Human Reproduction vol 11 no. 10 pp.2130-2133, 1996 Comparison of in-vitro falloposcopy with tubal histology in the diagnosis of Fallopian tube pathology S.Rimbach1, D.Wallwiener, C.Barth, D.Heberling and G.Bastert Department of Obstetrics and Gynecology, Vosstrasse 9, University of Heidelberg, D-69115 Heidelberg, Germany 'To whom correspondence should be addressed In order to assess the diagnostic quality of falloposcopy in relation to pathomorphology, a consecutive series of 30 Fallopian tubes obtained from surgical salpingectomy cases were prospectively examined by in-vitro falloposcopy and histology. Falloposcopy was performed using an over-thewire catheterization system and a 0.5 mm falloposcope with 3000 pixels. Assessment of the specimens included the description of lumen geometry, intraluminal changes and status of the mucosal surface. Falloposcopy classified 14 tubes as normal and 16 pathological. Histology resulted in 17 normal versus 13 pathological tubes. Pathologies included lumen obstructions and dilatations, intraluminal synechiae and mucosal damage. Sensitivity and specificity of falloposcopy were calculated to be 0.85 and 0.71; positive and negative predictive values were 0.69 and 0.86. It was concluded that falloposcopic findings indeed reflect and successfully differentiate normal and pathological conditions allowing adequate and reproducible image interpretation. However, variations of the diagnostic accuracy with the type of pathology and the tubal segment have to be taken into account before clinical consequences are drawn from a falloposcopic investigation. Key words: falloposcopy/infertility/reproductive surgery/tubal endoscopy Introduction First attempts to visualize intraluminal pathology in tubal sterility date back to the year 1970, when Mohri et al. (1970) described the use of a flexible glass fibre endoscope for intratubal observations. More than a decade later, the method started to gain clinical importance, mainly with the work of Henry-Suchet et al. (1981, 1985), Cornier (1982) and Brosens et al. (1987), who used tuboscopy to predict reproductive outcome and the chances of tubal reconstructive surgery. Whereas they approached the tube by its distal end, limiting the tuboscopic evaluation to fimbria and ampulla, a transcervical access was described in 1990 by Kerin et al (1990), allowing visualization over the entire tubal length including intramural and isthmic segments. This technique has since been referred to as falloposcopy. Already, a number of reports exist in the literature 2130 establishing clinical scores for falloposcopic findings (Kerin et al., 1992; Lower et al., 1992; Dunphy and Pattinson, 1994; Rimbach et al, 1994). However, so far, no study has systematically evaluated falloposcopic images in comparison to histopathology. This verification, however, seems of utmost importance to ensure reliable and reproducible image interpretation. Falloposcopy is on the threshold of becoming an important infertility investigation technique, but its ability to describe intraluminal findings adequately, especially to differentiate accurately normal and pathological tubal conditions, has yet to be proved. The aim of the present study was therefore to assess the diagnostic quality of falloposcopy in relation to histomorphology. Material and methods Specimens A consecutive series of 30 Fallopian tubes were prospectively examined by falloposcopy and histology (Table I). The tubes were obtained from hysterectomy cases (n = 11), unilateral salpingectomies (n = 6) and proximal tubal microsurgery for sterilization reversal (n = 8) or proximal occlusion (n = 5). Falloposcopy procedure Falloposcopy was performed in vitro immediately after removal of the organ using an over-the-wire catheterization system and a 0.5 mm falloposcope with 3000 pixels (Conceptus Inc., San Carlos, CA, USA) under conunuous fluid irrigation with Ringer's solution. Falloposcopic findings were instantly recorded on standardized documentation sheets. Histology The procedure lasted <5 min overall time per tube and the specimen was then immediately fixed in formalin before histological preparation. After paraffin embedding, routine histological serial cuts from the different tuba! segments (intramural, isthmic, ampullary and fimbrial) as available were stained with haematoxylin and eosin for bght microscopy The histologist was blinded to the result of the falloposcopy Table L Sources of specimens for in-vitro falloposcopy Hysterectomy + salpingectomy 11 Unilateral salpingectomy Microsurgery for stenlizaiion reversal Microsurgery for proximal occlusion Total 5 30 O European Society for Human Reproduction and Embryology Falloposcopy versus tubal histology Table H. Morphological assessment cntena and parameters as applied during falloposcopy and for histology Lumen geometry regular obstructed obliterated dilated debns/plug polyp synechiae (thin/solid) septation intact atrophic disturbed intact reduced Intraluminal findings Status of the mucosal surface Fold architecture Table HI. Diagnoses of normal versus pathological tubes according to the results of falloposcopy and histology Falloposcopy Histology Normal Pathological 14 17 16 13 False negative False positive Figure 1. Falloposcopic picture of a normal ampulla. •Endometnosis with moderate dilatation (n = 1), inflammatory epithelial proliferations (n = 1) "Mucosal atrophy (n = 5, four isthmic, one ampullary), one case including thin synechiae Analysis Assessment of the specimens used the same descriptive morphological cntena for both methods, falloposcopy and histology the lumen geometry was recorded as regular, obstructed, obliterated or dilated; the presence of intraluminal changes and the status of the mucosa were recorded (Table II) Biometncal analysis included the determination of sensitivity and specifity of falloposcopy as well as calculation of negative and positive predictive values Results Falloposcopic findings As Table EH shows, 14 of 30 tubes were found by falloposcopy to have a non-dilated, patent lumen, intraluminal findings absent, giving the visual impression of an intact mucosal layer characterized by a velvet-like, smooth surface and, depending on the tuba! segment, floating primary and secondary mucosal folds. Those tubes were described as normal (Figure 1). The other 16 tubes appeared pathological Two were found to have a distally dilated lumen, one appeared proximally obstructed and two were completely obliterated. Intraluminal findings in four tubes showed filmy synechiae, and in one tube, solid synechiae crossing the lumen (Figure 2). In 14 tubes the mucosa was described as flattened along with reduced fold structures in five tubes (Figure 3). Thus, among the 30 tubes evaluated, 14 were considered normal and 16 pathological by falloposcopy. Histological diagnosis Histology revealed 17 normal and 13 pathological tubes (Table HI) The pathological specimens included seven sactosalpmges, Figure 2. Falloposcopic picture of solid intraluminal synechiae three cases of tuba! endometnosis, two cases of tuba! fibrosis and one case of salpingitis isthmica nodosa. All 17 normal cases were characterized by patent lumina with regular diameter, absence of intraluminal findings, predominantly cylindrical epithelium and the presence of well vascularized pnmary and secondary fold structures distributed according to the anatomical segments of the tube. The pathological diagnoses were associated with lumen dilatation in seven cases (five distal, two proximal), obstruction in two cases (proximal) and obliteration in one case (proximal), intraluminal synechiae in seven cases (including four cases of thin non-vascularized formations and three cases of solid vasculanzed pseudofollicular septations), flattening of the mucosa in eight cases (among those seven in isthmus and ampulla, one in isthmus), disturbed mucosal structure in 2131 S.Rimbacta el at were concerned in detail, lumen patency was correctly diagnosed in all cases with only one case of subtotal fibrotic obstruction incorrectly-diagnosed as obliteration. In contrast, dilation of the lumen was correctly described only in two cases but missed in five cases. Intraluminal falloposcopic findings were confirmed by histology in three of four cases of synechiae, but only one of three cases of solid septation apparent in the histological specimens was correctly described by falloposcopy. In 14 falloposcopic diagnoses of flattened mucosa, only eight could be verified by histology. No case of mucosal atrophy described in histology was missed by falloposcopy, whereas four mucosal changes by inflammation and endometnosis were not detected in falloposcopy. Five cases of reduced fold architecture in the ampullary part were confirmed histologically, but two cases of histologically diagnosed fold destruction along with septation were missed by falloposcopy Figure 3. Falloposcopic picture of partial mucosal atrophy in a sactosalpinx Table IV. Test quality parameter and predictive values of falloposcopy in comparison to histology as a reference Test parameter P value Sensitivity (%) Specificity (%) Positive predictive value Negative predictive value 0.85 071 0 69 0 86 four cases (two luminal endometriosis and two inflammatory epithelial proliferative changes) and reduced fold structures in seven cases. In addition, histology revealed a number of pathologies not interfering with the lumen side of the examined tubes. Among these, there was one case of tubal wall endometnosis, one case of subserosal endosalpingiosis, four cases of thickened muscular layer and one case of fibrotic changes within the wall not extending towards the mucosa. In one case, Walthardcell nodules were found in the subserosal layer. Comparison of falloposcopic and histological data The falloposcopic diagnosis of normal was therefore correct in 12 tubes and false in two, missing in one case endometriotic infiltration of the isthmic mucosa along with moderate dilation, in one other inflammatory epithelial proliferations within an otherwise normal mucosa. The diagnosis of pathological was correct in 11 tubes and false in five. In all five cases the mucosa was described atrophic, four times in the isthmic and one time in the ampullary region. In one case, thin intraluminal synechiae were additionally seen not being confirmed by histology. As a result, sensitivity and specifity of the procedure were calculated as 0.85 and 0.71 respectively; positive and negative predictive values were 0 69 and 0.86 (Table IV). As far as the different morphological evaluation criteria 2132 Discussion The results of the present study suggest that falloposcopy allows differentiation of normal and pathological tubal conditions in reasonable agreement with histology. Nevertheless, inherent limitations of the method as well as typical traps for possible misinterpretation of falloposcopic images became equally apparent A careful interpretation of the results given above and discussed below certainly needs to take into account the in-vitro setting of the study. Whereas ln-vivo falloposcopy allows successful intraluminal visualization only in a variable percentage of the cases, the m-vitro examination usually results in technically sufficient quality. The organ can easily be manipulated and white-out, vision-disturbing light reflexes etc. can be eliminated. On the other hand, artefacts are potentially caused by the in-vitro situation such as tubal dilatation. Therefore the results of m-vitro falloposcopy may not reflect in-vivo images in all cases. Histologically confirmed endotubal pathologies were detected by falloposcopy with a high sensitivity of 85%, a result corresponding to earlier data by Hershlag et al. (1991), whose observations were restricted to distal salpingoscopy but who also found a good relationship to histological findings for severe pathologies. The positive predictive value of 69% in our study, however, indicates that the diagnosis 'pathological' can only be considered true in about two thirds of cases. Whereas the diagnosis 'normal' is correct in 86% of cases (negative predictive value), pathologies were falsely described in morphologically normal tubes in almost 30% of the cases. For example, it proved most difficult to discriminate atrophic from normal mucosa in the proximal tube. Folds, as the most reliable parameter for interpretation, are physiologically flat and rare in this segment of the tube, and the mucosa gives an impression of atrophy per se with its even surface in a tunnelshaped geometry. In contrast, the diagnoses of severe lesions such as obstructive fibrosis or intraluminal synechiae were usually Falloposcopy versus tuba] histology accurate, both in the intramural and isthmic tubal segments. In particular, the reproducible diagnosis of synechiae may be of utmost clinical importance, since Dunphy and Greene (1995) have shown a significant association between intraluminal adhesions and the occurrence of ectopic pregnancy. Tubal wall pathologies, well known for their prognostic impact (Fortier and Haney, 1985; Wiedemann et al., 1987), may be associated with intraluminal lesions and then accessible for falloposcopic diagnosis. If strictly localized within the wall, as observed in cases of subacute and chronic inflammation, endometriosis and also fibrosis, they are, however, missed by falloposcopy for obvious reasons. Another clinically most important limitation to falloposcopic investigation became apparent during this study. Septations in high degree sactosalpinges, also known for their important clinical impact (De Bruyne et al, 1989), were easily misinterpreted, considering that one of the compartments is only the tubal lumen surrounded by flattened epithelium. Depending on the clinical situation, the diagnostic assessment of both proximal as well as distal tubal disease may therefore require complementary methods such as laparoscopic and salpingoscopic inspection for complete information. In conclusion, the present study shows that falloposcopic findings indeed reflect and successfully differentiate normal and pathological conditions of the Fallopian tube. The use of defined pathomorphological criteria allows adequate and reproducible image interpretation. The accuracy of the interpretation and therefore the diagnostic quality of the method varies, however, with the type of pathology and the tubal segment. Both have to be taken into account before clinical decisions are made from a falloposcopic investigation. Lower, A , Magurness, S , Djahanbakhch, O and Grudzinskas, J (1992) Transcervical tuba] endoscopy (falloposcopy) - a clinically useful tool? GynaecoL Endosc, 1, 155—158. Mohri, T, Mohn, C and Yamadon, F. (1970) Tubaloscope flexible glass fibre endoscope for intratubal observations Endoscopy, 2, 226 Rimbach, S., Wallwiener, D. and Bastert, G (1994) Tuben-Endoslcopiemirumal invasive Diagnostik bei gestorter Eileiterfunktion Minimal Invasive Medrnn, 5, 9-12 Wiedemann, R, Scheidel, P., Wiesinger, H and Hepp, H (1987) Die Pathologie des proximalen Tuhenverschlusses - morphologische Auswertungen Gebunsh. FrauenheiUc, 47, 96-100 Received on October 26, 1996, accepted on July 31, 1996 References Brosens, I., Boeckx, W., Delamn, Ph et aL (1987) Salpmgoscopy: a new preoperative diagnostic tool in tubal infertility? Br J Obstet Gynaecol, 94, 722-728 Cornier, E (1982) La fibroscopie en gynecologie la fibrohysteroscopie et la fibrotuboscopie Nouv. Prtsse Med, 11, 2841-2843 De Bruyne, E, Puttemans, P, Boeckx, W and Brosens, I. (1989) The clinical value of salpmgoscopy in tuba) infertility FertiL StenL, 51, 339-340 Dunphy, B and Greene, C (1995) Falloposcopic carinulauon, oviductal appearances and prediction of treatment independent intrautenne pregnancy Hum. Reprod, 10, 3313-3316 Dunphy, B and Pattinson, H A (1994) Office falloposcopy, a tertiary level assessment for planning the management of infertile women AusL N. Z. J ObstcL GynecoL, 34, 189-190. Fortier, K J and Haney, A F (1985) The pathologic spectrum of uterotubal junction obstruction. 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