The role of colonoscopy in the differential diagnosis of inflammatory bowel disease Jerome D. Waye, MD New York, New York
Definitive colonoscopic criteria have been developed for the differential diagnosis of ulcerative and granulomatous colitis. Colonoscopy should not be performed in all patients with inflammatory bowel disease but may be quite useful in certain situations, such as strictures, filling defects seen on barium enema, and in preoperative evaluation.
Ulcerative colitis and granulomatous colitis may be separated as distinct diseases in the great majority of patients by simple methods such as a history and a sigmoidoscopic examination. Radiographic studies may supplement these and provide the proper diagnosis in almost all patients with inflammatory bowel disease. Many criteria have been developed for the radiographic differentiation between these 2 entities, and it has become evident that colonoscopic criteria may be developed to assist the endoscopist in making the proper differential diagnosis between these 2 types of inflammatory bowel disease.',2 The colonoscopic guidelines described herein have evolved from my experience in over sao cases of inflammatory bowel disease. Infectious diseases of the colon such as amebiasis, tuberculosis, and shigellosis should be excluded by the appropriate diagnostic procedures and will not be discussed in this paper.
Diverticular disease of the colon is not an "inflammatory bowel disease," and mention will be made of this entity only as relates to its endoscopic differentiation from granulomatous colitis, INDICATIONS FOR COLONOSCOPY Although all patients with inflammatory bowel disease should have barium contrast radiographic investigation of the colon and small bowel, colonoscopy should be performed only in those patients in whom a specific indication arises. In fact, colonoscopy is contraindicated in the patient with the onset of acute severe ulcerative colitis. In these patients, who may be quite toxic and have profuse bloody diarrheal discharge, the diagnosis can usually be made by history and sigmoidoscopic examination. Passage of a colonoscope through an acutely inflamed, edematous colon may be dangerous and could result in bowel
From the Mount Sinai School of Medicine of the City University of New York, Mount Sinai Hospital, New York, New York. Reprint requests: Jerome D. Waye, MD, 1065 Park Avenue, New York, New York 10028.
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perforation. In general, if the patient cannot be adequately prepared for colonoscopy the procedure should not be performed. For example, in the patient with toxic dilatation of the colon in whom it is obvious that neither purgation nor enemas should be given, colonoscopy should not be considered. When all other diagnostic modalities are unsuccessful, colonoscopy with the criteria detailed herein, may be of benefit in making the differential diagnosis between the 2 types of inflammatory bowel disease. The ability of the colonoscopist to recognize subtle color changes and friability, added to the capability of taking biopsies of the mucosa (and of any lesions seen), allows the endoscopist to use different criteria than the radiologist to arrive at the differentiation between ulcerative and granulomatous colitis. Endoscopy is especially useful in the inspection of colonic strictures and in the evaluation of unusually large polypoid tumors occasionally seen in patients with colitis.) An accurate evaluation of the extent of disease may be particularly important in the patient with granulomatous colitis in whom an operation is contemplated. If disease is discovered endoscopically in the low sigmoid colon, the surgeon may have to plan his operation differently than he would if biopsies of that area were normal. On several occasions in my experience, preoperative colonoscopy has established the presence of radiographically undetected inflammatory disease in patients with Crohn's colitis. Preparation of the patient Cathartics should not be given to any patient during an exacerbation of colitic activity or for several weeks thereafter. Patients with chronic liquid diarrhea need not receive cathartics in preparation for the exami nation, but a liquid diet for 24 or 48 hours before the procedure will help to insure the absence of any large particulate matter within the colon. If the patient has loose stools but less than 3 bowel movements daily, a mild cathartic such as citrate of magnesi a or even castor oi I (pri mari Iy a sma II-bowel cathartic) may be administered on the night before the examination, following 24 hours of a liquid diet. In all patients, even those with liquid bloody diarrhea, proper mechanical cleansing of the colon with enemas is necessary. A tap water enema should be given at 3 hours and 2 hours prior to the examination. The 2 hour time-lapse before the procedure allows complete evacuation of the enema fluid and permits the enema-induced irritability and colonic spasm to subside. Unless the patient receives an adequate preparation, colonoscopy should not be performed. Medication used during colonoscopy is the same as that for "routine" endoscopy, viz. 50 mg. of meperidine and 5 mg to 15 mg of diazepam given intravenously. The contracted, tubular colons found in patients with longstanding colitis frequently renders the examination extremely easy for the patient and for the examiner. COMPLICATIONS In the acutely inflamed bowel with thinning of the bowel wall, the use of "slide-by" techniques theoretically may result in perforation, whereas the normal bowel may be more compliant to pressure with the tip of the instrument. This "complication" may be more theoretical than real, for it has not been reported thus far. Extreme caution must be used during any colonoscopic examination, and only gentle pressure should be exerted during endoscopy of the inflamed colon. Most strictures in inflammatory bowel disease may be traversed with the colonoscope, and, here again, the examiner must be gentle in attempting to guide the instrument VOLUME 23, NO.3, 1977
through the narrowed segments of bowel. Even strictures which appear quite narrow on barium enema examination actually may be easily negotiated with the colonoscope, and the actual intraluminal site of the stricture may not be discernible to the colonoscopist. 4 I have produced a microperforation at the site of a distal stricture in attempting to bypass that area to inspect a more proximal strictured segment. A pericolonic abscess developed that required surgical drainage. In all cases of inflammatory bowel disease the examiner must guard against producing a large loop in the sigmoid colon with an increased risk of perforation. Continued straightening of the instrument by pulling it back (withdrawal) after advancement of the tip will serve to prevent such loop formation.' Mucosal friability may cause bleeding following passage of the 'scope whether or not biopsies are taken. Biopsy-induced bleeding has never been a problem, and in my experience with over 10,000 biopsies of the colon, I have encountered only 1 episode of significant bleeding, this in a case of von Willebrand's disease wherein the easily controlled bleeding diathesis was discovered only following colonoscopic biopsies. ULCERATIVE COLITIS Insofar as this is a mucosal disease, the tiny (2 mm) specimens of the mucosa obtainable by biopsy forceps are helpful in determining whether colonic inflammation exists at a microscopic level but is not discernible to visual inspection with the unaided human eye. s Berkowitz and co-workers 6 demonstrated in ulcerative proctitis that the extent of biopsy-proven, microscopic evidence of· mucosal inflammation was greater than the visual estimate of disease in approximately 50% of cases. The following 10 points describe the colonoscopic findings in ulcerative colitis. (1) Rectal Involvement. The mucosa of the rectum is usually involved in ulcerative colitis. Characteristically the disease extends proximally from the anal verge. As a counter-point to this rule, it should be noted that I have made the diagnosis of ulcerative colitis in 3 patients with no evidence, either visually or microscopically, of rectal disease and without radiographic changes on the barium enema. One of these patients who presented with rectal bleeding, mild diarrhea, and a normal barium enema examination progressed to severe toxic dilatation of the colon and had a total colectomy for her ulcerative colitis. (2) Erythema. The normal fine network of interlacing blood vessels is lost in ulcerative colitis. The mucosal surface of the involved segment becomes diffusely erythematous and individual blood vessels cannot be identified (Figure 1). Erythema of the colonic wall is the earliest visual manifestation of disease in ulcerative colitis. The transition from abnormal to uninvolved colon does not occur abruptly but rather takes place over the span of 3 to 6 cm. (3) Granularity. Diffuse fine mucosal granularity is quite characteristic of early ulcerative colitis. Granularity appears as an uneven surface which reflects multiple highlights, resembling wet sandpaper (Figure 2). (4) Friability. Friability is frequently closely associated with granularity but represents a further stage in the evolution of colitis. The mucosal surface may ooze blood,. and this "friability" even in the absence of rubbing the instrument over the mucosa is usually responsible for the bleeding seen in ulcerative colitis (Figure 3). Although ulcerations do bleed, most of the bleeding in ulcerative colitis appears to be due to seepage 151
of blood across the entire inflamed mucosal surface. In the absence of spontaneous bleeding, milder degrees of friability may be noticed once the instrument has passed by an area and can be seen as a line of fine petechia-like hemorrhages. (5) Edema. Edema may cause the interhaustral septa to be thickened and blunted, and the edges of the septa may appear rounded rather than the paper-fold sharpness seen in the normal colon. Such edematous septa are obviously not infiltrated with tumor since their configuration can be changed easi Iy with pressure from the tip of the instrument or by using the biopsy forceps as a probe. (6) Ulcerations. Ulcerations are usually fairly superficial and characteristically occur in areas of grossly diseased mucosa. The mucosa surrounding ulcerations is invariably granular and erythematous without any evidence of the normal vascular pattern (Figure 4). This is an important colonoscopic point in the distinction between ulcerative and granulomatous colitis. (7) Bridging. Mucosal bridging is much more characteristic of ulcerative than granulomatous colitis, as these bridges are formed by ulceration with submucosal undermining. As healing occurs, the undermined segment of mucosa may heal by re-epithelialization of its undersurface and still remain attached at both ends: a "bridge" will then be formed (Figure 5). Bridge formation may also be seen in the noncolitic postoperative patient who has had a segment of colon inverted into the lumen during surgery with loose tissue fragments healing together to span the operative site. (8) Pseudopolyps. Pseudopolyps frequently occur and may vary from several millimeters to several centimeters in their greatest dimension. Pseudopolyps are usually taller than they are wide and project from the mucosal surface like fingers (Figure 6). The larger sessile pseudopolyps may resemble carcinomas, and biopsies will render the correct diagnosis. Pseudopolyps have a characteristic histologic pattern enabling the pathologist to make the proper diagnosis on the small specimens of tissue that are obtai nable by colonoscopic biopsy. Pseudopolyps have no malignant potential, and if the diagnosis can be definitively established by biopsy and if it can be established that a pseudopolyp accounts for a filling defect seen on barium enema examination, a colectomy may be avoided. (9) Contiguity. The mucosal disease in ulcerative colitis is contiguous from its origin at the rectum to the point of transition to normal mucosa, and skip-areas are not seen. When ulcerative colitis is universal, there are no areas of normal mucosa throughout the entire colon. In healed phases of ulcerative colitis, scattered pseudopolyps and telangiectasia may be the only signs that provide testimony to areas of previous involvement. Rarely is healing associated with such complete mucosal regeneration that the normal colonic vascular pattern is completely restored. (10) Carcinoma. The incidence of carcinoma in ulcerative colitis bears a close correlation with the duration of disease in those patients with universal colitis. Although most carcinomas are easily recognized colonoscopically, some may be diagnosed only with difficulty. Obtaining multiple mucosal biopsies of visibly suspicious areas is extremely important in making the diagnosis of early carcinoma because those lesions that are large and visible on radiographic examination usually have already spread beyond the confines of the colon.
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I have discovered early carcinoma on biopsy of a nonspecific small mucosal elevation. Once the carcinoma has grown to the point where it is visible radiographically, the carcinoma may resemble any other colonic neoplasm. In the search for carcinoma, timing of colonoscopy in patients with longstanding universal colitis has been random. The addition of cytology to routine biopsies may be of value. Williams 7 suggests multiple biopsies every 1 to 3 years with the high-risk group of patients, but I believe that yearly colonoscopy and biopsies are necessary to detect carcinoma in a curable stage.
GRANULOMATOUS COLITIS The colonoscopic appearance of granulomatous colitis is different from ulcerative colitis because the disease is transmural. Deeper layers of the bowel wall may participate in the inflammatory process while the overlying mucosal surface may be uninvolved. The following 10 points list the major colonoscopic findings in granulomatous colitis: (1) Normal Rectum. The rectal mucosa will frequently appear normal to visual inspection as well as on biopsy. Granulomatous colitis often affects the right side of the bowel with little or no involvement of the left colon. The presence of normal rectal mucosa should alert the examiner to the possibility of granulomatous rather than ulcerative colitis. (2) Asymmetry. The involvement seen may be asymmetrical in distribution, with one wall appearing perfectly normal and the opposite wall showing evidence of disease (Figure 7). The distribution of lesions in granulomatous colitis is patchy and accounts for the asymmetry frequently seen in this disease. (3) Cobblestoning. Cobblestoning is a characteristic and almost pathognomonic feature of granulomatous colitis (Figure 8). Colonoscopically, this involvement appears like bumpy pavement-stones in a repetitive but not symmetric pattern. Ulcerations mayor may not be present in the area of the cobblestoning. The mucosal surface overlying the cobblestoning may appear normal inasmuch as sub-mucosal involvement creates the unevenness of the mucosa although the mucosa itself need not be affected. (4) Normal Vasculature. Friability is not usually encountered except in the far-advanced stage of granulomatous colitis. The mucosa does not ooze blood diffusely as is seen in ulcerative colitis. The characteristic mucosal erythema seen in ulcerative colitis is not present in Crohn's disease, and the vascular pattern may be normal even in areas of diseased bowel. (5) Edema. The interhaustral septa are thickened and blunted, similar to that seen in ulcerative colitis. (6) Ulcerations in Normal Mucosa. Ulcerations in granulomatous colitis are not only more frequent than in ulcerative colitis but characteristically occur in areas of grossly normal mucosa (Figure 9). This is a major differential diagnostic point between the 2 types of colitis. Except for advanced stages of disease, the mucosa immediately surrounding ulcerations appears normal with a normal vascular pattern. Ulcerations that occur in areas of grossly normal mucosa should alert the examiner to the diagnosis of granulomatous colitis. (7) Serpigenous Ulcers. Ulcerations are frequently serpigenous and may course for several centimeters longitudinally along the bowel wall (Figure 70). These ulcers rarely bleed and are surrounded by a narrow rim of erythema. (8) Pseudopolyps. Pseudopolyps occur as frequently in GASTROINTESTINAL ENDOSCOPY
Figures 1-11. See text for description. VOLUME 23, NO.3, 1977
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granulomatous colitis as in ulcerative colitis. There is no differential point between the pseudopolyps of one as opposed to the pseudopolyps of the other. (9) Skip-Areas. Skip-areas are frequent in granulomatous colitis, and areas of diseased bowel may be interspersed between areas of normal bowel. (10) Amyloidosis. Three cases of amyloidosis have been discovered on "routine" biopsies of patients with granulomatous colitis. All biopsies showing amyloid were taken from areas of grossly normal appearing mucosa. In 1 patient the amyloid deposits were still present on repeated colonoscopic biopsy 4 years later in spite of the lack of any active disease. STOMAL INSPECTION Following total colectomy for inflammatory bowel disease, dysfunction of the ileostomy stoma is occasionally encountered. Proof of the cause of this dysfunction may be difficult, whether it be mechanical such as adhesions or edema or whether the dysfunction may be due to ileal inflammation implying the presence of Crohn's disease. Barium studies of the stoma, either by reflux enema or by peroral ingestion, may not lead to a definitive diagnosis. In these instances, the colonoscope or a similar fiberoptic instrument can be passed into the stoma in a retrograde fashion with complete visualization of the ileal mucosa for distances of 50 cm or farther. 8 Not only can the mucosa be inspected, but the presence of erythema, edema, and ulcerations can be identified and biopsies may be taken. Endoscopy of the ileal stoma is probably the easiest and most definitive method of reaching a diagnosis in most cases of "ileostomy dysfunction." A "continent ileostomy" may occasionally leak air or ileal material, and the nature of the problem may be identified by fiberoptic intubation with a U-turn technique for inspection of the stomal nipple. DISCUSSION The presence of pseudopolyps lends no support to the differential diagnosis between either of the 2 types of inflammatory bowel disease. Narrowing of the lumen or strictures can occur in both diseases. Colonoscopy may be extremely useful in differentiating benign from malignant strictures. Because completely extra mucosal carcinomas are unusual in ulcerative colitis, visual inspection of the stricture as well as multiple biopsies from the narrowed segment will provide an accurate diagnosis in almost every case. Smaller fiberoptic instruments may be safely used for inspection of narrow strictures if the ordinary colonoscope is too large to enter them. Diverticulitis with lumenal narrowing may be confused with a stricture of granulomatous colitis, but in diverticulitis pus is seen in the lumen, and the narrowed segment is easily traversed with the colonoscope. Cobblestoning is not present in the narrowed segment of acute diverticular inflammation. Colonoscopic biopsies are quite small because the diameter of the closed biopsy cup is approximately 2 mm. These tiny fragment biopsies usually do not reach the submucosa, and it is only rarely that I have been able to find granulomas in the biopsy specimens submitted in Crohn's colitis. In myexperience, the small biopsy specimens do not directly aid in the differentiation between ulcerative and granulomatous colitis. However, Geboes and Vantrappen 9 and FrGhmorgen 'O '" have reported that specimens from 24% and 26%, respectively, of their patients with Crohn's disease have included granulomas when biopsies were taken from the edge of large ulcers or from tiny ulcerations. I have found that if biopsies are taken adjacent to an ulceration and the mucosa is reported as "normal," 154
a point will have been made for the diagnosis of granulomatous colitis. Multidirectional control of the instrument tip permits "target biopsies" from any visible lesion or segment of mucosa throughout the colon. The pinpoint accuracy of the biopsy site provides a high yield of correct diagnoses when a carcinoma is present in spite of the small size of the biopsy specimens. With proper therapy, most cases of inflammatory bowel disease progress to a healing phase. In the patient with chronic disease and a deformed, foreshortened, and misshapen colon, radiographic assessment of disease activity may be difficult or impossible. Furthermore, in patients with chronic, longstanding, "burnt-out" disease, assessment of activity by history may be quite incorrect. In several such patients with but a single formed bowel movement each day, without any malaise, and without any physical or laboratory evidence of active disease, I found colonoscopy to show moderate activity of colitis with erythema, granularity, friability, and multiple ulcerations (Figure 11). This activity of the disease was detected only by direct visualization ofthe mucosa. The question of course arises, and cannot be answered at this time, as to whether those patients with longstanding but "quiescent" colitis who develop carcinoma actually are the same patients that have a low-grade inflammatory process extending over several years but in whom there was previously no method of direct mucosal visualization for assessment of such activity. The criteria cited above will assist the colonoscopist in rendering the correct diagnosis of the type of inflammatory bowel disease in the vast majority of patients with ulcerative and granulomatous colitis. The enumeration of these criteria is intended to complement and not to replace the other diagnostic modalities available to the physician. Colonoscopic examination need not be performed on all patients with inflammator.y bowel disease but should be reserved for those cases in whom a specific problem arises. The most important application of colonoscopy in inflammatory bowel disease lies in the evaluation of strictures, the identification of pseudopolyps and their differentiation from carcinoma, and in the preoperative evaluation of patients with granulomatous bowel disease. Only future studies will answer the question of whether colonoscopy with biopsies and cytology12 repeated at intervals will yield a significant number of curable carcinomas in chronic ulcerative colitis.
REFERENCES 1. WAVE 10: Colonoscopy: a clinical view. Mt Sinai J Med 42:1,1975 2. WAVE 10: The colonoscopic appearance of granulomatous colitis and ulcerative colitis, in Proceedings, 1st Asian-Pacific Congress of Endoscopy,
Kyoto, Japan 1973 3.
TAWlLE NT,
PRIEST RJ, SCHUMAN BM: Colonoscopy in inflammatory bowel disease. Gastrointestinal Endoscopy 22: 11, 1975
4. OILAWARI IB, PARKINSON C, RIDELL RH, LOOSE H, WILLIAMS CB: Colonoscopy in the investigation of ulcerative colitis. Gut 14:426, 1973 5. WARWICK RRG, SUMERLING MD, GILMOUR HM, SHEARMAN OIC:
Colonoscopy and double contrast barium enema examination in chronic ulcerative colitis. Am J Roentgenol 117:292, 1973 6. OAS KM, FARID T, BERKOWITZ 1M: Value of colonoscopy in the investigation of inflammatory bowel disease. Gastroenterology 66:681,1974 7. WILLIAMS CB, london, England. Personal communication. 8. WAVE JO: lIeoscopy: evaluation of ileoscopy dysfunction. Am J Gastro
65:360, 1976 9. GEBOES K, VANTRAPPEN G: The value of colonoscopy in the diagnosis of Crohn's disease. Gastrointestinal Endoscopy 22:18,1975 10. FRUHMORGEN P: Diagnosis of inflammatory diseases of the colon by coloscopy. Acta Gastro-en! Be/g. 37:154, 1974 11. DEMLING L, CLASSEN M FRUHMORGEN P: Atlas of Enteroscopy. New York,
Springer-Verlag, 1975 12. KATZ S, SHERLOCK P, WINAWER SI: Rectocolonic exfoliative cytology. Am J Dig Dis 17:1109, 1972 GASTROINTESTINAL ENDOSCOPY
Definitive colonoscopic criteria have been developed for the differential diagnosis of ulcerative and granulomatous colitis. Colonoscopy should not be performed in all patients with inflammatory bowel disease but may be quite useful in certain situations, such as strictures, filling defects seen on barium enema, and in preoperative evaluation.
Ulcerative colitis and granulomatous colitis may be separated as distinct diseases in the great majority of patients by simple methods such as a history and a sigmoidoscopic examination. Radiographic studies may supplement these and provide the proper diagnosis in almost all patients with inflammatory bowel disease. Many criteria have been developed for the radiographic differentiation between these 2 entities, and it has become evident that colonoscopic criteria may be developed to assist the endoscopist in making the proper differential diagnosis between these 2 types of inflammatory bowel disease.',2 The colonoscopic guidelines described herein have evolved from my experience in over sao cases of inflammatory bowel disease. Infectious diseases of the colon such as amebiasis, tuberculosis, and shigellosis should be excluded by the appropriate diagnostic procedures and will not be discussed in this paper.
Diverticular disease of the colon is not an "inflammatory bowel disease," and mention will be made of this entity only as relates to its endoscopic differentiation from granulomatous colitis, INDICATIONS FOR COLONOSCOPY Although all patients with inflammatory bowel disease should have barium contrast radiographic investigation of the colon and small bowel, colonoscopy should be performed only in those patients in whom a specific indication arises. In fact, colonoscopy is contraindicated in the patient with the onset of acute severe ulcerative colitis. In these patients, who may be quite toxic and have profuse bloody diarrheal discharge, the diagnosis can usually be made by history and sigmoidoscopic examination. Passage of a colonoscope through an acutely inflamed, edematous colon may be dangerous and could result in bowel
From the Mount Sinai School of Medicine of the City University of New York, Mount Sinai Hospital, New York, New York. Reprint requests: Jerome D. Waye, MD, 1065 Park Avenue, New York, New York 10028.
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perforation. In general, if the patient cannot be adequately prepared for colonoscopy the procedure should not be performed. For example, in the patient with toxic dilatation of the colon in whom it is obvious that neither purgation nor enemas should be given, colonoscopy should not be considered. When all other diagnostic modalities are unsuccessful, colonoscopy with the criteria detailed herein, may be of benefit in making the differential diagnosis between the 2 types of inflammatory bowel disease. The ability of the colonoscopist to recognize subtle color changes and friability, added to the capability of taking biopsies of the mucosa (and of any lesions seen), allows the endoscopist to use different criteria than the radiologist to arrive at the differentiation between ulcerative and granulomatous colitis. Endoscopy is especially useful in the inspection of colonic strictures and in the evaluation of unusually large polypoid tumors occasionally seen in patients with colitis.) An accurate evaluation of the extent of disease may be particularly important in the patient with granulomatous colitis in whom an operation is contemplated. If disease is discovered endoscopically in the low sigmoid colon, the surgeon may have to plan his operation differently than he would if biopsies of that area were normal. On several occasions in my experience, preoperative colonoscopy has established the presence of radiographically undetected inflammatory disease in patients with Crohn's colitis. Preparation of the patient Cathartics should not be given to any patient during an exacerbation of colitic activity or for several weeks thereafter. Patients with chronic liquid diarrhea need not receive cathartics in preparation for the exami nation, but a liquid diet for 24 or 48 hours before the procedure will help to insure the absence of any large particulate matter within the colon. If the patient has loose stools but less than 3 bowel movements daily, a mild cathartic such as citrate of magnesi a or even castor oi I (pri mari Iy a sma II-bowel cathartic) may be administered on the night before the examination, following 24 hours of a liquid diet. In all patients, even those with liquid bloody diarrhea, proper mechanical cleansing of the colon with enemas is necessary. A tap water enema should be given at 3 hours and 2 hours prior to the examination. The 2 hour time-lapse before the procedure allows complete evacuation of the enema fluid and permits the enema-induced irritability and colonic spasm to subside. Unless the patient receives an adequate preparation, colonoscopy should not be performed. Medication used during colonoscopy is the same as that for "routine" endoscopy, viz. 50 mg. of meperidine and 5 mg to 15 mg of diazepam given intravenously. The contracted, tubular colons found in patients with longstanding colitis frequently renders the examination extremely easy for the patient and for the examiner. COMPLICATIONS In the acutely inflamed bowel with thinning of the bowel wall, the use of "slide-by" techniques theoretically may result in perforation, whereas the normal bowel may be more compliant to pressure with the tip of the instrument. This "complication" may be more theoretical than real, for it has not been reported thus far. Extreme caution must be used during any colonoscopic examination, and only gentle pressure should be exerted during endoscopy of the inflamed colon. Most strictures in inflammatory bowel disease may be traversed with the colonoscope, and, here again, the examiner must be gentle in attempting to guide the instrument VOLUME 23, NO.3, 1977
through the narrowed segments of bowel. Even strictures which appear quite narrow on barium enema examination actually may be easily negotiated with the colonoscope, and the actual intraluminal site of the stricture may not be discernible to the colonoscopist. 4 I have produced a microperforation at the site of a distal stricture in attempting to bypass that area to inspect a more proximal strictured segment. A pericolonic abscess developed that required surgical drainage. In all cases of inflammatory bowel disease the examiner must guard against producing a large loop in the sigmoid colon with an increased risk of perforation. Continued straightening of the instrument by pulling it back (withdrawal) after advancement of the tip will serve to prevent such loop formation.' Mucosal friability may cause bleeding following passage of the 'scope whether or not biopsies are taken. Biopsy-induced bleeding has never been a problem, and in my experience with over 10,000 biopsies of the colon, I have encountered only 1 episode of significant bleeding, this in a case of von Willebrand's disease wherein the easily controlled bleeding diathesis was discovered only following colonoscopic biopsies. ULCERATIVE COLITIS Insofar as this is a mucosal disease, the tiny (2 mm) specimens of the mucosa obtainable by biopsy forceps are helpful in determining whether colonic inflammation exists at a microscopic level but is not discernible to visual inspection with the unaided human eye. s Berkowitz and co-workers 6 demonstrated in ulcerative proctitis that the extent of biopsy-proven, microscopic evidence of· mucosal inflammation was greater than the visual estimate of disease in approximately 50% of cases. The following 10 points describe the colonoscopic findings in ulcerative colitis. (1) Rectal Involvement. The mucosa of the rectum is usually involved in ulcerative colitis. Characteristically the disease extends proximally from the anal verge. As a counter-point to this rule, it should be noted that I have made the diagnosis of ulcerative colitis in 3 patients with no evidence, either visually or microscopically, of rectal disease and without radiographic changes on the barium enema. One of these patients who presented with rectal bleeding, mild diarrhea, and a normal barium enema examination progressed to severe toxic dilatation of the colon and had a total colectomy for her ulcerative colitis. (2) Erythema. The normal fine network of interlacing blood vessels is lost in ulcerative colitis. The mucosal surface of the involved segment becomes diffusely erythematous and individual blood vessels cannot be identified (Figure 1). Erythema of the colonic wall is the earliest visual manifestation of disease in ulcerative colitis. The transition from abnormal to uninvolved colon does not occur abruptly but rather takes place over the span of 3 to 6 cm. (3) Granularity. Diffuse fine mucosal granularity is quite characteristic of early ulcerative colitis. Granularity appears as an uneven surface which reflects multiple highlights, resembling wet sandpaper (Figure 2). (4) Friability. Friability is frequently closely associated with granularity but represents a further stage in the evolution of colitis. The mucosal surface may ooze blood,. and this "friability" even in the absence of rubbing the instrument over the mucosa is usually responsible for the bleeding seen in ulcerative colitis (Figure 3). Although ulcerations do bleed, most of the bleeding in ulcerative colitis appears to be due to seepage 151
of blood across the entire inflamed mucosal surface. In the absence of spontaneous bleeding, milder degrees of friability may be noticed once the instrument has passed by an area and can be seen as a line of fine petechia-like hemorrhages. (5) Edema. Edema may cause the interhaustral septa to be thickened and blunted, and the edges of the septa may appear rounded rather than the paper-fold sharpness seen in the normal colon. Such edematous septa are obviously not infiltrated with tumor since their configuration can be changed easi Iy with pressure from the tip of the instrument or by using the biopsy forceps as a probe. (6) Ulcerations. Ulcerations are usually fairly superficial and characteristically occur in areas of grossly diseased mucosa. The mucosa surrounding ulcerations is invariably granular and erythematous without any evidence of the normal vascular pattern (Figure 4). This is an important colonoscopic point in the distinction between ulcerative and granulomatous colitis. (7) Bridging. Mucosal bridging is much more characteristic of ulcerative than granulomatous colitis, as these bridges are formed by ulceration with submucosal undermining. As healing occurs, the undermined segment of mucosa may heal by re-epithelialization of its undersurface and still remain attached at both ends: a "bridge" will then be formed (Figure 5). Bridge formation may also be seen in the noncolitic postoperative patient who has had a segment of colon inverted into the lumen during surgery with loose tissue fragments healing together to span the operative site. (8) Pseudopolyps. Pseudopolyps frequently occur and may vary from several millimeters to several centimeters in their greatest dimension. Pseudopolyps are usually taller than they are wide and project from the mucosal surface like fingers (Figure 6). The larger sessile pseudopolyps may resemble carcinomas, and biopsies will render the correct diagnosis. Pseudopolyps have a characteristic histologic pattern enabling the pathologist to make the proper diagnosis on the small specimens of tissue that are obtai nable by colonoscopic biopsy. Pseudopolyps have no malignant potential, and if the diagnosis can be definitively established by biopsy and if it can be established that a pseudopolyp accounts for a filling defect seen on barium enema examination, a colectomy may be avoided. (9) Contiguity. The mucosal disease in ulcerative colitis is contiguous from its origin at the rectum to the point of transition to normal mucosa, and skip-areas are not seen. When ulcerative colitis is universal, there are no areas of normal mucosa throughout the entire colon. In healed phases of ulcerative colitis, scattered pseudopolyps and telangiectasia may be the only signs that provide testimony to areas of previous involvement. Rarely is healing associated with such complete mucosal regeneration that the normal colonic vascular pattern is completely restored. (10) Carcinoma. The incidence of carcinoma in ulcerative colitis bears a close correlation with the duration of disease in those patients with universal colitis. Although most carcinomas are easily recognized colonoscopically, some may be diagnosed only with difficulty. Obtaining multiple mucosal biopsies of visibly suspicious areas is extremely important in making the diagnosis of early carcinoma because those lesions that are large and visible on radiographic examination usually have already spread beyond the confines of the colon.
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I have discovered early carcinoma on biopsy of a nonspecific small mucosal elevation. Once the carcinoma has grown to the point where it is visible radiographically, the carcinoma may resemble any other colonic neoplasm. In the search for carcinoma, timing of colonoscopy in patients with longstanding universal colitis has been random. The addition of cytology to routine biopsies may be of value. Williams 7 suggests multiple biopsies every 1 to 3 years with the high-risk group of patients, but I believe that yearly colonoscopy and biopsies are necessary to detect carcinoma in a curable stage.
GRANULOMATOUS COLITIS The colonoscopic appearance of granulomatous colitis is different from ulcerative colitis because the disease is transmural. Deeper layers of the bowel wall may participate in the inflammatory process while the overlying mucosal surface may be uninvolved. The following 10 points list the major colonoscopic findings in granulomatous colitis: (1) Normal Rectum. The rectal mucosa will frequently appear normal to visual inspection as well as on biopsy. Granulomatous colitis often affects the right side of the bowel with little or no involvement of the left colon. The presence of normal rectal mucosa should alert the examiner to the possibility of granulomatous rather than ulcerative colitis. (2) Asymmetry. The involvement seen may be asymmetrical in distribution, with one wall appearing perfectly normal and the opposite wall showing evidence of disease (Figure 7). The distribution of lesions in granulomatous colitis is patchy and accounts for the asymmetry frequently seen in this disease. (3) Cobblestoning. Cobblestoning is a characteristic and almost pathognomonic feature of granulomatous colitis (Figure 8). Colonoscopically, this involvement appears like bumpy pavement-stones in a repetitive but not symmetric pattern. Ulcerations mayor may not be present in the area of the cobblestoning. The mucosal surface overlying the cobblestoning may appear normal inasmuch as sub-mucosal involvement creates the unevenness of the mucosa although the mucosa itself need not be affected. (4) Normal Vasculature. Friability is not usually encountered except in the far-advanced stage of granulomatous colitis. The mucosa does not ooze blood diffusely as is seen in ulcerative colitis. The characteristic mucosal erythema seen in ulcerative colitis is not present in Crohn's disease, and the vascular pattern may be normal even in areas of diseased bowel. (5) Edema. The interhaustral septa are thickened and blunted, similar to that seen in ulcerative colitis. (6) Ulcerations in Normal Mucosa. Ulcerations in granulomatous colitis are not only more frequent than in ulcerative colitis but characteristically occur in areas of grossly normal mucosa (Figure 9). This is a major differential diagnostic point between the 2 types of colitis. Except for advanced stages of disease, the mucosa immediately surrounding ulcerations appears normal with a normal vascular pattern. Ulcerations that occur in areas of grossly normal mucosa should alert the examiner to the diagnosis of granulomatous colitis. (7) Serpigenous Ulcers. Ulcerations are frequently serpigenous and may course for several centimeters longitudinally along the bowel wall (Figure 70). These ulcers rarely bleed and are surrounded by a narrow rim of erythema. (8) Pseudopolyps. Pseudopolyps occur as frequently in GASTROINTESTINAL ENDOSCOPY
Figures 1-11. See text for description. VOLUME 23, NO.3, 1977
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granulomatous colitis as in ulcerative colitis. There is no differential point between the pseudopolyps of one as opposed to the pseudopolyps of the other. (9) Skip-Areas. Skip-areas are frequent in granulomatous colitis, and areas of diseased bowel may be interspersed between areas of normal bowel. (10) Amyloidosis. Three cases of amyloidosis have been discovered on "routine" biopsies of patients with granulomatous colitis. All biopsies showing amyloid were taken from areas of grossly normal appearing mucosa. In 1 patient the amyloid deposits were still present on repeated colonoscopic biopsy 4 years later in spite of the lack of any active disease. STOMAL INSPECTION Following total colectomy for inflammatory bowel disease, dysfunction of the ileostomy stoma is occasionally encountered. Proof of the cause of this dysfunction may be difficult, whether it be mechanical such as adhesions or edema or whether the dysfunction may be due to ileal inflammation implying the presence of Crohn's disease. Barium studies of the stoma, either by reflux enema or by peroral ingestion, may not lead to a definitive diagnosis. In these instances, the colonoscope or a similar fiberoptic instrument can be passed into the stoma in a retrograde fashion with complete visualization of the ileal mucosa for distances of 50 cm or farther. 8 Not only can the mucosa be inspected, but the presence of erythema, edema, and ulcerations can be identified and biopsies may be taken. Endoscopy of the ileal stoma is probably the easiest and most definitive method of reaching a diagnosis in most cases of "ileostomy dysfunction." A "continent ileostomy" may occasionally leak air or ileal material, and the nature of the problem may be identified by fiberoptic intubation with a U-turn technique for inspection of the stomal nipple. DISCUSSION The presence of pseudopolyps lends no support to the differential diagnosis between either of the 2 types of inflammatory bowel disease. Narrowing of the lumen or strictures can occur in both diseases. Colonoscopy may be extremely useful in differentiating benign from malignant strictures. Because completely extra mucosal carcinomas are unusual in ulcerative colitis, visual inspection of the stricture as well as multiple biopsies from the narrowed segment will provide an accurate diagnosis in almost every case. Smaller fiberoptic instruments may be safely used for inspection of narrow strictures if the ordinary colonoscope is too large to enter them. Diverticulitis with lumenal narrowing may be confused with a stricture of granulomatous colitis, but in diverticulitis pus is seen in the lumen, and the narrowed segment is easily traversed with the colonoscope. Cobblestoning is not present in the narrowed segment of acute diverticular inflammation. Colonoscopic biopsies are quite small because the diameter of the closed biopsy cup is approximately 2 mm. These tiny fragment biopsies usually do not reach the submucosa, and it is only rarely that I have been able to find granulomas in the biopsy specimens submitted in Crohn's colitis. In myexperience, the small biopsy specimens do not directly aid in the differentiation between ulcerative and granulomatous colitis. However, Geboes and Vantrappen 9 and FrGhmorgen 'O '" have reported that specimens from 24% and 26%, respectively, of their patients with Crohn's disease have included granulomas when biopsies were taken from the edge of large ulcers or from tiny ulcerations. I have found that if biopsies are taken adjacent to an ulceration and the mucosa is reported as "normal," 154
a point will have been made for the diagnosis of granulomatous colitis. Multidirectional control of the instrument tip permits "target biopsies" from any visible lesion or segment of mucosa throughout the colon. The pinpoint accuracy of the biopsy site provides a high yield of correct diagnoses when a carcinoma is present in spite of the small size of the biopsy specimens. With proper therapy, most cases of inflammatory bowel disease progress to a healing phase. In the patient with chronic disease and a deformed, foreshortened, and misshapen colon, radiographic assessment of disease activity may be difficult or impossible. Furthermore, in patients with chronic, longstanding, "burnt-out" disease, assessment of activity by history may be quite incorrect. In several such patients with but a single formed bowel movement each day, without any malaise, and without any physical or laboratory evidence of active disease, I found colonoscopy to show moderate activity of colitis with erythema, granularity, friability, and multiple ulcerations (Figure 11). This activity of the disease was detected only by direct visualization ofthe mucosa. The question of course arises, and cannot be answered at this time, as to whether those patients with longstanding but "quiescent" colitis who develop carcinoma actually are the same patients that have a low-grade inflammatory process extending over several years but in whom there was previously no method of direct mucosal visualization for assessment of such activity. The criteria cited above will assist the colonoscopist in rendering the correct diagnosis of the type of inflammatory bowel disease in the vast majority of patients with ulcerative and granulomatous colitis. The enumeration of these criteria is intended to complement and not to replace the other diagnostic modalities available to the physician. Colonoscopic examination need not be performed on all patients with inflammator.y bowel disease but should be reserved for those cases in whom a specific problem arises. The most important application of colonoscopy in inflammatory bowel disease lies in the evaluation of strictures, the identification of pseudopolyps and their differentiation from carcinoma, and in the preoperative evaluation of patients with granulomatous bowel disease. Only future studies will answer the question of whether colonoscopy with biopsies and cytology12 repeated at intervals will yield a significant number of curable carcinomas in chronic ulcerative colitis.
REFERENCES 1. WAVE 10: Colonoscopy: a clinical view. Mt Sinai J Med 42:1,1975 2. WAVE 10: The colonoscopic appearance of granulomatous colitis and ulcerative colitis, in Proceedings, 1st Asian-Pacific Congress of Endoscopy,
Kyoto, Japan 1973 3.
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PRIEST RJ, SCHUMAN BM: Colonoscopy in inflammatory bowel disease. Gastrointestinal Endoscopy 22: 11, 1975
4. OILAWARI IB, PARKINSON C, RIDELL RH, LOOSE H, WILLIAMS CB: Colonoscopy in the investigation of ulcerative colitis. Gut 14:426, 1973 5. WARWICK RRG, SUMERLING MD, GILMOUR HM, SHEARMAN OIC:
Colonoscopy and double contrast barium enema examination in chronic ulcerative colitis. Am J Roentgenol 117:292, 1973 6. OAS KM, FARID T, BERKOWITZ 1M: Value of colonoscopy in the investigation of inflammatory bowel disease. Gastroenterology 66:681,1974 7. WILLIAMS CB, london, England. Personal communication. 8. WAVE JO: lIeoscopy: evaluation of ileoscopy dysfunction. Am J Gastro
65:360, 1976 9. GEBOES K, VANTRAPPEN G: The value of colonoscopy in the diagnosis of Crohn's disease. Gastrointestinal Endoscopy 22:18,1975 10. FRUHMORGEN P: Diagnosis of inflammatory diseases of the colon by coloscopy. Acta Gastro-en! Be/g. 37:154, 1974 11. DEMLING L, CLASSEN M FRUHMORGEN P: Atlas of Enteroscopy. New York,
Springer-Verlag, 1975 12. KATZ S, SHERLOCK P, WINAWER SI: Rectocolonic exfoliative cytology. Am J Dig Dis 17:1109, 1972 GASTROINTESTINAL ENDOSCOPY
