ACCELERATION OF SMALL BOWEL CONTRAST STUDY BY CHOLECYSTOKININ

Transcription

1 G A S T R O E ~ ~ E R O L O G Y Copyright 1970 by The Williams & Wilkins Co. Vol. 58, No.5 Printed in U.S.A. ACCELERATION OF SMALL BOWEL CONTRAST STUDY BY CHOLECYSTOKININ JULIUS G. PARKER, M.D., AND THOMAS C. BENEVENTANO, M.D. Department of Gastroenterology, Division of Medicine and Division of Radiology, Montefiore Hospital and Medical Center, Bronx, New York Intravenous cholecystokinin was used to stimulate small bowel peristaltic activity and to permit rapid small bowel contrast study in 26 adults on 27 occasions. An accelerated passage time of 15 min or less through the small bowel was obtained in 22 studies. This decreased transit time was observed in 8 normal individuals, 7 patients with granulomatous enteritis, 5 with celiac sprue, and 1 with ileostomy following colonic resection for ulcerative colitis. The 5 patients with transit times exceeding 15 min consisted of 3 normal subjects, 1 with progressive systemic sclerosis of the small bowel, and 1 with granulomatous enterocolitis. Of these 5, 2 normal subjects and 1 patient with granulomatous enterocolitis had transit times of 25, 60, and 30 min, respectively. Side effects were limited to transitory abdominal cramps and nausea. Previously documented abnormalities were reconfirmed by this rapid method. The small bowel in patients with celiac sprue and granulomatous enteritis or enterocolitis was as responsive to cholecystokinin as in normal subjects. Examination of the small bowel by barium meal is frequently a time-consuming and unrevealing study. The use of intramuscular prostigminel- 3 to decrease transit time has not gained acceptance, while the ingestion of cold barium or barium meal followed by cold saline has not been helpful. The use of cholecystokinin as a safe and effective agent to speed contrast media through the small bowel was first described by the French radiologists Monod 4 and Morin et al. 5 In a review of the clinical aspects of cholecystokinin by Jorpes and Mutt in 1969,6 no reference is made to any such American study. Since Received August 5, Accepted November 21, A preliminary report of this work was made at the postgraduate course "The lleum: Function and Malfunction" at the annual meeting of the American Gastroenterological Association, May 13 to 14, 1969, held in Washington, D. C. Address requests for reprints to: Dr. Julius G. Parker, Department of Medicine, Montefiore Hospital and Medical Center, Bronx, New York there was no reported experience with such use of cholecystokinin in this country, a study was undertaken to reexamine this technique and to evaluate its utility in accelerating and refining contrast studies of the small bowel. Materials and Methods Eleven normal patients and 15 subjects with known disease of the small bowel were selected for this initial investigation. None had clinical evidence of gallbladder disease. In normal subjects, the effect of cholecystokinin on passage time could be ascertained and, in patients with disease, the known pathology could be redocumen ted. Although age was not considered a contraindication, no pediatric patient was included. Only patients with suspected small bowel obstruction were excluded, since any increased peristaltic activity and force in these subjects was potentially unsafe. The study was performed in the following manner. A preliminary scout film of the abdomen was made. The subject then drank 24 ounces of colloidal barium sulfate mixture. Thirty minutes later, a second scout film was

2 680 PA.RKER A.ND BENEVENTANO Vol. 58, No. 5 obtained to document the distribution of barium in the stomach and small bowel. The cholecystokinin used, Vitrum, contained 100 Ivy dog units per vial and was administered 30 min after barium ingestion in all patients. The first 8 patients received 100 Ivy units, while the remaining 18 subjects received 50 units. The hormone was dissolved in 10 ml of normal saline and injected intravenously over a I-min period. Films of the abdomen were obtained at 1, 3, 5, 7, and 10 min after the cholecystokinin administration. After the 7-min film, the patient was fluoroscoped and cinerecordings of small bowel activity were made. If the ileocecal sphincter was not visualized within 10 min, subsequent films were made at 15-, 30-, 60-, 90-, and 120-min intervals. The patient remained supine on the radiographic table during the first 30 min of the study. When the small bowel study continued over 2 hr owing to the lack of passage of barium into the ileocecal sphincter area, the study was continued in a routine fashion with hourly films. Results This method was used 27 times in 26 subjects, 12 females and 14 males, ranging in age from 18 to 74 years. One subject was studied on two occasions during a I-year interval. The transit time through the small bowel after cholecystokinin injection was 15 min or less on 22 occasions in 21 patients (table 1). Four subjects had transit times of 25, 30, 60, and 120 min. TABLE 1. Summary of results Age Sex Cholecyst<>kinin Transit time Side effects' Diagnosis Before chole After chole cystokinin" cystokinin Cramp Nausea IllY units min 51 M 100 N.D. 9 Normal 33 F 100 N.D. 10 Normal 40 F 100 N.D. 7 Normal 72 F 100 N.D. 15 Normal 31 F 100 N.D. 120 Normal 69 M 100 N.D. 1 Normal 57 F 50 N.D. 25 Normal 68 F 50 N.D. 60 Normal 48 F 50 N.D. 1 Normal F 50 N.D. 10 Normal 50 F 50 3 Normal 58 M Celiac sprue 58 M Celiac sprue 64 M Celiac sprue 59 M Celiac sprue 61 M Celiac sprue 49 F 50 N.D. 420 Progressive systemic sclerosis 52 F Postcolectomy for ulcerative coli- tis with normally functioning ileostomy 21 M Granulomatous enterocolitis M Granulomatous enteritis M 300 Granulomatous enteritis 64 M Granulomatous enterocolitis 19 M Granulomatous enterocolitis 18 M 50 N.D. 7 Granulomatous enterocolitis 74 F 50 N.D. 3 Granulomatous enteritis 35 M Granulomatous enteritis 20 M Granulomatous enterocolitis, N.D., not done. ; Graded on the scale 1 to 3, minimal to moderate.

3 May 1970 SMALL BOWEL CONTRAST STUDY 681 FIG. 1. M. S., MHMC X-ray , 21-year-old male with granulomatous enterocolitis. A, a 3 1 /2-hr routine contrast study with distal ileum barely visualized and without diagnostic findings. B, a cholecystokinin study performed 1 week later demonstrating the typical findings in granulomatous ileitis with separation of the loops of bowel, nodularity, coarsening of the mucosa, and small fistulae (arrow). One female with progressive systemic sclerosis of the small bowel had a transit time of 7 hr. Vomiting did not occur in any subject. Eight patients experienced transient nausea. Minimal abdominal cramps developed in 12 subjects and moderate cramps in 2, shortly after the completion of the cholecystokinin administration. Within 7 to 10 min, all symptoms had completely subsided and no late sequelae appeared. The difference in transit time before and after cholecystokinin administration in 2 patients is shown in figures 1 and 2. In 13 control studies on 12 patients, the administration of cholecystokinin markedly reduced the transit time in each instance. The control studies preceded the cholecystokinin examinations by 2 weeks or less. Discussion In this study, the interval of transit time extended from 30 min after the ingestion of 24 ounces of colloidal barium sulfate mixture until that moment when the head of the barium column was first seen in the cecum. This conforms with the generally accepted definition of transit time. Kim 7 recently reported the transit time in a study of 315 patients without gastrointestinal disease. These subjects ranged from 19 to 80 years and consisted of 168 females and 149 males. The transit time varied from 15 min to 5 hr, with a mean of 84 min. It was 2 hr or less in 83% of the subjects, with only 3 patients requiring more than 4 hr. A somewhat longer normal transit time of 2 to 3 hr is quoted by Texter.s No systematic studies in vari-

4 682 PARKER AND BENEVENTANO Vol. 58, No.5 FIG. 2. G. W., MHMC X-ray 47,700, 59-year-old male with biopsy-proven celiac sprue. A, illustrates a routine study after 3 1 /, hr with contrast barely visible in the cecum. B, within 5 min after cholecystokinin injection, note obvious thickening of the valvulae and dilation of the bowel. The barium has entered the colon (arrow) within this 5-min period. ous diseases of the small bowel are available for comparison. A 30-min waiting period was used to permit sufficient barium to enter the duodenum and jejunum, thus ensuring a satisfactory contrast study. This technique was essentially similar to that described by Monod,4 Morin et al.,5 and Backlund. 9 These authors found that the cholecystokinin small bowel study was usually unsatisfactory if the hormone was administered prior to the passage of a sufficient quantity of barium into the jejunum. Seven years after the discovery of cholecystokinin, Sandblom and co-workers 10 reported that the hormone initiated duodenal peristalsis in experimental animals. Torsoli et al. 11 described relaxation of the second portion of the duodenum after intravenous administration of cholecystokinin. Using cineradiography, they documented the unusual appearance of the duodenal loop consisting of distension, marked prominence of the transverse mucosal folds, and only occasional peristaltic activity. Antiperistaltic waves and pendular movements of the duodenum were also seen. In 15 subjects, Adlercreutz and colleagues 12 demonstrated that cholecystokinin caused an initial duodenal dilation and decreased tonus, but that this was almost immediately replaced by an increased tonus and accelerated peristalsis. The cholecystokinin effect was noted to persist over a 7-min period. On the other hand, Dahlgren 13 reported that 1 min after cholecystokinin injection, duodenal peristalsis was stimulated, but that within 3 min all activity had subsided. Marked peristaltic activity of the human colon after cholecystokinin was seen with cineradiography by Grossi et al. 14 The in vitro effect of cholecystokinin upon the small bowel musculature was studied by Denton and Gershbein. 15 They found that the hormone induced simultaneous contractions of cir-

5 May 1970 SMALL BOWEL CONTRAST STUDY 683 cular and longitudinal preparations of guinea pig ileum. Such an effect upon the human jejunal and ileal muscular layers could explain the response seen in this study. Responsiveness of the small bowel involved by granulomatous enteritis was documented in all of the patients tested. By cineradiography, it was demonstrated that an apparently fixed cicatricial segment of bowel could contract under the influence of cholecystokinin so that the lumen was nearly emptied of its contrast material. To observe the vigorous peristaltic activity in the 5 patients with active sprue was rather surprising. Although the mucosa was grossly abnormal by jejunal biopsy and barium contrast study, the effective stimulation by cholecystokinin with acceleration of transit was, in all regards, comparable with that seen in normal subjects. This would suggest that the circular and longitudinal muscle layers of the small bowel in sprue are as responsive to cholecystokinin stimulation as are those in the normal. The possibility, therefore, arises that in sprue and similar primarily mucosal disease there may be a deficiency of cholecystokinin to explain the disordered peristaltic activity so regularly seen. fudeed,in a recent abstract, Di Magno et al. 16 presented evidence of a marked decrease or absence of pancreozymin in patients with sprue. Since Jorpes and Mute' and Grossman1 8 believe that pancreozymin and cholecystokinin are a single entity, such absence of pancreozymin in sprue, if confirmed, would perforce include cholecystokinin. The absence of any detectable small bowel response to cholecystokinin in the single subject with progressive systemic sclerosis could be ascribed to a failure of the usual small bowel muscle stimulation. Although either fibrosis or atrophy of the smooth muscle might result in such lack of contraction, the major defect in progressive systemic sclerosis of the intestinal tract has been documented as smooth muscle atrophy rather than fibrous tissue replacement Difficulties encountered during this investigation consisted primarily of nausea and abdominal cramps. These side effects were not severe and did not persist beyond 7 to 10 min. fu 3 normal subjects, active peristalsis occurred for approximately 20 min, but the barium did not reach the ileocecal valve during this period of time. Although the reason for this relative delay was not apparent by clinical or roentgen evidence, we believe that such responses could be circumvented, if necessary, by a second administration of cholecystokinin if within the first 20 to 30 min there has not been visualization of the entire small bowel. Since cholecystokinin has a rather evanescent action, it may be necessary to employ more than a single administration. It may also be possible to obtain the maximal peristaltic effect with smaller amounts of hormone than have been used in this study. These preliminary studies indicate that cholecystokinin is an effective stimulant of small bowel peristaltic activity. Its ability to hasten the completion of a study while permitting close observation of the patient during this entire period is a distinct clinical advantage. A prime benefit of this technique is the opportunity to visualize the terminal ileum and ileocecal sphincter area in a rapid and more precise manner than can be obtained by present methods. The demonstration of known pathological changes by this technique indicated that no apparent diagnostic artifacts were produced. Until more experience is gained, we have some reservations regarding routine clinical use of cholecystokinin in small bowel contrast studies. It would appear that its prime benefit will be, for the moment, in those instances in which routine study has failed to explain the etiology of a prolonged transit time or has not clearly demonstrated a suspected area of pathological change. As a possible method of distinguishing between mucosal disease or muscle disease of the small bowel, the cholecystokinin technique may prove to be valuable. REFERENCES 1. Ingelfinger, F. J The modification of intes tinal motility by drugs. New Eng. J. Med. 229:

6 684 PARKER AND BENEVENTANO Vol. 58, No, 5 2. Margulis, A. R., and P. Mandelstam The use of parenteral neostigmine in the roentgen study of the small bowel. Radiology 76: Friedenberg, M. J., W. H. McAlister, and A. R. Margulis Roentgen study of the small bowel in adults and children with neostigmine. Amer. J. Roentgen. 88: Monod, E Action entero-kinetique de la cecekin. Arch. Mal. Appar. Dig. 53: Morin, G., F. Bescancon, A. Grall, R. Jouve, and C. R. Debray Technique d'acce!eration du grele. Arch. Mal. Appar. Dig. 54: Jorpes, J. E., and V. Mutt Clinical aspects of gastrointestinal hormones secretin and cholecystokinin. Scand. J. Gastroent. 9: Kim, S. K Small intestinal transit time in the normal small bowel study. Amer. J. Roentgen. 104: Texter, E. C Pressure and transit in the small intestine. Amer. J. Dig. Dis. 13: Backlund, V Cholecystokinin vid rontgenundersokningar. Svensk. Lak-Tidn. 64: Sandblom, P. H., U. L. Voegtlin, and A. C. Ivy The effect of cholecystokinin on the choledochonduodenal mechanism. Amer. J. Physiol. 113: Torsoli, A., M. L. Ramorino, C. Colagrande, and G. Demaio Experiments with cholecystokinin. Acta Radiol. 55: Adlercreutz, E., T. Petterson, H. Adlercreutz, P. Gribbe, and C. Weglius Effect of cholecystokinin on duodenal tonus and motility. Acta Med. Scand. 167: Dahlgren, S Cholecystokinin: pharmacology and clinical use. Acta Chir. Scand. 357: suppl Grossi, F. B., B. Messini, T. Del Duca, M. Ricci, and M. Messini Peristaltic activity of the colonic mass in sequence after the administration of "cecekin." Clin. Ter. 37: Denton, R. W., and L. 1. Gershbein Contraction of circular and longitudinal guinea pig ileal sections by cholecystokinin concentrates and histamine. Science 119: Di Magno, E. P., V. L. W. Go, and W. H. J. Summerskill Pancreozymin secretion is impaired in sprue (abstr.). Gastroenterology 56: Jorpes, J. E., and V. Mutt Cholecystokinin and pancreozymin, one single hormone? Acta Physiol. Scand. 66: Grossman, M. I Gastrointestinal hormones. Med. Clin. N. Amer. 52: Heinz, E. R., A. J. Steinberg, and M. A. Sachner Roentgenographic and pathologic aspects of intestinal scleroderma. Ann. Intern. Med. 59: D'Angelo, W. A., J. F. Fries, A. T. Masi, and L. E. Shulman Pathologic observations in systemic sclerosis (scleroderma). A study of fifty-eight autopsy cases and fifty-eight matched controls. Amer. J. Med. 46: