Deep Endometriosis – Diagnosis, Impact of Surgical Treatment, … · 2020-01-30 · Deep...

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Deep Endometriosis – Diagnosis, Impact

of Surgical Treatment, Future Perspectives

on Therapies (Didactic)

PROGRAM CHAIR

Charles E. Miller, MD

Charles Chapron, MDTamer A. Seckin, MD

Camran R. Nezhat, MDJim Tsaltas, MD

Professional Education Information Target Audience Educational activities are developed to meet the needs of surgical gynecologists in practice and in training, as well as, other allied healthcare professionals in the field of gynecology. Accreditation AAGL is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AAGL designates this live activity for a maximum of 3.75 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. DISCLOSURE OF RELEVANT FINANCIAL RELATIONSHIPS As a provider accredited by the Accreditation Council for Continuing Medical Education, AAGL must ensure balance, independence, and objectivity in all CME activities to promote improvements in health care and not proprietary interests of a commercial interest. The provider controls all decisions related to identification of CME needs, determination of educational objectives, selection and presentation of content, selection of all persons and organizations that will be in a position to control the content, selection of educational methods, and evaluation of the activity. Course chairs, planning committee members, presenters, authors, moderators, panel members, and others in a position to control the content of this activity are required to disclose relevant financial relationships with commercial interests related to the subject matter of this educational activity. Learners are able to assess the potential for commercial bias in information when complete disclosure, resolution of conflicts of interest, and acknowledgment of commercial support are provided prior to the activity. Informed learners are the final safeguards in assuring that a CME activity is independent from commercial support. We believe this mechanism contributes to the transparency and accountability of CME.

Table of Contents

Course Description ........................................................................................................................................ 1 Disclosure ...................................................................................................................................................... 3 Endometriosis and Hysterectomy C.R. Nezhat ................................................................................................................................................... 5 The Use of Robotic Assistance in the Treatment of Deep Endometriosis C.E. Miller ................................................................................................................................................... 11 The Impact of Surgical Treatment of Endometriosis on Infertility J. Tsaltas ..................................................................................................................................................... 15 Complications T.A. Seckin .................................................................................................................................................. 20 The Impact of Surgical Treatment of Endometriosis on Pelvic Pain C.E. Miller ................................................................................................................................................... 24 Therapeutic Strategies for the Treatment of Extra Pelvic Endometriosis – Diaphragm, Lungs, Pleura C.R. Nezhat ................................................................................................................................................. 33 Perspectives on the Future Treatment of Endometriosis C. Chapron .................................................................................................................................................. 42 Cultural and Linguistics Competency ......................................................................................................... 56

PG 211 Deep Endometriosis – Diagnosis, Impact of Surgical Treatment,

Future Perspectives on Therapies (Didactic)

Charles E. Miller, Chair Faculty: Charles Chapron, Camran R. Nezhat, Tamer A. Seckin, Jim Tsaltas

Course Description

Due to the inexperience in appreciating the diagnosis prior to surgery, the complexity of the surgery itself, and the potential need for a multidisciplinary approach, many women with deep endometriosis are not satisfactorily treated at the time of the initial laparoscopic surgery. This course demystifies the surgical approach to deep endometriosis. This includes hysterectomy and endometriosis, robot-assisted laparoscopy for deep endometriosis, the impact of surgery for endometriosis on pain and infertility, strategies for the treatment of extra pelvic endometriosis, and a discussion on future treatments for endometriosis. Teaching will be enhanced with interactive video session, featuring all faculty members.

Learning Objectives At the conclusion of this course, the participant will be able to: 1) Discuss strategies for laparoscopic hysterectomy in the presence of severe endometriosis; 2) describe how robotic surgery can enhance the treatment of deep endometriosis; 3) discuss the impact of surgical therapy for endometriosis on infertility and pelvic pain; 4) detect extra pelvic endometriosis and discuss surgical treatment; and 5) discuss future treatments for endometriosis.

Course Outline 1:30 Welcome, Introductions and Course Overview C.E. Miller 1:35 Endometriosis and Hysterectomy C.R. Nezhat C.R. Nezhat 2:00 The Use of Robotic Assistance in the Treatment of Deep Endometriosis C.E. Miller 2:20 The Impact of Surgical Treatment of Endometriosis on Infertility J. Tsaltas 2:40 Complications T.A. Seckin 2:55 Video/Interactive Session, Q&A All Faculty 3:25 Break 3:40 The Impact of Surgical Treatment of Endometriosis on Pelvic Pain C.E. Miller 4:05 Therapeutic Strategies for the Treatment of Extra Pelvic Endometriosis – Diaphragm, Lungs, Pleura C.R. Nezhat

1

4:30 Perspectives on the Future Treatment of Endometriosis C. Chapron 4:55 Video/Interactive Session, Q&A All Faculty 5:30 Course Evaluation

2

PLANNER DISCLOSURE The following members of AAGL have been involved in the educational planning of this workshop and have no conflict of interest to disclose (in alphabetical order by last name). Art Arellano, Professional Education Manager, AAGL* Viviane F. Connor Consultant: Conceptus Incorporated Frank D. Loffer, Executive Vice President/Medical Director, AAGL* Linda Michels, Executive Director, AAGL* Jonathan Solnik Other: Lecturer - Olympus, Lecturer - Karl Storz Endoscopy-America SCIENTIFIC PROGRAM COMMITTEE Arnold P. Advincula Consultant: CooperSurgical, Ethicon Women's Health & Urology, Intuitve Surgical Other: Royalties - CooperSurgical Linda Bradley Grants/Research Support: Elsevier Consultant: Bayer Healthcare Corp., Conceptus Incorporated, Ferring Pharmaceuticals Speaker's Bureau: Bayer Healthcare Corp., Conceptus Incorporated, Ferring Pharm Keith Isaacson Consultant: Karl Storz Endoscopy Rosanne M. Kho Other: Honorarium - Ethicon Endo-Surgery C.Y. Liu* Javier Magrina* Ceana H. Nezhat Consultant: Intuitve Surgical, Lumenis, Karl Storz Endoscopy-America Speaker's Bureau: Conceptus Incorporated, Ethicon Women's Health & Urology William H. Parker Grants/Research Support: Ethicon Women's Health & Urology Consultant: Ethicon Women's Health & Urology Craig J. Sobolewski Consultant: Covidien, CareFusion, TransEnterix Stock Shareholder: TransEnterix Speaker's Bureau: Covidien, Abbott Laboratories Other: Proctor - Intuitve Surgical FACULTY DISCLOSURE The following have agreed to provide verbal disclosure of their relationships prior to their presentations. They have also agreed to support their presentations and clinical recommendations with the “best available evidence” from medical literature (in alphabetical order by last name). Charles E. Miller Grants/Research Support: Covidien, Femasys, Olympus, Novartis, Abbott Laboratories Consultant: Covidien, Femasys, Abbott Laboratories, Ferring Pharm Charles Chapron* Camran R. Nezhat* Tamer A. Seckin*

3

Jim Tsaltas Grants/Research Support: Covidien, Merck Serono Scott G. Chudnoff* Asterisk (*) denotes no financial relationships to disclose.

4

DisclosureDisclosure

I have no financial relationships to disclose.I have no financial relationships to disclose.

Describe techniques for safe laparoscopic Describe techniques for safe laparoscopic accessaccess

Describe techniques used in difficult Describe techniques used in difficult hysterectomieshysterectomieshysterectomieshysterectomies

Describe techniques used to address difficult Describe techniques used to address difficult adhesions during laparoscopyadhesions during laparoscopy

Describe your Describe your anticipated anticipated procedureprocedure

Estimated blood Estimated blood lossloss

Estimated durationEstimated duration Preoperative Preoperative

antibioticsantibiotics Test your equipment prior to the patient entering the operating room

Review normal anatomyReview normal anatomy

How to develop retroperitoneal dissectionHow to develop retroperitoneal dissection

Discuss preoperative planningDiscuss preoperative planning Discuss preoperative planningDiscuss preoperative planning

Examine proper instrumentation and techniques for Examine proper instrumentation and techniques for dissection dissection

Review possible complications and managementReview possible complications and management

5

Step 1 Step 1 –– Know the AnatomyKnow the Anatomy

Abdominal wallAbdominal wall LigamentsLigaments Avascular spacesAvascular spaces

ParaPara--vesical spacevesical space VesicoVesico--vaginal spacevaginal space VesicoVesico--uterine spaceuterine space RectoRecto--vaginal spacevaginal space

Vascular structuresVascular structuresThe course of inferior epigastric vessels

Obliterated Umbilical Lig.

Urachus

SymphysisPubis

Posterior aspect of anterior abdominal wall

Cervix

The vesicouterine and vesicovaginal spaces

Obturator internus muscle

Right obturator nerveRi ht blit t d

Right Obturator artery

Right external iliac artery and vein

Right obliterated umbilical artery

Right paravesical space and its structures

*Recto-uterine

Space

*

A

Recto-vaginal Space

B

The rectovaginal space is completely developed.The appearance of space A) in a non-hysterectomized patients, and B) in a hysterectomized patients

6

A B*

Intraperitoneal view of the sacral promontory and the location of the bifurcation of Aorta (*)

Left common iliac artery

Inferior vena cava

Left common iliac vein

Right common iliac artery

Anatomic relationships of the bifurcation of the Aorta, inferior vena cava and sacral promontory

The middle sacral vessels are in the midline on the sacrum.

Bladder

Rectum

Left ureter Right ureter

The relationship of bladder, ureters and rectum after a radical hysterectomy

Ureter

Common iliac artery

The ureter cross over the common iliac artery

Step 2 Step 2 -- Patient PositioningPatient Positioning

The patient is in supine positionThe patient is in supine position The thighs are not flexed so that the suprapubic and The thighs are not flexed so that the suprapubic and

lateral trocars may be maneuveredlateral trocars may be maneuvered Nasogastric tubeNasogastric tube is placed before procedureis placed before procedure

Operative Gynecologic Laparoscopy: Principles and techniques Nezhat 2000. Mc Graw-Hill

7

The buttocks are hanging 2-3 inches off the table

Endotracheal tube

Oral‐gastric tube Ensure the patient is completely

relaxed.

Step 3 Step 3 –– Palpation of aortaPalpation of aorta

The aorta and sacral promontory are palpated

Operative Gynecologic Laparoscopy: Principles and techniques Nezhat, 2000. Mc Graw-Hill

8

Palpate the abdominal aorta.

Step 4 Step 4 –– Insertion of Veress needleInsertion of Veress needle

Veress needle is grasped by the shaft and directed posteriorly at a 90° angle. Inset shows elevation of skin and subcutaneous tissue by towel clips.

Operative Gynecologic Laparoscopy: Principles and techniques Nezhat, 2000. Mc Graw-Hill

Standard laparoscopyStandard laparoscopy Two to three 5 mm portsTwo to three 5 mm ports

2 lateral2 lateral

1 pr1 pr p bip bi 1 supra1 supra--pubicpubic

RoboticRobotic Three to four 5Three to four 5--8 mm ports8 mm ports

Similar configurationSimilar configuration

Configuration may be altered depending on surgeryConfiguration may be altered depending on surgery

Continuation…..Continuation…..

Before positioning the robotic cart, pressure points Before positioning the robotic cart, pressure points must be carefully paddedmust be carefully padded

In the case of an airway emergency or cardiac In the case of an airway emergency or cardiac arrest resuscitating the patient requires disengagingarrest resuscitating the patient requires disengagingarrest, resuscitating the patient requires disengaging arrest, resuscitating the patient requires disengaging the robotic instruments before backing the cart the robotic instruments before backing the cart away from the OR table away from the OR table

Avoid head docking and use side or between legs Avoid head docking and use side or between legs docking when possible.docking when possible.

9

Thank You !Thank You !Thank You !Thank You !

Fellows

Elizabeth Buescher MDJackie Miller, DO

Elizabeth Buescher MD

Chandhu Paka, MDM. Ali Parsa, MD

10

The Use of Robotic Assistance in the Treatment of Deep Endometriosis

Charles E. Miller, MD, FACOG

• President, International Society for Gynecologic Endoscopy (ISGE)

• President, AAGL (2007-2008)

• Clinical Associate Professor, Department OB/GYN, University of Illinois at Chicago, Chicago, IL USA

• Director of Minimally Invasive Gynecologic Surgery, Advocate Lutheran General Hospital, Park Ridge, IL USA

• Director, AAGL/SRS Fellowship in Minimally Invasive Gynecologic Surgery, Advocate Lutheran General Hospital, Park Ridge, IL USA

Disclosure

• Grants/Research Support: Covidien, Femasys, Olympus, Novartis, Abbott Laboratories

• Consultant: Covidien Femasys Abbott• Consultant: Covidien, Femasys, Abbott Laboratories, Ferring Pharm

2


Objectives

1. List two advantages of robotic assisted surgery.

2. List two areas where robotics positively assists minimally invasive gynecologic surgery.

3. Discuss the impact of robotic surgery on the treatment of superficial and deep endometriosis.

3

ROBOTIC SURGERY HAS PROVEN TO BE A

VIABLE ALTERNATIVE FOR MULTIPLE

PROCEDURES IN MINIMALLY INVASIVE

GYNECOLOGIC SURGERY


GYNECOLOGIC SURGERY

4

• Advantages of robotic assistance in minimally invasive gynecologic surgery

– Eliminates tremor (filters movement)

– Scales down hand movement (more precise)

– Stereoscopic viewer at console


– Enables 3D imaging

– Steady image

– Advanced ergonomics – instrument articulation provides seven degrees of movement (mimics human wrist movement and eliminates fulcrum effect)

– Reduces physician fatigue

5

Disadvantages of Robotic Assistance in Minimally Invasive Gynecologic Surgery

• Cost– Robot $1.5 - $1.75 million

– Reposable instruments (10 time use) - $250 (average cost per use)


• Lack of tactile feedback (visual haptics)

• Need for well qualified assistant

• Learning curve (albeit short)

• Potential loss of laparoscopic (suturing) skills

6

11

Robotic Assisted Laparoscopic Hysterectomy


7

Payne TN, et al., JMIG 2008; 15(3): 286-91Payne TN, et al., Obstet Gynecol 2010; 115(3): 535-42Payne TN, et al., J Robotic Surg 2010; 4: 11-17Boggess JF, Obstet Gynecol 2009; 114: 585-593Scandola M, JMIG 2011; 18(6): 705-15

Robotic Assisted Radical Hysterectomy for Cervical Cancer


8Lowe MP, Gynecol Oncol 2009; 113:191-4Cantrell LA, Gynecol Oncol 2010; 117: 260-5

Robotic Assisted Hysterectomy for Endometrial Cancer


9

Gaia G, Obstet Gynecol 2010; 116: 1422-31Mok ZW, Int J Gynecol Cancer 2012; 22(5): 819-25Paley PJ, Am J Obstet Gynecol 2011; 204: 551.e1-9Lau S, Obstet Gynecol 2012; 119(4): 717-24Leitao MM, Gynecol Oncol 2012; 125(2): 394-9. Epub 2012 Feb 1Lim PC, JMIG 2010; 17(6): 739-48Gehrig PA, Gynecol Oncol 2008; 111: 41-5

Robotic Assisted Hysterectomy Sacrocolpopexy


10

Siddiqui NY, Am J Obstet Gynecol 2012; 206(5): 435.e1-5. Epub 2012 Feb 1Seror J, World J Urol 2012; 30(3): 393-8. Epub 2011 Aug 20

Robotic Assisted Myomectomy


11

Advincula A, et al., JMIG 2007; 14(6):698-705Barakat E, Obstet Gynecol 2011; 117: 256-65

The Last Frontier

Robot Assisted Endometriosis Surgery for Deep Infiltrative Surgery


12

Currently, literature is comprised of only feasibility studies, no large case series and certainly no

randomized controlled reports.

12

Robotic Assisted Endometriosis Surgery for Deep Infiltrative Disease


N =1 N=7 stage III, 2 stage IV

13

Averbach M, Arq Gastroenterol 2010; 47(1):116-118Nezhat C, Fertil Steril 2010; 94(7): 2758-60Frick AC, JSLS 2011; 15: 396-99Brudie LA, J Robotic Surgery, published on-line October 2011Tan SJ, Taiwanese J Obstet Gynecol 2012; 51:18-25Dulemba J, J Robotic Surg, published on-line June 2012Ercoli A, Hum Reprod 2012; 27(3):722-26

N=2

N=80 stage IV (2 parametrium, 6 rectovaginal septum, 10 sigmoid serosa, 4 cecum)

N=2

N=26 stage IVN=12


• 22 consecutive robot assisted complete laparoscopic excisions of deep infiltrative endometriosis with colorectal involvement 3/10 to 5/11

– Segmental resection• N=12

• Median nodule 35mm


– Shaving• N=10

• Median nodule 30mm

– Surgical technique• Umbilical access vs. right periumbilical (bowel resection)

– Instrumentation• Monopolar scissors

• Monopolar hook

• Bipolar forceps

• Large needle holder

14Ercoli A, Hum Reprod 2012; 27(3):722-26



Surgical and Anatomopathologic Findings




Post Operative FindingsSix Month Follow Up

Pre and post operative symptoms on VAS analogue scale (19 patients)




• Median operative time and hospitalization comparable to historical conventional laparoscopy data 1,2,3

• Median blood loss and blood transfusion rate improved

17

1 Ercoli A, Hum Reprod 2012; 27(3):722-262 Ruffio G, Surg Endosc 2010; 24: 63-673 Fanifani F, Fertil Steril 2010; 94: 444-494 Darai E, Surg Endosc 2007; 21: 1572-77

• Median blood loss and blood transfusion rate improved over historical conventional laparoscopy data 1,2

• Rectovaginal fistula in 13 patients undergoing vaginal resection (major risk at conventional laparoscopy) 1,4


Despite the recognized advantage of increased precision in robotic assisted surgery, deep infiltrative endometriosis creates increased


challenges for the robotic surgeon

18

13



400189 420189 8MM DOUBLE FENESTRATED GRASPER 3.00400208 420208 8MM THORACIC GRASPER 3.00400177 420177 5MM BOWEL GRASPER 3.50 Very Low400278 420278 8MM GRASPING RETRACTOR 4.00400139 420139 5MM SCHERTEL GRASPER 5.00400143 420143 5MM MARYLAND DISSECTOR 5.00400176 420176 5MM BULLET NOSE DISSECTOR 5.00400207 420207 8MM TENACULUM FORCEPS 6.00400145 420145 5MM DeBAKEY FORCEPS 6.00400203 420203 8MM PERICARDIAL DISSECTOR 6.00

Jaw Closing Force At Tip (N) RankIS1200 P/N IS2000 P/N Instrument Name

Cannula Size

19

400173 420173 5MM HARMONIC CURVED SHEARS 6.50 Low400174 420174 8MM HARMONIC CURVED SHEARS 6.50400227 420227 8mm PK DISSECTING FORCEPS 6.50400048 420048 8MM LONG TIP FORCEPS 6.50400049 420049 8MM CADIERE FORCEPS 7.00400190 420190 8MM COBRA GRASPER 7.00400146 420146 5MM CURVED SCISSORS 7.50400121 420121 8MM FINE TISSUE FORCEPS 8.50400205 420205 8MM FENESTRATED BIPOLAR FORCEPS 8.50400141 420141 5MM ROUND TIP SCISSORS 9.00400110 420110 8MM PRECISE BIPOLAR FORCEPS 9.00400172 420172 8MM MARYLAND BIPOLAR FORCEPS 9.00400171 420171 8MM MICRO BIPOLAR FORCEPS 9.50 Medium400033 420033 8MM BLACK DIAMOND MICRO FORCEPS 9.50400117 420117 5MM NEEDLE DRIVER 9.50400178 420178 8MM CURVED SCISSORS 10.00400181 420181 8MM RESANO FORCEPS 10.00400036 420036 8MM DeBAKEY FORCEPS 11.50400179 420179 8MM MONOPOLAR CURVED SCISSORS 12.00400093 420093 8MM PROGRASP FORCEPS 12.00 High400001 420001 8MM POTTS SCISSORS 12.50400007 420007 8MM ROUND TIP SCISSORS 12.50400006 420006 8MM LARGE NEEDLE DRIVER 16.00400209 420209 8MM SUTURECUT NEEDLE DRIVER 17.00 Very High400194 420194 8MM MEGA NEEDLE DRIVER 19.00

References• Payne TN, et al., JMIG 2008; 15(3): 286-91

• Payne TN, et al., Obstet Gynecol 2010; 115(3): 535-42

• Payne TN, et al., J Robotic Surg 2010; 4: 11-17

• Boggess JF, Obstet Gynecol 2009; 114: 585-93

• Scandola M, JMIG 2011; 18(6): 705-15

• Lowe MP, Gynecol Oncol 2009; 113: 191-4

• Cantrell LA, Gynecol Oncol 2010; 117: 260-5

• Gaia G, Obstet Gynecol 2010; 116: 1422-31

• Mok ZW, Int J Gynecol Cancer 2012; 22(5): 819-25

• Paley PJ, Am J Obstet Gynecol 2011; 204: 551.e1-9

• Lau S, Obstet Gynecol 2012; 119(4): 717-24

• Leitao MM, Gynecol Oncol 2012; 125(2): 394-9. Epub 2012 Feb 1

• Lim PC, JMIG 2010; 17(6): 739-48

• Gehrig PA Gynecol Oncol 2008; 111: 41 5• Gehrig PA, Gynecol Oncol 2008; 111: 41-5

• Siddiqui NY, Am J Obstet Gynecol 2012; 206(5): 435.e1-5. Epub 2012 Feb 1

• Seror J, World J Urol 2012; 30(3): 393-8. Epub 2011 Aug 20

• Advincula A, JMIG 2007; 14(6): 698-705

• Barakat E, Obstet Gynecol 2011; 117: 256-65

• Averbach M, Arq Gastroenterol 2010; 47(1): 116-118

• Nezhat C, Fertil Steril 2010; 94(7): 2758-60

• Frick AC, JSLS 2011; 15: 396-99

• Brudie LA, J Robotic Surgery, pub online Oct 2011

• Tan SJ, Taiwanese J Obstet Gynecol 2012; 51: 18-25

• Dulemba J, J Robot Surg, pub online Jun 2012

• Ercoli A, Hum Reprod 2012; 27(3): 722-26

• Ruffio G, Surg Endosc 2010; 24: 63-67

• Fanifani F, Fertil Steril 2010; 94: 444-49

• Darai E, Surg Endosc 2007; 21: 1572-77

20

14

What evidence supports surgical interventions in the

management of endometriosis-related infertility

AAGL - 2012Dr Jim Tsaltas

President AGESHead Of Gynaecolgical Endoscopy

Southern Health & Monash Medical CentreMonash University

Senior Infertility Specialist Melbourne IVF

Disclosures Grants/Research Support: Covidien, Merck Serono

Scope of my talk What evidence supports surgical intervention in the management of

endometriosis-related infertility

Introduction

y

Topics considered in preparation Minimal to Mild Endometriosis Endometriomas DIE (deep infiltrating endometriosis) Inclusive of rectovaginal and colorectal endometriosis

Surgical technique Adhesion prevention Pre and post surgical adjunct medical therapy Repeat surgery Place of surgery for failed IVF No surgery at all

I have taken the starting point that the patient has been diagnosed with endometriosis and they are infertile

In preparation of this talk

Diagnosis modality can include examination, ultrasound, laparoscopy

The infertile population we review are couples with no significant male factor infertility, the female partner is ovulatory and has patent tubes

Intervene at 12 mths of infertility if under age of 35 or at 6 months if 35 or over

The use of laparoscopic surgery in the treatment of subfertility related to minimal and mild endometriosis may improve future fertility

Surgery involving ablation/excision (+/- adhesiolysis) is effective compared

Minimal – Mild Endometriosis

g y g ( y ) pto diagnostic laparoscopy

Evidence is high quality 2 RCTs (Marcoux et al 1997, Gruppo Italiano 1999) Meta analysis of the two Marcoux strong positive effect whereas Gruppo Italiano reported a small negative effect

Jacobson et al – Cochrane review 2010 Limitations of studies discussed by Cochrane and Vercellini etal (2009)

Consensus: On weight and high grade of evidence laparoscopic surgery is recommended for minimal – mild endometriosis to enhance fertility Importance of ongoing laparoscopic skills training Surgery must remain an option – Barri etal 2010

Minimal to Mild: surgical treatment for subfertility

paper population intervention control treatment stats

Marcoux, Canada

Laparoscopic surgery in infertile women with minimal or mild endometriosis NEJM 1997; 337(4):217-22

341 infertile women, 20-39yo, infertile >12m (median 31m)

Diagnostic lap –randomised to resection/ablation or diagnosis only

Follow up 36 weeks or until 20 if i d

29/169 pregnant –17.7%

50/172 pregnant –30.7%

Difference significant p<0.0006

20w if conceived

Gruppo italiano per lo studio dell’endometrioisi

Ablation of lesions or no treatment in minimal-mild endometriosis in infertile women: a randomised trial.

Human reproduction 1999; 14(5): 1332-4

101 <36yo

Infertile >2 years

Lap endo stage I-II AFS

Diagnostic or ablation/excision +/- adhesiolysis

No histology required

Follow up 9m, could have 3m medical treatment

13/47 (28.9%)

12/54 (23.5%)

Longer infertility 40-50% each group had med therapy post op incl GnRHAg

No difference between groups

Powered to detect 2.5 diff in treatment group (based on Hughes metaanalysis & presupposed baseline fecundity in diagnostic group of 25% -probable overestimate, thus underpowered)

15

Will break down into endometriomas (ovarian disease) and also rectovaginal /DIE(including colorectal endometriosis) Must remember they are not separate entities and may co

Moderate to severe endometriosis

Must remember they are not separate entities and may co –exist and according to the literature endometriomas are often markers of more severe disease (Banerjee 2008, Chapron 2009) For this discussion I will separate the discussion into: management of Ovarian disease(endometriomas) management of rectovaginal endometriosis/DIE (including colorectal

disease) Need to consider place of surgery, associated symptoms such

as pain, access and costs of both surgery and IVF. Laparoscopic skill acquisition and training are vital.

Many studies have been produced to discuss this topic Guidelines to date – ESHRE(2008), ASRM(2006), NHS(2010) – There may

be a possible benefit

Ovarian endometriomas

p What is the Data? Laparoscopic cystectomy by excisional surgery for endometriomata 4cm or

greater improves fertility(spontaneous pregnancy rates) compared to drainage and coagulation (Beretta 1998, Alborzi 2004). Many other observational studies show an increased pregnancy rate after surgery for endometriomas with a weighted mean of 50% - summarized in Vercellini 2009 and listed in bibliography of this talk

As well as improved fertility rates excision has lower recurrence of endometriomas and symptoms (Hart 2008 and updated 2011 – cochrane review) as compared to drainage and coagulation

High quality as are RCT – limitation not including expectant arm in trial –may downgrade evidence to moderate quality as we do not know true rate of pregnancy with no surgery

Based on the above evidence Weight of other studies

Decisions to treat

Other symptoms attributed to the endometriosis – significant pain, impact on patients QOL, histological diagnosis, reduce risk of cyst complications, improve access for IVF if required and reduce risk of post IVF abscess formation. (Garcia-Velasco 2009 Tubal and Male factor infertility Access to trained surgeons and IVF Must no look at surgery and IVF as competing interests but

rather as complementary therapeutic strategies (Barri 2010, Littman 2005, Adamson 2005)

Early studies suggested minimal if any damage to the ovarian reserve after surgical treatment for endometriomas –

Issues related to treatment

(Loh 1999, Donnez 2001, Canis 2001)

Recent studies however have demonstrated damage to the ovarian reserve Methodology to assess this includes D2 FSH, AFC, Ovarian

reserve, response to gonadotrophins in IVF and AMH

(Somigliani 2003, Somigliani 2006, Chang 2010, Benaglia 2010, Hirokawa 2011)

Damage may also relate to size of endometrioma being excised (Roman 2010)

Care with surgical technique Excision is preferred method

Reducing Risks

Care with identification of planes Minimize diathermy and conserve all ovarian tissue possible Recent small randomized clinical trial – shows potential less reduction in

ovarian reserve when suturing is used for haemostasis – AFC outcome measure (Coric 2011)

Combined technique – excisional surgery and also ablative surgery for 10 –20% of endometrioma wall next to hilus (Donnez 2010)

AMH excellent marker Group should consider recommendation of routine AMH testing pre and 3

mths post endometrioma surgery Group should consider egg freezing prior to recurrent endometrioma

surgery in young patient with low AMH not trying to conceive

16

Evidence of moderate to high grade exists to recommend excisional surgery for endometriomas 4cm or more to

Ovarian EndometriomasConsensus statement proposal

improve fertility. Appropriate skill and training is required for safe and complete excision. It is important to minimize ovarian damage and further studies are required to ascertain if suturing for haemostasis is superior. Surgeons should consider measurements of ovarian reserve pre and post operative to help counsel patients.

Small study looked at reduction of post operative adhesions by suture to close the ovary for haemostasis compared to

Adhesions

traditional diathermy.(endometriomas) RCT – favored suturing – Pellicano 2008 This is now our practice

2 Cochrane reviews Ahmad 2010 – Barrier agents for adhesion prevention after

gynaecological surgery Do reduce post operative adhesions

No data regarding pregnancy outcome

Metwally 2011 – Fluid and pharmacological agents for adhesion prevention after gynaecological surgery

Adhesions (cont)

There is no evidence of a benefit of using the above agents as an adjunct during pelvic surgery for improving pregnancy outcomes

Consensus:

No data to support the routine use of adhesion barriers to improve pregnancy outcomes

Early studies suggested improvement in fertility rates after management of DIE (Chapron 1999)

Since that time a number of articles have been published discussing this

Surgery for Rectovaginal Lesions

p gissue

Severe endometriosis which infiltrates the posterior vaginal wall and anterior rectal wall is one of the most challenging surgical issues we face as gynaecologists.

There have now been a number of studies on this topic. Studies are either retrospective, observational or prospective.

Surgery may be challenging and the risks of intraoperative and post operative morbidity not negligible

Surgery should only be performed with the appropriate multidisciplinary set up

Pregnancy rates from studies quoted vary from 23 - 57% (recent review Meuleman 2011) These studies vary in quality and the grade of evidence are mostly low quality with occasional moderate quality studies

Ferrero 2009 Pregnancy after bowel resection Surgery Laparoscopy – 57.6%, Laparotomy – 23.6% Surgical technique based on the preference of the colorectal surgeon

Recent Studies of interest

g q p g Laparoscopy superior to laparotomy No Spont Pregn in women over 35 after surgery

Stepniewska A 2009 3 Groups Greater than 1 year infertility (average – 2.5 years) Retrospective cohort study with longitudinal evaluation of clinical outcomes 60 – severe pain request bowel surgery – spont pregn 12/30, IUI 0/5, IVF – 5/13 40 – no consent for bowel surgery(all other endo removed) - Spont Pregn 7/23,

IUI o/3, IVF – 1/13 55 – Stage 3 -4 endo but no bowel endo - spont pregn 24/34, IUI – 4/6, IVF – 4/6 Best outcomes in patients who had stage 3 – 4 endometriosis without bowel

involvement

Vercellini 2006 105 women – 44 chose surgery, 61 expectant management

Studies Continued

g y, p g

Patients self selected

Surgery by laparotomy for severe rectovaginal endometriosis

24 month follow up

Surgery – 44.9%

Expectant management – 46.8%

Bias as stated by authors – patients with more pain and potentially more aggressive disease chose surgery and this may influence pregnancy rates

17

Barri 2010 Observational study 825 patients aged 20 – 40 years(mean age 35.3) with infertility and endometriosis –

2001 t 2008

Studies Continued

2001 to 2008 Mean length of infertility – 3.2+/- 2.3 years Diagnosed – stage 3 – 4 AFS Endometriosis Many with endometriomas 483 patients – surgery – 262 spont pregn 58.5% 221 patients – no pregnancy – 144 IVF – 184 Oocyte retrieval and 56 pregnancies IVF chosen by 173 patients who chose no surgery – 68 pregnancies (patients matched) Again age is an issue in both groups (35 yoa) Surgery only - <35 – 229/372, >35 – 33/111 Group 3 – no treatment – 20/69 – 11.8% Good study – favoring surgery If under 35 – Ivf at 12 months, if over 35 – Ivf at 6months

Deep Infiltrating Endometriosis and IVF

IVF only (n=105) Surgery + IVF (n=64) P value

Infertility duration (months) 29 ± 20 35 ± 18 .01

Total dose of FSH (IU) 2380 ± 911 2542 ± 1012 .01

Number of oocytes retreived 10 ± 5 9 ± 5 .04

Fertilisation rate (%) 77.9 78 .76

No. of top quality embryos / patient .59 ± 1 .57 ± 1 .48

No. of embryos transferred 3 ± 1 3 ± 1 1

Implantation rate (%) 19 ± 25.1 32.1 ± 30.6 .03

Pregnancy rate (%) 24 41 .004

(Bianchi et al J Min Invas Gyn 2009)

Debate between the need for bowel resection vs shaving technique only for deep rectovaginal endometriosis

Surgical Technique

Donnez 2010 Prospective analysis of 500 cases 388 patients wished to conceive – 221(57%) spontaneous

pregnancy 167 – needed IVF – failure to conceive after 12 months of trying

or immed IVF due to male factor(25% of this group) 107 conceived

Overall pregnancy rate of 84%

Total Group – 257 patients - colorectal endo (to 30/8/2010

75 Infertility

Our DataTsaltas J, Cooper M, Reid G

5 e t ty 19/75 – 25.3% Infertility, 56/75 – 74.7% pain and infertility

43 segmental resection, 28 disc excision, 4 multiple procedures

7 lost to follow up, 11 no longer wished to conceive

57 available to follow up still wishing to conceive Pregn rate – 73.6 % 25.9% - spont, 68.5% ART (IVF), 5.6% mode of pregn not recorded

Decision to treat When and how to treat each patient has become much more

individualized Full discussion about options Full discussion about options Place of IVF and/or surgery Consider patients age, male factor, ovarian reserve, ability to

access the ovary safely for OPU, endometriosis pain symptoms and impact on QOL Pre-Operative Ultrasound to assess the size and level of

invasion of the rectal lesion Consent can be appropriately obtained Plan mode of probable surgery – shave, disc, excise Post op – LDR and IVF immed or set time for spont conception

pre IVF

Infertile patients with severe endometriosis including colorectal disease should consider surgery as an alternative t IVF Th RCT t l t th

Severe endometriosis including colorectal disease: Consensus

to IVF. There are no RCT or meta-analyses to answer the question whether the surgical excision of severe endometriosis will enhance pregnancy rates. However recent studies of better quality and larger numbers suggest an improvement in pregnancy rates. Surgery should only be undertaken with appropriate consent and understanding of the risks. Women should be given a full understanding of all available options to help with conception. Surgery for this major disease should be managed by the appropriate multidisciplinary team.

18

Cochrane review

Furness 2004

Medical Therapy before or after surgery

Furness 2004 Pre and post-operative medical therapy for endometriosis

surgery

No evidence of benefit to surgery alone

Consensus – no benefit of medical therapy before or after endometriosis surgery for infertility

Limited information is available on the effect of second line surgery for recurrent endometriosis in infertile women.

No RCT: repeat surgery vs expectant management; IVF vs repeat surgery Studies

Repeat Surgery

Studies Fedele 2006 – 1993 to 2002 305 primary surgeries and 54 reoperations for recurrent endometrioma in the same ovary of the primary

cyst Pregnancy rate – Primary – 40.8%, Secondary – 32.4% The surgical Procedure might be technically more challenging and involves a greater risk of further

impairment of function. Vercellini 2009 – review article Analysis of the literature – achieving a pregnancy after repetitive surgery was almost half that observed after

primary surgery 2 cycles of IVF better than repeat surgery

Adamson 2005 Disadvantages of surgery – potential damage to ovarian reserve, morbidity, a potential longer time to conception

compared to IVF and lack of trained surgeons ESHRE 2005 Final decision should consider presence of pain symptoms and large endometriomas. Pain and refusal to proceed

to IVF still constitutes an indication for repeat surgery

No evidence to recommend repeat surgery over IVF

However should consider surgery if increasing pain,

Consensus on repeat surgery

o e e s ou d co s de su ge y c eas g pa ,enlarging endometrioma and no desire for IVF. Surgery can be complex and appropriate consent needs to be obtained.

Grade of Evidence is Low

More studies required

Littman 2005 Study in a tertiary IVF and Endoscopy centre

Failed IVF no previous surgery

Retrospective case series 29 patients with prior IVF failures – 22 conceived after

laparoscopic treatment of endometriosis 15 spontaneous conceptions 7 IVF Pregnancies Authors believe that complete and thorough microsurgical

eradication of endometriosis allows patients to conceive without further IVF therapy and may help optimize success for those who require subsequent IVF cycles

Prospective cohort study – Bianchi 2009 – Previously discussed

Surgery may play a role in patients who have failed IVF treatment and endometriosis. It may be inappropriate to

Consensus – surgery post IVF

continue with repeated IVF cycles without considering surgery to excise the endometriosis. Excision of endometriosis may enhance opportunity to conceive spontaneously and even enhance Ivf outcomes.

Level of evidence - low

ConclusionWe have a responsibility to know the evidence and be able to

present it to our patients in a measured and informed manner

Surgery and IVF should not be seen as competing interests but as an integral part of the treatment equation

The appropriate multidisciplinary team needs to be available to manage many of these complex issues and patients

Must consider the ovarian reserve and its preservation following our intervention

19

Preventing Complications of Deep Endometriosis Surgery:

Traps, Tips & Tricks

Tamer A. Seckin, MD, FACOG, ACGEDirector, Park East Gynecology & Surgery

Tamer A. Seckin, MD

Founder & President, Endometriosis Foundation of America

Preceptor, AAGL Minimally Invasive Gynecologic Surgery Fellowship

North Shore LIJ‐Lenox Hill HospitalNew York City, New York

Author has no financial relationships to disclose.

Tamer A. Seckin, MD

Endometriosis is a debilitating, costly disease fraught with diagnosticdelay, high treatment failure and recurrence. True surgical resection andtreatment poses formidable challenges even the hands of experiencedclinicians. In an effort to assist surgeons to provide optimal surgicalintervention for women with endometriosis, this segment will reviewrecognition and impact of procedural complications and identifyappropriate strategies to reduce morbidity and thus optimize patientoutcome

Tamer A. Seckin, MD

outcome.

At the conclusion of this segment, the participant will be able to:1) discuss common complications of surgery for deep disease; and2) describe techniques for reduction, management and prevention.

If we are to achieve significant progress for women with endometriosis, we must

emphasize the single most important step of action:

Improve the quality of surgery

Tamer A. Seckin, MD

Improve the quality of surgery.

~Tamer Seckin, MD, FACOG

Deep Endometriosis• Deep endometriosis together with cystic ovarian

endometriosis represents most severe form of disease1

• Defined as endometriosis infiltrating deeper than 5‐6 mmunder the peritoneum2

• Excision remains treatment of choice for subsequent fertilityand pelvic pain3;

Tamer A. Seckin, MD

• Difficult to treat due to proximity of and common infiltrationin and around bowel, ureter, uterine artery4

• Surgery for deep endometriosis may be “more difficult thansurgery for cancer”5

Video/photo of deep diseaseINSERT HERE

Tamer A. Seckin, MD

20

Q: Which surgical procedure is 100% safe?A: The one that is not performed.1

• Laparoscopy largely safe and effective

• Gold standard for endometriosis treatment

• Associated with decreased morbidity andd d 2

Tamer A. Seckin, MD

admission periods2

• However, traumatic complications may stilloccur3 (e.g. bowel, bladder or gastricperforation; large vessel or ureteral injury)

First, Do No Harm…but if complications do occur, timely recognition and

proper management are key• Complications of laparoscopy becoming increasingly less

common; approximately 3.2 per 1000 cases1, 2

• Primarily related to three categories:3

complications of access; physiologic complications of the

Tamer A. Seckin, MD

p f ; p y g p fpneumoperitoneum; complications of operativeprocedure

• Common4 complications related to deep endometriosissurgery:

Intestinal, Bladder, Ureteral

Potential Complications of Deep Endometriosis Surgery• Postoperative urinary retention1

• Rectovaginal fistula2

• Ureterovaginal fistula3

• Ureteric damage requiring radiological stenting4

• Ureter injury7

C l i /B l8

Tamer A. Seckin, MD

• Colonic/Bowel8

• Nerve injury9

• Anastomotic Leak

• Rectovesical Fistula

• Ureterorectal Fistula

Incidence• May relate to surgeon experience & severity of pathology

present1

• Certain complications are unpreventable2; others may not betrue complications3 (e.g. unintentional entry to bowel incases of severely fibrotic, rectovaginal disease should not beviewed as complication but rather, a necessity for effective

Tamer A. Seckin, MD

treatment)

• Inferior epigastric vessels most common complications,followed by bowel/intestinal4

• Bladder injury rates comparable (0.02%‐8.3%); most commonin LAVH)5

Source N Rate % Description

Koninckx PR 1996 212 3.7 bowel wall had to be resected in 6.3% n=13Complications were one ureter lesion and seven late bowel perforations with peritonitis-onlyCO2-laser endoscopic excision of deep endometriosis

Benbara 2008 40 22.5six digestive fistulas (12.5%), three anastomotic

strictures (6%), one ureterovaginal fistula (2%), and oneureteral stricture (2%

Mohr C, Nezhat FR2005

187 5 One rectovaginal, one uretrovaginal fistula, one anastomotic leak, 2 strictures d38, 23, and 6% for segmental resection,disc excision, and shaving, respectively

Darai E, 2007 71 12.664 segmental resection 9 cases (14% actual comp rate)

six rectovaginalfistula and three pelvic abscesses.

W Kondo, M Canis2010

226 9.324, 17.6, and 6.7% of women who underwent

segmental resection, excision of the nodule and suture, andshaving, respectively

Urinary and colorectal complications following deep endometriosis surgery

11Tamer A. Seckin, MD

Minelli 2009 436 8.7 16 recto vaginal, 5 Leak, 2 vesicovagianal, 4 ureter Fistulas

Dousset , Chapron2010

100 6-8 6 (2 anastomosis leak and 4 rectovaginal fistula)2 Urinary Leak OPEN cases

Slack, McVeigh, Koninckx2007

124 4.30 segmental resection,

96 disc excision, and shaving, 4 Rectovaginal Fistula, 2 Ureter fistulas

Kovoor, Wattiez,2010

21 14.7 2 vesicovaginal fistula Only Bladder resections

Cavalries 2011 55 9 4 complication 2 anastomotic leak, one bleeding, one bowel injury transanal circular stapler anastomosis ( 52 patients)

Fern, Wattiez 2007 54 3.7 One fistula, one ureter injury -Only ureterolysis

1526 9.57

Despite These Potential Risks…

• Laparoscopic complete excision ofendometriosis offers long‐term relief in mostpatients and should be considered the “GoldStandard.”1

Tamer A. Seckin, MD

Standard.

• Minimally invasive access is generally very welltolerated with reasonable incidence ofcomplication and low recurrence rate.2

21

Video/Photo of complication(s)INSERT HERE

Tamer A. Seckin, MD

Precautionary Pearls

• Multidisciplinary approach is imperative1

• Expertise and skill of surgeon should be weighted againstdifficulty of excision and complexity of disease2

• Meticulous post‐operative care3

• Expect complications and be prepared to promptly address

Tamer A. Seckin, MD

• Expect complications and be prepared to promptly addressthem4

• Do not be trapped into delaying effective surgicalintervention, i.e. discoid resection, as primary treatment forwell‐selected patients with deeply infiltrating endometriosisand related debilitating symptoms

Tips & Tricks for Risk Reduction & Management

• Videoregistration & Consent

• Appropriate operator training

• Scrupulous adherence to proper technique

Tamer A. Seckin, MD

• Adequate pre‐operative preparations

e.g. imaging, bowel prep, medical pretreatment, etc.

Videoregistration1

• “Videorecording of procedure is expected to increase quality while decreasing costs” ‐Koninckx

• Increases alertness, slows speed of intervention, leads to improved timely diagnosis and

Tamer A. Seckin, MD

leads to improved timely diagnosis and intervention in complications

• Medicolegal support of surgeon performance

Operator Training• “When in doubt, refer the patient out”

• Complications diminish with increasingexperience

Tamer A. Seckin, MD

• Planning for complete surgicalexcision…should be “ensured by a team ofexperts familiar with endometriosis, itsmultiple manifestations, and itsmanagement.”‐Mereu, et al.1

Scrupulous Adherence to Proper Technique: Ureter

• Ureteral injury can be caused by ligation, ischemia, resection, transection,crushing, or angulation; particularly troublesome sites includesinfundibulopelvic ligament, ovarian fossa and ureteral tunnel (Nezhat)1

• Knowledge of pelvic path key to prevention2

• Retroperitoneal laparoscopic isolation and inspection of both uretershelps diagnose ureteral involvement, which may be silent3

• Appropriate use of preoperative IVP and MRI with contrast in selectpatients may diagnose obstruction and allow surgical planning5

• Preoperative cystoscopy and ureteral stent application

Tamer A. Seckin, MD

• Preoperative cystoscopy and ureteral stent application

• Protect ureter using hydrodistention and resecting affected peritoneum4

• Intraoperative repairs include partial resection and anastomosis, suturing,stenting7

• Do not hesitate to consult urologist (Nezhat et. al.)

22

Scrupulous Adherence to Proper Technique: Bowel• Adequate pre‐operative preparations e.g. bowel prep (though currently

debated), medical pretreatment can facilitate minimal access, reduce riskof infection1 and permit successful management/repair2

• Transrectal MRI and transrectal ultrasonography may be useful in pre‐operative evaluating depth of disease infiltration3

• Avoid Blunt Dissection, as this may result in small bowel obstruction4

• Copious lavage, antibiotic coverage are essential in small colonic wounds5

• Meticulous anatomic recognition and isolation6

Tamer A. Seckin, MD

g

• Team‐oriented approach reduces operator fatigue and potential forimpaired judgment7

• Careful suturing techniques intraoperatively can repair coloniclacterations8

• Resecting part of bowel wall followed by endoscopic suturing may beuneventful; suggesting that opening of rectum during resection of deependometriosis should not be considered a true complication9

Scrupulous Adherence to Proper Technique: Bladder

• Risks include perforation, laceration, thermal damage;bladder injuries are 2 to 3 times more common than ureteralinjuries1

• Care must be taken not to damage intramural part of ureterduring removal of deep disease2

• Ensure complete pre‐operative drainage of bladder3

Tamer A. Seckin, MD

• Continuous monitoring of gaseous distention of urinary bag can aid inearly detection of bladder perforation6

• Laser ablation, adhesiolysis in anterior Douglas Pouch maypredispose to injury if backstop or hydrodissection not used4

• Injuries of >5mm require closure and drainage; lacerationscan be repaired by experienced laparoscopist5

• More significant injuries are managed according to extent,location, and mode of injury6

Summary• Timely referrals to multidisciplinary team (e.g. gynecologic

endoscopist, colorectal surgeon, urologist) can reduce risk andfacilitate effective treatment; advanced surgical skills andanatomical knowledge are required for deep resection and shouldbe primarily performed in tertiary referral centers

• Careful pre‐operative planning, informed consent,videoregistration of benefit to both surgeon and patient

Tamer A. Seckin, MD

• Meticulous adherence to ‘best practice’ techniques is requisite toreduce morbidity and ensure effective management ofcomplications

• Although excision is technically demanding, operativecomplications remain at low risk

• Complete excision of deep disease is essential to improvesymptomatology and reduce recurrence

Koninckx, Timmermans, Meuleman, Penninckx. Complications of CO2-laser endoscopic excision of deep Endometriosis. Human Reproduction vol 11 no 10 pp 2263-2268, 1996.

Reich, 2011. Proceedings of the 2nd Annual Conference on Endometriosis, Endometriosis Foundation of America.

Farr Nezhat, Camran Nezhat, Ceana Nezhat. Averting complications of Laparoscopy: Pearls from 5 patients. OBG Management August 2007 Vol.19 No 8 pages 69-80.

Jae Hee Woo, Guie Yong Lee, Hee Jung Baik. Bladder perforation during laparoscopy detected by gaseous distention of the urinary bag: a report of two cases.Korean J Anesthesiol 2011 April 60(4): 282-284.

Nezhat C, Berger GS, Nezhat FR, Buttram, VC, Nezhat C, eds. Operative laparoscopy: preventing and managing complications. In: Nezhat CR, ed. Endometriosis:Advanced Management and Surgical Techniques. Springer-Verlag; 1995. Print.

Chapron C, Fauconnier A, Goffinet F, Bréart G, Dubuisson JB. Laparoscopic surgery is not inherently dangerous for patients presenting with benign gynaecologicpathology. Results of a meta-analysis. Hum Reprod. 2002;17:1334–1342.

Perugini RA, Callery MP. Complications of laparoscopic surgery. In: Holzheimer RG, Mannick JA, editors. Surgical Treatment: Evidence-Based and Problem-Oriented. Munich: Zuckschwerdt; 2001. From: http://www.ncbi.nlm.nih.gov/books/NBK6923. Last accessed 10/1/12.

Seckin ,T. Proceedings of the 2nd Annual Conference on Endometriosis, Endometriosis Foundation of America; 2010 New York

Koninckx, Timmermans, Meuleman, Penninckx. Complications of CO2-laser endoscopic excision of deep Endometriosis. Human Reproduction vol 11 no 10 pp 2263-2268, 1996.

Tamer A. Seckin, MD

Slack A, Child T, Lindsey I, Kennedy S, Cunningham C, Mortensen N, Koninckx P, McVeigh E. Urological and colorectal complications following surgery forrectovaginal endometriosis. BJOG 2007;114:1278–1282.

Camanni et al. Laparoscopic conservative management of ureteral endometriosis: a survey of eighty patients submitted to ureterolysis. Reproductive Biology andEndocrinology 2009, 7:109.

Giudice, Linda, Johannes Leonardus Henricus Evers, and D. L. Healy. Endometriosis: Science and Practice. Chichester, West Sussex: Wiley-Blackwell, 2012. Print.

Koninckx, Ussia, Adamyan, Wattiez, Donnez. Deep Endometriosis: Definition, Diagnosis & Treatment. Fertil Steril Vol. 98, No. 3, September 2012.

Koninckx PR. Videoregistration of surgery should be used as a quality control. J Minim Invasive Gynecol 2008;15:248–53.

Mereu, Gagliardi, Clarizia, Mainardi, Landi, Minelli. Laparoscopic management of ureteral endometriosis in case of moderate-severe hydroureteronephrosis. FertilSteril 2010 Jan;93(1):46-51. Epub 2008 Nov 5.

Seracchioli et al. Importance of Retroperitoneal Ureteric Evaluation in Cases of Deep Infiltrating Endometriosis. Journal of Minimally Invasive Gynecology, Vol 15, No4, July/August 2008.

Makai, Isaacson. Complications of Gynecologic Laparoscopy. Clinical Obstetrics & Gynecology Volume 52, Number 3, 401–411.

• Christel Meuleman1, Carla Tomassetti1, André D'Hoore2, Ben Van Cleynenbreugel3, Freddy Penninckx2, Ignace Vergote1 and Thomas D'Hooghe Surgical treatment of deeply infiltrating endometriosis with colorectal involvement Hum. Reprod. Update (2011) 17 (3): 311‐326 1,*

• W Kondo, N Bourdel, S Tamburro, D Cavoli, K Jardon, B Rabischong, R Botchorishvili, JL Pouly, G Mage, M Canis Complications after surgery for deeply infiltrating pelvic endometriosis BJOG: An International Journal of Obstetrics & Gynecology Volume 118, Issue 3, pages 292–298.

• Slack A, Child T, Lindsey I, Kennedy S, Cunningham C, Mortensen N, Koninckx P, McVeigh E. Urological and colorectal complications following surgery for rectovaginal endometriosis. BJOG 2007;114:1278–1282.

• Emile Darai, MD, PhD,a,

* Isabelle Thomassin, MD,b

Emmanuel Barranger, MD,aRomain Detchev, MD,

a Annie Cortez, MD,

c

Sydney Houry, MD,d

Marc Bazot, MbD. Feasibility and clinical outcome of laparoscopiccolorectal resection for endometriosis American Journal of Obstetrics and Gynecology (2005) 192, 394–400

• Bertrand Dousset, MD,* Mahaut Leconte, MD,* Bruno Borghese, MD,† Anne‐Elodie Millischer, MD,‡Gilles Roseau, MD,§ Sylviane

Tamer A. Seckin, MD

Arkwright, MD, and Charles Chapron, MD†; Complete Surgery for Low Rectal EndometriosisLong‐term Results of a 100‐Case Prospective Study Annals of Surgery • Volume 251, Number 5, May 2010

• Tamer Seckin, MD Endometriosis Committee: Deep Endometriosis Surgery of Pelvic Sidewalls Proceedings of SLS 20th Anniversary Meeting and Endo Expo2011 GENERAL SESSION: BEST OF LAPAROSCOPY UPDATES Thursday, September 15, 2011 Beverly Hills

• Virginia Frenna, MD, Leonor Santos, MD, Eric Ohana, MD, Charles Bailey, MD, and Arnaud Wattiez, MD. Laparoscopic management of ureteral endometriosis:Our experience. Journal of Minimally Invasive Gynecology (2007) 14, 169–171

23

The Impact of Surgical Treatment of Endometriosis on Pelvic Pain


• President, International Society for Gynecologic Endoscopy (ISGE)

• President, AAGL (2007‐2008)

• Clinical Associate Professor, Department OB/GYN, University of Illinois at Chicago, Chicago, IL USA

• Director of Minimally Invasive Gynecologic Surgery, Advocate Lutheran General Hospital, Park Ridge, IL USA

• Director, AAGL/SRS Fellowship in Minimally Invasive Gynecologic Surgery, Advocate Lutheran General Hospital, Park Ridge, IL USA


Disclosures:

Grants/Research Support: Covidien, Femasys, Olympus, Novartis, Abbott LaboratoriesConsultant: Covidien, Femasys, Abbott Laboratories, Ferring Pharm


Objectives

1. List three different methods for the treatment of deep infiltrative endometriosis involving the rectum.

2. List three reasons why literature related to deep infiltrative endometriosis is difficult to interrupt.

3. Discuss the quality of life following bowel resection.

Pain descriptions reported by 113 women with endometriosis and 36 women with an apparently normal pelvis


Ballard K, et al., Fertil Steril 2010; 94(1): 20‐7

Pain descriptions reported by 41 women with a diagnosis of superficial endometriosis and 72 women with deep endometriosis



Associations between pain area and site of endometriosis in 113 women


with endometriosis


24

• Fauconnier (2002)

– Retrospective study 225 women with symptomatic deep infiltrating endometriosis

• Frequency– Severe dysmenorrhea

» Increased adhesions of Pouch of Douglas» Decreased parity

– Dyspareunia» Increased uterosacral ligament deep infiltrating endometriosis


» Decreased bladder deep infiltrating endometriosis

– Non‐cyclic pelvic pain» Increased bowel deep infiltrating endometrioses» Decreased in infertile women

– Dyschezia during menstruation » Increased deep infiltrating endometriosis of vagina

– Lower urinary symptoms» Increased deep infiltrating endometriosis of bladder» Decreased in women with lower BMI

– GI Symptoms» Increased bowel or vaginal deep infiltrating endometriosis

Fauconnier A, et al.; Fertil Steril 2002; 78: 719‐26

• Relationship between stage, site and morphological characteristics of pelvic endometriosis and pain

– Gruppo Italiano per lo Studio dell’Endometriosi (2001)


• Multi center cross sectional observational study

• N = 469

• First laparoscopy or laparotomy for endometriosis and pain of ≥ 6 months duration

– No clear cut association with either

Gruppo Italiano per lo Studio dell’Endometriosi, Hum Reprod 2001; 16(12): 2668‐71

• N = 133– 96 patients with endometriosis and pain

– 37 patients with pelvic pain and no endometriosis

• Results – women with endometriosis

Relating Pelvic Pain Location to Surgical Findings of Endometriosis


Results women with endometriosis– Lower body mass indexes

– More likely Caucasian

– More previous surgeries

– More frequent dysmenorrhea

– More frequent dysmenorrhea with incapacitation

– Dysuria associated with superficial bladder endometriosis• Other lesions, including endometriomas, not associated with pain in the same

location

– Lesion depth, disease burden, lesion number, or endometriomas not associated with pain

Hsu A, Obstet Gynecol 2011; 118(2): 223‐30

• Weir, E (2005)

– 7,993 patients ≥ 15 years who underwent “minor” or “intermediate” conservative surgery for early disease in Ontario, Canada


g y y ,

• Follow up 4 years

• Additional surgical treatment 27%, hysterectomy 12%

Weir E, et al.; JMIG 2005; 12(6): 486‐93

The Impact of Surgical Treatment of Endometriosis on Pelvic PainEffect of surgery for stage I – IV disease

Pain recurrence or re‐operation rates reported after first‐line conservative surgery for symptomatic endometriosis

Vercellini P; Human Reprod Update 2009; 15(2): 177‐88

• Effect of surgery for stage I – IV disease: non comparative studies

– Vignali (2005)

• Pain recurrence 24% (greater in younger patients)


• Lesion recurrence 13% (greater with cul‐de‐sac obliteration)

– Vercellini (2006)

• 24% recurrence at 3 years

– Stage I – 33%, Stage II – 24%, Stage III – 21%, Stage IV – 19%

• Only significant covariate – age (seen also by Cheong, 2008)

Vignali M, et al.; JMIG 2005; 12(6): 508‐13Ferrero S, et al.; Hum Reprod 2007; 22(4): 1142‐8Vercellini P, et al.; Hum Reprod 2006; 21(1): 2679‐85Cheong Y, et al.; J Obstet Gynaecol 2008; 28(1): 82‐5

25

• Effect of surgery for stage I – IV disease: non comparative studies

– Shakiba (2008)

• Relative risk of repeat surgery


– Age 19‐28: 1.75 – 4.76

– Age 30‐39: 1

Surgery Free at: 2 years 5 years 7 years

19‐29 63.9 33.3 27.8

30 ‐39 88.0 58.0 43.3

> 40 85.7 76.2 76.2

Shakiba K, et al.; Obstet Gynecol 2008; 111(6): 1285‐92

• Effect of surgery for stage I – IV disease: controlled studies

– 3 randomized controlled studies

1. Sutton et al., 1994


Sutton et al., 1997

2. Abbott et al., 2004

3. Jarrell et al., 2005

Jarrell et al., 2007

Sutton CJ, et al.; Fertil Steril 1994; 62(4): 696‐700Sutton CJ, et al.; Fertil Steril 1997; 68(6): 1070‐4Abbott J, et al., Fertil Steril 2004; 82(4): 878‐84Jarrell J, et al., J Obstet Gynaecol Can 2005; 27(5): 477‐85Jarrell J, et al.; J Obstet Gynaecol Can 2007; 29(12): 988‐91


– Sutton (1994)

• Double blind study

• 63 women with minimal/moderate endometriosis

• Laparoscopy for pelvic pain


• Laparoscopy for pelvic pain

• 32 laser vaporization of endometriosis plus uterosacral nerve ablation

• 31 expectant management

• At 6 months – 63% improved in laser group, 23% improved in expectant group

– Sutton (1997)

• One year follow up

• Per Sutton, pain relief in 90%

• Per intention to treat: success is 56% in laser group, 23% in control group

• Absolute benefit of surgery at one year – 33%

Sutton CJ, et al.; Fertil Steril 1994; 62(4): 696‐700Sutton CJ, et al.; Fertil Steril 1997; 68(6): 1070‐1074


– Abbott (2004)

• 39 women laparoscopy – minimal to severe endometriosis– 20 excision


– 19 expectant

• Subsequent laparoscopy at six months to excise all lesions

• Symptom improvement at six months – excision 80%, no treatment 0%

• 33 women with second look – 15 excision group, 18 expectant

Pain improvement 6 months after second look

‐ Original excision – 53%

‐ Expectant – 83%

Second line surgery less effective

Abbott J, et al., Fertil Steril 2004; 82(4): 878‐84


– Jarrell (2005)

• 29 women – mild to moderate endometriosis and severe symptoms

l


– 15 laparoscopic excision

– 14 observational laparoscopy

• Pain diaries at baseline 3, 6, 12 months

– No significant difference in visual analogue pain score

– 45% reduction excision

– 33% reduction observation

» Similar to dropouts – 42% excision, 33% observation

Jarrell J, et al., J Obstet Gynaecol Can 2005; 27(5): 477‐85


– Jarrell (2007)

• Long term follow up


• 12 – 14 years overall repeat surgery

– 48% observational group

– 52% excision group

– Correlated to original pain

– No correlation with age, stage or excision

Jarrell J, et al.; J Obstet Gynaecol Can 2007; 29(12): 988‐91

26

• Excision versus ablation

– Wright (2005)

• Randomized trial


• N = 141 (mild endometriosis)

– Follow up at six months

» Average difference in pain score and pre and post surgery

• Excision ‐ 11.2

• Ablation – 8.7

Wright J., et al.; Fertil Steril 2005; 83: 1830‐1836

NS

• Impact of modality on treatment of ovarian endometrioma

– Systematic literature reviews• Chapron (2002) 1

• Vercellini (2003) 2

• Hart (2005) 3


( )

– Laparoscopic excision of pseudocyst versus drainage and electrocoagulation of pseudocyst

• Excision– Reduced rate of recurrence (OR 0.41; 95% CI 0.18 – 0.93)

– Reduced rate of reoperation (OR 0.21; 95% CI 0.05 – 0.79)

– Reduced rate of dysmenorrhea (OR 0.15; 95% CI 0.06 – 0.38)

– Reduced rate of dyspareunia (OR 0.08; 95% CI 0.01 – 0.51)

– Reduce rate of non‐menstrual pelvic pain (OR 0.10; 95% CI 0.02 – 0.56)

1 Chapron C, et al.; Human Reprod Update 2002; 8: 591‐5972 Vercellini P, et al.; Am J Obstet Gynecol 2003; 188: 606‐6103 Hart RJ, et al.; Cochrane Database Syst Rev 2005; 5: CD004992

• Endometrioma surgery

– Beretta (1998)

• 64 patients randomized, cystectomy versus fenestration/coagulation


• Endometrioma > 3 cm

• Recurrence of symptoms (months)

– Excision – 19

– Fenestration/coagulation – 9.5

Beretta P, et al.; Fertil Steril 1998; 70: 1176 ‐ 1180

Significant

• Endometrioma surgery

– Alborzi (2007)

• 100 patients randomized, cystectomy versus fenestration/coagulation


• Recurrence of symptoms at two years

– Excision – 15.8%

– Fenestration/coagulation – 56.7%

• Rate of repeat Surgery– Excision – 5.8%

– Fenestration/coagulation – 22.9%

Alborzi S, et al.; Fertil Steril 2007; 88: 507 ‐ 509

Significant

• According to Cochrane meta‐analysis:

– Uterosacral ligament ablation does not improve relief due to dysmenorrhea (OR 0.77; 95% CI 0.43 – 1.39)


– Presacral neurectomy does improve relief due to dysmenorrhea (OR 3.14; 95% CI 1.59 – 6.21)

Latthe PM, et al.; Acta Obstet Gynecol Scand 2007; 86: 4‐15

• Zullo (2003)

– Randomized trial (laparoscopic presacral neurectomy and conservative surgery versus conservative surgery)

N 141 ( d t i i t 1 10)


• N = 141 (endometriosis stage 1‐ 10)

• Pain relief at six months

– Laparoscopic presacral neurectomy – 87.3%

– Conservative surgery – 60.3%

• Pain relief at 12 months

– Laparoscopic presacral neurectomy – 85.7%

– Conservative surgery – 57.1%

Zullo F, et al.; Am J Obstet Gynecol 2003; 189:720‐721

27

• Endometriosis infiltrating the vaginal and anterior rectal walls cause symptoms such as deep dyspareunia, dyschezia, and dysmenorrhea 1,2,3

• Rectovaginal endometriosis has limited tendency to progress 4

– 88 women watched for six years

The Impact of Surgical Treatment of Endometriosis on Pelvic PainEffect of surgery for deep infiltrating disease

– Greater than 90% had no endometriosis increase

• Up to 16.7% of patients have deep infiltrating endometriosis in Pouch of Douglas 5,6,7

• 5.3 – 12% of patients with endometriosis have deep infiltrating endometriosis of the bowel

– 73% have rectal involvement 8,9,10

1 Vercellini P, et al.; Fertil Steril 1996; 65: 299‐3042 Vercellini P, et al.; JMIG 2004; 11: 153‐1613 Vercellini P, et al.; Semin Reprod Endocrinol 1997; 15: 251‐2614 Fedele L, et al.; Am J Obstet Gynecol 2004; 191: 1539‐15425 Chapron C , et al.; Obstet Gynecol Scand 2001; 80: 349‐3546 Koninckx PR, et al.; Fertil Steril 1992; 58: 924‐9287 Chapron C, et al.; Ann NY Acad Sci 2001; 943: 276‐2808 Wills HJ, et al.; Aust NZ J Obstet Gynaecol 2008; 48: 292‐2959 Koninckx PR, et al; Hum Reprod 1996; 11: 2263‐226810 Redwine DB, et al.; Fertil Steril 2001; 76: 358‐365

• Surgical Treatment of Deeply Infiltrative Endometriosis with

Deep Colorectal Involvement

– Chapron (2006)


• Intestinal endometriosis often multifocal and multicentric

• N=426 (172 DIE)

Rectum/Rectosigmoid ‐ 65.7%

Sigmoid ‐ 17.4%

Cecum/Ileocecal junction 4.1%

Appendix 6.4%

Small Bowel 4.7%

Omentum 1.7%

WES 2011 Consensus on Endometriosis

Preoperative Diagnosis Using Imaging

• Transvaginal Ultrasonography

• MRIMRI

• Excretory Urography / Uro‐MRI

• Rectal Echoendoscopy

“BETWEEN A ROCK AND A HARD PLACE”


Effect of surgery for deep infiltrating disease

Incomplete resection negatively impacts success; radical interventions increase risk of major complications, such as ureteral and rectal injuries.

Koninckx PR, et al; Hum Reprod 1996; 11: 2263‐2268 Fedele L, et al.; Am J Obstet Gynecol 2004; 191: 1539‐1542Ford J, et al.; BJOG 2004; 111: 353‐356


Effect of surgery for deep infiltrating disease

More than 30 case series published in English peer reviewed journals since 2000 evaluating radical conservative surgery for rectovaginal endometriosis causing pain

• Deficiencies of studies which preclude the ability to make recommendations

– Most studies observational, or retrospective and non comparative– Numbers in studies generally small– Disease extent including depth of penetration often not well described– Surgical access inconsistent– Proportion of women undergoing colorectal surgery highly variable; i.e. aggressive vs. conservative– Colorectal surgery varies (shaving, disk resection, low anterior resection)– Major intra and post operative complications vary – 0% to 13%– Follow up usually short– Dropouts not included– Use of medical treatment post operatively not reported– Surgical outcome is operator dependent– Publications bias (poor results may defer from publishing)– Heterogeneity of patient populations– Incorporation of dropouts

28


• Vercellini, et al. (2006)

– Single controlled trial – not randomized, rather patient preference

– N = 105 with infertility and painN = 105 with infertility and pain

• 61 expectant

• 44 laparotomy

– 7 low anterior rectal resection

– 6 ureterolysis

– 1 segmental bladder resection

• No severe intra operative complications

• 1 left uteroperitoneal fistula ‐ ureterolysis

Vercellini P, et al.; Am J Obstet Gynecol 2006; 195: 1303‐1310


• Vercellini, et al. (2006)

Dysmenorrhea * Dyspareunia ** Dyschezia **

Percentage free of moderate – severe symptoms

* Dysmenorrhea most frequent symptom reported

** Most evident advantage to surgery

*** At two years, significant delays with surgery ‐ (dysmenorrhea p = 0.001, dyspareunia p = 0.001, dyschezia p = 0.008)

Vercellini P, et al.; Am J Obstet Gynecol 2006; 195: 1303‐1310

y y p yExpectant12 months 34.6 37.1 65.324 months *** 24.5 48.2 57.4

Surgery12 months 59.8 86.2 86.324 months *** 38.9 72.9 78.1

The Impact of Surgical Treatment of Endometriosis on Pelvic PainEffect of surgery for deep infiltrating diseaseTime to recurrence of symptoms during follow-up of 105 women with rectovaginal endometriosis who had conservative surgery at laparotomy (dashed line) or expectant management (straight line).

Vercellini P; Human Reprod Update 2009; 15(2):177‐88

• Muelemann (2011)

– 49 studies, 3,894 patients (72.7% resection, 9.8% discs, 17.4% shaving)

• 2‐3 cm does not insure free margins

• Discectomy ‐ 40% show endometriosis @ time of bowel resection


• Recurrence

– Total: resection 5.8% mixed 17.6%

– Visual histology: resection 2.5% mixed 5.7%

• Post op pain ‐ post op hormones, <50% patient based reports (<18% VAS)

• QOL did improve, however only 4% of data was prospective

• N = 41– 25 colorectal resection

– 16 nodule excision

Surgical Management of Deep Infiltrating Endometriosis of the Rectum


• Results– No differences in recurrence

– Symptom free at two years:

Dysmenorrhea Dyspareunia Non‐Cyclic Pain

Colorectal Resection 80% 65% 43%

Nodule Excision 62% 81% 69%

Roman H, Hum Reprod 2011; 26(2): 274‐81

• Deep infiltrating endometriosis of the rectum

– Darai (2010)

• Randomized trial of laparoscopically assisted versus open colorectal resection for endometriosis

– 52 women randomized


– 52 women randomized

– Median follow up – 19 months

– Findings» Each showed significant improvement in digestive symptoms

• Dyschezia – p < 0.0001, diarrhea ‐ p < 0.01, bowel pain and cramping ‐ p < 0.0001, back pain ‐ p = 0.001

» No difference in quality of life between groups» Median blood loss less in laparoscopic group ‐ p < 0.05» Total number of complications higher in open surgery group – p = 0.04)» Pregnancy rate higher in laparoscopic group ‐ p = 0.006

Darai E, Ann Surg 2010; 251: 1018‐1023

29

• 70‐80% short term pain relief

• Success declined with time

– By one year many patients required analgesia or hormonal therapy 1,2,3


– By one year many patients required analgesia or hormonal therapy , ,

– Medium term recurrence of lesions – 20% 4,5,6

– 25% repeat surgery 7,8,9,10

1 Anaf V, et al.; JAAGL 2001; 8: 55‐602 Thomassin I, et al.; Am J Obstet Gynecol 2004; 190: 1264‐12713 Fleisch MC, et al.; Euro J Obstet Gynecol Reprod Biol 2005; 123: 224‐2294 Fedele L, et al.; Am J Obstet Gynecol 2004; 190: 1020‐10245 Brouwer R, et al.; Anz J Surg 2007; 77: 562‐5716 Kristensen J et al.; Acta Obstet Gynecol Scand 2007; 86: 1467‐14717 Reich H, et al.; J Reprod Med 1991; 36: 516‐5228 Nezhat C, et al.; Br J Obstet Gynaecol 1992; 99: 664‐6679 Mohr C, et al.; JSLS 2005; 9: 16‐2410 Mereu L et al.; JMIG 2007; 14: 463‐469

• Deep infiltrating endometriosis of the rectum

– Roman (2011)

• No evidence to support risk of recurrences less with colorectal resection versus rectal nodule excision 1


– DeCicco (2010)

• In 34 articles describing 1,889 bowel resections, the following was noted:

– Level of bowel resection and size of lesions were poorly reported

– Indicators for bowel resection variable, and rarely accurate

– Surgery duration varied widely

– Endometriosis not always confirmed at pathologic evaluation 2

1 Roman H, et al.; Hum Reprod 2011; 26: 274‐2812 DeCicco C, et al.; BJOG 2011; 118: 285‐291

Post Operative Complications Post Bowel Resection

• Urinary retention ‐most common

– Due to damage to parasympathetic plexus – bladder denervation

– Decreased risk with nerve sparing techniques 1,2,3


p g q

• Rectovaginal Fistula – second most common

– Risk as high as 10%

– Lowered risk if rectal tumor not opened 4,5

– Hemoperitoneum, anastomotic leaks, ureteral fistula/uroperitoneum, bowel perforation, pelvic abscess, temporary ileostomy, post‐op bowel or ureteral stenosis

1 Volpi E, et al.; Surg Endosc 2004; 18: 109‐1122 Possover M, et al.; J Am Coll Surg 2005; 21: 913‐9173 Landi S, et al.; Hum Reprod 2006; 21: 774‐7814 Darai E, et al.; Am J Obstet Gynecol 2005; 192: 394‐4005 Dubernard G, et al.; Hum Reprod 2006; 21: 1243‐1247

• Design – Prospective

– SF – 36 health status questionnaire (preoperative and 6 months postoperative)

Quality of life after laparoscopic segmental rectosigmoid resection of nodule shaving for deep infiltrating endometriosis with bowel involvement


postoperative)

– N = 100

• Results– Significant improvement (p < 0.0005) in all pain related symptoms,

physical and mental health

– No difference is post op SF‐36 scores whether treatment via intestinal nodule shaving or segmental intestinal resection (p > 0.005)

Mabrouk, M, et al., Health and Quality of Life Outcomes, 2011, 9:98

Mean (± standard deviation) preoperative and postoperative scores of the scale of SF‐36



Mabrouk, M, et al., Heath and Quality of Life Outcomes, 2011, 9:98

Mean improvement (± standard deviation) of SF‐36 scores six months after surgery



Mabrouk, M, et al., Heath and Quality of Life Outcomes, 2011, 9:98

30

Quality of life after segmental resection of the rectosigmoid by laparoscopy in patients with deep infiltrating endometriosis

• Design – Prospective

– SF – 36 health status questionnaire (preoperative and 1 year postoperative)


Bassi MA, et al., JMIG 2011; 18(6): 730‐3

– N = 151

• Results– Significant improvement (p < 0.001) in all pain related symptoms, physical

and mental health


Degrees of pain (scale 0‐10) recorded before and after laparoscopic treatment (N = 151)




Scores of the SF‐36 questionnaire applied before and 1 year after



applied before and 1 year after laparoscopic treatment in 151 women with rectosigmoid

endometriosis

• Prospective pathologic analysis of 45 surgical specimens of bowel endometriosis obtained by laparoscopic segmental resection of the sigmoid.


• 89.3% of lesions with effected circumference greater than 40% impacted the submucous mucous layers of the bowel

• Proceed with bowel resection

Abrao MS, et al., JMIG 2008; 15(3): 280‐5. Epub 2008 Mar

Effect of surgery for deep infiltrating bowel diseaseEffect of surgery for deep infiltrating bowel disease

“The choice of the best surgical approach in the


management of deep infiltrating endometriosis of the rectum (DIER) is the subject of a debate that is far

from being closed”

Roman H, et al.; Hum Reprod 2011; 26: 274‐281

ReferencesBallard K, et al., Fertil Steril 2010; 04(1): 20‐7

Fauconnier A, et al., Fertil Steril 2002; 78: 719‐26

Gruppo Italiano per lo Studio dell’Endometriosi, Hum Reprod 2001; 16(12): 2668‐71

Hsu A, Obstet Gynecol 2011; 118(2): 223‐30

Weir E, et al., JMIG 2005; 12(6): 486‐93

Vercellini P, Human Reprod Update 2009; 15(2): 177‐88

Vignali M, et al., JMIG 2005; 12(6): 508‐13

Ferrero S, et al., Hum Reprod 2007; 22(4): 1142‐8

Vercellini P, et. al., Human Reprod 2006; 21(1): 2679‐85

Cheong Y, et al., J Obstet Gynaecol 2008; 28(1): 82‐5

Shakiba K, et al., Obstet Gynecol 2008; 111(6): 1285‐92

Sutton CJ, et al., Fertil Steril 1994; 62(4): 696‐700

Sutton CJ, et al., Fertil Steril 1997; 68(6): 1070‐4

Abbott J, et al., Fertil Steril 2004; 82(4): 878‐84

Jarrell J, et al., J Obstet Gynaecol Can 2005; 27(5): 477‐85

Jarrell J et al., J Obstet Gynaecol Can 2007; 29(12): 988‐91

Wright J, et al., Fertil Steril 2005; 83: 1830‐1836

Chapron C, et al., Human Reprod Update 2002; 8: 591‐97

Vercellini P, et al., Am J Obstet Gynecol 2003; 188: 606‐610

Hart RJ, et al., Cochrane Database Syst Rev 2005; 5: CD004992

Beretta P, et al, Fertil Steril 1998; 70: 1176‐80

Alborzi S, et al., Fertil Steril 2007; 88: 507‐9

Latthe PM et al., Acta Obstet Gynecol Scand 2007; 86: 4‐15

Zullo F, et al., Am J Obstet Gynecol 2003; 189: 720‐721

Vercellini P, et al., Fertil Steril 1996; 65: 299‐304

Vercellini P. et al., JMIG 2004; 11: 153‐61

Fedele L, et al., Am J Obstet Gynecol 2004; 191: 1539‐42

Chapron C, et al., Obstet Gynecol Scand 2001; 80: 349‐54

Koninckx PR, et al., Fertil Steril 1992; 58: 924‐28

Chapron C, et al., Ann NY Acad Sci 2001; 943: 276‐80

Willis HJ, et al., Aust NZ J Obstet Gynaecol 2008; 48: 292‐95

Abrao MS, Miller CE, Ob.Gyn. News – Master Class in Gynecologic Surgery, Aug 2011

Koninckx PR, et al., Hum Reprod 1996; 11: 2263‐2268

31

References Cont’d

Redwine DB, et al., Fertil Steril 2001; 76: 358‐65

Ford J, et al., BJOG 2004; 111: 353‐56

Vercellini P, et al., Am J Obstet Gynecol 2006; 195: 1303‐10

Roman H, Hum Reprod 2011; 26(2): 274‐81

Darai E, Ann Surg 2010; 251: 1018‐23

Anaf V, et al., JAAGL 2001; 8: 55‐60

Thomassin I, et al., Am J Obstet Gynecol 2004; 190: 1264‐71

Fleisch MC et al., Euro J Obstet Gynecol Reprod Biol 2005; 123: 224‐29

Fedele L, et al., Am J Obstet Gynecol 2004; 190: 1020‐24

Brouwer R, et al., Anz J Surg 2007; 77: 562‐71

Kristensen J, et al., Acta Obstet Gynecol Scand 2007; 86: 1467‐71

Reich H et al J Reprod Med 1991; 36: 516‐22Reich H, et al., J Reprod Med 1991; 36: 516‐22

Nezhat C, et al., Br J Obstet Gynaecol 1992; 99: 664‐67

Mohr C, et al., JSLS 2005; 9: 16‐24

Mereu L, et al., JMIG 2007; 14: 463‐69

DeCicco C, et al., BJOG 2011; 118: 285‐91

Volpi E, et al., Surg Endosc 2004; 18: 109‐112

Possover M, et al., J Am Coll Surg 2005; 21: 913‐17

Landi S, et al., Human Reprod 2006; 21: 774‐81

Darai E, et al., Am J Obstet Gynecol 2005; 192: 394‐400

Dubernard G, et al., Hum Reprod 2006; 21: 1243‐1247

Mabrouk M, et al., Health and Quality of Life Outcomes, 2011; 9:98

Bassi MA et al., JMIG 2011; 18(6): 730‐3

Abrao MS, et al., JMIG 2008; 15(3): 280‐5. Epub 2008 Mar

32

Video Assisted Laparoscopy Video Assisted Laparoscopy in Treatment of Extra Pelvic in Treatment of Extra Pelvic

EndometriosisEndometriosisC N h t MDC N h t MDCamran Nezhat, MDCamran Nezhat, MD

Clinical Professor Department of OBGYN UCSFClinical Professor Department of OBGYN UCSFAdjunct Clinical Professor Department of OBGYN & SurgeryAdjunct Clinical Professor Department of OBGYN & Surgery

Stanford University Medical CenterStanford University Medical CenterCenter for Special Minimally Invasive and Robotic SurgeryCenter for Special Minimally Invasive and Robotic Surgery

Palo Alto, CAPalo Alto, CAwww.Nezhat.orgwww.Nezhat.org

ObjectivesObjectives

Discuss the Discuss the concept of concept of extragenitalextragenital endometriosisendometriosis

Review relevant pathophysiology and anatomy of Review relevant pathophysiology and anatomy of extragenitalextragenital endometriosisendometriosis

Review Review surgical principles related to treatment of surgical principles related to treatment of extensiveextensive extragenitalextragenital endometriosisendometriosisextensive extensive extragenitalextragenital endometriosisendometriosis

Extragenital EndometriosisExtragenital Endometriosis

Most common sitesMost common sites–– GI tractGI tract

–– Urinary tractUrinary tract

Remote sitesRemote sites–– LungsLungs

–– SkinSkin

–– Nervous systemNervous system

–– RetinaRetina

–– Adrenal glandAdrenal gland

Extragenital EndometriosisExtragenital Endometriosis

Occurs in 1Occurs in 1--12% of patients with 12% of patients with endometriosisendometriosisIt can occur in the absence of visible pelvic It can occur in the absence of visible pelvic diseasediseasediseasediseaseEndometriosis has been reported in almost Endometriosis has been reported in almost all body structuresall body structures

Nezhat et al. EndometriosisAdvanced Management & Surgical Techniques.Springer-Verlag, 1995.

SymptomsSymptoms

PainPain

BleedingBleeding

Organ dysfunctionOrgan dysfunction

Di erse and p ling res lting fromDi erse and p ling res lting fromDiverse and puzzling resulting from Diverse and puzzling resulting from functioning endometrial tissue or functioning endometrial tissue or scarring in the affected sitescarring in the affected site

Relation to the menstrual cycle offers a clue to the diagnosis

Bowel EndometriosisBowel EndometriosisIncidenceIncidence

Rectum and sigmoidRectum and sigmoid 76%76%AppendixAppendix 18%18%CecumCecum 5%5%

33

Incidence ofIncidence ofBowel EndometriosisBowel Endometriosis

Redwine et al.Redwine et al. 415/1545415/1545(26%)(26%)

Jerby et al.Jerby et al. 30/50930/509(5.9%)(5.9%)

NezhatNezhat 187/3201187/3201(5.8%)(5.8%)

Study of 1,573 Women treated Study of 1,573 Women treated for endometriosisfor endometriosis

Incidence ofIncidence ofBowel EndometriosisBowel Endometriosis

––5.4%5.4% gastrointestinal involvementgastrointestinal involvement––65%65% rectum or rectosigmoid rectum or rectosigmoid

involvementinvolvement

Prystowsky et al., 1988

Suspect Bowel Endometriosis Suspect Bowel Endometriosis in the presence of:in the presence of:

Palpable tumor in the rectovaginal septumPalpable tumor in the rectovaginal septum

Rectal bleeding with mensesRectal bleeding with menses

Constipation with mensesConstipation with menses

Diarrhea with mensesDiarrhea with menses

Pain after surgical removal of all Pain after surgical removal of all recognizable lesionsrecognizable lesions

Bowel EndometriosisBowel Endometriosis

Treatments:Treatments:–– Segmental resectionSegmental resection

–– Disk excisionDisk excision

–– ShavingShaving

–– Rectal wall excisionRectal wall excision

–– AppendectomyAppendectomy


Treatment dependent on:Treatment dependent on:Depth of lesionDepth of lesion–– Depth of lesionDepth of lesion

–– LocationLocation

–– Experience of surgeonExperience of surgeon


Gynecologists are often uncomfortable Gynecologists are often uncomfortable operating on the bowel.operating on the bowel.

G l b f ili ithG l b f ili ithGeneral surgeons may be unfamiliar with General surgeons may be unfamiliar with endometriosis.endometriosis.

34

Bowel Endometriosis:Bowel Endometriosis:Preop ConsiderationsPreop Considerations

Consider bowel prep in all nonConsider bowel prep in all non--emergent patientsemergent patients

With fixed mucosa, full thickness With fixed mucosa, full thickness penetration must be anticipatedpenetration must be anticipated

Deep rectosigmoid resection and Deep rectosigmoid resection and anastomosis should be anticipatedanastomosis should be anticipated

Laparoscopic TreatmentLaparoscopic Treatmentof Bowel Endometriosisof Bowel Endometriosis

AuthorsAuthors NoNo Average Average AgeAge

SymptomsSymptoms Previous Previous SurgeriesSurgeries

J bJ b 3030 34 (2234 (22 49)49) P i (100%)P i (100%) (0(0 6)6)JerbyJerby 3030 34 (2234 (22--49)49) Pain (100%)Pain (100%) (0(0--6)6)

NezhatNezhat 187187 35 (2135 (21--56)56) Pain (99%)Pain (99%) (1(1--6)6)

Jerby BL, Kessler H, Falcone T, Milsom JW. Laparoscopic management of colorectal endometriosis. Surg Endosc 1999;13:1125-8.Mohr C, Nezhat FR, Nezhat CH, Seidman DS, Nezhat CR. Fertility considerations in laparoscopic treatment of infiltrative bowel endometriosis. JSLS 2005;9:16-24.


AuthorsAuthors NoNo Superficial/Superficial/ShavingShaving

Disc Disc ExcisionExcision

Excision Excision ResectionResection

JerbyJerby 3030 23 (77%)23 (77%) 5 (17%)5 (17%) 7 (23%)7 (23%)

NezhatNezhat 187187 102 (54.5%)102 (54.5%) 47 (25%)47 (25%) 38 (20.3%)38 (20.3%)



AuthorsAuthors Small Small BowelBowel

CecumCecum AppendixAppendix RectoRecto--sigmoidsigmoid

RectumRectum

JerbyJerby 00 2 (7%)2 (7%) 2 (7%)2 (7%) 10 (33%)10 (33%) 29 (93%)29 (93%)

NezhatNezhat 7 (3.7%)7 (3.7%) 3 (1.6%)3 (1.6%) 4 (2%)4 (2%) 74 74 (39.5%)(39.5%)

128 (68%)128 (68%)


Urinary Tract EndometriosisUrinary Tract Endometriosis

Presents in about 20% of women with Presents in about 20% of women with endometriosisendometriosis

Symptoms include frequency, urgency, Symptoms include frequency, urgency, dysuria, and hematuriadysuria, and hematuria

Bladder EndometriosisBladder Endometriosis

Most common site of genitourinary Most common site of genitourinary tract endotract endo

Pathological confirmation is crucialPathological confirmation is crucial 11Pathological confirmation is crucial Pathological confirmation is crucial –– 1 1 out of 15 cases of deeply infiltrating out of 15 cases of deeply infiltrating bladder endo was adenosarcomabladder endo was adenosarcoma

Nezhat et al. Fertil Steril Oct 2002;78(4):872Nezhat et al. Fertil Steril Oct 2002;78(4):872--5.5.

35

Ureter Obstruction with Ureter Obstruction with HydroureterHydroureter

Endo of genitourinary tract is Endo of genitourinary tract is common however it causescommon however it causescommon, however, it causes common, however, it causes compression and obstruction in <1%compression and obstruction in <1%

Laparoscopic Treatment Laparoscopic Treatment of Ureteral Endometriosisof Ureteral Endometriosis

UreterolysisUreterolysisVaporization and excision of endometriosisVaporization and excision of endometriosisUreterotomy or segmental ureteral resectionUreterotomy or segmental ureteral resectionRetrograde internal ureteral stentRetrograde internal ureteral stentOne layer repair (4One layer repair (4--0 Polydioxanone)0 Polydioxanone)Postoperative ureterogramPostoperative ureterogram

Urinary Tract Endo:Urinary Tract Endo:Preop ConsiderationsPreop Considerations

UrinalysisUrinalysis

Preoperative cystoscopyPreoperative cystoscopy

IVP IVP –– if ureter involvement is suspectedif ureter involvement is suspected

Consultation with urologyConsultation with urology

Urinary Tract EndometriosisUrinary Tract Endometriosis

Study of 28 women with deeply infiltrating Study of 28 women with deeply infiltrating urinary tract endometriosisurinary tract endometriosis–– 7 Bladder endometriosis7 Bladder endometriosis

21 Ureter endometriosis21 Ureter endometriosis–– 21 Ureter endometriosis21 Ureter endometriosis

IncidenceIncidence–– October 1989 October 1989 –– September 1994September 1994

28 (1.3%) in 2,226 women28 (1.3%) in 2,226 women

Nezhat C, Nezhat F, Nezhat CH, Nasserbakhat F, Rosati M, Seidman D. Urinary tract endometriosis treated by laparoscopy. Fertility and Sterility 1996;66(6):920-24.

Inclusion CriteriaInclusion Criteria

Bladder Bladder –– Full thickness or deep musclaris involvementFull thickness or deep musclaris involvement

UreterUreterC l t ti l t l b t tiC l t ti l t l b t ti–– Complete or partial ureteral obstructionComplete or partial ureteral obstruction

–– Ureteral wall involvementUreteral wall involvement


Technique Technique –– BladderBladder

Full thickness resection and repairFull thickness resection and repair 66

Resection without mucosaResection without mucosa 11

F l th t 10F l th t 10 14 d14 d 77Foley catheter x 10Foley catheter x 10--14 days14 days 77–– Cystogram prior to discontinuing foleyCystogram prior to discontinuing foley


36

Bladder EndometriosisBladder Endometriosis7 women7 women

AgeAge 2929--39 (avg. 30)39 (avg. 30)

Pelvic painPelvic pain 66

MenouriaMenouria 11


Results Results –– BladderBladder

ComplicationsComplications 00

RecurrenceRecurrence 00

Subsequent surgerySubsequent surgery 22–– Recurrence of pelvic painRecurrence of pelvic pain 11

–– EndometriomaEndometrioma 11


Technique Technique –– UreterUreter

Partial obstructionPartial obstruction 1717–– Ureterolysis and excision of endoUreterolysis and excision of endo 1010–– Partial wall resectionPartial wall resection 77

RepairRepair 22No repairNo repair 55No repairNo repair 55

Internal stent x 2Internal stent x 2--8 weeks8 weeks 1313 Pelvic DrainPelvic Drain 44

Complete resection andComplete resection andreanastomosisreanastomosis 44


Ureter EndometriosisUreter Endometriosis21 women21 women

AgeAge 2424--46 (avg. 35)46 (avg. 35)

Pelvic painPelvic pain 2121

Localized painLocalized pain 1414

Back PainBack Pain 1111

FollowFollow--upup–– 55--33 months33 months


Results Results –– UreterUreter

Hospital stayHospital stay 11--6 days (avg 1.8)6 days (avg 1.8)ComplicationComplication 11–– Pleural effusionPleural effusion

Pain reliefPain relief 20 (95%)20 (95%)Pain reliefPain relief 20 (95%)20 (95%)Ureteral patencyUreteral patency 2121Functioning kidneyFunctioning kidney 2020Subsequent surgerySubsequent surgery 22–– MesotheliomaMesothelioma 11–– Ovarian remnantOvarian remnant 11


Lung and Lung and DiaphragmDiaphragm

EndometriosisEndometriosis

37

Historical PerspectiveHistorical Perspective

Endometriosis of the lung parenchyma was first Endometriosis of the lung parenchyma was first described by Schwarz in 1938.described by Schwarz in 1938.Spontaneous pneumothorax associated with Spontaneous pneumothorax associated with menstrual cycles (catamenial pneumothorax) was menstrual cycles (catamenial pneumothorax) was described as early as 1958.described as early as 1958.–– Schwarz O. Endometriosis of the Lung.Schwarz O. Endometriosis of the Lung. Am J ObstetAm J ObstetSchwarz O. Endometriosis of the Lung. Schwarz O. Endometriosis of the Lung. Am J Obstet Am J Obstet

Gynecol. Gynecol. 1938;36:8871938;36:887--889.889.–– Maurer ER, Schaal JA, Mendez FL, Jr. Chronic Maurer ER, Schaal JA, Mendez FL, Jr. Chronic

recurring spontaneous pneumothorax due to recurring spontaneous pneumothorax due to endometriosis of the diaphragm. endometriosis of the diaphragm. J Am Med Assoc. J Am Med Assoc. Dec 13 1958;168(15):2013Dec 13 1958;168(15):2013--2014.2014.

–– Lillington GA, Mitchell SP, Wood GA. Catamenial Lillington GA, Mitchell SP, Wood GA. Catamenial pneumothorax. pneumothorax. JAMA. JAMA. Mar 6 1972;219(10):1328Mar 6 1972;219(10):1328--1332.1332.

Incidence Endometriosis Incidence Endometriosis Lung/DiaghragmLung/Diaghragm

38.8% Diaphragm affected 38.8% Diaphragm affected

29.6% Pleura affected29.6% Pleura affected–– Foster DC, Stern JL, Buscema J, Rock JA, Foster DC, Stern JL, Buscema J, Rock JA,

Woodruff JD. Pleural and parenchymal Woodruff JD. Pleural and parenchymal pulmonary endometriosis. Obstet Gynecol pulmonary endometriosis. Obstet Gynecol 1981;58:5521981;58:552--6.6.

Catamenial PneumothoraxCatamenial Pneumothorax

2222--37% of those who present with 37% of those who present with catamenial pneumothaces have implants catamenial pneumothaces have implants in the pleura or diaphragm at VATSin the pleura or diaphragm at VATS–– Foster DC, Stern JL, Buscema J, Rock JA, Foster DC, Stern JL, Buscema J, Rock JA,

Woodruff JD. Pleural and parenchymal Woodruff JD. Pleural and parenchymal pulmonary endometriosis. Obstet Gynecol pulmonary endometriosis. Obstet Gynecol 1981;58:5521981;58:552--6.6.

PathophysiologyPathophysiology

RightRight--side predominance (up to 92%)side predominance (up to 92%)–– RoussetRousset--Jablonski C, Alifano M, PluJablonski C, Alifano M, Plu--Bureau Bureau

G, et al. Catamenial pneumothorax and G, et al. Catamenial pneumothorax and endometriosisendometriosis--related pneumothorax: clinical related pneumothorax: clinical ppfeatures and risk factors. Hum Reprod features and risk factors. Hum Reprod 2011;26:23222011;26:2322--9.9.


Metastatic model Metastatic model -- Transdiaphragmatic Transdiaphragmatic passage of air from genital tract through passage of air from genital tract through diaphragmatic perforationsdiaphragmatic perforations

Crutcher RR Waltuch TL Blue ME RecurringCrutcher RR Waltuch TL Blue ME Recurring–– Crutcher RR, Waltuch TL, Blue ME. Recurring Crutcher RR, Waltuch TL, Blue ME. Recurring spontaneous pneumothorax associated with spontaneous pneumothorax associated with menstruation. J Thorac Cardiovasc Surg menstruation. J Thorac Cardiovasc Surg 1967;54:5991967;54:599--602.602.


Sampson’s theory of retrograde menstruation Sampson’s theory of retrograde menstruation along with understanding of peritoneal along with understanding of peritoneal circulation from pelvis to right paracolic gutter circulation from pelvis to right paracolic gutter allows endometrial cells to reach the right allows endometrial cells to reach the right subdiagphragmatic areasubdiagphragmatic areagp ggp gHepatic ligaments represent barriers Hepatic ligaments represent barriers –– favor favor right sideright side–– Vercellini P, Abbiati A, Vigano P, et al. Vercellini P, Abbiati A, Vigano P, et al.

Asymmetry in distribution of diaphragmatic Asymmetry in distribution of diaphragmatic endometriotic lesions: evidence in favour of the endometriotic lesions: evidence in favour of the menstrual reflux theory. Hum Reprod menstrual reflux theory. Hum Reprod 2007;22:23592007;22:2359--67.67.

38


Hormonal model implicates high Hormonal model implicates high prostaglandin Fprostaglandin F22 at ovulation, which may at ovulation, which may result in vasospasm and associated result in vasospasm and associated ischemia in the lungs. This, in turn and in ischemia in the lungs. This, in turn and in combination with prostaglandincombination with prostaglandin--induced induced bronchospasm, may result in alveolar bronchospasm, may result in alveolar rupture and subsequent pneumothoraxrupture and subsequent pneumothorax–– Rossi NP, Goplerud CP. Recurrent Rossi NP, Goplerud CP. Recurrent

catamenial pneumothorax. catamenial pneumothorax. Arch Surg. Arch Surg. Aug Aug 1974;109(2):1731974;109(2):173--176.176.

TreatmentTreatment

MultiMulti--disciplinary approachdisciplinary approachCombined VideoCombined Video--assisted thoracoscopic assisted thoracoscopic surgery (VATS) and LSC surgery (VATS) and LSC -- definitive definitive diagnosis and surgical treatmentdiagnosis and surgical treatment–– Chemical pleurodesis pleurectomy andChemical pleurodesis pleurectomy and–– Chemical pleurodesis, pleurectomy, and Chemical pleurodesis, pleurectomy, and

segmental resection segmental resection –– Treatment of intraTreatment of intra--abdominal and subabdominal and sub--

diaphragmatic endometriosis; BSO in select diaphragmatic endometriosis; BSO in select casescases

Nezhat C, Nicoll LM, Bhagan L, et al. Endometriosis of Nezhat C, Nicoll LM, Bhagan L, et al. Endometriosis of the diaphragm: four cases treated with a combination of the diaphragm: four cases treated with a combination of laparoscopy and thoracoscopy. laparoscopy and thoracoscopy. J Minim Invasive J Minim Invasive Gynecol. Gynecol. SepSep--Oct 2009;16(5):573Oct 2009;16(5):573--580.580.

Diaphragmatic EndometriosisDiaphragmatic Endometriosis

24 women underwent 24 women underwent laparoscopic treatment of laparoscopic treatment of endometriosis of the diaphragmendometriosis of the diaphragm–– 17 patients had 217 patients had 2--5 lesions of 5 lesions of

endo on the diaphragm <1cmendo on the diaphragm <1cm–– 7 women had numerous lesions 7 women had numerous lesions

scattered across the diaphragmscattered across the diaphragm

Lesions were bilateral in 8 Lesions were bilateral in 8 patients, limited to R patients, limited to R hemidiaphragm in 14, L hemidiaphragm in 14, L hemidiaphragm in 2hemidiaphragm in 2Endo infiltrated the muscular Endo infiltrated the muscular layer of the diaphragm in 7 layer of the diaphragm in 7 patientspatients

Nezhat CH, Seidman D, Nezhat F, Nezhat C. Laparoscopic surgical management of diaphragmatic endometriosis. Fertil Steril 1998;69(6):1048‐1055.

Liver Liver EndometriosisEndometriosisEndometriosisEndometriosis

Endometriosis of the LiverEndometriosis of the Liver

• Extremely rare entity • First described in 1986 by Finkel et al• Difficult to diagnose• Often misdiagnosed preoperatively asOften misdiagnosed preoperatively as

echinococcal or amebic cyst, pyogenicabscess, cystadenoma, hematoma, or metastatic disease

Nezhat C, Kazerooni T, Berker B, Lashay N, Fernandez S, Marziali M. Laparoscopic management of hepatic endometriosis: Report of two cases and review of the literature. JMIG. 2005;12:196-200.

PrevalencePrevalenceOnly 17 cases reported in the literatureOnly 17 cases reported in the literatureAge ranges from 21Age ranges from 21--6262Lesion size ranged from 2.7Lesion size ranged from 2.7--24 cm24 cm16/17 patients had symptomatic RUQ pain16/17 patients had symptomatic RUQ painOnly 2/17 patients reported catamenial painOnly 2/17 patients reported catamenial painOnly 5 cases correctly diagnosed Only 5 cases correctly diagnosed preoperativelypreoperativelyyy9/17 patients had their pelvis evaluated for 9/17 patients had their pelvis evaluated for endometrioisendometriois–– 6 had pelvic endometriosis6 had pelvic endometriosis–– 8 did not have pelvis evaluated8 did not have pelvis evaluated

Nezhat C, Kazerooni T, Berker B, Lashay N, Fernandez S, Marziali M. Laparoscopic management of hepatic endometriosis: Report of two cases and review of the literature. JMIG. 2005;12:196‐200.

39

PathophysiologyPathophysiologyMany theories for the origin of hepatic Many theories for the origin of hepatic endometriosis including:endometriosis including:–– implantation theoryimplantation theory–– coelomic theorycoelomic theory–– metaplasia theorymetaplasia theory–– induction theoryinduction theory–– autoimmune theoryautoimmune theory

We believe lymphovascular spread also plays aWe believe lymphovascular spread also plays aWe believe lymphovascular spread also plays a We believe lymphovascular spread also plays a role due to intraparenchymal location in some role due to intraparenchymal location in some patientspatientsRight lobe predominanceRight lobe predominance–– Possibly due to clockwise perioneal fluid flowPossibly due to clockwise perioneal fluid flow


Endometriosis of the Liver: Endometriosis of the Liver: TreatmentTreatment

14 cases treated with laparotomy14 cases treated with laparotomy

1 case treated with danazol (pt declined 1 case treated with danazol (pt declined surgery)surgery)surgery)surgery)

2 cases treated laparoscopically2 cases treated laparoscopically


Liver EndometriosisLiver Endometriosis

First 15 cases reported in the First 15 cases reported in the literature were treated by literature were treated by laparotomylaparotomy

Report of 2 cases treated Report of 2 cases treated l i lll i lllaparoscopicallylaparoscopicallyNezhat C et al. Laparoscopic management of hepatic Nezhat C et al. Laparoscopic management of hepatic

endometriosis: report of two cases and review of the literature. J endometriosis: report of two cases and review of the literature. J Minim Invasive Gynecol. 2005 MayMinim Invasive Gynecol. 2005 May‐‐Jun;12(3):196Jun;12(3):196‐‐200.200.

CitationsCitations1. Nezhat et al. EndometriosisAdvanced Management & Surgical Techniques.

Springer-Verlag, 1995

2. Jerby BL, Kessler H, Falcone T, Milsom JW. Laparoscopic management of colorectal endometriosis. Surg Endosc 1999;13:1125-8.Mohr C, Nezhat FR, Nezhat CH, Seidman DS, Nezhat CR. Fertility considerations in laparoscopic treatment of infiltrative bowel endometriosis. JSLS 2005;9:16-24

3. Nezhat et al. Fertil Steril Oct 2002;78(4):872Nezhat et al. Fertil Steril Oct 2002;78(4):872--55

4. 4. Nezhat C, Nezhat F, Nezhat CH, Nasserbakhat F, Rosati M, Seidman D. Urinary tract endometriosis treated by laparoscopy. Fertility and Sterility 1996;66(6):920-24

5. 5. Schwarz O. Endometriosis of the Lung. Schwarz O. Endometriosis of the Lung. Am J Obstet Gynecol. Am J Obstet Gynecol. 1938;36:8871938;36:887--889.889.

6. 6. Maurer ER, Schaal JA, Mendez FL, Jr. Chronic recurring spontaneous pneumothorax due to Maurer ER, Schaal JA, Mendez FL, Jr. Chronic recurring spontaneous pneumothorax due to endometriosis of the diaphragm. endometriosis of the diaphragm. J Am Med Assoc. J Am Med Assoc. Dec 13 1958;168(15):2013Dec 13 1958;168(15):2013--20142014..

7. Lillington GA, Mitchell SP, Wood GA. Catamenial pneumothorax. 7. Lillington GA, Mitchell SP, Wood GA. Catamenial pneumothorax. JAMA. JAMA. Mar 6 1972;219(10):1328Mar 6 1972;219(10):1328--1332.1332.

8. 8. Foster DC, Stern JL, Buscema J, Rock JA, Woodruff JD. Pleural and parenchymal Foster DC, Stern JL, Buscema J, Rock JA, Woodruff JD. Pleural and parenchymal pulmonary endometriosis. Obstet Gynecol 1981;58:552pulmonary endometriosis. Obstet Gynecol 1981;58:552--6.6.

9. 9. RoussetRousset--Jablonski C, Alifano M, PluJablonski C, Alifano M, Plu--Bureau G, et al. Catamenial pneumothorax and endometriosisBureau G, et al. Catamenial pneumothorax and endometriosis--

related pneumothorax: clinical features and risk factors. Hum Reprod 2011;26:2322related pneumothorax: clinical features and risk factors. Hum Reprod 2011;26:2322--99..10. Crutcher RR, Waltuch TL, Blue ME. Recurring spontaneous pneumothorax associated with Crutcher RR, Waltuch TL, Blue ME. Recurring spontaneous pneumothorax associated with

menstruation. J Thorac Cardiovasc Surg 1967;54:599menstruation. J Thorac Cardiovasc Surg 1967;54:599--602602..

11. Vercellini P, Abbiati A, Vigano P, et al. Asymmetry in distribution of diaphragmatic 11. Vercellini P, Abbiati A, Vigano P, et al. Asymmetry in distribution of diaphragmatic endometriotic lesions: evidence in favour of the menstrual reflux theory. Hum Reprod endometriotic lesions: evidence in favour of the menstrual reflux theory. Hum Reprod 2007;22:23592007;22:2359--6767

12. Rossi NP, Goplerud CP. Recurrent catamenial pneumothorax. 12. Rossi NP, Goplerud CP. Recurrent catamenial pneumothorax. Arch Surg. Arch Surg. Aug Aug 1974;109(2):1731974;109(2):173--176176

13. Nezhat C, Nicoll LM, Bhagan L, et al. Endometriosis of the diaphragm: four cases 13. Nezhat C, Nicoll LM, Bhagan L, et al. Endometriosis of the diaphragm: four cases treated with a combination of laparoscopy and thoracoscopy. treated with a combination of laparoscopy and thoracoscopy. J Minim Invasive J Minim Invasive Gynecol. Gynecol. SepSep--Oct 2009;16(5):573Oct 2009;16(5):573--580580

1414 N h t CH S id D N h t F N h t C L i i l t f14. 14. Nezhat CH, Seidman D, Nezhat F, Nezhat C. Laparoscopic surgical management of diaphragmatic endometriosis. Fertil Steril 1998;69(6):1048-1055

15. Nezhat C et al. Laparoscopic management of hepatic endometriosis: report of two Nezhat C et al. Laparoscopic management of hepatic endometriosis: report of two cases and review of the literature. J Minim Invasive Gynecol. 2005 Maycases and review of the literature. J Minim Invasive Gynecol. 2005 May--Jun;12(3):196Jun;12(3):196--200200

THANK YOU !THANK YOU !THANK YOU !THANK YOU !

40

Fellows

Elizabeth Buescher MDJackie Miller, DO

Elizabeth Buescher MD

Chandhu Paka, MDM. Ali Parsa, MD

41

Perspectives on

the Future Treatment

of Endometriosis

Professor Charles Chapron, MDHead of Department,

Université Paris Descartes,

Sorbonne Paris Cité

Faculté de Médecine, AP-HP,

GHU Ouest, CHU Cochin, Paris, France

Disclosure Slide

N fi i l l ti hiNo financial relationships to disclose

Learning Objectives Slide

At the conclusion of this activity,th ti i t ill b bl t dithe participant will be able to discuss

the modalities of future medico-surgical therapeutic options in the

management of endometriosis

Gynecology Surgical unit:

C Chapron, B Borghese, P Santulli, H Foulot, MC Lafay-Pillet, A Bourret, G Pierre, A Bititi, C Souza

Medical unit:A Gompel, G Plu-Bureau

Laboratory: GeneticD Vaiman, F Mondon, S Barbaux

Laboratory: ImunulogyB Weill, F Batteux, C Nicco, C Chéreau

Reproductive endocrinology unit:D de Ziegler V Gayet,I Streuli, FX Aubriot

Intestinal surgeryB Dousset, M Leconte.

C cco, C C é eau

Laboratory: Reproducive biologyJP Wolf, V Lange, K Pocate,JM Kuntzman, C Chalas

Statistical unitF Goffinet, de Mouzon J

D de Ziegler, Professor and Head, Reproductive Endocrinology and Infertility unit,A Gompel, Professor and Head, Medical Gynecological unit,

C Chapron, Professor and Chair, Dpt Gynecology Obstetrics II and Reproductive Medicine

Endometriosis: Perspectives on the Future Treatment

ENDOME

Delay for diagnosis

ETRIOSIS

Endometriosis: Diagnosis process

Onset ofthe symptoms

Surgical diagnosisand

treatment

6 to 10 years

42


16 centers10 countriesN = 745 osis

Nnoaham et al., Fertil Steril (2011)

3.3 ± 3.6 years

10.7 ± 9.3 years


Age of 1st pelvic symptoms

Onset of symptoms

Ballweg ML (2004)

Adolescents 67.1%

Adults 39.2%

Greene et al., Fertil Steril (2009)


Age of 1st pelvic symptoms

Onset of Time from seekingsymptoms medical attention

to diagnosis

Ballweg ML (2004)

Adolescents 6.0 ± 0.2 years

Adults 2.0 ± 0.3 years

Greene et al., Fertil Steril (2009)

Endometriosis: Progressive disease ? Age and incidence of endometriotic lesions

SUP

Koninckx et al., Fertil Steril (1991)

SUP

OMADIE

Surgery for intestinal DIEn = 100 patients; Minimum of follow-up: 5 years

Predictive factors for transient neurogenic bladder

Parameters Transient neurogenic bladderYes (n = 16) No (n = 84) pn % n %

A ≥ 35 6 37 28 33 NSAge ≥ 35 6 37 28 33 NSBMI > 25 4 25 16 19 NSMultiple previous surgery 10 62 38 45 NSAdditional intestinal resction 2 12 7 8 NSColoanal anastomosis 9 56 7 8 < 0.001Associated hysterectomy 4 25 4 5 < 0.01N DIE lesions ≥ 4 11 69 44 52 < 0.05

Dousset and Chapron Ann Surg (2010)

Severe ureteral endometriosisDelay for diagnosis

(n = 52 patients)

PatientsPatients

N %

Nephrectomy 11 21.1

Chapron – Dousset (2011)

!!!!!!!

43


ENDOME

Risk of recurrences

ETRIOSIS

Deep endometrisois:Recurrences after surgical treatment

Pain recurrence or re-operation rate (%)

I

Cumulative 36- month probability of moderate to severe dysmenorrhea

Vercellini et al., Hum Reprod Update (2009)

II

III

IV53%


ENDOMEETRIOSIS

Multifocal disease

DEEPLY INFILTRATING ENDOMETRIOSIS: LOCATION (n = 877 patients)

Main N Associated lesions Total

lesion USL Va Bl In Ur

R L B

BLADDER 66 2 9 6 5 66 88BLADDER 66 2 9 6 5 66 88

USL 340 88 170 164 422

VAGINA 102 15 20 40 102 177

INTESTINE 313 56 40 186 177 33 594 1088

URETER 56 5 10 44 34 10 94 63 260

877 166 249 440 318 109 688 63 2035

Chapron (September 2011)Multifocality +++

Intestinal endometriosis Anatomic distribution

(n = 360 patients)

Main characteristics N %

Bifocal intestinal DIE

MRI: intestinal DIE

- Unique without other DIE lesions 35 9.7

- Multifocal intestinal DIE lesions 175 48.6

- Associated left/ right lesions 67 18.6

Chapron - Dousset (September 2011)

Deep endometriosisGlobal approach

Chapron et al.,Hum Reprod (2006)

DIE is not« an organ pathology »

Vaginal DIE

44


ENDOMEETRIOSIS

Heterogeneous disease

Deep Endometriosis: Clinical symptoms

Endometriosis

Pelvic pain InfertilityPelvic pain Infertility

Endometriosis: Heterogeneity

Superficialendometriosis

Ovarian endometriomas

LeftOMA

EndometriosisDeep infiltratingendometriosis

BladderDIE

VaginalDIE

BilateralKissingOMAs

Deep endometriosis: Definitions

Hum Reprod (2010)

JC Noel (2010)

JC Noel (2010)

Invasion ofthe muscularis propria

Endometriosis: Associations

OMAPelvic pain Infertility

SUP OMAs

DIE

Deep endometriosis:Frequency of associated ovarian endometriomas

(n = 636 patients)

Main lesion Associated OMAs

N n %

Right OMA with adhesions Bilateral Omas: « Kissing ovaries »

BLADDER 51 8 15.7

USL 279 49 17.6

VAGINA 93 19 20.4

URETER 29 13 44.8

INTESTINE 184 86 46.7

Total 636 175 27.5Chapron unpublished,

(2010)

Right OMA

45

Deeply infiltrating endometriosis(n = 500 patients).

Results according to the presence of OMA

OMA - OMA + P-value a

Mean number of DIE lesions 1.64 ± 1.0 2.51 ± 1.72 < 0.0001

rAFS score

Implants 6.7 ± 4.9 28.1 ± 10.1 < 0.0001

Adhesions 16.5 ± 23.7 36.2 ± 28.7 < 0.0001

Total 23.6 ± 25.7 65.6 ± 33.1 < 0.0001Total 23.6 25.7 65.6 33.1 < 0.0001

a Pearsons’ Chi-square test

Main DIE lesion R OR 95% CI P-value

USL 0.118 - - NS

Vagina 5.98 1.70 1.1-2.6 0.014

Bladder 0.137 - - NS

Intestine 34.5 3.59 2.3-5.6 < 0.0001

Ureter 8.6 3.91 1.4-10.4 0.003

OR, odds-ratio; CI: confidence interval Chapron et al., Fertil Steril (2009)

Deeply infiltrating endometriosisand ovarian endometriomas

Fertil Steril (2009)


ENDOMEETRIOSIS

Results of hormonal treatment

Deep endometriosis: Medical treatments

Hum Reprod, 2009

Deep endometriosis: E and P receptors in the smooth muscle component

Bladder DIE: ER

Noel - Chapron et al, Fertil Steril (2010)

Bladder DIE: ER Bladder DIE: PR

RVS DIE: PR

RVS DIE: ER


ENDOME

Delay for diagnosis

Risk of recurrences

ETRIOSIS

Multifocal disease



46


ENDOME

Earlier diagnosis

Delay for diagnosis

ETRIOSIS

Endometriosis: Management options

Future:Importance of questionning ?

Endometriosis DIE

Endometriosis: Body Mass Index

Lafay Pillet, Chapron et al., Hum Reprod (2012)

Endometriosis: Body Mass Index

Lafay Pillet, Chapron et al., Hum Reprod (2012)Association between BMI and Osis

DIE: Importance of questionning

Parameters Group A Group B p OR 95%CINo DIE DIE(n = 131) (n = 98)

Family history of Osis 6 (4.6%) 13 (13.3) 0.02 3.2 (1.2 - 8.8)

Chapron et al., Fertil Steril (2011)


Parameters Group A Group B p OR 95%CI

No DIE DIE

(n = 131) (n = 98) ( ) ( )

Absenteeism from school

during menstruation 33 (25.2%) 37 (37.7%) 0.04 1.7 (1 - 3)


47


Parameters Group A Group B p OR 95%CI

No DIE DIE

(n = 131) (n = 98)

Prescription of OCPs

because of severe

primary dysmenorrhea 15 (25.9%) 29 (58.0%) 0.001 4.5 (1.9 – 10.4)

Age (years) 18.1 ± 3.2 16.5 ± 2.4 0.07

Duration of use (years) 5.1± 3.8 8.4 ± 4.7 0.02


Fertil Steril (2011)

Endometriosis and oral contraceptives

EndometriosisOral

contraceptivesEndometriosis contraceptives

Two conclusions

Endometriosis: Risk factors

Chapron et al., J Ped Adol Gynecol (2011)

DIE +++


ENDOME

Complete surgicalexeresis

Risk of recurrences

ETRIOSIS

Deep intestinal endometriosis:Previous surgical history for endometriosis

Ann Surg (2010)

Previous surgery for Osis 82%

Operative laparoscopy 59%Open surgery 29%Multiples procedures 48%Hysterectomy 5%

48

Deep endometriosis: Prevention of recurrences after surgical treatment

MultifocalityPreop work-up

Complete surgical exeresis

Surgeon’sexperience

Carmona, Fertil Steril (2009)

CI for sigmoid location: 30%Intestinal Multifocality: 50%% of circumference affectedLymphatic dissemination

Op procedure: Resection >>> Shaving

experience

Abrao et al., Fertil Steril (2006)

DIE with colorectal involvement

Bowel surgery performed n %

Bowel resection anastomosis 737 39 9Bowel resection anastomosis 737 39.9

Full-thickness disc excision 375 20.3

Shave / superficial excision 679 36.8Meuleman et al., Hum Reprod Update (2011)

DIE with colorectal involvementPostoperative recurrence

Proven osis recurrence N n %

Bowel resection anastomosis 812 20 2 46Bowel resection anastomosis 812 20 2.46

Full-thickness disc excision865 49 5.66

Shave / superficial excision

Meuleman et al., Hum Reprod Update (2011)

Deep endometriosis: preoperative diagnosis

Hum Reprod(2009)


ENDOMEETRIOSIS

Multidisciplinaryapproach

Multifocal disease

Endometriosis: Centers of excellence

d’Hooghe and Hummelshoj (Hum Reprod, 2006)

49

Painful OMAsNecessity to reconsider

the management

OMAs DIE

VAS

≥ 7« Severe » OMAs

InstestineUreter

USLVaginaBladder

« Isolated » OMAs

Preoperative work-up: ImagingReferral center

Chapron – Santulli et al.,Hum Reprod (2012)

Deep endometriosis: Multidisciplinary approach

Earlier +++

Clinical examination

Infertility Pain

QuestioningEpidemiologyEnvironment

Earlier +++endometriosis

diagnosis

Imaging

Ovarian reserve

Endocrinology

GynecologistsRadiologists

Sonographers

Endometrial biopsies

Anatomo - pathologyReferral center for Osis

Specific consultations for adolescents


ENDOMEETRIOSIS

PhenotypeHeterogeneous

disease

DIE: Biomarkers Preoperative serum IL-33 levels

VAS Dysmenorrhea VAS GI symptoms

Santulli, Batteux and Chapron (Hum Reprod, 2012)

Total number of DIE lesions

Worst DIE lesion

Endometriosis: Epigenetic changesChromosal distribution of

methylated and demethylated promoter regions

Promoter regions

Demethylated: uniformly distributed

Methylated: Subtelomeric

B Borghese, C Chapron, D Vaiman Mol Endocrinol (2010)

Endometriosis: Epigenetic changes

Borghese, Vaiman, Chapron Am J Pathol (2012)

DNMT3L

50

12

34

5

67

8

91

011

12

13

14

15

16

17

18

19

20

21

22

X

Case control study :Genetic polymorphisms of matrix metalloproteinases (MMPs) 12 and 13

MMPs genetic polymorphysms

Haplotype protectorMMP12‐MMP13 Borghese, Chapron et al., Mol Endocrinol 2008

Borghese, Chapron et al., Hum Reprod 2008

Association avec SUP: OR 27.6

GWAS in endometriosisPrecise endometriosis lesions’ phenotype

SUP OMA DIE

OR = 2.22 OR = 2.09

Association avec DIE OR = 2.09

Borghese, Vaiman and Chapron Am J Hum Genet 2012


ENDOMEETRIOSIS

Non hormonal treatment


Endometriosis: New non hormonal medical options

Mitogen-activatedf

Expert Opin Emerging Drugs (2012)

Deep endometriosisAnti-angiogeneticagents

Matrix metalloproteinasesinhibitors

COX-2inhibitors

Aromataseinhibitors

Histone deacetylaseinhibitors

Immunomodulators

protein kinaseinhibitors

Antioxydants

Nuclear factorKappa β inhibitors

Perossisome proliferatoractivated receptor-Ƴ

Statins

TNF blockers

Endometriosis: New non hormonal medical options

Rocha, Reis and Petraglia Expert Opin Investig Drugs (2012)

Ovarian endometrioma: Oxidative stress

X 2.5

X 7.75

Hydrogen peroxyde production

+ 50% + 65%

Cellular proliferation

Ngô, Chapron, Batteux Am J Pathol (2009)

Effect of NAC on H2O2 production

Effect of NAC on cellular proliferation

51

Ovarian endometrioma: Oxidative stress

Control E-trial cells

E-troticcells NAC


Quantitative analysis: Optic density ratio pERK / ERKThe rate of proliferation of endometriotic cells

is increased through the activation of the ERK pathway as a consequence of high constitutive endogenous oxidative stress

ControlE-trial cells

E-troticcells NAC

Ovarian endoetrioma:Oxidative stress

Contrôle

Control

Invivo

Histological score:2.0 ± 0.25

Histological score:1.19 ± 0.13

p < 0.05

NAC N-acetylcysteine


Endometriosis: Oxidative stressFuture

ROSQuantitative analysis:

Optic density ratio pERK / ERK

Activation de pERK

Prolifération

pERKinhibitor X

Endometriosis: Role of protein kinase inhibitorsProliferation Proliferation Proliferation

Ngô, Chapron, Batteux J Pathol (2010)

Untreated Untreated

***: p < 0.001

Endometriosis: Role of protein kinase inhibitors

Ngô, Chapron, Batteux J Pathol (2010)

In vivo with mouse model: Pathology score

***: p < 0.01

Deep endometriosis:Oxidative stress

O2.-

H2O2

DIE cells proliferation

39%

Leconte, Dousset, Chapron and Batteux, Am J Pathol (2011)

Cellular production of ROS: basal levels

NO39%

68%

52

Deep Endometriosis: Oxidative stressEndometriotic cell

proliferation Proliferative rate


Effects on N- Acetyl-L-Cysteine: Antioxydant molecule

**** ****

Deep Endometriosis: Oxidative stress

control control Eutopic EEutopic E DIE DIE

Epithelial Stromal


p

DIE cells proliferation is increased through the activation of the ERK pathway,

as a consequence of high constitutive endogenous ROS production

Quantitative analysis: Optic density ratio pERK / ERK

Es

Deep Endometriosis: Oxidative stressFuture +++

ROS

Effect of protein tyrosine kinase inhibitor A77-1726

(selective ERK inhibitor +++)on cell proliferation

Activation de pERK

Prolifération

pERKinhibitor X

Leconte, Dousset, Chapron and Batteux, Am J Pathol (2011)Eutopic E

DIEDIEEutopic E Eutopic E

Epithelial Stromal

on cell proliferation

- 87% - 93% - 95% - 88%

Deep Endometriosis: the mTOR/AKT pathway

Quantitative Quantitative l i

Quantitative l i f


analysis of AKT

analysis of pAKT

analysis of phospho-p70S6K

DIE: Effect of mTOR/AKT Inhibitor (Temsirolimus)

Effect of Temsirolimus (selective mTOR/AKT inhibitor +++)

on cell proliferation

Invitro


DIE: Effect of mTOR/AKT Inhibitor (Temsirolimus)

Invivo

Untreated

Glands

Stroma

Fibrosis

Treated(3 weeks after)

Leconte, Dousset, Chapron and Batteux, Am J Pathol (2011)p < 0.01

2.44 ± 0.181.19 ± 0.25

53

Take home messages

Management and strategy:Endometriosis

and- Global approach

-Multidisciplinary approach

- New non hormonal treatments

Patients

Global approach

Take home messages


and Pelvic pain- Global approach

- Multidisciplinary approach


Patients

Pelvic painGlobal approach

Take home messages





Patients

Pelvic pain

Infertility

Global approach

Take home messages





Patients

Pelvic pain

Infertility

Global approach

Surgery

Medical Ttt

ART


ENDOME

Earlier diagnosis

Complete surgicalexeresis

Delay for diagnosis

Risk of recurrences

ETRIOSIS

Multidisciplinaryapproach

Phenotype

Non hormonal treatment

Multifocal disease



PresidentsFelice Petraglia

(Siena, Italy)Charles Chapron (Paris, France)

Hans Rudolf Tinnemberg (Giessen, Germany)

54

References list (1)Nnoham KE, Hummelshoj L, Webster P, d’Hooghe T, de Cicco Nardone F, de Cicco Nardone C,

Jenkinson C, Kennedy S, Zonderevan KT: Impact of endometriosis on quality of life and work productivit: a multicenterstudy across ten countries. Fertil Steril 2011; 96: 366-373.

Greene R, Stratton P, Cleary SD, Ballweg ML, Sinaï N: Diagnostic experience among 4,334 women reporting surgically diagnosed endometriosis. Fertil Steril 2009; 91: 32-39.

Koninckx PR, Meuleman C, Demeyere S, Lessafre E, Cornillie FJ: Suggestive evidence that pelvic endometriosis is a progresive disease, whereas deeply infiltrating endometriosis is associated with pelvic pain. Fertil Steril 1991, 55: 759-765.

Dousset B, Leconte M, Borghese B, Millischer AE, Roseau G, Arkwright S, Chapron C: Complete surgery g g p p g yfor low rectal endometriosis : long term results of a 100-case prospective study. Ann Surg. 2010; 251 (5): 887-895.

Vercellini P, Crosignani PG, Abbiati A, Somigliana E, Vigano P, Fedele L: The effect of surgery for symptomatic endometriosis: the other side of the story. Hum Reprod Update 2009; 15: 177-188.

Chapron C, Chopin N, Borghese B, Foulot H, Dousset B, Vacher-Lavenu MC, Vieira M, Hasan W, Bricou A:Deeply infiltrating endometriosis: Pathogenetic implications of the anatomic distribution.Hum Reprod 2006; 21(7): 1839-1845.

Chapron C, Bourret A, Chopin N, Dousset B, Leconte M, Amsellem-Ouazana D, de Ziegler D, Borghese B: Surgery for bladder endometriosis: Long term results and concomitant management of associated posterior deep lesions. Hum Reprod 2010; 25 (4): 884-889.

References list (2)Chapron C, Piétin-Vialle C, Borghese B, Davy C, Foulot H, Chopin N: Deeply infiltrating endometriosis:

Associated ovarian endometriomas is a marker for greater severity of the disease.Fertil Steril 2009, 92: 453-457.

Vercellini P, Crosignani PG, Somigliana E, Berlanda N, Barbara G, Fedele L: Medical treatment for rectovaginal endometriosis: what is the evidence? 2009; 24: 2504-2514.

Noel J.C; Chapron C; Bucella D; Buxant F; Peny M.O; Fayt I; Borghese B; Anaf V: Estrogen and progesterone receptors in smooth muscle component of deep infiltrating endometriosis.Fertil Steril. 2010, 93: 1774-1777.

Chapron C, Lafay-Pillet MC, Monceau E, Borghese B, Ngô C, Souza C, de Ziegler D: Questioning patients about their adolescent history can identify markers associated with deepinfiltrating endometriosis. Fertil Steril 2011, 95 (3): 877-881.

Chapron C, Souza C, Borghese B, Lafay-Pillet MC, Santulli P, Bijaoui G, Goffinet F, de Ziegler D: Oral contraceptives and endometriosis : the past use of oral contraceptives for treating severe primary dysmenorrhea is associated with endometriosis, especially deep infiltrating endometriosis.Hum Reprod 2011; 26(8): 2028-2035 .

Lafay-Pillet MC, Schneider A, Borghese B, Santulli P, Souza C, Streulli I, de Ziegler D, Chapron C : Deep infiltrating endometriosis is associated with markedly lower body mass index (BMI) : a 476 case-control study. Hum Reprod 2012; 27(1): 265-272

References list (3)

Chapron C, Borghese B, Streuli I, de Ziegler D: Markers of adult endometriosis detectable in adolescence. J Ped Adol Gynecol 2011; 24: S7-S12.

Meuleman C, Tomasetti C, d’Hoore A, Van Cleynenbreugel B, Penninckx F, Vergote I, d’Hooghe T: Surgical treatment of deeply infiltrating endometriosis with colorectal involvement. Hum Reprod Update 2011, 17: 311-326.

Carmona F, Martinez-Zamora A, Gonzalez X, Gines A, Bunesch L, Balasch J: Does the learning curve of conservative laparoscopic surgery in women with rectovaginal endometriosis impairthe recurrence rate. Fertil Steril 2009; 92: 868-875.

Abrao MS, Podagec S, Dias Jr JA, Averbach M, Garry R, Ferraz Silva LF, Carvalho FM: Deeply infiltrating endometriosis affecting the rectum and lymph nodes. Fertil Steril 2006; 86: 543-547.

Chapron C, Chiodo I, Leconte M, Amsellem-Ouazana D, Chopin N, Borghese B, Dousset B: Severe ureteral endometriosis: the intrinsic type is not so rare after complete surgical exeresis of deep endometriotic lesions. Fertil Steril 2010, 93: 2115-2120.

Piketty M, Chopin N, Dousset B, Millischer-Bellaische AE, Roseau G, Leconte M, Borghese B, Chapron C: Preoperative work-up for patients with deeply infiltrating endometriosis: transvaginal ultrasonography must definitely be the first line imaging examination. Hum Reprod. 2009; 24 (3): 602-607.

References list (4)d’Hooghe T and Hummelshoj L: Multi-disciplinary centers/networks of excellence for endometriosis

management and research: a proposal. Hum Reprod 2006; 21; 2743-2748.

Chapron C, Santulli P, de Ziegler D, Noel JC, Anaf V, Streuli I, Foulot H, Souza C, Borghese B: Ovarian endometrioma : severe pelvic pain is associated with deeply infiltrating endometrisosis.Hum Reprod 2012; 27(3): 702-711.

Santulli P, Borghese B, Chouzenoux S, Vaiman D, Borderie D, Streuli I, Goffinet F, de Ziegler D, Weill B, Batteux F, Chapron C: Serum and peritoneal IL-33 levels areelevated in deeply infiltratingendometriosis. Hum Reprod 2012 ; 27 (7) 2001-2009.endometriosis. Hum Reprod 2012 ; 27 (7) 2001 2009.

Borghese B, Barbaux S, Mondon F, Santulli P, Pierre G, Vinci G, Chapron C, Vaiman D: Research resource : Genome-wide profiling of methylated promoters in endometriosis reveals a subtelomeric location of hypermethylation. Mol Endocrinol 2010; 24 (9): 1872-1885.

Borghese B, Chiche JD, Vernerey D, Chenot C, Mir O, Bijaoui G, Bonaiti-Pellié C, Chapron C. : Genetic polymorphisms of matrix metalloproteinase MMP-12 and MMP-13 gene are implicated in endometriosis progression.Hum Reprod 2008, 23(5): 1207-1213.

Borghese B, Mondon F, Noel JC, Fayt I, Mignot MT, Vaiman D, Chapron C: Gene expression profile for ectopic versus eutopic endometrium provides new insights into endometriosis oncogenetic potential. Mol Endocrinol 2008; 22 (11): 2557-2562.

References list (5)Borghese B, Santulli P, Héquet D, Pierre G, de Ziegler D, Vaiman D, Chapron C: Genetic polymorphisms

of DNMT3L involved in hypermethylation of chromosal ends are associated with greater risk of developping ovarian endometriosis. Am J Pathol 2012; 180 (5): 17811-786.

Borghese B, Tost J, de Surville M, Busato F, Le Tourneur F, Mondon F, Vaiman D;,Chapron C: Identification of susceptibility genes for superficial, ovarian and deep infiltrating endometriosis using a pooling-based genome-wide association study. 2012 (submitted for publication).

Streuli I, de Ziegler D, Borghese B, Santulli P, Batteux F, Chapron C: New treatment strategies and emerging drugs in endometriosis Expert Opin Emerging Drugs 2012; 17(1): 83-104emerging drugs in endometriosis. Expert Opin Emerging Drugs 2012; 17(1): 83-104.

Rocha AL, Reis FM, Petraglia F: New trends for the medical treatment of endometriosis. Expert Opin Investig Drugs 2012; 21: 905-919.

Ngô C, Chéreau C, Nicco C, Weill B, Chapron C; Batteux F: Reactive oxygen species controls endometriosis progression. Am J Pathol 2009; 175 (1): 225-234.

Ngo C, Nicco C, Leconte M, Chéreau C, Arkwright S, Vacher-Lavenu MC, Weill B, Chapron C, Batteux F: Protein kinase inhibitors can control the progression of endometriosis in vitro and in vivo. J Pathol 2010; 222 (2): 148-157.

References list (6)

Leconte M, Nicco C, Ngô C, Chéreau C, Chouzenoux S, Marut W, Guibourdenche J, Arkwright S, Weill B, Chapron C, Dousset B, Batteux F: The mTOR/AKT inhibitor temsirolimus prevents deep infiltrating endometriosis in mice. Am J Pathol 2011; 179: 880-889.

Leconte M, Nicco C, Ngô C, Arkwright S, Chéreau C, Guibourdenche J, Weill B, Chapron C, eco e , cco C, gô C, g S, C é eau C, Gu bou de c e J, e , C ap o C,Dousset B, Batteux F: Antiproliferative effect of cannabinoid agonists on deep infiltrating endometriosis. Am J Pathol 2010; 177 (6): 2963-2970.

55

CULTURAL AND LINGUISTIC COMPETENCY Governor Arnold Schwarzenegger signed into law AB 1195 (eff. 7/1/06) requiring local CME providers, such as

the AAGL, to assist in enhancing the cultural and linguistic competency of California’s physicians

(researchers and doctors without patient contact are exempt). This mandate follows the federal Civil Rights Act of 1964, Executive Order 13166 (2000) and the Dymally-Alatorre Bilingual Services Act (1973), all of which

recognize, as confirmed by the US Census Bureau, that substantial numbers of patients possess limited English proficiency (LEP).

California Business & Professions Code §2190.1(c)(3) requires a review and explanation of the laws

identified above so as to fulfill AAGL’s obligations pursuant to California law. Additional guidance is provided by the Institute for Medical Quality at http://www.imq.org

Title VI of the Civil Rights Act of 1964 prohibits recipients of federal financial assistance from

discriminating against or otherwise excluding individuals on the basis of race, color, or national origin in any of their activities. In 1974, the US Supreme Court recognized LEP individuals as potential victims of national

origin discrimination. In all situations, federal agencies are required to assess the number or proportion of LEP individuals in the eligible service population, the frequency with which they come into contact with the

program, the importance of the services, and the resources available to the recipient, including the mix of oral

and written language services. Additional details may be found in the Department of Justice Policy Guidance Document: Enforcement of Title VI of the Civil Rights Act of 1964 http://www.usdoj.gov/crt/cor/pubs.htm.

Executive Order 13166,”Improving Access to Services for Persons with Limited English

Proficiency”, signed by the President on August 11, 2000 http://www.usdoj.gov/crt/cor/13166.htm was the genesis of the Guidance Document mentioned above. The Executive Order requires all federal agencies,

including those which provide federal financial assistance, to examine the services they provide, identify any

need for services to LEP individuals, and develop and implement a system to provide those services so LEP persons can have meaningful access.

Dymally-Alatorre Bilingual Services Act (California Government Code §7290 et seq.) requires every

California state agency which either provides information to, or has contact with, the public to provide bilingual

interpreters as well as translated materials explaining those services whenever the local agency serves LEP members of a group whose numbers exceed 5% of the general population.

~

If you add staff to assist with LEP patients, confirm their translation skills, not just their language skills.

A 2007 Northern California study from Sutter Health confirmed that being bilingual does not guarantee competence as a medical interpreter. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2078538.

US Population

Language Spoken at Home

English

Spanish

AsianOther

Indo-Euro

California

Language Spoken at Home

Spanish

English

OtherAsianIndo-Euro

19.7% of the US Population speaks a language other than English at home In California, this number is 42.5%

56

http://www.imq.org/

http://www.usdoj.gov/crt/cor/pubs.htm

http://www.usdoj.gov/crt/cor/13166.htm

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2078538

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