Major Complications of Coloscopy: Bleeding and Perforation Joseph E. Geenen, MD, Milton G. Schmitt, Jr., MD, Wallace C. Wu, MD, BS, and Walter J. Hogan, MD
The overall frequency and types of complications associated with diagnostic coloscopy and coloscopic polypectomy are unknown. A statewide survey of coloscopists was conducted to determine the morbidity and mortality associated with coloscopy. Twenty-eight physicians performed a total of 1,106 coloscopic procedures. 9 colonic perforations and 5 episodes of colonic bleeding resulted in a 1.3% complication rate. Explanations for several of the complications are identified and preventive measures proposed. 1 patient died of an unrecognized perforation of the sigmoid colon, resulting in a 0.09% mortality rate. Of 14 complications reported in this series, 12 occurred during the early experience (less than 40 procedures) of the coloscopist. Training programs in coloscopy need to be established in order to reduce the morbidity and mortality associated with a physician's early coloscopic experience. T h e fiberoptic coloscope is g a i n i n g widespread acceptance as a useful tool for the diagnosis and m a n a g e m e n t of diseases of the colon (1-6). Coloscopes are readily available and are being used by physicians from diverse medical disciplines. T r a i n i n g and experience a m o n g coloscopists varies. Recent editorials have expressed concern for the safety of this procedure and the necessity to define the morbidity and mortality currently associated with coloscopy (7, 8). A l t h o u g h complications occurring with fiberoptic coloscopy have been reported (3, 9 14), the true incidence and possible causes of these complications have not been systematically surveyed. From the Department of Medicine, Racine Medical Clinic and Milwaukee County General Hospital, Medical College of Wisconsin, Milwaukee, Wisconsin. Presented at the annual meeting of the American Society for Gastrointestinal Endoscopy, San Francisco, California, May 21, 1974. Dr. Sehmitt is supported by a Special Post-Doctoral Research Fellowship Award (5-F03-AM-53883) from the National Institute of Arthritis, Metabolic and Digestive Diseases, NIH, Bethesda, Maryland. Address for reprint requests: Dr. Joseph E. Geenen, Racine Medical Clinic, 5625 Washington Avenue, Racine, Wisconsin, 53406.
Digestive Diseases,Vol. 20, No. 3 (March 1975)
A regional survey of coloscopists has been conducted to ascertain the incidence and types o f complications resulting from diagnostic coloscopy and coloscopic polypectomy. T h i s survey further enables us to identify the a p p a r e n t causes of certain coloscopic complications and to propose p r e c a u t i o n a r y measures.
MATERIALS AND METHODS We surveyed 38 physicians in the state of Wisconsin who had purchased coloscopes from American Cystoscope Makers, Inc., (Pelham Manor, New York) or Olympus Corporation of America (New Hyde Park, New York). Each physician was asked to review the records of patients upon whom he had performed coloscopy and to complete a questionnaire which included (1) the number of diagnostic coloscopies and coloscopic polypectomies performed; (2) the types of complications which occurred with the use of the coloscope; and (3) the treatment and clinical course of each patient in whom a complication occurred. After the questionnaires were returned, each physician who reported a complication was personally intervieWed and the circumstances surrounding the complication were thoroughly investigated.
RESULTS T w e n t y - n i n e physicians responded to the questionnaire. O n e physician had purchased an
231
GEENEN ET AL
_
6_
Number of
5_
4.
Physicians 3. .
E
1
0
I0
20
I
30
40
t
50 "/~1( ~ ~ 0
250
Total Number of Colonoscopies per Physician Fig 1. Twenty-eight physicians performed a total of 1,106 procedures. This graph shows the number of coloscopies done by each endoscopist.
instrument but had not performed coloscopy. All nonresponding physicians were personally contacted and indicated that they had performed 5 or less coloscopies at the time of the survey. The nonresponding physicians were not included in the results since they had not answered the questionnaire and, therefore, the reliability of their verbal replies indicating an absence of complications is uncertain. T h e number of coloscopies performed by each responding physician varied from 5 to 231 (Figure 1). Nineteen physicians performed less than 40 procedures; nine performed more than 40. The total number of coloscopies reported was 1,106 and there were 14 (1.3%) complications. 7 (0.9%) complications occurred with 814 diagnostic coloscopies and 7 (2.4%) complications occurred with 292 coloscopic polypectomies. Of the 14 complications reported, 5 were significant colonic bleeding (rectal bleeding with falling hematocrit reading) and 9 were colonic perforations (Table 1). Of the 9 patients with colonic perforation, 8 had immediate surgery with no postoperative sequelae. 1 patient died as a result of unrecog232
nized perforation. This patient had an uneventful polypectomy and was observed in the hospital for 3 days without symptoms or abnormal physical findings. He was discharged to a nursing home but returned on the 8th postoperative day moribund and died within hours after admission. He had complained of abdominal pain for 36 hours prior to his death. Autopsy revealed perforation of the sigmoid colon in an area with multiple diverticula, which was remote from the polypectomy site. The explanations for colonic perforation in this survey were determined to be the following: Perforation of the sigmoid colon in 4 patients occurred during mechanical manipulation of the coloscope, ie, advancing instrument tip cautiously along colon wall when unable to visualize lumen ("slide-by" maneuver); counterclockwise rotation of the sigmoid loop (alpha maneuver); or straightening of the sigmoid loop during passage of the instrument. In each of these instances there was acute angulation or fixation of the sigmoid colon caused by postoperative adhesions, diverticulosis, or inflammatory disease (radiation colitis). Colonic perDigestive Diseases, Vol. 20, No. 3 (March 1975)
COMPLICATIONS OF COLOSCOPY Table 1. Complications in 1,106 Coloscopic Procedures
Procedure
Diagnostic coloscopy Coloscopic polypectomy Total
Cases (N)
Perforations (N)
Surgical intervention for perforation (N)
Bleeding (N)
Surgical intervention for bleeding (N)
814
7 (0.9%)
7
0
0
292
2* (0.7%)
1
5 (1.7%)
2
1,106
9 (0.8%)
8
5 (0.5%)
2
"1 death.
foration occurred in 2 patients from improper use of the electrosurgical unit. In 1 of these cases, an attempt was made to transect a polyp with an eleetrodelike knife after the snare loop had broken. In the other, perforation resulted from an excessively high coagulation current used during ball-tip coagulation of a bleeding biopsy site. The causes of the remaining 3 perforations are less clear, but they appear to have been caused by colonic wall disruption secondary to air insufflation during coloscopic examination. 5 significant bleeding episodes (4 during first 24 hours; after 8 days) resulted from coloscopic polypectomy utilizing snare cautery. 3 patients received blood transfusions; 2 patients (1 with immediate bleeding, 1 with bleeding after 8 days) required operative intervention to control bleeding and bleeding from the polypectomy site was confirmed at surgery. 2 bleeding episodes occurred following "rapid" transection of the polyp by the cautery snare and were probably due to inadequate coagulation. The causes of bleeding in the other 3 cases are unknown. 9 additional patients passed small amounts of blood (no change in hematocrit reading) at variable intervals following polypectomy (2-7 days), but required no blood replacement and are not considered cases of "major complications." The overall complication rate for coloscopic procedures in this survey is 1.3%, and the mortality rate is 0.09%. Of the 14 complications, 12 Digestive Diseases, Vol. 20, No. 3 (March 1975)
(85 %) happened during the coloscopist's first 40 procedures (Figure 2). Nine physicians who performed more than 40 procedures each performed a total of 771 procedures. 8 complications occurred during their first 360 procedures, whereas only 2 complications occurred in their subsequent 411 procedures. The remaining 4 complications occurred during procedures performed by the 19 physicians who performed less than 40 procedures each. DISCUSSION
Scattered reports by coloscopists with varying experience from specialized centers throughout the world list colonic perforation (3, 9, 11-13), with 1 death (13), bleeding (912), retroperitoneal emphysema (14), colonic submucosal air dissection (12), and splenic rupture (9) as complications which have occurred following coloscopy and coloseopic polypectomy. The incidence of major complications reported for these specialized centers has ranged from 0.1% to 1.7% (9-12). The current overall incidence of complications associated with coloscopy among coloscopists in a statewide community is unknown. For this reason, a survey was conducted among coloscopists in Wisconsin to obtain this information. As with all attempts at assessing the complication rate of a medical or surgical procedure, not based on individual chart review, there may be underreporting of the complications and our incidence should be considered a minimal rate. 233
GEENEN ETAL .
.
Number
3.
of
Complications
2.
0
10
20
30
40
50
60
190
200
Number oF Colonoscopies at Time of Complication
Fig 2. Relationship between the occurrence of complications and the number of coloscopic examinations performed by the endoscopist up to that time.
The 28 coloscopists in this survey are a diverse group of specialists, ie, gastroenterologists, general surgeons, rectal surgeons, radiologists, and general practitioners. Many of these physicians have received no formal training in coloscopy. In most instances, instructions supplied by the instrument manufacturer, or techniques demonstrated at postgraduate seminars or described in the literature, are their only training for their first coloscopies. Colonic perforation and postpolypectomy bleeding were the two complications encountered in this survey. Of 9 colonic perforations, 4 resulted from mechanical manipulation of the coloscope; 2 resulted from improper use of the electrosurgical unit; and 3 appeared to result from air insuffiation associated with the procedure. These data indicate that colonic perforation during coloscopy may be minimized by certain precautions: (1) Mechanical straightening or uncoiling of a loop of colon by manipu lation of the coloscope should be carefully performed, utilizing short periods of intermittent fluoroscopic observation; (2) Patients should not be oversedated during coloscopy, for pain may be indicative of excessive stress on the colon wall or its peritoneal attachments; (3) 234
Knowledge of the performance and capabilities of the electrosurgical equipment is essential, (4) Colonic air insufflation during instrumentation should be kept to a minimum, particularly when diverticulosis or colitis is present. (5) Postpolypectomy patients should receive careful outpatient followup for 7-10 days. We feel that the risk of colonic perforation during fiberoptic coloscopy can be reduced if these guidelines are followed. All 5 instances of significant colonic bleeding in this series occurred following coloscopic polypectomy. The endoscopist must avoid mechanically transecting the polyp with the wire loop snare prior to application of adequate cuttingcoagulation current. Such a situation was responsible for 2 of the bleeding episodes. Of the 14 complications reported, 12 (85%) occurred during the coloscopist's first 40 procedures. The American Society for Gastrointestinal Endoscopy has recently proposed that guidelines be established for minimum training in endoscopy. This survey suggests that a trainee in coloscopy should perform approximately 40 coloscopic examinations under the direct supervision of an experienced coloscopist before he performs the procedure alone. TrainDigestive Diseases, Vol. 20, No. 3 (March 1975)
COMPLICATIONS OF COLOSCOPY
ing programs in coloscopy need to be established in order to reduce the morbidity and mortality associated with a physician's early coloscopic experience. REFERENCES
1. Wolff Wl, Shinya H, Geft~en A, Ozaktay SZ: Colonofiberoscopy. A new and valuable diagnostic modality. Am J Surg 123:180-184, 1972 2. Hansen LK: Cotonoscopy. A study of 50 cases. Stand J Gastroenterol 6:687-691, 1971 3. Teague RH, Salmon PR, Read AE: Fiberoptic examination of the colon: A review of 255 cases. Gut 14:139-142, 1973 4. Nagy GS: Fibrecolonoscopy. Med J Aust 1:378-382, 1973 5. Classen M: Fiberendoscopy of the intestine. Gut 12:330-338, 1971 6. Morrissey JF: Gastrointestinal endoscopy. Gastroenterology 62:1241-1268, 1972
Digestive Diseases, Vol. 20, No. 3 (March 1975)
7. Colcher H: Hospital privileges of performing gastrointestinal endoscopy. JAMA 225:58, 1973 8. Bloom BS, Goldhaber SZ, Sugarbaker PH, O'Connor NE: Fiberoptics: Morbidity and cost. N Engl J Med 288:368-369, 1973 9. Wolff WI, Shinya H: A new approach to colonic polyps. Ann Surg 178:367-378, 1973 10. Berci G, Panish J, Morgenstern L: Diagnostic colonoscopy and colonoscopic polypectomy. Arch Surg 106:818-819, 1973 11. Spencer R J, Coates HL, Anderson M J: Colonoscopic polypectomies. Mayo Clin Proc 49:4043, 1974 12. Sugarbaker PH, Vineyard GC: Fiberoptic colonoscopy. A new look at 01d problems. Am J Surg 125:429~431, 1973 13. Meyers DS: Colonoscopy. N Engl J Med 288:974, 1973 14. Lezak MG, Boldhamer M: Retroperitoneal emphysema after colonoscopy. Gastroenterology 66:118-120, 1974
235
The overall frequency and types of complications associated with diagnostic coloscopy and coloscopic polypectomy are unknown. A statewide survey of coloscopists was conducted to determine the morbidity and mortality associated with coloscopy. Twenty-eight physicians performed a total of 1,106 coloscopic procedures. 9 colonic perforations and 5 episodes of colonic bleeding resulted in a 1.3% complication rate. Explanations for several of the complications are identified and preventive measures proposed. 1 patient died of an unrecognized perforation of the sigmoid colon, resulting in a 0.09% mortality rate. Of 14 complications reported in this series, 12 occurred during the early experience (less than 40 procedures) of the coloscopist. Training programs in coloscopy need to be established in order to reduce the morbidity and mortality associated with a physician's early coloscopic experience. T h e fiberoptic coloscope is g a i n i n g widespread acceptance as a useful tool for the diagnosis and m a n a g e m e n t of diseases of the colon (1-6). Coloscopes are readily available and are being used by physicians from diverse medical disciplines. T r a i n i n g and experience a m o n g coloscopists varies. Recent editorials have expressed concern for the safety of this procedure and the necessity to define the morbidity and mortality currently associated with coloscopy (7, 8). A l t h o u g h complications occurring with fiberoptic coloscopy have been reported (3, 9 14), the true incidence and possible causes of these complications have not been systematically surveyed. From the Department of Medicine, Racine Medical Clinic and Milwaukee County General Hospital, Medical College of Wisconsin, Milwaukee, Wisconsin. Presented at the annual meeting of the American Society for Gastrointestinal Endoscopy, San Francisco, California, May 21, 1974. Dr. Sehmitt is supported by a Special Post-Doctoral Research Fellowship Award (5-F03-AM-53883) from the National Institute of Arthritis, Metabolic and Digestive Diseases, NIH, Bethesda, Maryland. Address for reprint requests: Dr. Joseph E. Geenen, Racine Medical Clinic, 5625 Washington Avenue, Racine, Wisconsin, 53406.
Digestive Diseases,Vol. 20, No. 3 (March 1975)
A regional survey of coloscopists has been conducted to ascertain the incidence and types o f complications resulting from diagnostic coloscopy and coloscopic polypectomy. T h i s survey further enables us to identify the a p p a r e n t causes of certain coloscopic complications and to propose p r e c a u t i o n a r y measures.
MATERIALS AND METHODS We surveyed 38 physicians in the state of Wisconsin who had purchased coloscopes from American Cystoscope Makers, Inc., (Pelham Manor, New York) or Olympus Corporation of America (New Hyde Park, New York). Each physician was asked to review the records of patients upon whom he had performed coloscopy and to complete a questionnaire which included (1) the number of diagnostic coloscopies and coloscopic polypectomies performed; (2) the types of complications which occurred with the use of the coloscope; and (3) the treatment and clinical course of each patient in whom a complication occurred. After the questionnaires were returned, each physician who reported a complication was personally intervieWed and the circumstances surrounding the complication were thoroughly investigated.
RESULTS T w e n t y - n i n e physicians responded to the questionnaire. O n e physician had purchased an
231
GEENEN ET AL
_
6_
Number of
5_
4.
Physicians 3. .
E
1
0
I0
20
I
30
40
t
50 "/~1( ~ ~ 0
250
Total Number of Colonoscopies per Physician Fig 1. Twenty-eight physicians performed a total of 1,106 procedures. This graph shows the number of coloscopies done by each endoscopist.
instrument but had not performed coloscopy. All nonresponding physicians were personally contacted and indicated that they had performed 5 or less coloscopies at the time of the survey. The nonresponding physicians were not included in the results since they had not answered the questionnaire and, therefore, the reliability of their verbal replies indicating an absence of complications is uncertain. T h e number of coloscopies performed by each responding physician varied from 5 to 231 (Figure 1). Nineteen physicians performed less than 40 procedures; nine performed more than 40. The total number of coloscopies reported was 1,106 and there were 14 (1.3%) complications. 7 (0.9%) complications occurred with 814 diagnostic coloscopies and 7 (2.4%) complications occurred with 292 coloscopic polypectomies. Of the 14 complications reported, 5 were significant colonic bleeding (rectal bleeding with falling hematocrit reading) and 9 were colonic perforations (Table 1). Of the 9 patients with colonic perforation, 8 had immediate surgery with no postoperative sequelae. 1 patient died as a result of unrecog232
nized perforation. This patient had an uneventful polypectomy and was observed in the hospital for 3 days without symptoms or abnormal physical findings. He was discharged to a nursing home but returned on the 8th postoperative day moribund and died within hours after admission. He had complained of abdominal pain for 36 hours prior to his death. Autopsy revealed perforation of the sigmoid colon in an area with multiple diverticula, which was remote from the polypectomy site. The explanations for colonic perforation in this survey were determined to be the following: Perforation of the sigmoid colon in 4 patients occurred during mechanical manipulation of the coloscope, ie, advancing instrument tip cautiously along colon wall when unable to visualize lumen ("slide-by" maneuver); counterclockwise rotation of the sigmoid loop (alpha maneuver); or straightening of the sigmoid loop during passage of the instrument. In each of these instances there was acute angulation or fixation of the sigmoid colon caused by postoperative adhesions, diverticulosis, or inflammatory disease (radiation colitis). Colonic perDigestive Diseases, Vol. 20, No. 3 (March 1975)
COMPLICATIONS OF COLOSCOPY Table 1. Complications in 1,106 Coloscopic Procedures
Procedure
Diagnostic coloscopy Coloscopic polypectomy Total
Cases (N)
Perforations (N)
Surgical intervention for perforation (N)
Bleeding (N)
Surgical intervention for bleeding (N)
814
7 (0.9%)
7
0
0
292
2* (0.7%)
1
5 (1.7%)
2
1,106
9 (0.8%)
8
5 (0.5%)
2
"1 death.
foration occurred in 2 patients from improper use of the electrosurgical unit. In 1 of these cases, an attempt was made to transect a polyp with an eleetrodelike knife after the snare loop had broken. In the other, perforation resulted from an excessively high coagulation current used during ball-tip coagulation of a bleeding biopsy site. The causes of the remaining 3 perforations are less clear, but they appear to have been caused by colonic wall disruption secondary to air insufflation during coloscopic examination. 5 significant bleeding episodes (4 during first 24 hours; after 8 days) resulted from coloscopic polypectomy utilizing snare cautery. 3 patients received blood transfusions; 2 patients (1 with immediate bleeding, 1 with bleeding after 8 days) required operative intervention to control bleeding and bleeding from the polypectomy site was confirmed at surgery. 2 bleeding episodes occurred following "rapid" transection of the polyp by the cautery snare and were probably due to inadequate coagulation. The causes of bleeding in the other 3 cases are unknown. 9 additional patients passed small amounts of blood (no change in hematocrit reading) at variable intervals following polypectomy (2-7 days), but required no blood replacement and are not considered cases of "major complications." The overall complication rate for coloscopic procedures in this survey is 1.3%, and the mortality rate is 0.09%. Of the 14 complications, 12 Digestive Diseases, Vol. 20, No. 3 (March 1975)
(85 %) happened during the coloscopist's first 40 procedures (Figure 2). Nine physicians who performed more than 40 procedures each performed a total of 771 procedures. 8 complications occurred during their first 360 procedures, whereas only 2 complications occurred in their subsequent 411 procedures. The remaining 4 complications occurred during procedures performed by the 19 physicians who performed less than 40 procedures each. DISCUSSION
Scattered reports by coloscopists with varying experience from specialized centers throughout the world list colonic perforation (3, 9, 11-13), with 1 death (13), bleeding (912), retroperitoneal emphysema (14), colonic submucosal air dissection (12), and splenic rupture (9) as complications which have occurred following coloscopy and coloseopic polypectomy. The incidence of major complications reported for these specialized centers has ranged from 0.1% to 1.7% (9-12). The current overall incidence of complications associated with coloscopy among coloscopists in a statewide community is unknown. For this reason, a survey was conducted among coloscopists in Wisconsin to obtain this information. As with all attempts at assessing the complication rate of a medical or surgical procedure, not based on individual chart review, there may be underreporting of the complications and our incidence should be considered a minimal rate. 233
GEENEN ETAL .
.
Number
3.
of
Complications
2.
0
10
20
30
40
50
60
190
200
Number oF Colonoscopies at Time of Complication
Fig 2. Relationship between the occurrence of complications and the number of coloscopic examinations performed by the endoscopist up to that time.
The 28 coloscopists in this survey are a diverse group of specialists, ie, gastroenterologists, general surgeons, rectal surgeons, radiologists, and general practitioners. Many of these physicians have received no formal training in coloscopy. In most instances, instructions supplied by the instrument manufacturer, or techniques demonstrated at postgraduate seminars or described in the literature, are their only training for their first coloscopies. Colonic perforation and postpolypectomy bleeding were the two complications encountered in this survey. Of 9 colonic perforations, 4 resulted from mechanical manipulation of the coloscope; 2 resulted from improper use of the electrosurgical unit; and 3 appeared to result from air insuffiation associated with the procedure. These data indicate that colonic perforation during coloscopy may be minimized by certain precautions: (1) Mechanical straightening or uncoiling of a loop of colon by manipu lation of the coloscope should be carefully performed, utilizing short periods of intermittent fluoroscopic observation; (2) Patients should not be oversedated during coloscopy, for pain may be indicative of excessive stress on the colon wall or its peritoneal attachments; (3) 234
Knowledge of the performance and capabilities of the electrosurgical equipment is essential, (4) Colonic air insufflation during instrumentation should be kept to a minimum, particularly when diverticulosis or colitis is present. (5) Postpolypectomy patients should receive careful outpatient followup for 7-10 days. We feel that the risk of colonic perforation during fiberoptic coloscopy can be reduced if these guidelines are followed. All 5 instances of significant colonic bleeding in this series occurred following coloscopic polypectomy. The endoscopist must avoid mechanically transecting the polyp with the wire loop snare prior to application of adequate cuttingcoagulation current. Such a situation was responsible for 2 of the bleeding episodes. Of the 14 complications reported, 12 (85%) occurred during the coloscopist's first 40 procedures. The American Society for Gastrointestinal Endoscopy has recently proposed that guidelines be established for minimum training in endoscopy. This survey suggests that a trainee in coloscopy should perform approximately 40 coloscopic examinations under the direct supervision of an experienced coloscopist before he performs the procedure alone. TrainDigestive Diseases, Vol. 20, No. 3 (March 1975)
COMPLICATIONS OF COLOSCOPY
ing programs in coloscopy need to be established in order to reduce the morbidity and mortality associated with a physician's early coloscopic experience. REFERENCES
1. Wolff Wl, Shinya H, Geft~en A, Ozaktay SZ: Colonofiberoscopy. A new and valuable diagnostic modality. Am J Surg 123:180-184, 1972 2. Hansen LK: Cotonoscopy. A study of 50 cases. Stand J Gastroenterol 6:687-691, 1971 3. Teague RH, Salmon PR, Read AE: Fiberoptic examination of the colon: A review of 255 cases. Gut 14:139-142, 1973 4. Nagy GS: Fibrecolonoscopy. Med J Aust 1:378-382, 1973 5. Classen M: Fiberendoscopy of the intestine. Gut 12:330-338, 1971 6. Morrissey JF: Gastrointestinal endoscopy. Gastroenterology 62:1241-1268, 1972
Digestive Diseases, Vol. 20, No. 3 (March 1975)
7. Colcher H: Hospital privileges of performing gastrointestinal endoscopy. JAMA 225:58, 1973 8. Bloom BS, Goldhaber SZ, Sugarbaker PH, O'Connor NE: Fiberoptics: Morbidity and cost. N Engl J Med 288:368-369, 1973 9. Wolff WI, Shinya H: A new approach to colonic polyps. Ann Surg 178:367-378, 1973 10. Berci G, Panish J, Morgenstern L: Diagnostic colonoscopy and colonoscopic polypectomy. Arch Surg 106:818-819, 1973 11. Spencer R J, Coates HL, Anderson M J: Colonoscopic polypectomies. Mayo Clin Proc 49:4043, 1974 12. Sugarbaker PH, Vineyard GC: Fiberoptic colonoscopy. A new look at 01d problems. Am J Surg 125:429~431, 1973 13. Meyers DS: Colonoscopy. N Engl J Med 288:974, 1973 14. Lezak MG, Boldhamer M: Retroperitoneal emphysema after colonoscopy. Gastroenterology 66:118-120, 1974
235
