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Differential Effects of Surgical Suture Materials in 1,2-Dimethylhydrazine- Induced Rat Intestinal Neoplasia1

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Differential Effects of Surgical Suture Materials in 1,2-Dimethylhydrazine- Induced Rat Intestinal Neoplasia1 •t,F [CANCER RESEARCH 44, 2827-2830, July 1984] Differential Effects of Surgical Suture Materials in 1,2-Dimethylhydrazine- induced Rat Intestinal Neoplasia1 Ronald N. Calderisi and Hugh J. Freeman2 Department of Medicine (Gastroenterology). University oíBritish Columbia Faculty of Medicine and Cancer Research Center, Vancouver, British Columbia V6T 1W5 Canada ABSTRACT bowel tumors. The cecum was selected for suture placement, since this is a relatively resistant site to tumor development in The incidence, distribution, size, and histopathology of rat this animal model. The results indicate that specific types of small and large bowel tumors induced by sequential administra suture materials promote tumor induction locally in the rat cecum, tion of 1,2-dimethylhydrazine followed by cecal placement of one while stainless steel significantly increased tumors at a distal of six differing types of suture materials were systematically colonie site "downstream" from the cecum. examined. In addition, measurements of /3-glucuronidase activi ties in large bowel contents followed by fecal trace metal deter minations were done. The results indicate that specific slowly MATERIALS AND METHODS absorbed and nonabsorbable suture materials in the absence of Animals and Diets. Weaned male Wistar rats (Simonsen Laboratories, a surgical anastomosis promote tumor induction locally in the rat Inc., Gilroy, CA) weighing 140 to 160 g were administered water ad cecum. In addition, cecal suture material composed of multifila- libitum at all times and standard laboratory chow pellets (Ralston Purina ment stainless steel wire enhanced tumor development at a Co., St. Louis, MO). Rats were randomly assigned to one of 7 groups "downstream" site in the distal colon, paralleling increased fecal using suspended wire mesh cages to reduce coprophagia. Relative /3-glucuronidase activities at this site and implicating a possible humidity and environmental air temperature were constant, and a 12-hr luminally mediated mechanism for colon tumor development in light-dark cycle was imposed in a carcinogen containment animal facility. Carcinogenesis. All rats were weighed weekly and received 1,2- this animal model. dimethylhydrazinedihydrochloride (Aldrich Chemical Co., Milwaukee, Wl) administered as 12 weekly s.c. 25-mg/kg injections. This was prepared INTRODUCTION as a 0.5% solution in 1 mM EDTA (Mallinckrodt, Inc., St. Louis, MO) adjusted to pH 6.5 with sodium bicarbonate. Previous studies had The use of carcinogen-induced animal models to examine established this as an effective regimen in our laboratory for small and factors that may influence the pathogenesis of gastrointestinal large bowel tumor induction (8,9,18). neoplasia is well recognized (1). The effects of various dietary Surgical Procedures. All animals were anesthetized with an i.p. factors, such as dietary fiber (4, 8, 9), as well as the influence of injection of pentobarbital (50 mg/kg body weight) and underwent lapa- various surgical procedures (17,18,26,27) have been examined. rotomy 6 weeks after the last carcinogen injection using the methods of In the past, the concept that chronic mucosal injury may promote Lambert (11). In 6 of the 7 animal groups, a single 3-0 suture was tumor development in the gastrointestinal tract has emerged inserted from serosa through mucosa to serosa, and a triplicate tie was securely applied with care to avoid tissue contraction or injury. All sutures largely from clinical observation. Increased colon cancer rates are reported in long-standing ulcerative colitis (6), foreign bodies were placed within 1 cm of the cecal tip on the antimesenteric aspect approximating the site of the appendix in humans. Suture groups in (23), fistulae (20), inflamed diverticulae (2), and long-standing cluded: surgical gut (absorbable; Ethicon Chromic; Ethicon Sutures, Ltd., tubercular (3) and amebic (5) lesions and observed to complicate Peterborough, Ontario, Canada); polyglycolic acid (absorbable, braided, ureterosigmoidostomy (13, 22). In recent years, a high incidence synthetic; Dexon "S"; American Cyanamid Co., Pearl River, NY); Poly- of tumors localized to anastomotic suture lines has been reported glactin 910 (absorbable, braided, synthetic; Ethicon Vicryl; Ethicon Su following small bowel or colon surgery in animals administered tures, Ltd.); surgical silk (nonabsorbable; Ethicon Silk; Ethicon Sutures, chemical carcinogens (17, 18, 26, 27). Possible mechanisms Ltd.); polypropylene (nonabsorbable, monofilament; Ethicon Prolene, suggested to explain these observations have included mucosal Ethicon Sutures, Ltd.); and stainless steel (nonabsorbable, multifilament hyperplasia frequently observed in animal intestine near anasto wire; Flexon; American Cyanamid Co.). Table 1 summarizes composition and properties of the different suture types. The abdominal wall was moses (17, 26) and chronic irritation induced by nonabsorbable then closed in all groups in 2 layers with 3-0 Dermalene monofilament foreign bodies (14, 17). However, no systematic study, to our polyethylene suture (American Cyanamid Co.). knowledge, has addressed the specific role, if any, of differing Necropsy Studies. Four weeks following surgery, animals were ad suture materials per se in experimental intestinal neoplasia. ministered an overdose of i.p. pentobarbital, and autopsies were carefully In this paper, the effects of 6 different classes of suture performed. The distribution, size, and incidence of small and large bowel materials were examined in rats initially treated with 1,2-di- tumors were recorded. Each tumor detected was oriented separately on monofilament mesh, placed in separate vials containing modified Bouin's methylhydrazine, an agent that induces both small and large fixative (750 ml aqueous saturated picric acid-250 ml 38% formaldehyde- 10 ml glacial acetic acid), embedded in paraffin, sectioned, and stained 1Supported by the National Cancer Institute of Canada and the Canadian with hematoxylin and eosin. Foundation for lleitis and Colitis. Fecal Enzymes. Fecal samples from cecum and distal colon in each 2 Recipient of Research Grant MA 6918 from the Medical Research Council of group of rats were individually collected at the time of the autopsy and Canada. To whom requests for reprints should be addressed, at Gastroenterology, processed as described by Reddy ef al. (15). ß-Glucuronidase activity ACU F-137, U. B. C. Health Sciences Center Hospital, 2211 Wesbrook Mall. Vancouver, British Columbia, Canada. was quantitated colorimetrically at 550 nm with a Bausch and Lornb Received April 26, 1983; accepted April 2, 1984. Model 710 spectrophotometer (Bausch and Lomb, Inc., Rochester, NY) JULY 1984 2827 Downloaded from cancerres.aacrjournals.org on October 5, 2021. © 1984 American Association for Cancer Research. R. N. Calderisi and H. J. Freeman Table 1 Suíurematerialsand properties Suture" Type Source Properties Surgical gut Chromic Collagenfrom animalintestine Absorption rapid; minimaltissue re treated with chromic salt solu- action tion PolyglycolicacidPolyglactin910Surgical homopolymerof gly- absorbed; minimaltissue re cohcacidSynthetic actionPolyglycolic copolymer of lactide acid more rapidly ab andglycolideRaw 910Verysorbed than Polyglactin silkPolypropyleneStainless silk, a natural protein fiber slowly absorbed; moderate tis silkwormPolymerspun by the suereactionNonabsorbable: ofpropyteneLow minimaltissue reac tionNonabsorbable; steelBraidedBraidedBraidedMonofilamentMultielementSyntheticcarbon-iron alloySlowly minimaltissue reac tion " All 3-0 size sutures; see text. 6 See Ref. 19. Table 2 Tumorfrequency in small and large bowel tumorsGroup8Control All bowel tumorsNo.bowel tumorsNo.bowel of of of of tumors/ of tumors/ ofanimals10(100)tumors/ animals10(100)"animal7.2±1.6Canimals9 animal1.7 animal5.5 (90) ±0.5 ±1.3 Surgicalgut 10(100) 5.6 ±0.7 8 (80) 1.7 + 0.4 9 (90) 3.9 ±0.8 Polyglycolicacid 10(100) 6.6 ±1.5 8 (80) 1.3 ±0.3 9 (90) 5.3 ±1.4 Polyglactin910 10(100) 6.4 ±0.7 10(100) 2.3 ±0.4 10(100) 4.1 ±0.4 Surgical silk 10(100) 6.4 ±0.6 8 (80) 1.6 ±0.4 10(100) 4.8 ±0.5 Polypropylene 10(100) 8.7 ±1.5 8 (80) 2.0 ±0.6 9 (90) 6.7 ±1.1 11.8 ±1.5"Small Stainless steelNo. 10(100)No. 10(100)No. 2.4 ±0.5Large10(100)No. 9.4 ±1.4" 8Ten/group for control and suture groups. " Numbers in parentheses,percentage of animals with tumors. c Mean ±S.E. " p < 0.05 (f test versus control group; see text). using phenolphthalein mono-0-glucuronic acid (Sigma Chemical Co., St. small bowel, and 407 (77%), in large bowel. Tumors were sessile Louis, MO) as the substrate (7). Protein concentrations were determined plaques or polypoid lesions and ranged in size from 1 to 22 mm by the method of Lowry ef al. (12). in greatest diameter. These findings are similar to those reported Fecal Trace Metals. Following these studies, a separate group of (8,9,18) for 1,2-dimethylhydrazine-treated rats. Although relative weaned male Wistar rats was used to determine fecal trace metals. After proportions of small intestinal tumors are greater in this experi 12 weeks of feeding, anesthesia and laparotomy were performed in 3 mental model compared to the proportions reported at small and groups of rats: controls without cecal suture and 2 cecal suture groups (surgical gut and stainless steel). Four weeks later, fresh stool samples large intestinal sites in humans, their distribution, relative size, were collected, weighed, ashed, weighed dry, and analyzed by atomic and histopathology are similar to those of human intestinal
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