Ophthalmic & Physiological Optics ISSN 0275-5408 Myopia control: the time is now For over a century parents have asked clinicians if anything Refractive development is regulated by visual feedback and can be done to slow the progression of myopia in their chil- the process can be manipulated by optical interventions.9,10 dren. Most practitioners shrug their shoulders, add another
Human Reproduction, Vol.24, No.3 pp. 602 – 607, 2009 Advanced Access publication on December 17, 2008 ORIGINAL ARTICLE Gynaecology Preoperative work-up for patients withdeeply inﬁltrating endometriosis:transvaginal ultrasonography mustdeﬁnitely be the ﬁrst-line imagingexamination Mathilde Piketty1, Nicolas Chopin1, Bertrand Dousset2,Anne-Elodie Millischer-Bellaische3, Gilles Roseau1, Mahaut Leconte2,Bruno Borghese1,4,5, and Charles Chapron1,4,5,6 1Department of Gynecology, Obstetrics II and Reproductive Medicine, Universite´ Paris Descartes, Faculte´ de Me´decine, AssistancePublique – Hoˆpitaux de Paris (AP-HP), Groupe Hospitalier Universitaire (GHU) Ouest, Centre Hospitalier Universitaire (CHU) Cochin, SaintVincent de Paul, Pavillon Lelong, 82, Avenue Denfert Rochereau, 75014 Paris, France 2Department of Digestive and Endocrine, Universite´Paris Descartes, Faculte´ de Me´decine, Assistance Publique – Hoˆpitaux de Paris (AP-HP), Groupe Hospitalier Universitaire (GHU) Ouest,Centre Hospitalier Universitaire (CHU) Cochin, Saint Vincent de Paul, Paris, France 3Department of Radiology, Universite´ Paris Descartes,Faculte´ de Me´decine, Assistance Publique – Hoˆpitaux de Paris (AP-HP), Groupe Hospitalier Universitaire (GHU) Ouest, Centre HospitalierUniversitaire (CHU) Cochin, Saint Vincent de Paul, Paris, France 4Institut Cochin, Universite´ Paris Descartes, CNRS (UMR 8104), Paris,France 5Inserm, Unite´ de Recherche U567, Paris, France 6Correspondence address. Tel: þ33-1-58-41-19-14; Fax: þ33-1-58-41-18-70; E-mail: email@example.com background: Transvaginal ultrasonography (TVUS) has important advantages compared with transrectal ultrasonography (TRUS): it isless invasive, is cost-effective, is a familiar and well-accepted approach, and anesthesia is not required. We compared the accuracy of TVUSand TRUS for diagnosing rectal wall involvement in patients presenting with histologically proved deeply inﬁltrating endometriosis (DIE).
methods: Prospective study of 134 patients with histologically proved DIE underwent preoperative investigations using both TVUS andTRUS. The radiologist (TVUS) and sonographer (TRUS) were unaware of the clinical ﬁndings but knew that DIE was suspected.
results: DIE was conﬁrmed histologically for all the patients. A rectal wall involvement was histologically proved for 75 patients (56%).
For the diagnosis of inﬁltration of the intestinal wall, TVUS and TRUS, respectively, had a sensitivity of 90.7% and 96.0%, a speciﬁcity of 96.5%and 100.0%, a positive predictive value of 97.1% and 100.0% and a negative predictive value of 88.9% and 95.2%.
conclusions: TVUS and TRUS have similar degrees of accuracy for predicting intestinal involvement. TVUS must be the ﬁrst-lineimaging process to perform for patients presenting with clinically suspected DIE. The question for the coming years is to deﬁne if it is necess-ary for TRUS to be carried out systematically in cases of clinically suspected DIE.
Key words: deep endometriosis / deeply inﬁltrating endometriosis / preoperative work-up / transvaginal ultrasonography / transrectalultrasonography the type of pain is related to location of the DIE lesions (Fauconnieret al., 2002), whereas the severity is correlated to depth of the DIE There are three types of endometriotic lesions: superﬁcial endome- nodules (Koninckx et al., 1991; Porpora et al., 1999; Chapron et al., triosis (peritoneal and/or ovarian), ovarian endometriomas and deeply inﬁltrating endometriosis (DIE). DIE is a speciﬁc entity, histo- Management of DIE can be either medical (Igarashi et al., 1998; logically deﬁned when endometriotic lesions penetrate more than Fedele et al., 2000; Fedele et al., 2001; Heﬂer et al., 2005; Vercellini 5 mm under the peritoneum (Koninckx et al., 1991). DIE is respon- et al., 2005; Razzi et al., 2007) or surgical (Urbach et al., 1998; sible for pelvic pain symptoms (Fauconnier and Chapron, 2005), and Chapron et al., 2003b; Darai et al., 2005; Vignali et al., 2005; & The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
For Permissions, please email: firstname.lastname@example.org Work-up for rectal wall involvement in deep endometriosis Ribeiro et al., 2006; Seracchioli et al., 2007). Success of surgery is cor- experienced radiologist (A.E.M.B.). Routine analysis of uterus and ovaries related with the radicality of the exeresis (Chopin et al., 2005). A sat- took place ﬁrst. Moreover, the protocol included the study of the peritoneal isfactory work-up (questioning, clinical examination, imaging) is surfaces (pouch of Douglas, vesicouterine pouch) and the retroperitoneal necessary preoperatively to establish the map of DIE lesions and to space (i.e. USL, torus uterinum and posterior fornix of the vagina). Theprobe was ﬁrst positioned in the lower vagina in front of the anal canal.
obtain the patient's consent (Chapron et al., 2004a).
The probe was moved slowly down and up to the posterior fornix of the Preoperative knowledge about intestinal inﬁltration is essential vagina. By moving the probe, all the anterior rectosigmoid space could be because, if surgery is decided, a speciﬁc intestinal surgical procedure analyzed. The normal aspect of the rectum/sigmoid colon muscularis will be necessary (Chapron et al., 2003b). In these situations, patients propria is hypoechoic and thin (,3 mm). Intestinal DIE was deﬁned as an must be informed preoperatively concerning the surgical risks (Landi irregular hypoechoic mass, with or without hypo/hyperechoic foci involving et al., 2006; Dubernard et al., 2008). Because clinical examination is the rectum/sigmoid colon muscularis propria (Bazot et al., 2007b). Particu- of limited use for establishing the extent of the DIE lesions lar attention was paid to the appendix and small. The aspect of torus uter- (Chapron et al., 2002; Abrao et al., 2007), it is necessary to use non- inum and USL was observed at the same time with sagittal and parasagittal invasive imaging processes prior to surgery. Transrectal ultrasonogra- views of hypoechoic and irregular nodules.
phy (TRUS) was demonstrated to be efﬁcient for the diagnosis ofrectal wall inﬁltration by DIE lesions (Chapron et al., 1998; Fedele et al., 1998; Delpy et al., 2005; Bazot et al., 2007a). Magnetic reson- TRUS was performed with an Olympus UM 160 Echoendoscope (SCOP ance imaging (MRI), also proposed, presents the great advantage of Medecine Olympus, 94150 Rungis, France) by a single examiner (G.R.). It offering the possibility of obtaining a complete pelvic evaluation with was carried out without sedation, 2 h after a rectal enema. Endoscopic a single imaging procedure (Siegelman et al., 1994; Kinkel et al., examination of the rectum and the distal sigmoid colon was ﬁrst performed, 1999; Bazot et al., 2004; Chapron et al., 2004b; Kataoka et al., placing the probe in the sigmoid colon, over the aortic bifurcation and/or 2005; Abrao et al., 2007). More recently, transvaginal ultrasonography the upper part of the body of the uterus. The probe was then slowly with- (TVUS), which is the imaging method of choice for diagnosis of endo- drawn allowing optimum imaging of rectal and sigmoid colon walls, withinstillation of water into the intestinal lumen and alternating use of 5, 7.5 metriomas (Mais et al., 1993; Guerriero et al., 1995), was proposed and 12 MHz frequencies. Normal intestinal wal s usually appear as a ﬁve- for the diagnosis of DIE (Gorell et al., 1989; Bazot et al., 2003; layer structure: the fourth hypoechoic layer corresponds to the muscularis Koga et al., 2003). This method of investigation offers the advantages propria. The surrounding areas were also imaged, with particular attention of accessibility and cost-effectiveness when compared with MRI and paid to the ovaries, cervix and body of the uterus, pouch of douglas, USL tolerability when compared with TRUS.
areas and torus uterinum. DIE showed up as hypoechoic peri-digestive The aim of this study is to compare the results of TVUS with those nodules of rounded or roughly triangular shape. A diagnosis of digestive of TRUS, which is the investigation of choice for the diagnosis of rectal tract inﬁltration was conﬁrmed when a hypoechoic thickening of the muscu- wall inﬁltration, and to clarify whether there are limits for TVUS.
laris propria was demonstrated at ultrasound (Chapron et al., 1998), eitherisolated or involved in an adjacent pelvic location.
Materials and Methods Statistical analysis Between January 2005 and July 2007, we performed a prospective study For each imaging process (TVUS and TRUS), sensitivity, speciﬁcity, positive during which time patients suffering from pelvic pain (alone or associated and negative predictive value (PPV and NPV), 95% conﬁdence intervals with infertility) underwent complete surgical exeresis of DIE lesions and kappa test of concordance in the diagnosis of rectal wall involvement (Chapron et al., 2003b). DIE was suspected in all cases preoperatively for patients presenting histologically proved DIE were calculated (McKen- (questioning, clinical examination, imaging). Diagnosis of DIE was histologi- zie et al., 1997). Data are presented as mean + SD.
cally proven for each patient. DIE lesions were classiﬁed in ﬁve locations(bladder, uterosacral ligament(s) (USL), vagina, intestine, ureter) accordingto a previous classiﬁcation (Chapron et al., 2006). For each patient, data were collected: (i) general patients' characteristics (age, gravidity, parity,height, weight); (ii) history of previous medical and/or surgical treatment During the study period, 134 patients were enrolled. Patients' charac- for endometriosis; (iii) preoperative painful symptoms scores (dysmenor- teristics are presented in Table I. Four hundred and ten (n ¼ 410) his- rhea, deep dyspareunia, non-cyclic chronic pelvic pain, gastrointestinal and tologically proved DIE lesions were removed during complete DIE lower urinary tract symptoms) according to visual analogue scale; (iv) stage surgical exeresis: USL (132 lesions; 32.2%); vagina (80 lesions; of the disease and mean revised American Fertility Society (AFS) scores 19.5%); bladder (22 lesions; 5.4%); intestine (163 lesions; 39.7%) (total, implant, adhesion) according to the AFS (AFS, 1985); (v) number and ureter (13 lesions; 3.2%). The mean number of DIE lesions per and location of DIE lesions (bladder, USL, vagina, intestine, ureter); (vi) patient was 3.1 + 2.1 (range 1 – 10). Fifty-one patients (n ¼ 51; existence of associated ovarian endometrioma.
38.1%) had an ovarian endometrioma associated with the DIE lesions.
All women underwent both TVUS and TRUS prior to surgery. The radi- Patient distribution, according to the main location of the DIE ologist (for the TVUS) and the sonographer (TRUS) were informed thatDIE was suspected but were blinded to the results of clinical ﬁndings Classiﬁcation (Chapron et al., 2006), was as follows: USL 25 patients and previous imaging examinations. They were asked whether there was (18.7%); vagina 23 patients (17.2%); bladder 11 patients (8.2%); intes- involvement of the digestive wall.
tine 66 patients (49.2%); and ureter 9 patients (6.7%) (Table II). Atotal of 75 patients (56.0%) presented with histologically proved intes- tinal involvement (the 66 patients classiﬁed as ‘intestine' and 9 as TVUS was performed with a Toshiba ultrasound machine, using a 5 –9 MHz ‘ureter') (Table II). The mean number of intestinal DIE lesions per transducer. TVUS was performed without bowel preparation by a single patient was 2.7 + 1.5 (range 1 – 9). For 70 patients (93.3%), the Piketty et al.
rectal and/or sigmoid DIE lesion. Ninety-six percent (96.0%; 72 Table I Characteristics of patients with DIE in the cases) of the patients presented a rectal wall inﬁltration. Appendix (n ¼ 8 patients) and omentum (n ¼ 3 patients) DIE lesions werenever isolated and always associated with rectal and/or sigmoid DIE Patients' characteristics (n 5 134) 32.1 + 5.0 (range 22 – 47) Among the patients with intestinal DIE lesions (n ¼ 75), only 34 0.7 + 1.1 (range 0 – 7) patients (45.3%) presented a single intestinal lesion (not taking 0.4 + 0.8 (range 0 – 5) omentum and appendix DIE lesions into account). Among the 41 164.7 + 7.6 (range 146 – 197) patients with more than one intestinal DIE lesions (not takingomentum and appendix DIE lesions into account), 21 patients pre- 59.6 + 10.6 (range 37 – 87) sented, associated with the rectal and/or sigmoid DIE lesions, a Previous treatment for endometriosis ‘right intestinal DIE lesion' located at the cecum and/or ileum Hormonal treatment (%) (cecum: n ¼ 4 patients; ileum: n ¼ 13 patients; cecum and ileum: 4 patients). So, for patients with rectal and/or sigmoid DIE lesions Mean number of previous surgeries 1.1 + 1.1 (range 0 – 4) (n ¼ 75), the rate of associated ‘right intestinal involvement' (ileum Preoperative painful symptoms scoresa,b,c and/or cecum) was 28% (n ¼ 21 patients) (Fig. 1).
7.8 + 1.9 (range 0 – 10) The sensitivity, speciﬁcity, PPV and NPV of TVUS and TRUS for the 5.3 + 3.0 (range 0 – 10) diagnosis of rectal wall involvement are presented in Table IV. TVUS Non-cyclic chronic pelvic pain 3.8 + 3.0 (range 0 – 10) and TRUS yielded a diagnosis of deep rectal endometriosis in 68 5.7 + 3.4 (range 0 – 10) (90.7%) and 72 patients (96.0%), respectively. The kappa test of con- Lower urinary tract symptoms 1.8 + 3.0 (range 0 – 10) cordance was 0.86 for TVUS and 0.96 for TRUS.
Mean implant score rAFSa,d 14.8 + 13.1 (range 4 – 46) Mean adhesion score rAFSa,d 29.2 + 26.8 (range 0 – 104) Mean total score rAFSa,d 44.0 + 35.7 (range 4 – 150) This prospective study demonstrates two points: ﬁrst, TVUS is accu- rate to diagnose intestinal wall involvement for patients with DIE and results are similar than those observed with TRUS; second, in cases of rectal DIE lesions, there are associated cecum and/or aData are presented as mean + SD.
ileum DIE lesions in 28% of the cases.
bSometimes more than one for the same patient.
c It is essential that these results, which agree with the conclusions of Visual analogue scale.
dScore according to the revised American Fertility Society Classiﬁcation (AFS, 1985).
two recent studies (Abrao et al., 2007; Bazot et al., 2007b), should betaken into consideration when treating DIE patients. If surgery isdecided, the DIE lesions must all be totally excised (Chapron et al., intestinal DIE lesions were associated with other DIE lesions (USL, 2003b; Chopin et al., 2005; Fedele et al., 2005; Vignali et al., 2005).
vagina, bladder, ureter).
Consequently, if there is any deep intestinal inﬁltration, a speciﬁc seg- The anatomic distribution of intestinal DIE lesions (163 lesions for mental intestinal resection procedure is required (Remorgida et al., 75 patients) is presented in Table III. All the patients presented a 2005; Abrao et al., 2008). Bowel segmental resection is by no Table II Distribution of patients according to main location of the DIE Associated lesions Values in parentheses are percentages.
aAccording to a previously published surgical classiﬁcation for DIE (Chapron et al., 2006).
bNumber of patients.
cNumber of histologically proven DIE lesions.
dEach lesion of bilateral pair counted as part of pair, so total number of individual lesions ¼ 212.
Bl, bladder; USL, uterosacral ligament; Va, vagina; Bl, bladder; Ur, ureter; In, intestine; R, right; L, left; B, bilateral.
Work-up for rectal wall involvement in deep endometriosis to establish a good basis for deciding on the treatment strategy in Table III Anatomic distribution of intestinal DIE agreement with her.
lesionsa in 75 patients Apart from its excellent diagnostic efﬁciency, TVUS has important advantages compared with TRUS. It is a less invasive means of inves- Intestinal DIE lesions tigation than TRUS, is cost-effective, familiar and well accepted by patients in obstetrics and gynecology, and can be used in all cases without anesthesia. Unlike TRUS, TVUS performs well for diagnosis 1.1 + 0.5 (range 0 – 4) of ovarian endometriomas (Bazot et al., 2007b), which are often 0.4 + 0.5 (range 0 – 2) associated with DIE lesions and must be considered as a marker for 0.1 + 0.4 (range 0 – 3) severity of the disease (Chapron et al., 2008). Furthermore, DIE 0.4 + 0.9 (range 0 – 6) lesions are frequently multifocal (Chapron et al., 2003b). In our experi- 0.1 + 0.3 (range 0 – 1) ence, intestinal DIE lesions are associated with other DIE locations 0.4 + 0.2 (range 0 – 1) (USL, vagina, bladder, ureter) in 93% of cases. TVUS gives better 2.7 + 1.5 (range 1 – 9) results than TRUS for the diagnosis of these associated DIE lesions, notably when there is inﬁltration of the USL and bladder (Bazot Some patients presented several intestinal DIE lesions.
et al., 2007b). Further work is required to establish whether TVUSshould be systematically combined in the future with water-contrastin the rectal lumen (Valenzano Menada et al., 2008) or saline solutionin the vagina (Dessole et al., 2003) and whether the use of ultrasoundtransmission gel improves the diagnosis accuracy (Guerriero et al.,2007). While, like others (Bazot et al., 2007b), we performed TVUSwithout bowel preparation, further studies will be necessary to ﬁndout if mechanical lower bowel cleansing using a rectal enema priorto the examination (Abrao et al., 2007) will improve TVUS accuracy.
Although TVUS is efﬁcient for the diagnosis of rectal involvement, this technique raises two controversial points. First, TVUS is anoperator-dependent procedure. Speciﬁc training for the practitionersis essential to understand the DIE TVUS imaging semiology. Sinceour radiologists came to the operating room to ﬁnd out for themselveswhat the problems facing us are and to understand the anatomy of theposterior pelvic compartment, we have seen better accuracy forthe imaging results. Second, intestinal DIE lesions are multifocal inthe digestive wall in almost one case out of two (Chapron et al., Figure 1 Intestinal endometriosis: the anatomic distribution oflesions in 134 patients with DIE.
2003b). In our experience, rectal lesions are associated with asecond intestinal lesion in 54.6% of cases (41/75) (Fig. 1). Similarly,rectosigmoid lesions are associated with ileo-cecum DIE lesions means an innocuous surgical procedure and presents a real risk of (cecum and/or terminal ileum) in 28% of cases (Fig. 1). These ‘high complications (Darai et al., 2007). This point is essential insofar as sigmoid' and/or ‘right bowel lesions' (cecum and/[E1]or ileum) will the patients concerned are young (32.1 + 5.0 years in this study) be more difﬁcult to diagnose with TVUS. Their frequency justiﬁes car- and present painful functional symptoms without any question of rying out a systematic complete intestinal work-up, since the number malignancy. Preoperative knowledge of the existence of intestinal inﬁl- and location of intestinal lesions governs the choice of surgical pro- tration is important in order to be able to inform the patient about the cedure. In case of a single intestinal lesion, and especially when it is various treatment possibilities together with their respective risks and isolated (without other associated DIE lesions in the bladder, the Table IV Sensitivity, speciﬁcity, positive and negative predictive value of TVUS and TRUS in the diagnosis of rectalinvolvement for patients presenting with DIE (n 5 134) PPV, positive predictive value; NPV, negative predictive value.
Piketty et al.
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Practice Problems for Test II Penicillin study. A biomedical research firm developed a new penicillin manufacturing process, and offered our company an exclusive right to use their method. The research firm provided us with their report. The penicillin yield (unit/mg) were measured for seven types of base blend (B1 to B7) to produce penicillin (see the box plots below). Method I and II refer respectively to the current method and the new method developed by the research firm.