COMPARISON OF POL YGLACTIC AND POLYGLYCOLIC ACID SUTURES IN REPRODUCTIVE TISSUE
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1 FERTILITY AND STERILITY Copyright 1977 The American Fertility Society Vol. 28, No. 11, November 1977 Printed in U.S.A. COMPARISON OF POL YGLACTIC AND POLYGLYCOLIC ACID SUTURES IN REPRODUCTIVE TISSUE DANIEL H. RIDDICK, M.D., PH,D,* CAMILLO T, DEGRAZIA, M,S, RONALD M, MAENZA, M,D, Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, and Department of Pathology, University of Connecticut School of Medicine, Farmington, Connecticut Polyglactic acid and polyglycolic acid suture materials were compared in rat uterine and abdominal wall tissues for inflammatory response and tissue fibrosis, By 90 days after surgery, the tissue inflammatory reaction and fibrosis were significantly less in response to polyglactic acid suture (Vicryl) in both uterus and skin as compared with the response to polyglycolic acid (Dexon), In addition, the over-all tissue response in skin was significantly greater than that in uterus for both suture materials, The potential importance of tissue fibrosis-particularly in oviductal surgery, over and above the formation of adhesions between one organ and another--is emphasized. It is concluded that (1) the magnitude of tissue response to suture material varies for different tissues, (2) the degree of tissue wall fibrosis does not necessarily correspond to external tissue adhesions, (3) adhesions are maximal at the surgical knots regardless of the suture material used, and (4) polyglactic acid suture material may be preferable to polyglycolic acid suture material for infertility surgery, in which a minimum of tissue reaction is imperative. It is well known that postoperative adhesions and general tissue reactivity are major factors involved in the failure or success of infertility surgery. Furthermore, it is recognized that tubal patency following a variety of oviductal plastic procedures does not result in conception or term pregnancies in many patients. Any alteration in technique or material resulting in decreased postoperative adhesions and tissue inflammatory response would offer the possibility of improving the rather discouraging results often obtained in tubal surgery. Polyglycolic acid (Dexon; kindly provided by Davis and Geck Division, American Cyanamid Co., Wayne, N. J.) has been recommended for infertility surgery as the least reactive suture material Received April 11, 1977; revised July 5,1977; accepted July 12, * Reprint requests: Daniel H. Riddick, M.D., Ph.D., Director of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Connecticut School of Medicine, Farmington, Conn available.' Polyglactic acid (Vicryl, Ethicon) has become available more recently, but its reactivity has not been compared with that of polyglycolic acid in reproductive tissues. Such a comparison should be carried out prior to the general acceptance of polyglactic acid as a suture material equivalent to polyglycolic acid for use in infertility surgery. This study was undertaken to compare the inflammatory response in reproductive tissues to polyglycolic acid and polyglactin. MATERIALS AND METHODS Forty mature virgin white rats were used for the study. They were divided into 2 groups of 20 rats each. One group was killed 14 days after surgery and the other group 90 days after surgery. The surgery involved a midline, lower abdominal, vertical incision under ether anesthesia and identification of the uterine horns. A 1-cm vertical incision was made in each uterine horn just above the bifurcation of the uterus. One horn was
2 Vol. 28, No. 11 POL YGLACTIC AND POL YGL YCOLIC ACID SUTURES IN REPRODUCTIVE TISSUE 1221 FIG. 1. Uterus, mild (1 +) inflammatory reaction at 14 days. The suture material is indicated by thearrow (hematoxylin and eosin, x32). sutured with polyglycolic acid suture and the other horn was repaired with polyglactin suture. Both materials correspond to U.S.P to mm diameter absorbable suture material. Thus, the quantity of suture material per unit length was equivalent for both materials. Similar atraumatic cutting needles were used with both suture materials. One-half ofthe abdominal wall incision was closed with the polyglycolic acid and the other half withpolyglactin suture. The skin was closed in a similar fashion with interrupted sutures. The same operator performed all procedures. All knots contained the same number of loops, and each incision was closed with the same number of nonlocking, running suture loops. Thus, reproducibility in terms of the surgical procedure was maximized. One-half of the animals were killed after 2 weeks, and tissue blocks were obtained from each uterine horn and from the upper and lower abdominal wall incisions. Care was taken to orient these blocks in reverse fashion to avoid the possibility of overlap of one suture material with the other for the abdominal wall tissue, The tissue blocks were- randomly numbered, fixed in 10% neutral buffered formalin, and embedded in paraffin; slides were made for histologic evaluation, using hematoxylin and eosin stain. All slides were read by the same pathologist, who did not have prior knowledge of which suture material was used in the tissue being read. The histologic evaluation, therefore, was made in a randomized, blind fashion. Tissue cuts were obtained so as to exclude suture knots and to have a similar amount of suture material in each section. The inflammatory response was graded from 0 to 4 on the basis of degree of inflammatory infiltrate and fibroblastic proliferation. Similar systems of grading tissue response have been reported previously.2,3 Cuts were made from different levels of each tissue, and the sections were read twice on separate occasions. The second group of 20 animals was killed at 90 days and the tissue was handled equivalently. Only after all tissue sections had been read and graded was the code broken and the results tabulated. Eight additional animals were studied by using either polyglycolic acid or polyglactic acid suture
3 1222 RIDDICK ET AL. to close the entire length of the abdominal incision to control for the possibility that the upper and lower portions of the incision might respond differently to the same suture material. These tissue blocks were also prepared 14 and 90 days after surgery and read in a randomized, blind fashion similar to that described above. RESULTS Figure 1 shows a representative section of November 1977 uterus 14 days after surgery. The area of fibroblastic response is limited and the cellular infiltrate is mild. An occasional giant cell can be seen. This is graded a 1 + reaction. Figure 2 shows a moderate to severe, or 3 + to 4 +, reaction in the uterus 14 days after surgery. The more extensive area of fibroblastic response and inflammatory cell infiltration is evident. Figure 3 shows a section of uterus obtained at 90 days demonstrating a mild, or 1 +, degree of tissue reaction. FIG. 2. Uterus, moderate to severe (3+ to 4+) inflammatory reaction at 14 days. The reaction consists primarily of mononuclear cells surrounding the suture material and extending for a considerable distance into the surrounding tissue. An early fibroblastic reaction is also present. The suture material is indicated by the arrow (hematoxylin and eosin, x32).
4 Vol. 28, No. 11 POL YGLACTIC AND POL YGL YCOLIC ACID SUTURES IN REPRODUCTIVE TISSUE 1223 The suture material is markedly degraded and the amount of fibrosis and inflammatory response is slight. Figure 4 shows a representative section of uterus obtained at 90 days demonstrating a moderate, or 3 +, degree of tissue reactivity. Giant cells are present, and the degree of inflammatory infiltration and fibroblastic response is significantly greater than that in the section shown in Figure 3. Sections obtained from the abdominal wall had a similar appearance except that the degree of inflammatory response was greater than that in the uterus. In Table 1 are compared the inflammatory reactions (graded on a scale of 1 to 4) to polyglycolic and polyglactin sutures at 14 and 90 days in uterus and skin. There was no difference in the response seen at 14 days in either uterus or skin. At 90 days the reaction to polyglycolic acid suture in both the uterus and the skin was significantly greater than the reaction to polyglactin, and more suture material remained undegraded in the tissue. The reaction seen in skin at both time periods and for both suture materials was greater than that seen in the uterus. Three FIG. 3. Uterus, mild (1 +) inflammatory reaction at 90 days. A few foreign-body giant cells are seen around fragments of residual suture material. The suture material is indicated by the arrow (hematoxylin and eosin, x 32).
5 1224 RIDDICK ET AL. November 1977 FIG. 4. Uterus, moderate (3 +) inflammatory reaction at 90 days. The suture material is surrounded by a mononuclear infiltration accompanied by foreign-body giant cells and fibrosis. The suture matl!rial is indicated by the arrow (hematoxylin and eosin, x32). animals in the 90-day study died prior to the completion of the study period. No suture site could be identified in an additional six animals at 90 days regardless of whether polyglycolic or polyglactin suture had been used. An attempt was made to quantitate the degree of adhesion formation found at necroscopy in each animal. All animals had slight to moderate adhesions, and no difference could be recognized for different suture materials. The one constant finding for both suture materials was that most of the adhesions had formed at the surgical knots. Finally, there was no histologic or gross difference between the upper portion of the abdominal wall closure and the lower portion when the same suture material was used for both portions. DISCUSSION A number of studies have appeared in the literature examining the response of various tissues to both polyglycolic acid and polyglactic acid We were unable to find a previous report investigating tissue response to either of these materials in TABLE 1. Histologic Grading" of Inflammatory Response to Polyglycolic (Dexon) and Polyglactic (Vicryl) Acid Suture Uterus 14 Days 90 Days Dexon Vicryl Dexon Vicryl 1.89 ± 0.15 b 1.95 ± ± ± 0.10 N = 20 N = 20 N=l1 N=l1 Nsr P < 0.05 "Sections were graded on a scale of 1 to 4. bvalues are means ± standard error. rns, Not significant. Skin 14 Days 90 Days Dexon Vicryl Dexon Vicryl 2.85 ± ± ± ± 0.19 N = 20 N = 20 N = 17 N = 17 NS P < 0.01
6 Vol. 28, No. 11 POL YGLACTIC AND POLYGL YCOLIC ACID SUTURES IN REPRODUCTIVE TISSUE 1225 female reproductive tissues, including tubes, ovaries, or uterus, animal or human. As was seen by a comparison of the tissue response in uterus and skin, there was a significant difference in the response of various tissues to the same suture material. Extrapolations from one tissue to another, therefore, are hazardous. Much attention has been given to the effect of adhesion formation between different tissues postoperatively, and to the deleterious effect these adhesions have on fertility. The importance of keeping the amount of exposed suture material to a minimum was demonstrated by the finding that most adhesions had formed at the site of the surgical knots. The importance of the inflammatory reaction and fibrosis within the wall of reproductive organs has been less well documented and appreciated. Extensive fibrosis in the wall of the oviduct could, for example, account in part for the difference observed between tubal patency and conception rates. This might also explain the relatively high rate of ectopic gestation seen after tubal surgery. Tubal motility, ovum transport, and physiologic tubal secretory activity might well be expected to be altered significantly by areas of extensive fibrosis in the tubal wall. We are currently investigating the relationship between intraorgan fibrosis in response to different suture materials, conception rates, and pregnancy outcome in an animal model. No similar studies could be found in the literature. REFERENCES 1. Garcia CR: Presented at the Thirtieth Annual Meeting of The American Fertility Society, Hollywood, Fla, April 4-7, Cutright DE, Beasley JD, Perez B: Histologic comparison of polyglactic and polyglycolic acid sutures. Oral Surg 32:165, Craig PH, WilliamsJA, DavisKW, MagownAD, Levy AJ, Bogdansky S, Jones JP: A biologic comparison of polyglactin 910 and polyglycolic acid synthetic absorbable sutures. Surgery 141:1, Watts DR, Carr SH, HohfRP: Poly(glycolic acid) sutures in canine vascular anastomoses. J Biomed Mater Res 10: 867, Axmith K, McCulloch C: A new synthetic suture: polyglycolic acid. Adv Ophthalmol 33:62, Milroy E: An experimental study of the calcification and absorption of polyglycolic acid and catgut sutures within the urinary tract. Invest UroI14:141, Bartholomew RS, Phillips CI, Munton CG: Vicryl (polyglactin 910) in cataract surgery. A controlled trial. Br J Ophthalmol 60:536, Auerbach R, Pearlstein MM: A comparison of polyglycolic acid (Dexon) nylon and silk sutures in skin surgery. J Dermatol Surg 1:38, Case GD, Glenn JF, Postlethwait RW: Comparison of absorbable sutures in urinary bladder. Urology 7:165, Shelor WC Jr, Witherington R: Comparison of polypropylene and polyglycolic acid suture in experimental vasovasostomy. Invest Urol 13:223, NuwayserES, WuTC,HotchkissRS,FarconEE,HulkaJJ, Mohr K, Poddar A: An absorbable artificial vas deferens for vasovasotomy. Trans Am Soc ArtifIntern Organs 21: 523, 1975 Acknowledgment. Special appreciation is expressed to Ms. Linda Hrubiec for her patience and skill in preparing the manuscript.
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