasone and lidocaine in the treatment of vulvar vestibulitis. Eur J Obstet Gynecol Reprod Biol 2003; 107: 년대한만성골반통학회제 3 차학술대회및연수강좌

113 김탁 : 만성골반통으로인한성교통과음문통의진단과치료는? 4. Bergeron S, Binik YM, Khalife S, Pagidas K, Glazer HI, Meana M, et al. A randomized comparison of group cognitive- behavioral therapy, surface electromyographic biofeedback, and vestibulectomy in the treatment of dyspareunia resulting from vulvar vestibulitis. Pain 2001; 91: Haefner HK. Critique of new gynecologic surgical procedures: surgery for vulvar vestibulitis. Clin Obstet Gynecol 2000;43: Wasserman J. Pharmacological treatment of vulvodynia. National Vulvodynia Association News Letters Spring 년대한만성골반통학회제 3 차학술대회및연수강좌 107

114 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 Treatment of Unexplained Chronic Pelvic Pain 정 혁 조선대학교의과대학산부인과학교실 DEFINITION OF CPP Chronic pelvic pain(cpp) is persistent pain in and around the pelvic cavity that has lasted for at least 6 months ACOG has defined CPP as lower abdominal noncyclical pain(acog, 2004) Not caused by pregnancy and not exclusively associated with intercourse CPP is not a disease, but rather a symptom that can be caused by several different conditions INTRODUCTION Common condition in women(asthma, migraine) 14% - 24% prevalence rates of CPP 10% of visits to gynecologists 20%-40% of laparoscopic procedures 15% of CPP are associated with endometriosis 30% of CPP: no visible laparoscopic pathology 18% of hysterectomies are performed 45% report diminished work capacity due to their pain 90% of women with CPP complain of dyspareunia specific cause remain unknown in many women 년대한만성골반통학회제 3 차학술대회및연수강좌

115 정혁 :Treatment of Unexplained Chronic Pelvic Pain Chronic Pelvic Pain: Health Impact General health scores are lower Associated disturbances of mood and energy levels (>50%) Depression is common Quality of life is decreased Restricted activity and decreased productivity Chronic Pelvic Pain: Health Care 61% no diagnosis given by physician 39% diagnosis given 25% endometriosis 49% a non-cycle related gynecologic disorder (e.g. yeast infection or chronic PID) 10% non-gynecologic disorder 16% other Chronic Pelvic Pain: Health Care 10% to 35% of laparoscopies are for CPP 9% to 80% of laparoscopies report abnormalities 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 109

116 V. Office Based Treatment II Age of women seen at the Pelvic Pain Clinic t s n tie a p f o r e b m u N Age 1 1 < >76 No data CAUSES OF CPP Gynaecological: endometriosis, adhesions (chronic pelvic inflammatory disease), leiomyoma, pelvic congestion syndrome and adenomyosis Gastrointestinal disease: constipation, irritable bowel syndrome, diverticulitis, diverticulosis, chronic appendicitis and Meckel s diverticulum Genitourinary disease: interstitial cystitis, bladder dyssynergia and chronic urethritis Myofascial disease: fasciitis, nerve entrapment syndrome and hernia (inguinal, femoral, spigelian, umbilical and incisional) Skeletal disease: scoliosis, L1-2 disc disorders, spondylolisthesis and osteitis pubis Psychological disorders: somatisation, psychosexual dysfunction and depression Neuropathic disorders: pudendal nerve entrapment and spinal cord neuropathies GYNECOLOGICAL CAUSES OF CPP Cyclic: Primary dysmenorrhea Endometriosis Adenomyosis Mittleschmertz Non-cyclic: Pelvic masses Adhesions Infections Non-gyn causes Related to intercourse: Endometriosis Vaginismus Vaginal atrophy Musculoskeletal Any non-cyclic cause could be exacerbated 년대한만성골반통학회제 3 차학술대회및연수강좌

117 정혁 :Treatment of Unexplained Chronic Pelvic Pain ASSOCIATE FACTORS OF CPP Drug or alcohol abuse Miscarriage Heavy menstrual flow Pelvic inflammatory disease Previous cesarean section Disease in the pelvis History of sexual abuse Psychological disease SYMPTOMS OF CPP Heavy and/or painful menstrual periods Pain in the abdomen or lower back Pain during intercourse Burning or stinging of the vulva Pain that is worse with urination or a bowel movement DIAGNOSIS OF CPP History Describe the type of pain (ache, sharp, burning, stabbing, etc.) Where is the pain located? Does it come and go or is the pain constant? Does anything make the pain better or worse? Is the pain related to the menstrual cycle? Is it related to bowel movements? Does it hurt during urination or sexual activity? Is there pain in other parts of the body? Has the patient had surgery in the pelvic area in the past? 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 111

118 V. Office Based Treatment II DIAGNOSIS: OBJECTIVE EVALUATIVE TOOLS Basic Testing Pap Smear Gonorrhea and Chlamydia Wet Mount Urinalysis Urine Culture Pregnancy Test CBC with Differential ESR or CRP PELVIC ULTRASOUND Specialized Testing MRI or CT Scan Endometrial Biopsy Laparoscopy Cystoscopy Urodynamic Testing Urine Cytology Colonoscopy Electrophysiologic studies Referral to Specialist Causes of CPP with Negative Laparoscopy Atypical Endometriosis, Pelvic congestion, Irritable bowel, Inflammatory Bowel disease, Pelvic Floor Tension Myalgia, leg length discrepancy, Pelvic Pain Posture, Sacroiliac joint disease, Intervertebral Disk Disease, Uterine retroversion, Genital Prolapse, Adenomyosis, Interstitial Cystitis, porphyria, bone metastasis,... Laparoscopic findings are negative in anywhere from 10% to 90% of women with chronic pelvic pain. When this occurs a woman is often told one or more of the following: (1) Nothing is wrong (2) Nothing can be done and she must learn to live with the pain. (3) The pain is in her head and she should see a psychiatrist (4) She should have a neurolytic procedure (such as uterine nerve transection or presacral neurectomy) or pain killers. (5) The only thing that is left to do is a hysterectomy 년대한만성골반통학회제 3 차학술대회및연수강좌

119 정혁 :Treatment of Unexplained Chronic Pelvic Pain MANAGEMENT OF CPP The management of women with CPP is usually complex and often requires a multidisciplinary approach Medical Surgical Supportive psychological therapy Medical treatment of CPP Medical treatment of CPP Antibiotics NSAIDs (non-opioids) Opioids Palmitoylethanolamide DL-phenylalanine Antidepressants Anticonvulsants Hormone therapy Physical therapy Nerve blocks (neurotoxic chemicals) 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 113

120 V. Office Based Treatment II Nonsteroidal Anti-Inflammatory Drugs NSAIDs have been studied extensively in randomized controlled trials NSAIDs are used empirically as a first-line medical treatment for CPP Recommended as the sole treatment of mild pain NSAIDS and anticonvulsants may be helpful where neuropathic features are present NSAIDs have two serious drawbacks First drawback has to do with ceiling effects Second major drawback of the non-opioids is their side effects for chronic pain Narcotic(opioids) These drugs include natural opiates and synthetic narcotics Opioids act by attaching to specific proteins called opioid receptors Powerful medications often used to manage pain The advantage of narcotics is there is no maximum dose, but they can affect breathing Opioids can have a clinically significant benefit, but current data on long-term use of these analgesics are limited Not recommended for CPP Differences between Opioid and Non-opioid Analgesics Non-opioids have a ceiling effect in analgesia (a maximum dose beyond which analgesic effect does not increase) Do not produce tolerance or physical dependence and are not associated with abuse or addiction They are antipyretic and all except acetamin- ophen are anti-inflammatory agents The primary mechanism of action of non-opioid analgesics is inhibition of prostaglandin formation Opioids work by acting on receptors located on neuronal cell membranes 년대한만성골반통학회제 3 차학술대회및연수강좌

121 정혁 :Treatment of Unexplained Chronic Pelvic Pain Antidepressants Meta-analysis improve pain tolerance, restore sleep patterns, and reduce depressive symptoms 1 Tricyclic antidepressant (nortriptyline) : amitriptyline, imipramine and clomipramine 2 Selective serotonin reuptake inhibitors (SSRIs) is less compelling 3 selective serotonin and norepinephrine reuptake inhibitors (SNRIs) Effective analgesic dose is often lower than that required to treat depression, and the onset of analgesic action usually is earlier Effectiveness of antidepressants in women with CPP is insufficient to draw conclusions Anticonvulsant FDA approved for the treatment of diabetic pain- ful polyneuropathy and postherpetic neuralgia Anticonvulsants have been shown to be effective for treating neuropathic pain, especially when the pain is lancinating or burning Carbamazepine, phenytoin, sodium valproate, gabapentin and clonazepam 50% reduction in pain with gabapentin : very popular in the management of CPP Gabapentin is effective in relieving indexes of allodynia and hyperalgesia Side effects are common and included symptoms such as drowsiness, dizziness, constipation, nausea and ataxia Palmitoylethanolamide seems to be very useful in controlling CPP associated with endometriosis (European J of Ob & Gy 2010) The presence of increased activated and degranulating mast cells in deep infiltrating endometriosis, and the close relationship between mast cells and nerves, strongly suggest that mast cells may contribute to the development of pain and hyperalgesia in endometriosis, possibly by exerting a direct effect on nerve structures derivatives play a role in controlling the inflammation associated with mast-cell activation 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 115

122 V. Office Based Treatment II Palmitoylethanolamide PE is a recently developed drug that inhibits mast cell activity PE may improve nerve function and reduce neuropathic pain. neuropathic pain and positive sensory symptoms significantly improved after treatment (P < 0.01) seems to be very useful in controlling CPP associated with endometriosis Other pharmacological strategies Adrenoceptor agonist Lofexidine Hydrochloride Alpha-2 agonists can induce analgesia by acting at three different sites: in brain, spinal cord and in peripheral tissues DL-phenylalanine potentiates the analgesic effect of opioids appears to potentiate pain relief by up-regulation of the endogenous analgesia system 년대한만성골반통학회제 3 차학술대회및연수강좌

123 정혁 :Treatment of Unexplained Chronic Pelvic Pain Progestins Progestins induce decidualization and acyclicity of endometriotic tissue MPA may be beneficial for patients with CPP secondary to endometriosis 73% of oral MPA in a 50-mg daily dose was effective in reducing pain scores in 50% Progestins may not relieve symptoms completely very useful in treating CPP by Pelvic congestion But the benefit was not sustained Nine months after discontinuation of treatment, the benefits of progestin therapy had largely disappeared Oral Contraceptives Initially employed as part of a pseudopregnancy regimen Initial management of primary dysmenorrhea Oral contraceptives were reported to be less effective than GnRh-a for relief of dysmenorrhea Similar efficacy to GnRH-a for relief of dyspareunia and nonmenstrual pain Oral contraceptives should be prescribed because of their low cost and low risk of severe side effects fail to have improvement of their pain on oral pils often have improvement in their pain when treated with agnrh-agonist Gonadotropin-releasing Hormone Agonist GnRH agonist appears to be more effective than other ovarian suppression drugs if the initial treatment is unsuccessful Dramatically reducing estradiol production (functional oophorectomy) Empiric use of GnRH-a decreases in dysmenorrhea, pelvic pain, and tenderness Oral contraceptives, danazol, GnRH agonists are not different in the relief of dyspareunia or nonmenstrual pain Post operative adjuvant GnRH-agonist treatment reduces the risk of recurrence of pelvic pain GnRH antagonists are rarely used but may be as effective as GnRH agonist 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 117

124 V. Office Based Treatment II Summary of medical treatment Multidisciplinary approach Comprehensive history including psychosocial factors must be taken NSAIDs or TCAs used most frequently for CPP The effectiveness of SSRI antidepressants for CPP has not been shown. Simple analgesics and anticonvulsants may be helpful where neuropathic features are present Narcotics are only recommended as a last-resort treatment for severe pelvic pain because of the risk of addiction Current evidence suggests treatment with the MPA for pelvic venous congestion, No difference in efficacy in available medical treatments for endometriosis, but some are limited due to side-effects New drugs are noticeable Surgical treatment of CPP Surgical treatment of CPP Surgery for CPP should be limited to the treatment of surgically correctable problems. There is no evidence that surgical removal of the reproductive organs relieves chronic pelvic pain Resection/ablation of lesions Surgical nerve ablation Hysterectomy with or without BSO Uterine Suspension Procedures Appendectomy Adhesiolysis Pain may not be controlled or may get worse. Adhesions may form at the surgical site, on the ovaries or fallopian tubes, or in the pelvis 년대한만성골반통학회제 3 차학술대회및연수강좌

125 정혁 :Treatment of Unexplained Chronic Pelvic Pain Surgical nerve ablation techniques 1. Presacral neurectomy 2. LUNA 3. Radio-Frequency ablation of uterine body The role of LUNA has been debated for decades Radio-Frequency ablation is noticeable Surgical nerve ablation techniques 1. Presacral neurectomy 10 25% of women with dysmenorrhea do not respond to medical management Excision of the superior hypogastric plexus PSN may be indicated for 1 and 2 dysmenorrhea unrelieved by traditional therapy It is unlikely that PSN would relieve pain arising from the ovaries Symptoms of 88% of women with midline pain were relieved Pain was significantly decreased following PSN-- 72% with dysmenorrhea, and 62% with CPP Considered for treatment of centrally located dys- menorrhea but has limited efficacy for CPP(ACOG, 2004) Heavy bleeding has been reported from accidental laceration of the middle sacral vein, constipation Surgical nerve ablation techniques 2. LUNA Resection or ablation of the uterosacral ligaments in patients with 1 dysmenorrhea or pelvic pain Short-term results for PSN and LUNA for dysmeno- rrhea seem to be similar(88%: 83%), PSN has better results in the longterm(82%:51%) No evidence that LUNA is beneficial for nonmens- trual pelvic pain The role of LUNA has been debated for decades Less effective than PSN(ACOG, 2004) LUNA does not appear to offer any added benefits beyond those that can be achieved with conser- vative surgery alone (ASRM 2008) LUNA is safe except for a few complications 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 119

126 V. Office Based Treatment II Surgical nerve ablation techniques 3. Laparoscopic Radiofrequency ablation RF to be very effective for primary and secondary dysmenorrhoea Response rate to RF for dysmenorrhea : >95% There was significant reduction of menorrhagia Serious postoperative complication is very rare The effects on fertility are uncertain RF : Results Pain score first year after procedure in MLARM and VUARM groups Pre-operation Pain score Post-operation P value MLARM 3.05 ± ± 0.78 < VUARM 2.97 ± ± 0.53 < Pain score is expressed as mean pain score±s.d. Statistical significant difference exists when P value<0.05. Hysterectomy with or without BSO When all other treatments fail, and no further fertility is desired Symptoms of CPP are decreasing the quality of life 20% of patients with CPP Hysterectomy for CPP with no extra-uterine pathology and found that about 70-80% were pain free at 1 year of followup(stovall et al. Maine Women s Health Study) 74% : complete resolution of pain, 21%:decreased but continued pain, and 5%: unchanged or increased pain Additional surgery in 5% to 10% Women who have significant relief of pelvic pain after a 2-month trial of a GnRH-A may be more likely to have relief of pelvic pain following TH BSO Followed by long-term estrogen replacement therapy 년대한만성골반통학회제 3 차학술대회및연수강좌

127 정혁 :Treatment of Unexplained Chronic Pelvic Pain Uterine Suspension Procedures No data supporting or refuting the place for uterine suspension as an adjunct in the treatment of endometriosis-associated pelvic pain. Individual practitioner experience can guide the use of this procedure Appendectomy may be indicated in selected patients with chronic pelvic pain the appendix may exhibit pathologic condition in 50% to 80% of patients with endometriosis or pelvic pain reports of complete relief in up to 97% of patients who have RLQ pain women with endometriosis and chronic RLQ pain are usually good candidates for appendectomy Adhesiolysis The role of adhesions in CPP is controversial Interestingly, adhesions are usually not described as an etiologic factor for pelvic pain in men ranging from no pain relief to pain relief in 90% of patients adhesions are found in approximately 25% of patients with chronic pelvic pain compared with 17% of those without The incidence of reformation of adhesions that were initially minimal/mild is approximately 33%, initially severe about 67%, and initially extensive about 90% Surgical adhesiolysis is not likely to benefit women with CPP unless they have dense vascularized Adhesions 년대한만성골반통학회제 3 차학술대회및연수강좌 121

128 V. Office Based Treatment II Combinations of treatments No data confirm that preoperative ovarian suppression has any benefit Postoperative ovarian suppression with GnRHa for 6 months has been associated with a longer interval to pain recurrence After surgery, ovarian suppression with oral contraceptives is often the best choice If complete resection of the endometriotic disease has not been possible Pelvic venous congestion Collection of symptoms including a dull, aching pain, aggravated by movement and sexual intercourse, which is associated with pelvic varicosities and congestion Analgesics MPA at a dose of 30mg daily for 6months Embolization Intractable pelvic pain due to venous congestion is treated by TH BSO Summary CPP is a poorly understood but important area Etiology Is not well known Multidisciplinary approach is vital Aim of the treatment : pain reduction, improved QoL and psychosocial functioning Simple analgesia and adjunctive therapy with anti-convulsants may be helpful in neuropathic features Palmitoylethanolamide seems to be very useful in CPP Ovarian suppression appears to be effective Adhesiolysis has not been shown to be of benefit PSN considered for treatment of centrally located dysmenorrhea but has limited efficacy for CPP LUNA does not appear to offer any added benefits Hysterectomy with BSO is generally reserved for women with debilitating symptoms 년대한만성골반통학회제 3 차학술대회및연수강좌

129 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 CPP 치료의 Medical and Surgical Treatment 실패시무엇을해야하나? 이철민 인제대학교의과대학상계백병원 Differential diagnosis of CPP Gynecologic - Adhesion - Endometriosis - Salpingo-oophoritis - Ovarian remnant syndrome - Pelvic congestion Gastrointestinal - Irritable bowel synd - Diverticulitits Genitourinary Recurrent cystourethritis Interstitial cystitis Neurologic Musculoskeletal Low back pain synd. Myofascial syndrome Management of CPP Drug therapy Surgery Cognitive-behavioral management Psychological management Socio-environmental problem management Complimentary and alternative therapy Treat chronic pain as a diagnosis Treat diseases that might be a cause of CPP Multidisciplinary approach 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 123

130 V. Office Based Treatment II Medications for CPP Three steps to find the reason for CPP Amnesis and examination Laparoscopy Consultant Medical treatment Neis KJ. Gynecol Endocrinol 2009 Laparoscopy as a 2nd step Gold standard for Dx Incidence of abnormal findings at laparoscopy : 30-83% - Endometriosis : 33% - Adhesion : 24% - No reason: 35% Neis KJ. Gynecol Endocrinol 2009 Cheong Y and Stones RW Best practice & research 년대한만성골반통학회제 3 차학술대회및연수강좌

131 이철민 :CPP 치료의 Medical and Surgical Treatment 실패시무엇을해야하나? Indications for Dx laparoscopy Suspicion for endometriosis CPP unresponsive to OCs and NSAIDs Progressive dysmenorrhea Diagnostic dilemma Laparoscopic findings in women Without CPP (%) With CPP (%) No pathology Endometriosis Adhesions Myomas Ovarian cysts Chronic CPP Others Abnormal finding < Neis KJ. Gynecol Endocrinol 2009 Cheong Y and Stones RW Best practice & research 2006 Correlation between laparoscopy & pelvic exam Pre-op pelvic exam Normal laparoscopic finding Abnormal laparoscopic finding Normal 300 (76%) 496 (56%) Abnormal 94 (24%) 397 (44%) Total 394 (100%) 893 (100%) Laparoscopy may detect potentially treatable pathology not detected by pelvic examination Ob Gy Survey 1993:48: 년대한만성골반통학회제 3 차학술대회및연수강좌 125

132 V. Office Based Treatment II Laparoscopy s influence on treatment decisions Image-based treatment plan Laparoscopic finding Laparoscopy contribution No. Rate (%) Observation Precise localization of trigger lesion Additional treatment instituted Observation treatment Observation or exploration Reveal normal anatomy Additional diagnostic procedure instituted Treatment Additional diagnostic procedure Localization of trigger lesion Discard unnecessary diagnostic procedures Observation Kang SB Surg Endosc 2007 Advantages of laparoscopy in the evaluation of CPP Increase accuracy of Dx - Best diagnostic method for endometriosis, adhesion, PID fold magnification is possible - Better view of CDS, ovarian fossae, upper abdomen - Allow histologic documentation of diagnosis Immediate surgical treatment is possible Differentiation between Gyn & non-gyn condition Patient reassurance Empiric Tx with GnRHa without laparoscopy Gynecologic suppression test (3M) (GnRHa) Positive Negative Consider laparoscopic surgery or hysterectomy Bowel workup program: Urinary workup if indicated; Psycologic evaluation if indicated 61% of patients who are later diagnosed with endometriosis get pain relief from GnRHa (placebo response rate, 34%) Continue to total 6M (ACOG 2004) Ling, Obstet Gynecol, 년대한만성골반통학회제 3 차학술대회및연수강좌

133 이철민 :CPP 치료의 Medical and Surgical Treatment 실패시무엇을해야하나? Advantages of laparoscopy in endometriosis Minimal to moderate endometriosis effectively relieve pain Sx relief in 90% at 1 yr F/U Laser ablation vs. no Tx 62.5 vs. 22.6% Adhesion and pain Incidence - Not known % found in laparoscopy due to CPP Stovall TG. J Reprod Med 1989 Mostly asymptomatic; not correlated to pain severity No pathognomonic sign on physical exam - Inspection during surgery is the only diagnosis Effect of adhesiolysis Study Type of study Follow-up (months) No. Setting of adhesiolysis Pain relief Comments Chan (36) Retrospective Laparotomy 65% No placebo arm Daniell (37) Retrospective Laparoscopy Laparotomy 67% No placebo arm Sutton (38) Retrospective Laparoscopy 84% No placebo arm Steege (4) Prospective Laparoscopy 56% No placebo arm Fayez (39) Prospective Laparoscopy 88% No placebo arm Saravelos (40) Retrospective Laparotomy Laparoscopy 51% No placebo arm Malik (5) Retrospective Laparoscopy 44% to 50% No placebo arm Bremers (41) Prospective Laparoscopy 16% No placebo arm Peters (35) Swank (42) Prospective, randomized with control Prospective, randomized with control Laparotomy Laparoscopy 46% (Tx arm) 42% (Placebo arm) 27% (Tx arm) 27% (Placebo arm) No difference between groups No difference between groups Mammoud. Fertil Steril 년대한만성골반통학회제 3 차학술대회및연수강좌 127

134 V. Office Based Treatment II Effect of adhesiolysis In terms of pain relief, adhesiolysis produced: Total or partial relief No change Worsening of pain 65% of patients 25% of patients 12% of patients May be effective for severe vascularized adhesion Effectiveness is questionable Thorough consultation before surgery is warranted Rodríguez Hidálgo N: Laparoscopía Ginecológica. Presencia Latinoamericano, Mexico No apparent pathology on laparoscopy Incidence 30-35% Does not mean absence of disease CPP but no endometriosis associated nor adhesion associated origin Council as a 3rd step Psychosomatic physician and/or pain therapy Orthopedist Gastroenterologist Urologist Neurologist 년대한만성골반통학회제 3 차학술대회및연수강좌

135 이철민 :CPP 치료의 Medical and Surgical Treatment 실패시무엇을해야하나? Psychosocial etiologies Depression Somatization Sexual & Physical abuse Substance abuse Eating disorder... Associated with Psychiatric problems Autonomic nerve system dysfunction associated with emotional stress (Tayler, 1954) High prevalence of depressive mood Hysterical personality (Vargyas, 1988) Tension and stress related conditions (Mezrow, 1994) Psychosomatic physician and/or pain therapy Ideally, psychologic evaluation by a professional specializing in pain psychology would be part of the initial evaluation and treatment of every patient with CPP - Gatchel RJ and Turk DC, 년대한만성골반통학회제 3 차학술대회및연수강좌 129

136 V. Office Based Treatment II 통증심리학 (Pain Psychology) 통증에대한심리적영향 - 급성통증과실험통증 - 만성통증 만성통증을잘유발하는심리과정과증후군 - 우울증과통증 - 신체화와건강염려증 심인성통증 통증행동과학습 Psychologic Symptoms of CPP Depressive mood Sleep disorder Somatic obsession Decrease of physical activity Decrease of libido Fatigue Distraction Strategy Music therapy Personal responsibility - Ex. I should have not break my ankle if I were more cautious 년대한만성골반통학회제 3 차학술대회및연수강좌

137 이철민 :CPP 치료의 Medical and Surgical Treatment 실패시무엇을해야하나? Role of Gastroenterologist Gastrointestinal causes of CPP - Irritable bowel syndrome - Chronic appendicitis - Inflammatory bowel disease - Diverticulosis - Diverticulitis - Meckel s diverticulum - Chronic constipation Urologic etiologies Interstitial cystitis Urethral syndrome Urinary tract infection Kidney stones... Musculoskeletal etiologies Myofascial pain syndrome (trigger points) Postural problems (scoliosis) Inflammation Joint pain Spinal injury 년대한만성골반통학회제 3 차학술대회및연수강좌 131

138 V. Office Based Treatment II Proposed nonmedical treatments Exercise Physical therapy Dietary modifications Complementary or alternative medicine (CAM) - Herbal and nutritional therapies - Magnetic field therapy - Acupuncture Conclusions Flow chart of referral and management of CPP Gynecologist with special interest in pain management Investigations +/- referral to pain team 1. Pain physician 2. Psychotherapist for cognitive behavioral therapy 3. Specialist pain nurse 4. Physiotherapist Chronic or acute admissions General practitioners Discharge or shared care with referral GP Cheong Y and Stones RW Best practice & research 년대한만성골반통학회제 3 차학술대회및연수강좌

139 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 VI. Office Based Treatment III: Perfect Master of CPP Control 좌장 : 이규섭 ( 부산의대 ), 오한진 ( 관동의대 )

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141 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 개원가에서할수있는다양한 TPI 의 Perfect Master 조창식 닥터조제통외과의원 통증치료를위한 Injection Tx. 신경간내주사 / 건초내주사 TPI 신경차단술증식치료 IMS 통증치료방법들의치료원리 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 135

142 VI. Office Based Treatment III: Perfect Master of CPP Control Pelvis area Myofascial pain 유발하는 Trigger Points 증식치료의관점 : Ligament 약화가국소통증과 referred pain 을유발한다는이론 골반주위근육들의 balance 년대한만성골반통학회제 3 차학술대회및연수강좌

143 조창식 : 개원가에서할수있는다양한 TPI 의 Perfect Master Posterior pelvic tilting Anterior Pelvic tilting 임신과근골격계통증 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 137

144 VI. Office Based Treatment III: Perfect Master of CPP Control 몸통앞부분의표층신경분포 몸통뒷부분의표층신경분포 통증치료술기들의임상적용및건강보험청구 년대한만성골반통학회제 3 차학술대회및연수강좌

145 조창식 : 개원가에서할수있는다양한 TPI 의 Perfect Master 신경간내주사 (KK061) 신경간내주사 (KK061) TPI( 근막동통주사자극치료 ) 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 139

146 VI. Office Based Treatment III: Perfect Master of CPP Control TPI(MM131, MM132) 장골서혜신경차단 (LA249) 장골서혜신경차단 (LA249) 명세서 우측하복부와서혜부의작열통으로내원함. 내원당시 VAS score 8 점이었고, ASIS 내측 2 cm, 상방 2 cm 지점을찌름점으로하여 0.5% 리도카인 5 ml 를주사하여동통이소실된것을확인하고치료를종결하였다. 치료후 VAS 는 3 점으로호전되었다 년대한만성골반통학회제 3 차학술대회및연수강좌

147 조창식 : 개원가에서할수있는다양한 TPI 의 Perfect Master 외측대퇴피신경차단 (LA275) 병명 : G571 명세서 : 대퇴의전방과외측으로방사되는작열통을주소로내원하여, AIIS 하방 2 cm, 내측 2 cm 지점을찌름점으로하여 0.5% 리도카인 5 ml 를주사후 VAS score 가 8 점에서 3 점으로호전됨을확인하고치료를종료하였다. 외측대퇴피신경차단 (LA275) Obturator Nerve block landmark 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 141

148 VI. Office Based Treatment III: Perfect Master of CPP Control Obturator Nerve block (LA273) 명세서 Obturator Nerve block (LA273) 대퇴의내측과무릎의내측으로방사되는작열통을주소로내원하여, 서혜부아래에서대퇴동맥의박동을촉지한후 동맥박동점내측, pubic tubercle 하방 2 cm, 내측 2 cm 지점을찌름점으로하여 0.5% 리도카인 5 ml 를주사후 VAS score 가 8 점에서 3 점으로호전됨을확인하고치료를종료하였다 년대한만성골반통학회제 3 차학술대회및연수강좌

149 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 통증치료의임상적용 Case 보고 강민아 누리여성의원 Abdominal wall pain Pain often constant or fluctuating: less often episodic Pain intensity possibly related to posture (e,g,,lying, standing, sitting) Pain not related to meals or bowel function or menses(?) No findings of an intra-abdominal process Abdominal tenderness unchanged or increased when abdominal wall is tensed (carnett s sign) Discrete, tender pain trigger point no more than a few centimeters in diameter With stimulation of trigger point, refferal of pain or spreading of pain over a large area 20 세미혼 MCD#1 Dysmenorrhea case1 원래 dysmenorrhea 있었으나최근심해짐 아침에진통제복용하였으나효과없고거동이불편함, 구역동반 초음파상특이소견없음 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 143

150 VI. Office Based Treatment III: Perfect Master of CPP Control case2 30세미혼 MCD #22 이틀전 cotus 후부터시작된하복부통증 아침은좀낫고저녁에심해지는것같다. 누워있으면좀낫고걸어다닐때더아픈거같다 질초음파상특이소견없음 CMT(-) 하복부전체에미약한압통, 군데군데압통점 34 세미혼 case3 MCD #16 규칙적월경력 몇달전부터생리시작시와끝날때골반이아팠으나이번달은계속골반이아프다 특히움직일시더아프고최근허리가안좋음. 초음파특이소견 (-) 하복부 tender point(-) 35 세미혼 직업여성 Coitus 시 vaginal pain Leukorrhea(-) case4 Vaginal & vulva : clear 초음파상특이소견없음 년대한만성골반통학회제 3 차학술대회및연수강좌

151 강민아 : 통증치료의임상적용 Case 보고 Case 5 41 세기혼 소변볼때우리하다 가만히있어도아래가신경이쓰인다. 자주마렵지는않은데약간덜눈것같은느낌이난다. 방광염약 3 일먹었는데아주약간호전됐다 U/A : WNL 33 세미혼 직업여성 피임약복용중 Case 6 어제저녁 coitus 후부터밑이빠질듯이아프다 간간이열감도있다, 아침에일어나니골반이아프다, 목도아프다. N/V (-/-), C/D (-/-) 초음파상특이소견없음 CMT(+) 하복부 tender point 관찰됨 Vagina & vulva : clear case6 일단 lab 나가고항생제 2 일분처방 열감이나목아픈거괜찮아졌으나, 여전히밑이빠질거같고아침에골반이너무아프다 CBC & CRP: negative 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 145

152 VI. Office Based Treatment III: Perfect Master of CPP Control 하복부의신경통 Ilioinguinal neuropathy (T12-L1) Genitofemoral neuropathy (L1-L2) Iliohypogastric neuropathy (T12-L1) Meralgia paresthetica (L2-L3) 신경통의주된증상 pain lancinating burning increased with hip flexion or activation of abdominal muscles hypo and hyper-esthesia temporal relationship to surgery pelvic floor dysfunction, Myofacial pain 년대한만성골반통학회제 3 차학술대회및연수강좌

153 강민아 : 통증치료의임상적용 Case 보고 Etiology the majority of cases result from surgical injury - pfannenstiel incision - appendectomy - laparoscopy (lower quadrant port placement) - inguinal hernia rapair - iliac bone harvesting etc. non surgical - muscle tear, sportsman hernia pathophysiology nerve damage from direct surgical trauma inflammation and scar formation inflammation and retraction from permanent mesh suture encirclement tack impingement fascial tear (external oblique aponeurosis) Risk Factor tight clothing obesity pregnancy scar tissue near the inguinal ligament, due to injury or past surgery walking, cycling or standing for long periods of time 향후환자군이증가될것으로예상됨 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 147

154 VI. Office Based Treatment III: Perfect Master of CPP Control Incidence pfannenstiel incision - 8.8% had moderate-severe pain - odds ration increased by 2.95>2 incision - 70% patients had pain at corners of incision -Loos M.J.et al 2008 Inguinal hernia - multiple studies raging from % for moderate to severe pain Diagnosis Primarily clinical History Exam - iliohypogastric: pain and tenderness at the scar - ilioinguinal: pain and tenderness at exit of inguinal canal and medial to anterior iliac crest - genitofemoral : hypo-esthesia anterior thigh below inguinal ligament Carnett's sign - abdominal wall flexion increases or does not change pain. with intraabdominal pathology flexion will decrease pain 신경차단청구코드 주상병은 M792X( 부위코드 ) Iliohypogastric block- la270 Genitofemoral block-la249 Iloinguinal block- la249 Lateral femoral cuteneous block-la275 G57.1Meralgia paraesthetica 년대한만성골반통학회제 3 차학술대회및연수강좌

155 강민아 : 통증치료의임상적용 Case 보고 case7 19세미혼 MCD # 일전부터시작된불쾌감을느낄정도의좌측하복통, 특히수술부위통증, 하루에열번정도 5-10 분간 mons area 에따끔거림. 내원 4 개월전 PID 로복강경 Hx 초음파상특이소견없음 Vulva : 특이소견없음 복부 : tender area(-) 29 세미혼 MCD #13 case8 일주일전부터시작된우측하복부땡기듯이아프다, 작년에도한동안이렇게아픈적이있었다. 최근몇개월동안 4-5Kg 체중증가 2 년전 Dermoid cyst 복강경 op.hx 초음파상특이소견없고 CMT(-), 하복부 tender point(-) Rt.inguinal lig. Area 주위미약한압통 44 세기혼 MCD#2 case9 어제부터시작된극심한생리통 ( 좌측골반에서시작된 lat.thigh area 가터질듯이아프다, 저번생리때도비슷함, 이번달더심해짐 내원일년전생리통 ( 하복부 ) 심해 myoma op. 하고 Mirena insertion 하심내원 4 개월전 mirena 가잘못되어 (?) endometriosis op. 와제거술같이하심, 그후지금같은생리통양상이나타남점점심해진다. 초음파상특이소견없음 년대한만성골반통학회제 3 차학술대회및연수강좌 149

156 VI. Office Based Treatment III: Perfect Master of CPP Control 년대한만성골반통학회제 3 차학술대회및연수강좌

157 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 VII. Special Lecture 좌장 : 김정구 ( 서울의대 ), 조진호 ( 차의과대학 )

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159 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 Visanne : A New Vision for Endometriosis Treatment Eun-Ju Lee Department of Obstetrics & Gynecology, Chung-Ang Univ. Hospital A common sense approach to medical treatment of endometriosis (Vercellini, 2011) 자궁내막증약물치료의목표 1) 장기간에걸친통증억제 2) 수술한후임신을시도하기전까지기간동안재발이나진행을예방 여러임상연구의결과를종합해볼때적어도 2/3 의환자에서는이러한목표를성취할수있는것을을고려하면일차적인약물치료로프로게스틴, 경구피임제를일차적인약제로고려하는것이바람직하다. Overview Chemistry, pharmacodynamics Basic research data Clinical data Drug-Related Adverse Events 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 153

160 VII. Special Lecture Chemical classification of synthetic progestogens Progestogens C-21 progestogens C-19 nortestosterone Spirolactone Pregnanes MPA Megestrol acetate Cyproterone acetate Trimegestone Estranes Norethindrone Noreth. acetate Ethynodiol diacetate Lynestrenol Norethynodrel Dienogest Gonanes Drospirenone Norgestrel Levonorgestrel Norgestimate Desogestrel Gestodene MPA = medroxyprogesterone acetate Pharmacological Properties Dienogest is a progestin that combines the properties of both 19-nortestosterone derivatives and progesterone derivatives Properties of 19-nortestosterone derivatives I. Strong progestational effect on endometrium II. Relatively short plasma half-life of approximately 9-10 hours III.High oral bioavailability >90% Oettel M et al. Drugs Today 1995; Sasagawa S et al. Steroids Properties of progesterone derivatives I. Good tolerability II. Anti-androgenic effects III.Anti-proliferative effects IV.Relatively moderate inhibition of gonadotropin secretion V. Mainly peripheral mode of action Steroid Receptor Activities of Progesterone and Selected Progestins Progestogenic activity Glucocorticoid activity Androgenic activity Mueck AO, Seeger H, Bühling KJ. Gynecol Endocrinol 2010;26: Anti-androgenic activity Antimineralocorticoid activity Progesterone + (+) + Dienogest Drospirenone Levonorgestrel ++ + Gestodene + + (+) MPA Norgestimate ++ + Norethisterone Desogestrel Cyproterone acetate 년대한만성골반통학회제 3 차학술대회및연수강좌

161 이은주 :Visanne : A New Vision for Endometriosis Treatment Pharmacokinetic Profile I. Absorption i. Rapidly and almost completely absorbed ii. High bioavailability (91%) after oral administration iii.not affected by food intake II.Distribution i. High circulating levels of free dienogest (~10%) ii. No binding to sex hormone binding globulin/corticosteroid binding globulin III.Metabolism i. Hydroxylation and conjugation ii. Mainly metabolised via CYP3A4 pathway iii.metabolites not endocrinologically active IV.Elimination i. Relatively short half-life (9 10 hours) ii. Elimination primarily via the kidney Oettel M et al. Eur J Contracept Reprod Health Care 1999; Visanne (Dienogest). Summary of Product Characteristics Dienogest: Relative Affinity for SHBG Dehydrotestosterone* Testosterone Gestodene Levonorgestrel Estradiol Norethisterone 3-Ketodesogestrel Equilin Estrone DHEA Androstenedione Estriol Dienogest SHBG, sex hormone binding globulin. % *Dehydrotestosterone = 100% DHEA, dehydroepiandrosterone % Oettel M et al. Drugs Today 1995; Oettel M et al. Eur J Contracept Reprod Health Care Pharmacodynamic Profiling Study Dose-dependency of pharmacodynamic parameters of dienogest was assessed in healthy women, with a focus on ovulation suppression i. Single centre, double-blind, randomized, parallel-arm ii. Participants randomized to dienogest 0.5, 1, 2, or 3 mg/day, for maximum of 72 days iii. Ovarian activity was assessed every third day (according to Hoogland) iv. Follicle size (transvaginal ultrasound), serum estradiol and progesterone levels v. Primary end-point = ovarian activity vi. Safety variables included adverse events, menstrual bleeding patterns, vital signs, laboratory tests, and physical examinations Klipping C, et al. J Clin Pharmacol 년대한만성골반통학회제 3 차학술대회및연수강좌 155

162 VII. Special Lecture Pharmacodynamic Study Results - Endometrial thickness Substantial suppression of endometrial growth already with lowest dose Results indicate a potent endometrial effect for dienogest Klipping C, et al. J Clin Pharmacol Nov 년대한만성골반통학회제 3 차학술대회및연수강좌

163 이은주 :Visanne : A New Vision for Endometriosis Treatment Pharmacodynamic Profiling Study Results : Ovarian Activity - E2 Levels Estradiol therapeutic window pg/ml* Pretreatment 0.5 mg 1 mg 2 mg 3 mg Estradiol Klipping C, et al. levels J Clin Pharmacol remained within suggested therapeutic window for the * Barberie R. J Repro Med 1998;43: treatment of endometriosis Effects on Ovarian Function I. Dienogest 2 mg plus ethinyl estradiol (0.03 mg)/day reliably inhibits ovulation 1 II. Visanne has not been directly studied for contraceptive efficacy non-hormonal methods should be used if contraception is required III. Available data show menses returns to normal within 2 months of treatment cessation 2 1. Foster RH & Wild MI. Drugs 1998; 2. Seitz C et al. Fertil Steril Dienogest : Basic research data 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 157

164 VII. Special Lecture Dienogest: Endometrial Specificity I. Potent endometrial activity i. Endometrial transformation activity assessment in humans (Kaufmann assay) and rabbits (McPhail test) 1,2 II.Strong effect on endometrium relative to ovulation i. Higher ratio of ovulation-inhibition dose to transformation dose than other progestins 2,3 III.Pronounced endometrial effect leads to pronounced secretory transformation and atrophy 4,5 i. Confirmed in in vitro, animal and clinical studies 1. Foster RH & Wilde MI. Drugs 1998; 2. Sasagawa S et al. Steroids 2008; 3. Oettel M et al. Drugs Today 1995; 4. Okada M et al. Mol Hum Reprod 2001; 5. Katsuki Y et al. Drugs Exp Clin Res Dienogest : Mechanism of Action in Endometriosis 1. Growth of endometrial lesions inhibited via: I. Central effects: Inhibition of gonadotropin secretion i. Hypoestrogenic, hypergestrogenic endocrine environment, causing decidualisation of endometrial tissue followed by atrophy of lesions 1,2 II.Local effects (preclinical findings): i. Direct inhibitory effect on proliferation of endometrium-like tissue (in addition to classical progestational effects) 1 ii. Impact on endometriosis-related inflammation 3 iii.modulation of metalloproteinases, which regulate the response of endometrium-like tissue to estrogen at the paracrine level 2 1. Shimizu Y et al. Mol Hum Reprod 2009; 2. Vercellini P et al. Hum Reprod Update 2003; 3. Katsuki Y et al. Eur J Endocrinol Anti-Proliferation and Anti-Inflammatory Effects of DNG Ex Vivo: Important Mediators (to use as predictive markers?) Inflammation E2 TNFα IL-8 NF-κB DNG Endometriosis Proliferation TNFα-induced IL-8 production is stimulated by E2, which is mediated by NF-κB.This is directly blocked by DNG by two effects: 1. Direct inhibition of NF-κB 2. Direct inhibition of estradiol in the ovary E2=estradiol; IL-8=interleukin-8; NF-κB=nuclear factor kappa B; TNFα=tumor necrosis factor α. Horie S, Harada T, Mitsunari M et al. Fertil Steril 2005;83: 년대한만성골반통학회제 3 차학술대회및연수강좌

165 이은주 :Visanne : A New Vision for Endometriosis Treatment Anti-proliferative Effects: Dienogest vs. Danazol and Buserelin 1. In vivo investigations: I. Experimental endometriosis induced by autotransplantation in rats II.Reduction of endometrial implant volume, comparable with danazol and buserelin Volume of endometrial implants (mm 3 ) Control Dienogest Danazol Buserelin OVX P<0.05; **P<0.01 versus control Dienogest (0.03, 0.1, 0.3 or 1 mg/kg per day, p.o.), Danazol (100 mg/kg per day, p.o.), Buserelin (30 mg/kg per day,s.c.), ovariectomy (OVX). Katsuki Y et al. Eur J Endocrinol Anti-inflammatory Effects in Experimental Endometriosis I. Experimental endometriosis induced by auto-transplantation in rats II. Peritoneal fluid: Amelioration of implant-induced alterations of immune system i. Increased natural killer cell activity ii. Decreased macrophage activity: reduction of interleukin-1ß production in macrophages (figure) III. Effects NOT seen with danazol and buserelin Interleukin-1 β (pg/ml) * ** Intact Control Dienogest *P<0.01 versus intact; **P<0.01 versus control Katsuki Y et al. Eur J Endocrinol Anti-angiogenic Effects in Animal Experiments 1. Different animal models: I. Chick embryo chorioallantoic membrane model assessment of embryonic angiogenesis II. Mouse dorsal air sac model of angiogenesis induced by S-180 mouse tumour cells Nakamura M et al. Eur J Pharmacol 년대한만성골반통학회제 3 차학술대회및연수강좌 159

166 VII. Special Lecture Dienogest: clinical data Pivotal Trials Main efficacy end-points Pelvic pain relief: VAS Pelvic pain relief: VAS Pelvic pain relief: VAS Bleeding pattern Comparator/ Blinding Leuprolide acetate/open Placebo/ double-blind None/open Treatment FAS Publication 2 mg/day dienogest 3.75 mg/4 weeks (IM) LA 24 weeks 2 mg/day 12 weeks 2 mg/day 12 months + 6 month treatment-free follow up 248 Strowitzki et al (2010) 198 Strowitzki et al (2010) 168 Petraglia et al (2012) FAS, full analysis set; IM, intramuscular; LA, leuprolide acetate; VAS, visual analogue scale Strowitzki T et al. Hum Reprod 2010 Strowitzki T et al. Eur J Obstet Gynecol Reprod Biol 2010 Petraglia et al. Arch Gynecol Obstet 2012 Reduction in Pelvic Pain Dienogest 2 mg vs. Leuprolide Acetate Dienogest 2 mg (n=90) Leuprolide acetate (n=96) 50 VAS (mm)* Change in VAS score: Dienogest: mm Leuprolide: mm -1.5 mm Weeks of treatment Non-inferior versus leuprolide acetate (P<0.0001) Per protocol set * mean ± SEM SEM, standard error mean; VAS, visual analogue scale. Strowitzki T et al. Hum Reprod 년대한만성골반통학회제 3 차학술대회및연수강좌

167 이은주 :Visanne : A New Vision for Endometriosis Treatment Total Symptoms & Signs Severity* Dienogest 2 mg vs. Leuprolide Acetate Total symptom sign severity (% patients) Dienogest 2 mg Leuprolide acetate Dienogest 2 mg Leuprolide acetate Week 0 Week 24 None Mild Moderate Severe Very severe Missing data not included. *Biberoglu & Behrman scale Strowitzki T et al. Hum Reprod 2010 Safety: Hypoestrogenic Effects Dienogest 2 mg vs. Leuprolide Acetate 2 1 A. Bone Mineral Density B. Hot Flushes Dienogest 2 mg Leuprolide acetate % Change in Bone Mineral Density Weeks of treatment Hot Flushes (days per week) Weeks of treatment Significant difference in favour of dienogest 2 mg versus leuprolide acetate (P=0.0003) Strowitzki T et al. Hum Reprod 2010 Data are mean ± SEM. SEM, standard error of the mean Note: Leuprolide acetate without addback Dienogest versus Leuprolide Acetate Change in Estradiol Levels Estradiol level (pg/ml) mean ± SEM Weeks of treatment Dienogest 2 mg Leuprolide acetate *mean ± SEM Strowitzki T et al. Hum Reprod 년대한만성골반통학회제 3 차학술대회및연수강좌 161

168 VII. Special Lecture Reduction of Pelvic Pain Dienogest 2 mg vs. Placebo Superiority versus placebo # P< after 4 weeks, * P< after 8 and 12 weeks Dienogest 2 mg Placebo VAS (mm) mean ± SEM 40 # * * Change in VAS score: mm mm mm Weeks of treatment SEM, standard error of the mean; VAS, visual analogue scale Strowitzki T, et al. Eur J Obstet Gynecol Reprod Biol 2010;151: Number of Bleeding/Spotting Days with Dienogest 2 mg Over Time Mean number of bleeding/spotting days Less than 1% discontinuation due to irregular bleeding Months Reference Period 1: n=281 2: n=248 3: n=156 4: n=146 5: n= Reference Period Strowitzki T et al. Eur J Obstet Gynecol Reprod Biol 2010 Strowitzki T et al. Hum Reprod 2010 Petraglia F et al. Arch Gynecol Obstet 2012 Visanne Product Monograph, October 12, 년대한만성골반통학회제 3 차학술대회및연수강좌

169 이은주 :Visanne : A New Vision for Endometriosis Treatment Results: Responder Analysis Dienogest is non-inferior to LA in responder rates at all of the thresholds LA, leuprolide acetate; VAS, visual analogue scale Error bars represent SEM. Data are per-protocol set. Strowitzki T, et al. Int J Gynecol Obstet 2012 (epub ahead of print) Results: Biberoglu & Behrman (B&B) Profile DNG and LA provided broadly equivalent relief of symptoms in substantial proportions of women By study end, most women were free of these symptoms DNG, dienogest; LA, leuprolide acetate Strowitzki T, et al. Int J Gynecol Obstet 2012 (epub ahead of print) Results: Physical Health Summary DNG provides additional QoL benefits relative to LA DNG LA Total Physical functioning scale Rolephysical scale Bodily pain scale General health scale SF-36 quality of life scores at study end (descriptive data) DNG, dienogest; LA, leuprolide acetate; QoL, quality of life Error bars represent SD. Data are per-protocol set. Strowitzki T, et al. Int J Gynecol Obstet 2012 (epub ahead of print) 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 163

170 VII. Special Lecture Results: Mental Health Summary DNG provides additional QoL benefits relative to LA DNG LA Total Vitality scale Social functioning scale Roleemotional scale Mental health scale SF-36 quality of life scores at study end (descriptive data) DNG, dienogest; LA, leuprolide acetate; QoL, quality of life; SD, standard deviation Error bars represent SD. Data are per-protocol set. Strowitzki T, et al. Int J Gynecol Obstet 2012 (epub ahead of print) Overall Summary Pivotal trials and meta-analyses demonstrate that treatment with DNG 2 mg/day provides: Consistent and effective reduction in pelvic pain associated with endometriosis Favourable safety and tolerability profile No significant hypoestrogenic side effects (ie, hot flushes, decrease in BMD) Strowitzki T et al. Hum Reprod 2010 Strowitzki T et al. Eur J Obstet Gynecol Reprod Biol 2010 Petraglia et al. Arch Gynecol Obstet 2012 Strowitzki T, et al. Int J Gynecol Obstet 2012 (epub ahead of print) Gerlinger C, et al. BMC Women s Health 2012 (epub ahead of print) Ongoing studies The safety of Visanne is monitored through: Ongoing clinical studies VISADO (Phase IIb): adolescent population VIPOS (Phase IV): real life setting Investigator-sponsored studies Spontaneous adverse event reporting To date, no safety signals have been identified 년대한만성골반통학회제 3 차학술대회및연수강좌

171 이은주 :Visanne : A New Vision for Endometriosis Treatment VISADO - Visanne study to assess safety in adolescents (Phase IIb) Study was required by EMA Design: A multi-center, open label, single-arm study to investigate the safety and efficacy of daily oral administration of 2 mg dienogest tablets for the treatment of endometriosis in adolescents over a treatment period of 52 weeks Patients: 111 adolescents (post-menarche up to age 18) enrolled Primary endpoint: BMD determined by DEXA Countries: Germany, Finland, France, Spain, Austria, Czech Republic Study Period: Feb Jun 2013 BMD, bone mineral density; DEXA, dual energy X-ray absorptiometry; EMA, European Medical Agency Visanne Post-approval Observational Study (VIPOS) Generating real life data in clinical practice (Phase IV) Study is a post-approval commitment to EMA Objective: To collect long-term safety (and efficacy) data Study Outline Controlled, prospective, non-interventional, cohort study with active surveillance Visanne vs all other endometriosis therapies Up to 6 years of follow-up Goal: 25,000 women and ~89,000 women-years Countries: Germany, Hungary, Poland, Switzerland, Ukraine, Russia Study Period: 2010 to 2016 EMA, European Medical Agency Clinical Trials.gov Identifier: NCT Drug-Related Adverse Events 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 165

172 VII. Special Lecture Adverse Event Profile I. Most frequently reported adverse reactions in clinical trials were headache (9.0%), breast discomfort (5.4%), depressed mood (5.1%) and acne (5.1%) 1 4 II.Adverse events generally mild to moderate and associated with low dropout rates III.The majority of patients treated with Visanne experience changes in their menstrual bleeding pattern IV.Adverse event profile acceptable in light of symptom improvement during treatment 1. Köhler G et al. Int J Gynaecol Obstet 2010; 2. Strowitzki T et al. Eur J Obstet Gynecol Reprod Biol 2010; 3. Strowitzki T et al. Hum Reprod 2010; 4. Seitz C et al. Fertil Steril Dienogest 2 mg and Body Weight 1. Dienogest is not associated with relevant changes in body weight Change from baseline in kg (mean ±SD) Week 12 Week 24 Week 52 Weeks of treatment Placebo Dienogest Leuprolide acetate Strowitzki T et al. Eur J Obstet Gynecol Reprod Biol 2010 Strowitzki T et al. Hum Reprod 2010 Petraglia et al. Arch Gynecol Obstet 2012 Pooled Data Impact on Bleeding Patterns Pooled analysis of bleeding pattern data from clinical study programme Bleeding and spotting Treatment period* Month 1?3 (n=290) Treatment period* Month 9?12 (n=149) Amenorrhea 2% 28% Infrequent 27% 24% Irregular 35% 22% Frequent 13% 3% Prolonged 38% 4% Normal (none of the above) 20% 23% Drop-out rate due to bleeding irregularities < 1 % Distributions of women with each menstrual bleeding pattern during dienogest 2 mg treatment* *Numbers add up to more than 100% because each patient could fall into more than one category. 1. Strowitzki T et al. Eur J Obstet Gynecol Reprod Biol. 2010; 2. Strowitzki T et al. Hum Reprod. 2010; 3. Seitz C et al. Fertil Steril 년대한만성골반통학회제 3 차학술대회및연수강좌

173 이은주 :Visanne : A New Vision for Endometriosis Treatment Overall Summary: adverse effects Dienogest 2 mg/day is generally well tolerated The most frequent (>5%) adverse drug reactions reported in pivotal trials were headache and breast discomfort including breast engorgement and breast pain The bleeding parameters showed a clear and consistent pattern of reduced intensity over time following prolonged treatment Available data do not suggest a negative impact of DNG on BMD BMD, bone mineral density; DMPA, depot-medroxyprogesterone acetate, DNG, dienogest Fraser IS, Contraception 1994; MEB-Second Clinical Assessment Report, July 2003; Momoeda M, et al. J Obstet Gynecol Res 2009; Strowitzki T et al. Eur J Obstet Gynecol Reprod Biol 2010; Strowitzki T et al. Hum Reprod 2010; Petraglia F et al. Arch Gynecol Obstet 2012; Takagi H, et al (Abstract); Visanne Product Monograph, October 12, Conclusions: Dienogest (Visanne ) A synthetic oral progestogen with strong progestational and moderate antigonadotrophic effects without androgenic, glucocorticoid or mineralocorticoid activity High oral bioavailability and half-life suitable for once-daily administration. Indicated a dosage of 2mg/day for the treatment of endometriosis A dosage of 2mg/day only moderately suppress estradiol level with few hypoestrogenic side effects 년대한만성골반통학회제 3 차학술대회및연수강좌 167

174 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 Current Management of Bladder Pain Syndrome (BPS) / Interstitial Cystitis (IC) Hyung-Lae Lee Department of Urology, Kyung Hee University Definition Interstitial cystitis : particular, severe inflammation of the urinary bladder (Skene, 1887) National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) criteria Pain associated with the bladder or urinary urgency glomerulations or Hunner s ulcer on cystoscopy under anesthesia 9 months or more of symptoms at lest 8 voids per day 1 void per night, and cystometric bladder capacity less than 350cc Since more than 60% of patients thought to have interstitial cystitis did not fulfill the NIDDK, it was evident that the criteria could not be used for diagnostic purposes. Definition Bladder pain syndrome European Society for the Study of Interstitial Cystitis (ESSIC, 2008) chronic pelvic pain, pressure, or discomfort perceived to be related to the urinary bladder accompanied by at least one other urinary symptom like persistent urge to void or urinary frequency. confusable diseases as the cause of the symptoms must be excluded. AUA clinical guideline on IC/ BPS in 2011 Symptom duration : more than 6 weeks 년대한만성골반통학회제 3 차학술대회및연수강좌

175 이형래 :Current Management of Bladder Pain Syndrome (BPS) / Interstitial Cystitis (IC) Confusable disease Classification (ESSIC) According to cystoscopic findings and biopsy Hunner s Lesion A positive finding that can confirm the diagnosis in patients who meet the definition criteria acute phase (inflamed, friable, denuded area) chronic phase (blanched, non-bleeding area) Provides a therapeutic option 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 169

176 VII. Special Lecture Glomerulation The finding of glomerulations on hydrodistention is variable and not consistent with clinical presentation Absence of glomerulation can lead to false negative assessment of patients who present with clinical findings consistent with IC/BPS Seen in many clinical situations Radiation therapy, defunctionalized bladders, bladder cancer, chemotherapeutic or toxic drug exposure, normal bladders 년대한만성골반통학회제 3 차학술대회및연수강좌

177 이형래 :Current Management of Bladder Pain Syndrome (BPS) / Interstitial Cystitis (IC) Treatment Principles for PBS Clinical trials are affected by patient variability, so do not insist on evidence based therapy No single treatment works for all patients Start with the most innocuous treatments Keep trying different treatments until good symptom relief occurs Many patients need combined treatments Make changes one at a time Evaluate each change (Sx score, diary) Conservative Treatment Dietary changes (B:2) Restricted diet Diet aids such as Prelief, Coffee Tamer Urinary alkalinization Bladder holding protocol (B:2) Keep voiding diary with time and amounts Gradually increase voiding interval Physical therapy (A:1) Biofeedback Soft tissue massage Stress reduction (B:2) Diet In some cases, certain foods/drinks worsen Sx No mechanism proven, but may involve: Acid content of foods Potassium content Biogenic amine precursors Bladder irritants (e.g.spices, caffeine) Problem : not all foods bother the same patients 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 171

178 VII. Special Lecture Diet : Practical Approach Give a list of foods that commonly worsen Sx (the ICA wed site has this) Avoid all foods on the list for 1-2weeks Try each food individually ; see if it worsens Sx Some foods may be tolerable if eaten with : Prelief (AkPharma) ph Choice (ph Sciences) Urinary Alkalinization Oral agents : anecdotal evidence only Intravesical ph 5 or 7.5 had similar effects on symptoms (BJUI 95 :91, 2005) Options for timing : Continual use As needed when symptoms flare With specific foods to make them tolerable Treatment Oral therapy Treatment Amitriptyline B 2 Duloxetine -C 4 Analgesics C 4 Garbapentin D 4 Hydroxyzine D 1 Methotrexate D 4 Sodium pentosanpoylsufate D 1 Misoprostol D 4 Cyslosporine C 3 Montellukast D 4 L-arginie -A 1 Nalmefene -A 1 Antibiotics regimens D 4 Nifedipine D 4 Azathioprine D 4 Quercetin D 4 Benzydamine D 3 Tanezumab D 1 Chloroquinie derivatives D 4 Suplatast tosilate D 3 Doxycycline D 3 Viatamine E D 4 Cimetidine C 년대한만성골반통학회제 3 차학술대회및연수강좌

179 이형래 :Current Management of Bladder Pain Syndrome (BPS) / Interstitial Cystitis (IC) Pentosanpolysulfate (PPS) Possible mechanisms of benefit in IC Replace deficient bladder glycoconijugates Bind and inactivate pro-inflammatory urine components (J Urol 168:289, 2002) Inhibit mast cell histamine release (J Urol 164:2119, 2000) Various anti-inflammatory effects Clinical Use of Oral PPS for IC 100 mg tid is usual; 200 bid easier for patients 300 tid not better (Urology 65:654, 2005) 3-6 months needed for maximum benefit Side effects Nausea/diarrhea Alopecia Weak anticoagulant activity Liver enzyme abnormalities 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 173

180 VII. Special Lecture Amitriptyline Possible mechanisms : H 1 receptor blocker Anticholinergic Sedation (improves sleep/ nocturia) Decreased nociception in CNS Usual dose : mg po qhs Ways to improve morning lethargy : Start with 10 mg and increase gradually Take at dinner time rather than bedtime Other side effects : Weight gain Constipation Palpitations, tachycardia Hydroxyzine H 1 receptor blocker Inhibits mast cell secretion and activation Urology 49 (sup 5A) :108, 1997 Urol Clin North Am 29 (3) : 649 Sedative effect improves sleep, nocturia Start with 10 mg qhs, increase gradually Ideally to 50 mg Lower dose if 50 not tolerable Up to 100 if 50 not effective Symptom relief can take 2-3 months Sedation is the only significant side effect Gabapentin Rationale: some patients may have neuropathic components to their pain Patient Selection for Gabapentin Failed conventional treatments Able to tolerate fatigue Able to afford the drug (no generic available) History suggests neuropathic pain 년대한만성골반통학회제 3 차학술대회및연수강좌

181 이형래 :Current Management of Bladder Pain Syndrome (BPS) / Interstitial Cystitis (IC) Immunosuppression Not a standard treatment Use with great caution Patient selection: failed conventional treatments understands risks, compliant with follow-up suspected autoimmune/inflammatory: - other autoimmune disease - inflammation on bladder biopsy Intravesical therapy Treatment Lidocaine C 2 Dimethylsulfoxids (DMSO) B 2 Heparin C 3 Hyaluronic Acid D 1 Chondroitin Sulfate D 4 PPS D 4 Capsaicin/RTX -A 1 BCG -A 1 Oxybutinin D 4 Botox (intramural) A 1 Endoscopic management Hydrodistension (C:3) Set the fluid bag at cm above the symphisis pubis Do not distend beyond a capacity of 1,000ml Repeat a maximum of five times or until there is no further increase in the volume of the distended bladder Complication : transient symptomatic aggravation, hematuria, necrosis, perforation 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 175

182 VII. Special Lecture Endoscopic management Endoscopic fulguration or TURB of Hunner s lesion (C:3) Surgical management Surgical options should be considered only when all conservative treatment failed. Methods Bladder augmentation cystoplasty Cystoplasty with supratrigonal resection Cystoplasty with subtrigonal cystectomy Total cystectomy and urethrectomy Level 3 evidence Grade C recommendation AUA guideline 년대한만성골반통학회제 3 차학술대회및연수강좌

183 이형래 :Current Management of Bladder Pain Syndrome (BPS) / Interstitial Cystitis (IC) IC/BPS: An unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than six weeks duration, in the absence of infection or other identifiable causes Basic Assessment History Frequency/Volume Chart Post-void residual Physical examination Urinalysis, culture Cytology if smoking Hx Symptom questionnaire Pain evaluation Clinical Management Principles - Treatments are ordered from most to least conservative; surgical treatment is appropriate only after other treatment options have been found to be ineffective (except for treatment of Hunner s lesions if detected) - Initial treatment level depends on symptom severity, clinician judgment, and patient preferences - Multiple, simultaneous treatments may be considered if in best interests of patient - Ineffective treatments should be stopped - Pain management should be considered throughout course of therapy with goal of maximizing function and minimizing pain and side effects - Diagnosis should be reconsidered if no improvement w/in clinicallymeaningful time-frame 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 177

184 VII. Special Lecture Basic Assessment History Frequency/Volume Chart Post-void residual Physical examination Urinalysis, culture Cytology if smoking Hx Symptom questionnaire Pain evaluation Dx Urinary Tract Infection TREAT & REASSESS Signs/Symptoms of Complicated IC/BPS Incontinence/OAB GI signs/symptoms Microscopic/gross hematuria/sterile pyuria Gynecologic signs/symptoms Consider: - Urine cytology -Imaging - Cystoscopy - Urodynamics - Laparoscopy - Specialist referral (urologic or non-urologic as appropriate) 년대한만성골반통학회제 3 차학술대회및연수강좌

185 이형래 :Current Management of Bladder Pain Syndrome (BPS) / Interstitial Cystitis (IC) TREAT AS INDICATED NORMAL Clinical Management Principles - Treatments are ordered from most to least conservative; surgical treatment is appropriate only after other treatment options have been found to be ineffective (except for treatment of Hunner s lesions if detected) - Initial treatment level depends on symptom severity, clinician judgment, and patient preferences - Multiple, simultaneous treatments may be considered if in best interests of patient - Ineffective treatments should be stopped - Pain management should be considered throughout course of therapy with goal of maximizing function and minimizing pain and side effects - Diagnosis should be reconsidered if no improvement w/in clinicallymeaningful time-frame First-Line Treatments General Relaxation/Stress Management Pain Management Patient Education Self-care/Behavioral Modification Second-Line Treatments Appropriate manual physical therapy techniques Oral: amitriptyline, cimetidine, hydroxyzine, PPS Intravesical: DMSO, heparin, Lidocaine Pain management 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 179

186 VII. Special Lecture Third-Line Treatments Cystoscopy under anesthesia w/ hydrodistension Pain Management Tx of Hunner s lesions if found Fourth-Line Treatments Neuromodulation Pain Management Fifth-Line Treatments Cyclosporine A Intradetrusor BTX Pain Management 년대한만성골반통학회제 3 차학술대회및연수강좌

187 이형래 :Current Management of Bladder Pain Syndrome (BPS) / Interstitial Cystitis (IC) Sixth-Line Treatments Diversion w/ or w/out cystectomy Pain management Substitution cystoplasty NOTE: For patients with end-stage structurally small bladders, diversion is indicated at any time clinician and patient believe appropriate AUA guideline 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 181

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189 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 VIII. State-of-the-Art SYMPOSIUM 좌장 : 김장흡 ( 가톨릭의대 )

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191 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 내가경험한자궁내막증환자의진단및치료의 Knowhow 오성택 전남대학교의과대학 자궁내막증의진단 1. 증상및이학적검사 골반내진상자궁내막증의심할만한소견 1 난소에종양이촉지 2 자궁골반인대나다글라스와부위에결절, 비후나압통 3 자궁이후굴되어고정 4 질직장중격부위에압통을지닌종창 (swelling) 이촉지 2. 진단복강경 현재까지가장확실한진단방법이다. 3. 혈청표지물질 (serum marker) : CA-125 1) CA-125는체강성상피 (coelomic epithelium) 에서유래한것이다. 2) 자궁내막증시혈중농도가증가한다. 3) 비점액성난소암, 자궁선근증, 자궁근종, 골반결핵및월경중에도증가하므로감별을요한다. 4) 자궁내막증 3-4 기에는유의하게증가하나 1-2기에는증가빈도가낮아현재자궁내막증의선별검사 (screening test) 로는부적합하다. 5) 주기적측정이자궁내막증의치료상의추적검사에도움이된다. 6) 단점을보완하려복강액에서 CA-125를측정하기도한다. 4. 영상진단법 (Imaging techniques) 1) 초음파검사 : 다른난소낭종, 자궁외임신, 난관난소농양등과구분이힘듦. 2) 전산화단층촬영 (computed tomography, CT): 진단에사용하는데한계가있다 년대한만성골반통학회제 3 차학술대회및연수강좌 185

192 VIII. State-of-the-Art SYMPOSIUM 3) 자기공명장치 (magnetic resornance imaging, MRI): 혈액으로된난소낭종을구분해냄. 4) 혈액으로된다른난소낭종과구분이어려운경우가많다. 5) Conventional T1- & T2-weighted imaging나 Fat-saturation T1-weighted imaging을이용하면좋다. 5. 청소년기의자궁내막증의진단골반통을지닌청소년의맨처음진단은 careful history taking부터시작하여야한다. 전술한바와같은청소년기의자궁내막증의통증의양상에주의하여진단을하도록하여야한다. 즉청소년기의자궁내막증은주기적생리통등을주소로하는성인과는달리비주기적통증과주기적통증이혼합된형태로주로나타나고방광과장관의증상이더주로나타나는특징을지니므로주기적통증즉생리통만을지닌청소년은일차성월경곤란증의가능성을먼저염두에두어야한다. 자궁내막증은유전적경향을지니므로가족력의세밀한조사도청소년기자궁내막증을진단하는데많은도움을주며, sexual abuse history도만성골반통의관리에서필요하므로반드시 check하도록하여야한다 ( Walling MK et al, 1994). 만약청소년이생리가규칙적이지않은경우, 반드시호르몬상태에대한전반적인검사와염색체검사는시행하여확인하여두는것이나중에수술후난소기능회복에있어서법적인문제로부터보다자유로울수있다. Physical exam은청소년기에는가능하지않은경우도있으나매우중요하므로반드시하도록노력하여야한다. 특히 müllerian abnormality는반드시 check 하여야하고비주기적통증인경우가많으므로자궁내막증이아닌위장관계, 비뇨기계및근골격계의다른원인에의한만성골반통의통증을감별하여야한다. 가능하다면 rectal-abdominal exam을시행하여자궁부속기종양이나 rectovaginal septum, uterosacral ligament, cul de sac 등의압통여부등을관찰한다 ( Redwine et al, 1990 ). 특히 Q-tip을이용하면 ( 질속에삽입하거나하여 ) transverse vaginal septum이나 imperforate or microperforate hymen을진단하기좋다고한다. laboratory test에는임신반응검사를포함하도록하는것이좋고, CBC와 ESR은급성혹은만성골반염을감별하는데유용하다. 소변검사와소변배양검사는비뇨기계원인의만성골반통과감별하는데유용하다. CA-125는진단하는데는도움이되나 false positive가많아 screening test로는부적절하고사춘기자궁내막증때는치료후 follow-up에도많은도움이되지않는다고한다 ( Pittaway DE and Fayez JA, 1986; Laufer MR et al, 2003 ). 초음파검사는난소종양이있는경우는도움이될수있으나 15세이전의청소년에서는자궁내막종이흔하지않으므로많은도움을주지못하며질식초음파는청소년기에는불가능한경우가많으며필요한경우는 rectal sonogram 을실시할수있다. CT scan은크게도움을주지못하고 MRI는난소종양이있는경우청소년기에많은 dermoid cyst와의감별에많은도움이되며아울러 genital tract anomaly의감별에도도움이되므로청소년기에는상당한도움이된다. 청소년기에난소종양을지니지않은만성골반통의경우, 특히생리통만심한경우에원발성월경곤란증이나복강내유착에의한통증과자궁내막증이구분이잘되지않는경우는일차 NSAIDs 치료를시작해보는것이추천되고있다 (Laufer et al, 2003). NSAIDs를치료하여반응이없는경우는 low-dose oral contraceptive (OCPs) 를사용하여치료반응을관찰하여반응이없는경우는자궁내막증에대한보다확실한검사즉복강경검사를시행하여야한다. Layfer 등 (1997) 에의하면 NSAIDs와 cyclic OCPs에반응하지않는사춘기여성의만성골반통중 69% 가자궁내막증이었다고한다. 성인에서처럼역시청소년기에도자궁내막증의가장확실한진단법은복강경검사이다. 그러나청소년은 년대한만성골반통학회제 3 차학술대회및연수강좌

193 오성택 : 내가경험한자궁내막증환자의진단및치료의 Knowhow 복강경상처에대하여매우민감한시기이므로되도록보이는상처를최소화하기위하여 trocar site를 umbilicus 에직접 vertical incision을넣어시행하도록하고 suprapubic trocar site도 symphysis pubis 1-2 cm 상방에서넣어나중에그위로 pubic hair가자랄수있도록하고되도록정확히대칭되도록 incision을하도록한다 (Laufer et al, 2003). 아울러가능하다면진단이나전기소작등간단한조작만을위한경우는 microlaparoscope를이용하도록한다. 청소년기의복강경검사때는성인과는다른몇가지주의점이있다. 즉청소년기에서의자궁내막증병변은전형적인병변보다는비전형적인병변이훨씬많으므로자궁내막증복강경검사에보다많은경험을가지거나지식을가지고복강경검사에임하여야한다. 청소년기에는주로 red flame like lesion이많다고하고 powder-burn lesion은청소년기에는흔하지않다고한다 (Davis GD et al, 1993). 그렇지만이러한 clear 및 red lesions는오히려전형적인병변보다훨씬통증을더많이동반한다고보고되고있다 (Demco L, 1998). 월경통과골반통은사춘기의청소년이흔히호소하는증상들이다. 이러한만성골반통을호소하는사춘기여성의약 % 가자궁내막증이라고보고되고있다 (Vercelllini P et al, 1989; Kontoavdis A et al, 1999). NSAIDs와경구용피임제가이들에가장먼저시도되는치료제이지만, 많은청소년기여성에서이들을사용함에도불구하고여전히골반통을호소하는경우가많다. 이런경우는반드시자궁내막증을감별하여야한다. 성인의자궁내막증의증상은주로주기적인골반통의형태로나타나지만사춘기에서는주기적이지않은통증의형태가성인보다훨씬많이나타난다고한다. Raney (1980) 의보고에의하면초경직후여성의 4-17% 가자궁내막증이라고보고하고있고, 과거에는자궁내막증은초경후상당한햇수가지나서야발생한다고믿어져왔으나최근보고에의하면자궁내막증이초경전에도발생한보고가있고, 초경후 1년혹은 5년에발생한증례를보고하고있다 (Laufer MR, 2000; Goldstein DP et al, 1979; Yamammoto K et al, 1997). 많은학자들의보고에의하면 50-70% 의사춘기여성에서 NSAIDs와경구용피임제로골반통을치료하는데실패하여복강경검사를시행한다고한다 (Reese KA et al, 1996; Laufer MR et al,1997; Laufer MR et al, 1998). 따라서청소년기의골반통으로부터보다빨리자궁내막증을감별해내야하고진단후보다빨리치료를시행함으로써이들공부하고있는청소년들이보다빨리이질환의고통으로부터자유롭게하여청소년기의삶의질을증진시키고자궁내막증에의하여올수있는낭종, 보다심한복강내유착, 불임, 심한만성골반통등을미리감소시키도록하여야한다. 청소년기의자궁내막증의증상은대개의경우주기적통증이주된증상이지만청소년기여성에서의자궁내막증은비주기적통증과주기적통증이함께나타나는경우가가장흔하다고한다 (Laufer MR, 1997). 아울러사춘기에서는성인에비하여장관이나방광증상이더흔하게나타나며, 자궁내막종의발현은 15세이전에는성인에서보다더드물게나타난다고한다 (Laufer MR, 1997). 자궁내막증의발생은유전적요인이어느정도관련있는것으로알려져있으며, first-degree 의 female relatives에서그렇지않은경우의발생률 1% 미만에비하여 6.9% 정도에서발생한다고한다 (Simson JL et al, 1980). 대개의경우어머니가자궁내막증으로고생한경우딸을데리고병원에오는경우가많으며, 이런경우는특별히더자궁내막증을감별하도록노력하여야한다. 특히청소년기에는자궁및질의선천적이상이있는경우가있으므로이러한경우도면밀히관찰하여감별하여야한다. Schifrin 등 (1973) 은 müllerian abnormality 지닌청소년기여성에서발생한자궁내막증의 6증례를보고하고있고, Sapilifo 등 (1973) 은이들에서 anomaly 교정후자궁내막증이호전됨을보고하고있다 년대한만성골반통학회제 3 차학술대회및연수강좌 187

194 VIII. State-of-the-Art SYMPOSIUM Table 1. Symptomes of adolescents with endometriosis (Laufer MR, 1997) Presenting Symptoms Percent Acyclic and cyclic pain 62.5 Acyclic pain 28.1 Cyclic pain 9.4 Gastrointestinal pain 34.3 Urinary symptoms 12.5 Irregular menses 9.4 Vaginal discharge 6.3 Table 2. Type of lesions and pain (Demco L, 1998) Type of lesion Association with pain Clear 76% Red 84% White 44% Black 22% 자궁내막증의치료 1. 약물치료 1) Danazol 치료후시행하는복강경검사결과 danazol은자궁내막증병변퇴행및감소에효과적이라고알려져있다 (60-94%). Telimaa 등 (1987) 은 danazol (600 mg/day) 치료 6개월후복강경검사상 40% 환자에서완전한퇴행을 20% 환자에서부분적퇴행을관찰하여위약투여군 (12%) 과는의의있는차이를보였다고하였으며 Fedele 등 (1989) 은같은용량으로 AFS score 12.1을 7.1로감소시킬수있었다고보고하였고 Salat-Baroux 등 (1988) 도 62% 의경증과중등도환자와 35% 의중증환자에서병변의크기와범위가줄었다고하였다 년 Buttram 등은 danazol 400, 혹은 800 mg/day 용량으로 6개월치료한결과골반내병변은 61%, 난소병변은 51% 퇴행되었으며난소자궁내막증은 1 cm 이상과이하에서각각 33% 와 71% 퇴행되었다고하였다. Danazol 치료로나타나는통증완화는치료첫달부터나타나기시작하여 2달이내에대부분환자가증상의호전을느끼게되는데무월경발생과일치하며약 80-90% 정도의여성에서효과가관찰된다. Moore 등 (1981) 은여러용량의치료효과를비교한시험에서 400 mg/day 이하로도중증환자에서효과적으로통증개선이되었다고주장하였으나저용량으로는통증의개선정도가적다는보고도있다. Danazol 600 mg/day 를사용한 Telimaa 등 (1987) 은치료중에도효과적이었고치료종료 6개월후에치료전보다통증정도가 76.3% 낮아졌으나위약투여군에서는 48% 의증가가있었다고하였다. 통증완화가치료의목적인경우저용량으로도효과적이나병변퇴행과재발방지를위해서는고용량투여가필요하며간혹반흔혹은유착에의해유발되는성교통혹은만성골반통은개선되지않는경우도있다. 자궁내막증의재발은 danazol 치료가자궁내막증병변을근본적으로제거하는치료가아니기때문에상당한예에서재발이발생한다. Dmowski와 Cohen (1978) 은치료마지막날에시행한복강경검사에서약 25% 가여전히진행성병변이라고보고하였고 Telimaa 등 (1987) 은치료종료 6개월후시행한복강경검사상 40% 년대한만성골반통학회제 3 차학술대회및연수강좌

195 오성택 : 내가경험한자궁내막증환자의진단및치료의 Knowhow 에서변화가없거나진행성병변이었다고보고하였으며 Barbieri 등 (1982) 은 6개월치료후증상과병변이첫해에 15% 재발하고그후매년 5 % 씩재발한다고보고하였다. 여러보고들을종합하여보면 Danazol 치료후통증재발률은 33-39% 로보고되고있고, 대부분치료종료후 6-12개월사이에일어난다고한다. 2) GnRH agonist GnRH agonist 치료가자궁내막증병변을감소시킨다는점은여러연구들에의하여입증되어왔다 (Henzl et al, 1988; 이등, 1989; Protocol 310 Study Group, 1990; Miller and Frank, 1992). GnRH agonist 치료후복강경을시행하였을때 endometriotic implants 에대한 AFS score가 50% 이상유의하게감소하였다. 유착 (adhesion) 에대한 score는 danazol의경우약간감소하거나증가한반면 GnRH agonist는 adhesion score가부분적인감소 (17-32%) 를보였다. GnRH agonist 치료는치료기간중골반통, 생리통, 성교통등통증증상의완화에있어매우효과적인것으로알려져있다 (Trabant et al, 1990; Nafarelin European Endometriosis Trial Group, 1992). 치료후상당수의환자에있어증상이재발되나그증상의정도가감소하는것으로보고되고있다 (Trabant et al, 1990; Nafarelin European Endometriosis Trial Group, 1992). 3) Gestrinone Gestrinone의자궁내막증과연관된통증완화효과는매우우수한것으로보고되고있으며 (90-97%), Coutinho 등 (1984) 은 gestrinone 6-8개월치료후 91% 환자에서통증완화와 55% 에서완전소실을관찰하였다고한다. 그러나 danazol과비교하여차이가없었다고보고되고있다. Coutinho 등 (1984) 은 gestrinone 6-8개월치료종료후높은통증소실률을보이나 1년후에는 31.1% 와 15.8% 에서통증이재발하였다고한다. Fedele 등 (1989) 은치료 1년후 57% 의통증재발률을보고하였으며, 이는 danazol의 53% 와는차이가없었다고보고하였다. 4) Estrogen/Progestogen (pseudopregnancy) 현재고용량의 estrogen/progestin 경구피임제보다는효과를가져올수있는최소용량의경구피임제가사용되고있다. 즉 μg의 ethinyl estradiol 을함유한어떤종류의저용량복합경구피임제도지속적으로사용할경우자궁내막증의치료에효과가있을수있다. 대개 6-12개월간사용하게되며, 이때월경통과골반통증상의호전은 60-95% 로보고되고있다. 한편치료중단후첫 1년동안의재발률은 17-18% 에이르며이후매년 5-10% 의재발률을보이는것으로보고된다. 1993년 Vercellini 등은중등도이상의골반통을가진자궁내막증환자에 GnRHa (goserelin) 와주기적저용량경구피임제를 6개월투여하여통증의경감정도를비교, 분석하였다. 치료 6개월후성교통은양군모두에서의미있게감소하였으며이중 goserelin이더우수한효과를보였고월경과상관없는통증또한양군에서모두의미있게감소하였으며월경통도경구피임제를복용한여성에서유의한감소를보였으나, 치료종료후 6개월내에양군에서모두통증이재발한것으로보고하였다. 자궁내막증의치료를위하여저용량경구피임제가사용되는경우는대개지속요법으로사용되는경우이며, 주기적요법으로사용한것에대한보고는서로엇갈리는보고가있어아직은주기적치료에대한것은논란이많다. Buttram은자궁내막증의정도와경구피임제의복용기간은연관성이없지만경구피임제를장기간복용한여성일수록중증의자궁내막증보다는경증의자궁내막증이생긴다고보고하였으며, Kirshon 등은이전에경구피임제를복용한여성에서자궁내막증의빈도가낮은것으로보고하였다. 반대로 Cramer 등과 Parazzini 등은오히려경구피임제의장기복용이자궁내막증의위험을증가시킨다고보고하였고, Balasch 등 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 189

196 VIII. State-of-the-Art SYMPOSIUM 도이전에경구피임제를복용했던경우자궁내막증이더많았다고보고하였다. 그러나 Moen은이전의경구피임제복용과자궁내막증과는관련이없는것으로보고한바있다. 이렇듯주기적경구피임제의사용이자궁내막증의발생률에어떤영향을미치는지는아직확실히규명되지않고있다. 5) 고농도 progestogen Progestogen only regimen은부작용이매우적어일반적으로환자들이경구피임제에의한 pseudopregnancy 요법보다훨씬잘적응한다고한다. MPA는 danazol 과비슷하게 AFS score와통증을감소시키고, danazol 보다가격이싸고, 부작용이적다. 치료효과는 3-6개월치료후나타난다. Luciano 등 (1988) 은 MPA (50 mg/day) 사용으로 AFS score가의의있게감소되었다고보고하였다. 1987년 Telimaa 등은 MPA (100 mg/day) 치료 6개월후복강경검사상 50% 환자에서자궁내막증병변을관찰할수없었으며, 이는 danazol 투여군 (40%) 과는차이가없으나위약투여군 (12%) 과는의의있는차이를보였다고하였다. 그외여러학자들에의해 Progestogen 치료후통증개선효과가아주우수하다고보고되어있다 (90% 이상 ). Moghissi와 Boyce (1976) 는 MPA 30 mg/day로 100% 의월경통소실을보고했고 MPA 100 mg/day를사용한 Telimaa 등 (1987) 은자궁내막증과관련된모든증상이위투약군보다의의있게경감되었으며, 치료종료 6개월후에치료전보다통증정도가 54% 낮아졌으나위투약군에서는오히려 48% 의증가가있었다고하였다. Progestogen 뿐만아니라모든약물치료후자궁내막증병변의완전한퇴행이이루어지지않기때문에많은환자에서월경재개와함께병변과증상의재발이빈번히나타난다. MPA 사용후 6개월에 12%, 2년내에 42% 의재발이관찰되었고 Telimaa 등 (1987) 은치료종료 6개월후시행한복강경검사상 37% 에서치료전에비해변화가없거나진행되고있음을보고하였다. Depot MPA는향후임신을원하지않고수술이불가능한여성에서사용할수있으며한달에한번씩 mg을투여한다. 특히 Depot MPA는자궁적출술후잔존기능난소가있는여성에서발생한자궁내막증재발때사용하면좋다고한다. 마지막주사후보통 3-6개월내에주기적배란이이루어지지만 18개월까지무배란이지속되는경우도있다. 따라서향후임신계획이있는여성에서는절대사용하면안된다. 6) Dienogest (Visanne) 자궁내막증통증치료에탁월한효과가있으나아직은더임상경험이필요하다. 2. 수술치료 1) 자궁내막종내용물의흡입혹은 drainage Frangeheim (1978) 은복강경하에서낭종의내용물을흡입한후 40% 에서만다시낭종이재발함을보고하였고 Fayez & Vogel (1991) 은치료후다시발생한자궁내막종의빈도가 drainage 단독및 stripping 과 laser 증발법에서서로차이가없다고보고하고있으나, 이에대한학자들의부정적인의견이많다. Vercellini 등 (1992) 은 33명의연구에서이치료전과 6개월후의자궁내막종의유의한크기변화를관찰할수없었으며이치료후 GnRH agonist 치료를시행하였으나별다른효과는관찰할수없었다고한다. Donnez 등 (1994) 은 80명의관찰에서역시 drainage 자체만으로는효과적이지못함을보고하고있으나이치료후 GnRH agonist 투여시완치는어려우나자궁내막종의크기와선분열상의감소는관찰할수있었음을보고하고있다. 낭종의내용물을흡입하고내부벽을관찰한다. 따라서자궁내막종내용물을흡입만하는것은권장할만한수술방법이아니다 년대한만성골반통학회제 3 차학술대회및연수강좌

197 오성택 : 내가경험한자궁내막증환자의진단및치료의 Knowhow 2) 자궁내막종의응고법및증발법 (coagulation and vaporization) 조직학적으로큰자궁내막종은그선과기질이 2 mm까지만난소조직을침투하므로, 낭종의벽을응고나증발을시킬때 3 mm 이상의조직파괴는필요없다고한다. 그러나작은자궁내막종은그침윤이상당히불규칙하여이러한응고나증발이완전히자궁내막증조직을파괴하지못하는경우가있으므로주의하여야한다. Laser에의한직접적인응고의침투효과는 krypton이나 argon의경우는 mm 정도깊이이지만실제응고되는깊이는약 2 mm까지이므로작은자궁내막종경우만주의하면충분한효과를거둘수있다고한다. Endocoagulator나 bipolar coagulator에의한응고역시보통 2 mm 정도깊이의응고가이루어진다. CO2 laser나고전위 unipolar electrode 를이용한증발법은깊이시행되는경향이있어필요한깊이보다더욱깊이시행될수있으므로시행시이깊이에대한세심한주의가필요하다. 3) 자궁내막종의박리술 (stripping) 난소에서낭종을박리해내는방법은 1987년 Semm 씨에의해기술되었다. 이는정상난소에대한열에의한손상이적고완전한낭종의제거를확인할수있기때문에권장되고있는방법으로먼저자궁내막종을주위유착으로부터박리하여낸다음 laser나 unipolar electride 혹은가위를사용하여아주작은절개를한후낭종내용물을완전히흡입세척한후절개부위를넓힌다. 그러나많은경우에서자궁내막종을주위조직으로부터박리하는도중에낭종이파열되어복강내내용물이흘러나오는경우가많다. 이러한파열자체가유착이나재발을유도하는위험성은없는것으로알려져있으나, 즉시낭종내남은내용물을전부흡입하고그후복강내흘러나온낭종내용물을흡입하고낭종내와복강내를따뜻한 lactated Ringer solution으로세척해주는것이좋다. 그이후넓혀진절개부위에서 sharp grasping 혹은 dissecting forcep을이용하여난소의장막과낭종의벽을분리하여낸다음, 난소장막과낭종벽을서서히반대방향으로잡아당겨둘사이를분리시킨다. 이때 3개의 forcep을사용하면매우도움을주며, 조직학적으로이때박리되는 plan은정상조직으로알려져있다 (Martin, 1991). 그리고 Martin 등 (1989) 은첫낭종절개및흡입세척후이절개부위주위를 CO2 laser를이용하여둥글게낭종의벽은다치지않고난소장막만을절개한후이를이용하여난소장막과낭종벽을분리하면보다편리하다고보고하고있다. Nezhat 등 (1989) 은이박리시두벽사이에 hydrodissection을이용하여부종을만든후박리하면박리가보다쉽다고보고하고있고, Kojima 등 (1990) 은원추형의특수박리봉과 Nd: YAG laser를이용하여박리하는방법을보고하고있다. 난소의 hilar 부위는매우단단히유착되어있어박리가상당히힘들고출혈이심한경우가많은데, 이경우 bipolar coagulator 를이용하여지혈시키면서조심스럽게박리하면대체로박리할수있으나매우힘든경우엔그부위만낭종벽을절제하고응고시키는수도있다. 4) Radical surgery 과거에는자궁내막증의치료로이용이많이되었으나현재는꼭필요한경우가아니면권장되고있지않다. 적응증은아이를다낳은여성에서전에시행한 conservative operation 으로증상의호전에실패한경우에한하여시행되고있다. 수술은반드시양쪽난소를제거하는 Total abdominal hysterectomy or laparoscopic hysterectomy (LAVH, TLH, LH, CISH) with bilateral salpingo-oophorectomy를하여야한다 년대한만성골반통학회제 3 차학술대회및연수강좌 191

198 VIII. State-of-the-Art SYMPOSIUM 3. Laparoscopic ovarian cystectomy 시의문제점 1) Principles of laparoscopic cystectomy (1) 반드시다른 malignant ovarian cyst나 malignant transformation을 r/o 하여야한다. (2) Cystectomy를하기전반드시먼저정상 anatomy를회복시켜야한다 : tube와 ovary를 adhesiolysis를통하여 mobilization (3) 특히 ovary는complete ovaryiolysis를시행하여야한다. (4) Endometrioma의모든 cyst wall을 complete하게제거하여야한다. 특히나이가많은여성에서는남은조직에서 malignant transformation이일어날수있기때문이다. (5) 난소에대한 trauma를최소화하여야하며 follicles를최대한 preserve해야한다. (6) Postoperative adhesion formation이나 reformation을최소화하여야한다. 2) Rule out of malignancy (1) Rule out of other malignant cyst Endometrioid adenocarcinoma of ovary는전 epithelial ovarian cancer의 15-20% 를차지하고있고, 이들 frank cancer의약 10-20% 에서주위에 benign endometriosis를가지고있다고한다 (Yu and Grimes, 1991). 그외 hemorrhagic content를지닌여러 cystadenocarcinoma도수술전에감별하여야한다. Ovarian cancer에대한 tumor marker check의 screening으로서의가치는아직명확하지는않으나감별하는데는상당한도움을준다. 그러나일반 stage I ovarian carcinoma의 50%, stage II carcinoma의 60% 에서 CA125가증가하므로 (Jacobs and Bast, 1989), CA125가증가하는 benign endometrioma와의감별을위하여서는 CA19-9, CA72-4, CEA, AFP, hcg 등의다른 tumor marker를항시같이검사하여야한다. Transabdominal ultrasonogram을이용한감별은시도되었으나 specificity에한계가있는것으로보고되어있고 (Cambell et al, 1989), transvaginal ultrasonogram을이용하면 95% 이상의 high sensitivity를가질수있다고보고되어있다 (Higgins et al, 1989; Nagell et al, 1991). Transvaginal color-flow Doppler가더욱도움이된다고는하나아직명확하지는않다. Malignancy를의심하게하는 sign에는 solid, irregular, fixed pelvic mass 등이있다. (2) Malignant transformation of endometrioma Endometrioma의 malignant transformation risk는상당히낮은것으로알려져있다. Chernobilsky's group (1979) 에의하면 194 ovarian endometriosis 환자중 7명 (4%) 에서 some degree의 atypia가발견됐다고한다. 그러나 endometrima의 malignant transformation의조기감별은상당히어려우므로 endometrioma의 lining 은 complete하게제거하도록노력하여야하며수술후반드시조직검사를시행하여야한다. 특히 10 cm 이상의 endometrioma는 malignant transformation 율이높으므로특히주의하여야한다. 수술중 malignancy 를감별하고복강내전파를막기위한방법에는다음과같은방법들이있다. 1 먼저 peritoneal cavity 전체를살펴보아 malignancy 의 sign이없는지관찰한다. : ascites, friable tissue, papillary growing tissue 등. 2 Routine 으로 peritoneal fluid의 aspiration. 3 Cyst는되도록위쪽면에서 open하고 aspiration하고 irrigation한다음 internal cyst wall을주의깊게관찰하여 malignancy의 sign이없는지관찰한다 년대한만성골반통학회제 3 차학술대회및연수강좌

199 오성택 : 내가경험한자궁내막증환자의진단및치료의 Knowhow 4 의심나는부위가있으면그조직을떼어 frozen biopsy를의뢰한다. 5 Malignancy가의심되면즉시 laparotomy로전환하여야한다. 3) 완전한 cyst wall의제거완전한 cyst wall의제거는 Cyst wall stripping 을통한 en bloc으로 cyst 제거하여야 cyst를완전하게제거할수있다. 이때젊은여성일수록되도록정상난소조직을최대한보호하여낭종 wall만을벗겨내도록 echleo 한노력하여야한다. Cyst size가클수록가능한한 cyst wall의 laser or electrocoagulation보다는 cyst wall의 stripping 이좋다. Cyst wall stripping 의완전한제거가능성때문에 Beretta P 등 (1998) 은두수술방법의비교에서수술후 dysmenorrhea (15.8% vs 52.9%) 재발이나 dyspareunia 재발 (10% vs 52.9%) 및 pregnancy rate (66.7% vs 23.5%) 에서 cystectomy가 drainage & coagulation보다훨씬수술후 outcome이좋았다고보고하고있다. 4) Endometrioma의 types Endometrioma는실제로그특징및발생상몇가지 types로구분이된다. 1 Type I (primary endometrioma) 실제자궁내막증조직에서발생된자궁내막종으로생각되며낭종내부조직이전부자궁내막조직으로덮여있으며 friable하고 stripping시박리가잘안되는특징이있다. 수술시다른 type에비하여난소의손상이더심하다. 2 Type II A (secondary endometrioma) 대개크기는 2-6 cm 정도이고기존에있던낭종표면에자궁내막증병변이침범하여낭종벽을 penetration 2013 년대한만성골반통학회제 3 차학술대회및연수강좌 193

200 VIII. State-of-the-Art SYMPOSIUM 은하지않았으나낭종내용물은 hemorrhagic 하게나타나는형태이다. 조직검사상낭종벽에서자궁내막조직을발견할수없어 hemorrhagic cystic teratoma나 hemorrhagic serous cystadenoma등의조직검사결과가나온다. 비교적박리가잘되는특징이있다. 3 Type II B (secondary endometrioma) Type II A와같으나자궁내막증병변이낭종벽을 penetration 하여낭종벽의일부에서자궁내막조직이발견된다. 대개크기는 3-12 cm 정도이고비교적박리가잘된다. 4 Type II C (secondary endometrioma) Type II B보다는더많은자궁내막증병변이낭종내로침범한경우이다. 크기는대개 3-20 cm 정도되고낭종벽의대부분에서자궁내막조직이발견되는것이보통이며낭종의박리가역시잘안되는특징이있다. 5) 거대 endometrioma 수술시의수술방법및주의점거대 endometrioma의 stripping은한쪽모서리에서 step by step으로 cyst가 tearing되지않게 en bloc으로 cyst를제거하여야만 cyst를 complete하게제거할수있다. Cystectomy 후의 ovary의큰 defect 때문에 dead space 없이완전하게 suture 하거나 bleeding control을해주어야만 postoperative hematoma를예방할수있다. Cyst가클수록 malignancy 가능성이높으므로조금이라도의심나는곳이있으면 frozen biopsy를시행하여야한다. 6) 수술후난소의봉합문제난소에서낭종을박리한후난소의결손부에대한처치는육안적봉합, 현미경적봉합, 복강경하봉합, glue 및전혀봉합하지않는여러방법이있다. 조직의유착은 ischemia와관계가깊다고알려져있으며 ischemia가심한경우에유착이더욱심해진다고 년대한만성골반통학회제 3 차학술대회및연수강좌