0022-5347 /85/~336-1087$02.00/D THE JOURNAL
Copyright\~' 1985 by The ',Nillia.ms & VVilki:ns Co.
ARIOUS AGENTS ON VAS DEFERENS
PATENCY ROBERT A. BERTRAM, CULLEY C. CARSON*
From the Department of Surgery, Division of Urology and the Department of Pathology, Division of Surgical Pathology, Duke University Medical Center, Durham, North Carolina
Vasography is a common diagnostic procedure utilized in evaluating the male genital tract for causes of azoospermia, for evaluation of persistent perineal pain and seminal vesiculitis, and recently used in the staging of prostate cancer. In order to evaluate the effects of injectable agents on the healthy vas deferens, 7 groups of 10 rats had the left vas deferens injected by vasopuncture with saline, 4 contrast agents, doxycycline and absolute alcohol. The animals were sacrificed 8 weeks later, and were examined for patency of the vas and inflammatory response. Results revealed that vasopuncture did not produce obstruction. Vasography with water-soluble contrast media does entail a low risk of inflammation in the rat, but produces no obstruction. Intra-vas injection of doxycydine, injected by some for treatment of chronic seminal vesiculitis and perineal pain, is not deleterious in the rat model.
Vasography, a common diagnostic procedure since 1913, is being utilized for evaluation of obstructive azoospermia, staging of prostate cancer, and in the evaluation and treatment of persistent perineal pain. 1 Some have used doxycycline instilled into the vas deferens, filling the ampullae and seminal vesicles in an attempt to relieve persistent perineal pain. 2 Results of vasographies are often reported without regard to the possible deleterious effect of vas obstruction. Conflicting reports exist in the literature regarding the effects of various contrast media on vas patency. In this study, we evaluated the effect of various agents on vas patency and inflammation in an animal model.
Accepted for publication February 12, 1985. *Requests for reprints: Duke University Medical Center, Box 3274, Durham, NC 27710. Read at Annual Meeting of the Southeastern Section, American Urological Association, Nashville, Tennessee, 1984.
Renograffin 76 Pant opaque
MATERIALS AND METHODS
Under ether anesthesia, 7 groups of 10 Wistar rats (125 to 175 gm.) had the left vas deferens injected with either saline, metrizamide, Renograffin Renograffin 76, Pantopaque, doxycycline or absolute alcohol respectively (fig. The right vas in each animal was exposed, but no injections were made, and thus was used as a sham operation in each animal. A transverse scrotal incision was made just inferior to the base of the penis, exposing both the and left vas. The left vas was identified and vasopuncture was n,ortn,,.rn,Prl in the manner described by Paulson et using a 25 gauge vein needle, 3 2 mL of the various agents 'Nere until fluid from the penis vvas noted. The pressure of injection was not measured. No evidence of extravasation was noted, and a suture was in the nPrn,,c.Q» connective tissue 4-0 to the site of The vas was then 1dEmt1fil2d, and a 4-0 nylon suture vvas placed in the perivasai connective tissue to mark the location of exposure and mobilization, The animals were sacrificed 8 weeks after the injection, and the vasa were examined for patency and inflammatory response (table From the resected vasa, at least 4 sections were examined, one from either end of the resected specimen and 2 from the midportion. Tissue samples were fixed in 10 per cent formalin, paraffin embedded, cut at 5 ,um. thickness and stained with hematoxylin and eosin. A portion of unaffected vas is displayed in figure 2. A mild inflammatory response included only minimal infiltration by neutrophils or lymphocytes, without obstruction or significant
Metrizamide Renograffin 30
Doxycycline Absolute ETOH
V R Co11trol
FIG. 1. Surgical technique for vas deferens injection.
L Vas reaction from injected agents
Sham Saline Metrizamide Renograffin 76% Renograffin 30% Pantopaque Vibramycin Absolute Alcohol
0 0 0 0
10 10 10 10 10 9
0 2 0 7
2 0 1 0 l
alteration of the lumina, epithelial lining or muscularis. Intraluminal abscess referred to the collection of neutrophils within the lumen, without evidence of permanent obstruction, stricture, or involvement of the epithelial lining or muscularis (fig. 3). Granulomatous inflammation with obstruction was defined as noncaseating granulomatous inflammation with multinucleated giant cells, neutrophils, lymphocytes and plasma cells causing metaplasia of the surface epithelium (fig. 4). Inflam-
BERTRAM, CARSON AND SZPAK
FIG. 2. Section of unaffected vas demonstrating patent lumen. (Hematoxylin and eosin, X255).
FIG. 3. Vas injected with Renograffin 76%. Collection of neutrophils is present within lumen. Surrounding muscular layers demonstrate infiltration by lymphocytes and some neutrophils. (Hematoxylin and eosin, X255).
mation and fibrosis of the wall resulted in accumulation of spermatozoa (fig. 5). RESULTS
One animal in the absolute alcohol group died on the first postoperative night; all others survived the full 8 weeks of the study. In the midportion of all specimens, the suture material in the perivascular connective tissue created a localized foreign body reaction, without affecting the adjacent walls or lumina of the vasa. In no animal was the response to suture material contiguous with observed changes in the vasa. The saline-injected group showed mild, acute and chronic inflammation in one animal on the injected side, left vas, and in 2 animals on the right or sham side. All lumens were patent and no abscesses were seen in this group. Metrizamide, a water soluble, non-ionic contrast material, produced no inflammatory reaction on the injected side in any animal. Renograffin 76 per cent, a water soluble contrast media, produced mild chronic inflammation in one injected vas deferens, and acute and chronic inflammation with intraluminal abscess formation in the injected vas deferens of 2 animals (fig. 3). No inflammation was encountered in the Control right vas deferens of any animal. Renograffin 30 per cent, a more dilute water soluble contrast media, produced acute and chronic inflammation in the injected vas of only one animal, with no visible inflammation or reaction noted in any of the right vas deferens. Pantopaque, an oil-based contrast agent, was associated with obstructive sperm granulomas in the left vas of 2 animals and an intraluminal abscess without obstruction in the left vas of another. Doxycycline produced no obstruction, inflammation or abscess formation in any of the animals. Absolute alcohol caused obstructing sperm granulomas in seven of nine animals on the injected side (figs. 4 and 5), with intraluminal abscess formation without obstruction in one additional animal. No sperm granuloma or obstruction was noted in any sham operated vas deferens. Vasopuncture alone did not produce vasal obstruction in this study, since no obstruction or inflammation was encountered in the group injected with normal saline.
FIG. 4. Section of vas injected with absolute alcohol demonstrating obstruction by spermatozoa and band of granulomatous inflammation. (Hematoxylin and eosin, x48).
Vasography is most commonly used for evaluation of severe oligospermia or azoospermia in infertility evaluations. Obstruction is a potentially correctable cause of post-germinal infertility; therefore, vasography is a necessary diagnostic modality. 5 At least one patent vas is necessary for sperm transport, and since vasography has been thought to result in stenosis of the
FIG. 5. Higher power of same obstructed vas demonstrating multinucleate giant cells (M), neutrophils (N) and masses of sperm (S). (Hematoxylin and eosin X375).
VASOGRAPHY: EFFECT GN VAS DEFERENS PATENCY
vas, unilateral studies have been recommended.4 Usually vasography is performed at the same time as testis biopsy. Some authors feel that vasography may cause scarring and stenosis, and therefore recommend it be performed at the same time as any planned bypass procedure. 6 Seminal vesiculography is sometimes used in evaluation of chronic perinea! pain, or for demonstration of infectious processes of the seminal vesicle. 7 Paulson has noted clinical improvement in 6 of 11 patients undergoing instillation of doxycycline (10 mg.Jee) into the vas deferens, filling the ampullae and seminal vesicles for persistent perinea! pain and postejaculatory discomfort. 2 However, use of this instillation in men during the reproductive years was contraindicated because of possible vasal stenosis caused by this tetracycline derivative. Doxycycline was found to cause no inflammation or lumen occlusion in this study. Cancer of the prostate may extend into the ejaculatory ducts even before it can be suspected by rectal examination. Prostatic cancer causes a narrowing of the lumen of the ejaculatory ducts, which have rigid and irregular contours, whereas in benign prostatic hypertrophy the ejaculatory ducts may be dilated because of pressure upon the verumontanum, but are usually symmetrical and regular. 8 Extension to the seminal vesicles with concomitant alteration in the vasogram would mean extracapsular extension, and would defer surgical treatment for this Stage C cancer. 9 Vasography in this group of patients can, also, be safely performed. Vasography is certainly not without risk. The major potential complication is occlusion of the vas. Most series of vasography are reported with little attention to this risk. Gordon and Clahassey evaluated vas deferens stricture formation after vasography in 50 guinea pigs, and found that 94 per cent showed no significant stenosis and implicated technical factors in those with obstruction. 6 They used 60 per cent Hypaque contrast and found that histologically significant inflammatory response was noted in only one of 50 animals. Fourcade and Jardin reported that the use of hypertonic contrast medium is not deleterious to the vas deferens, and the necessity of washing out the vas deferens with normal saline is far from obvious, as vas peristalsis clears the contrast medium by itself within a few hours. 9 Wagenknecht et al. sectioned the rat vas deferens and injected various contrast media into the distal portion of the vas, and then ligated both segments. 10 They examined the vas 3 to 4 months later, and felt that all contrast media induced a pronounced inflammatory response within the vasal wall. The wall and lumen of the vas deferens showed fewer abnormalities with lower concentrations of contrast media and more water soluble contrast media. These authors, therefore, recommended that only hydrophilic contrast media of low concentration be used
complete obstruction for vasography in humans. In this from sperm granuloma was noted, as expected, in the absolute alcohol group. Pantopaque, an oil based media, was associated with sperm granulomas in 2 of 10 animals. The water-based contrast media of different concentrations were not associated with significant inflammation, granulomas or compromise of patency in any animals. This result was in contrast to the finding of Wagenknecht. The difference in these results could have been due in part to the different modelso By dividing and ligating the vas deferens, they may have prevented normal vas peristalsis and seminal flow with clearing of injected fluid by this normal vasal flow. The lack of antegrade flow, as in obstruction, may enhance the inflammatory effects of these agents. In the rat model, vasography using water soluble contrast media is a safe procedure with only a low risk of inflammatory response. In extrapolating this to use in humans for diagnosis of obstructive azoospermia, staging of prostate cancer and evaluation of infectious processes involving the seminal vesicles, one should remember that the rat vas is thinner and more transparent than the human vas, and therefore is easier to cannulate and to be sure of intraluminal presence of the needle. In addition, the instillation of doxycycline into the vas deferens seems to have no ill effect on the patency of the vas deferens in the rat model. REFERENCES 1. Bellfield, W. T.: Skiagraphy of the seminal ducts. JAMA, 60: 800,
1913. 2. Paulson, D. F.: Pelvic pain syndrome in the male. U:rologist's Correspondence Club, March 19820 3. Paulson, D. F., Lindsey, C. M. and Anderson, E. E.: Simplified technique for vasography. Fertil. Steril., 25: 906, 1974. 4. Ford, K., Carson, C. C., Dunnick, N. R., Osborne, D. and Paulson, D. F.: The role of seminal vesiculography in the evaluation of male infertility. Fertil. Steril., 29: 180, 1978. 5. Carson, C. C.: Transurethral resection for ejaculatory duct stenosis and oligospermia. Fertil. Steril., 41: 482, 1984. 6. Gordon, J. A. and Clahassey, E. B.: Evaluation of stricture formation as a complication of vasopuncture and vasography in the guinea pig. Fertil. Steril., 29: 180, 1978. 7. Banner, M. P. and Hassler, R.: The normal seminal vesiculogram. Diag. Radio!., 128: 339, 1978. 8. Hebert, G., Bouchard, R. and Charron, J.: Vasoseminal vesiculography. AJR, 113: 735, 1971. 9. Fourcade, R. and Jardin, A.: Vaso-vesiculography: assessment in andrology and urology. Arch. Androl., 6: 273, 1981. 10. Wagenknecht, L. Vo, Becker, H., Langendorff, RM. and Schafer, H.: Vasography-clinical and experimental investigations. Andrologia, 14: 182, 1982.