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Recurrence and reoperation in Crohn's colitis
1426
SELECTED
SUMMARIES
RECURRENCE AND REOPERATION CROHN’S COLITIS Longo WE, Ballantyne Surgery, Yale University Connecticut) Treatment 1988;123:588-90.
GASTROENTEROLOGY
IN
GH, Cahow CE (Department of School of Medicine, New Haven, of Crohn’s colitis. Arch Surg
This study examines the recurrence of Crohn’s disease in a group of patients who were originally diagnosed as having disease limited to the colon and who then underwent surgery. The patients were retrospectively selected from all patients with Crohn’s colitis operated on from 1974 to 1984 at Yale. Any patient with evidence of extracolonic or small intestinal disease at the time of the first procedure was excluded. Of the 40 patients who met the inclusion criteria, 37 were available for follow-up. On the basis of standard clinical and histologic criteria, the patients were assigned to one of the following three groups: segmental colonic disease (21 patients); pancolitis with rectal sparing (6 patients); and proctocolitis (10 patients). The indication for the initial surgical procedure was intractability of disease in two-thirds of the patients and either an acute abdomen, obstruction, bleeding, or fistulization in the others. The initial operations performed on the patients with pancolitis or proctocolitis included 10 proctocolectomies for panproctocolitis and 6 abdominal colectomies in patients with rectal sparing (3 ileoproctostomies and 3 ileostomy and Hartmann pouch procedures). Among the 21 patients with segmental colonic disease, there were 9 right hemicolectomies with ileocolostomies, 8 left hemicolectomies (5 with primary anastomosis and 3 with end colostomies), 3 sigmoid resections, and 1 abdominoperineal resection with end colostomy. Intestinal continuity was established in 18 of the 21 patients with segmental colonic disease. Postoperative recurrence was defined as any evidence of Crohn’s disease by standard clinical, radiologic, and pathologic criteria. Average follow-up time was 5.5 yr. Recurrence of disease occurred in 19 of the 37 patients (51%). Disease recurred in about two-thirds of the patients with either segmental colectomies or total abdominal colectomies and in only 20% of the patients with proctocolectomies. Some patients had more than one recurrence and most of the patients whose disease recurred required further surgery. In 4 of the 6 patients who initially underwent abdominal colectomies and were initially free of rectal disease recurrence took place in the rectum, but not in the small intestine. Recurrences in the group who underwent segmental resection were in both the colon and the small intestine. At the end of the follow-up period, 81% of the 21 patients who had initially undergone segmental resection still had intestinal continuity. Comment. Discussions concerning the management of Crohn’s colitis are complicated by the variety of presentations and management options. It was only about 25 yr ago that the entity of Crohn’s disease involving the colon alone was accepted and recognized (Gut 1964;5:493-509; N Engl J Med 1963;269:379-85). It is now clear that Crohn’s colitis can involve patchy areas of the
Vol. 95, No. 5
colon, the whole colon, the whole colon sparing the rectum, and even the rectosigmoid alone. Defining recurrence of disease has also been problematic. Some authors use symptoms to define recurrence, others require radiologic or biopsy confirmation of disease, and some define recurrence of disease as disease requiring another surgical procedure. It is important in comparing studies to carefully describe the population and the criteria used for classification. In this retrospective review, the authors have carefully defined their study population of 37 patients. These were patients who had only colonic disease. There were initially three types of operations performed on the group: proctocolectomy, segmental colectomy, and total abdominal colectomy. Recurrence of disease was defined by evidence of disease on colonoscopic, barium, or pathologic study. In the group of patients that had proctocolectomies and ileostomies, 2 of 10 had disease recurrence and required small intestinal resections. In the group that had abdominal colectomies. 4 of 6 patients developed rectal disease and 3 of these underwent proctectomy. In the group of patients that had recursegmental resections, 13 of the 21 patients experienced rence. In this group, the sites of recurrence are, unfortunately, not described in detail, but recurrences occurred both proximal and distal to the anastomosis and in the small intestine. The strong point the authors make is that even though there was a high rate of reoperation in this group with segmental disease, 81% of the patients retained intestinal continuity during the period of observation. This study is weakened by the very short follow-up period of 5.5 yr. In a disease that has so high a recurrence rate and begins often at a young age, clinicians must look past a 5-yr follow-up in planning their management. The small number of patients is also a cause of concern, but on the other hand permits a detailed examination of the individual procedures and courses of the patients. Recurrence rates should probably not be reported solely as crude recurrence rates as was done here, but as actuarial curves where the number of patients at risk is taken into consideration. A number of studies have shown a marked increase in recurrence rates when actuarial curves are used (N Engl J Med 1975;293:68590). The authors examine the average age at time of presentation of disease and then compare that age with the average age at recurrence; actuarial curves would give a better idea of the time to recurrence. The rate of recurrence of disease after total proctocolectomy and ileostomy is a controversial issue, which this study in part addresses. Recurrence rates for Crohn’s disease after a first operation are reported by actuarial analysis to be between 70% and 90% (N Engl J Med 1975;293:685-90, Gastroenterology 1985;88: 1826-33). The present study had an overall crude recurrence rate of 51%, which would likely be higher using actuarial data. However, the crude recurrence rate after total proctocolectomy and ileostomy was 20%. similar to what some have found [World J Surg 1980;4:173-82). Previous attempts to study this issue are possibly complicated by reoperations for stoma1 dysfunction being erroneously labeled as recurrence of disease. The patients in the present study who underwent this operation had panproctocolitis. It remains unclear whether the rate of recurrence in the small intestine would be similarly low if patients with limited segmental disease also had a total proctocolectomy rather than segmental resection. The answer to this issue depends on how often patients with segmental colonic disease experience recurrence in the small intestine, and this is not agreed upon. Furthermore, the figure of 20% may not be accurate when larger numbers of patients are examined over longer periods of time using actuarial methods. The issue of where in the bowel recurrences occur remains unclear. There is a trend in the literature to suggest that recurrence
generally
occurs
proximal
to the
anastomosis
(Gut
November
SELIXTED
1988
1972;13:973-5), although this is disputed by others (Dig Dis Sci 1981:26:528-31). In this study, there were recurrences in the rectum after ileorectal anastomosis and recurrences in the small intestine after segmental colonic resection. What seems indisputable is that the likelihood of a recurrence of disease after any operation besides proctocolectomy and ileostomy is at least 60%-70% if not >90% over a long follow-up period. The authors argue that the recurrence rates notwithstanding, the best procedure to do is segmental resection of diseased bowel. The justification for this is that the quality of life is improved by delaying the need for permanent ileostomy. This conclusion, although it seems reasonable, i.e., save as much large bowel as possible and avoid ileostomy for as long as possible, may not necessarily be the best course for all patients. If the price of maintaining intestinal continuity is steroid treatment, repeated colonoscopies. continued physician visits, and further operations, some patients might choose the more definitive procedure of proctocolectomy and take the 20% chance of a small bowel recurrence, assuming the 20% recurrence rate is accurate. Current practice seems to be in line with the authors’ suggestions that segmental resection and intestinal continuity should be the aim of surgery. More studies are needed from centers where large numbers of patients with Crohn’s colitis are operated upon. The issue of small bowel recurrence after either proctocolectomy or segmental colonic resection needs further study. A.M. MAGUN. M.D.
VASCULAR ADDRESSINS: TISSUESPECIFIC ANTIGENS THAT MAY CONTROL LYMPHOCYTE HOMING TO LYMPHOID TISSUES PR, Berg EL, Rouse BTN, Bargatze RF, Butcher EC (Department of Pathology, Stanford University School of Medicine, Stanford, California, and Veterans Administration Medical Center. Palo Alto, California) A tissuespecific endothelial cell molecule involved in lymphocyte homing. Nature 1988;331:41-6. Streeter
Lymphocytes home to and enter specific tissues by adhering to and migrating through high endothelial venules, which are specialized cuboidal endothelial cells. This provides a regulatory mechanism for the trafficking of lymphocytes from one organ to another via the bloodstream and allows the homing of distinct lymphocyte subsets with tissue specificity. Streeter and coworkers have now identified endothelial cell recognition elements involved in tissue-specific lymphocyte interactions with high endothelial venules by the production of monoclonal antibodies. They produced two monoclonal antibodies that defined an endothelial cell surface antigen present on high endothelial venules in mucosal tissues and that is absent from high endothelial venules in nonmucosal sites. Furthermore, this antigen functions as a mucosa-specific endothelial cell marker and recognition element that is required for the selective extravasation of lymphocytes in mucosal lymphoid tissues. The monoclonal antibodies were produced by immunizing rats with endothelial cells isolated from mouse mesenteric and peripheral lymph nodes. The resultant hybridomas were screened for monoclonal antibodies that would stain mouse high endothelial venules by immunohistologic staining techniques. Two antibodies (MECA-89 and
SUMMARIES
1427
MECA-367) stained high endothelial venules in mucosal lymphoid organs and Peyer’s patches, but not high endothelial venules in peripheral lymph nodes. Mesenteric lymph nodes revealed a heterogeneous staining pattern, indicating that some high endothelial venules express mucosa-associated antigens whereas others do not. Both large and small intestinal lamina propria contained venules that stained with the monoclonal antibodies. Furthermore, lactating mammary gland, which is a mucosal tissue into which mucosa-specific lymphoblast populations such as immunoglobulin A plasma cell precursors home, also had venules that stained positively with the monoclonal antibody. In contrast, skin did not stain with either of the monoclonal antibodies. The antigen against which the antibodies were directed was identified as a protein of -62,000 (58,000-66,000) molecular weight. Functional assays demonstrated the biologic capabilities of the mucosa-specific antigen. Frozen sections of tissue were used to assess the ability of lymphocytes to bind to high endothelial venules. MECA-367 but not MECA-89 resulted in a 92% reduction in the ability of Peyer’s patch high endothelial venules to bind lymphocytes. Similarly, MECA-367 but not MECA-89 inhibited lymphocyte binding to mesenteric lymph node high endothelial venules by 52%. In contrast, neither monoclonal antibody had any effect on lymphocyte binding to peripheral lymph node high endothelial venules. Pretreatment of high endothelial venules with the monoclonal antibody MECA-367 inhibited binding, whereas pretreatment of lymphocytes did not alter high endothelial venule binding capabilities. Streeter and coworkers then utilized cells capable of binding to high endothelial venules in a tissue-specific manner and found that MECA367 could completely block the binding of a mucosal high endothelial venule-specific binding cell line (TKl) to high endothelial venules in Peyer’s patches and mesenteric lymph nodes. In contrast, MECA-367 had no effect on the binding of the peripheral lymph node-specific cell line (38C13) to peripheral or mesenteric lymph node high endothelial venules. Thus, the monoclonal antibody MECA-367 was able to specifically interfere with lymphocyte recognition of high endothelial venules via a blocking of mucosa-specific recognition systems. In contrast, the monoclonal antibody MECA-89, although similar in its staining pattern and similar in the nature of the antigen being recognized, did not block adherence. Finally, Streeter and coworkers examined the physiologic effects of blockade of lymphocyte homing by injecting mice with MECA-367 monoclonal antibody. Chromium 51-labeled mesenteric lymph node cells were then injected into the mice 4 h later. Treatment with MECA.-367 resulted in nearly complete (97%) blockade of lymphocyte binding to Peyer’s patches and a partial (37%) reduction in homing and localization of lymphocytes into mesenteric lymph nodes. Comment. At least three independent lymphocyte, high endothelial venule recognition systems have been identified that are capable of mediating lymphocyte binding to high endothelial venules in either peripheral lymph nodes. mucosal lymphoid tissues, or the synovium of inflamed joints. The present important and excellent study by Streeter and coworkers defines antigens on
SELECTED
SUMMARIES
RECURRENCE AND REOPERATION CROHN’S COLITIS Longo WE, Ballantyne Surgery, Yale University Connecticut) Treatment 1988;123:588-90.
GASTROENTEROLOGY
IN
GH, Cahow CE (Department of School of Medicine, New Haven, of Crohn’s colitis. Arch Surg
This study examines the recurrence of Crohn’s disease in a group of patients who were originally diagnosed as having disease limited to the colon and who then underwent surgery. The patients were retrospectively selected from all patients with Crohn’s colitis operated on from 1974 to 1984 at Yale. Any patient with evidence of extracolonic or small intestinal disease at the time of the first procedure was excluded. Of the 40 patients who met the inclusion criteria, 37 were available for follow-up. On the basis of standard clinical and histologic criteria, the patients were assigned to one of the following three groups: segmental colonic disease (21 patients); pancolitis with rectal sparing (6 patients); and proctocolitis (10 patients). The indication for the initial surgical procedure was intractability of disease in two-thirds of the patients and either an acute abdomen, obstruction, bleeding, or fistulization in the others. The initial operations performed on the patients with pancolitis or proctocolitis included 10 proctocolectomies for panproctocolitis and 6 abdominal colectomies in patients with rectal sparing (3 ileoproctostomies and 3 ileostomy and Hartmann pouch procedures). Among the 21 patients with segmental colonic disease, there were 9 right hemicolectomies with ileocolostomies, 8 left hemicolectomies (5 with primary anastomosis and 3 with end colostomies), 3 sigmoid resections, and 1 abdominoperineal resection with end colostomy. Intestinal continuity was established in 18 of the 21 patients with segmental colonic disease. Postoperative recurrence was defined as any evidence of Crohn’s disease by standard clinical, radiologic, and pathologic criteria. Average follow-up time was 5.5 yr. Recurrence of disease occurred in 19 of the 37 patients (51%). Disease recurred in about two-thirds of the patients with either segmental colectomies or total abdominal colectomies and in only 20% of the patients with proctocolectomies. Some patients had more than one recurrence and most of the patients whose disease recurred required further surgery. In 4 of the 6 patients who initially underwent abdominal colectomies and were initially free of rectal disease recurrence took place in the rectum, but not in the small intestine. Recurrences in the group who underwent segmental resection were in both the colon and the small intestine. At the end of the follow-up period, 81% of the 21 patients who had initially undergone segmental resection still had intestinal continuity. Comment. Discussions concerning the management of Crohn’s colitis are complicated by the variety of presentations and management options. It was only about 25 yr ago that the entity of Crohn’s disease involving the colon alone was accepted and recognized (Gut 1964;5:493-509; N Engl J Med 1963;269:379-85). It is now clear that Crohn’s colitis can involve patchy areas of the
Vol. 95, No. 5
colon, the whole colon, the whole colon sparing the rectum, and even the rectosigmoid alone. Defining recurrence of disease has also been problematic. Some authors use symptoms to define recurrence, others require radiologic or biopsy confirmation of disease, and some define recurrence of disease as disease requiring another surgical procedure. It is important in comparing studies to carefully describe the population and the criteria used for classification. In this retrospective review, the authors have carefully defined their study population of 37 patients. These were patients who had only colonic disease. There were initially three types of operations performed on the group: proctocolectomy, segmental colectomy, and total abdominal colectomy. Recurrence of disease was defined by evidence of disease on colonoscopic, barium, or pathologic study. In the group of patients that had proctocolectomies and ileostomies, 2 of 10 had disease recurrence and required small intestinal resections. In the group that had abdominal colectomies. 4 of 6 patients developed rectal disease and 3 of these underwent proctectomy. In the group of patients that had recursegmental resections, 13 of the 21 patients experienced rence. In this group, the sites of recurrence are, unfortunately, not described in detail, but recurrences occurred both proximal and distal to the anastomosis and in the small intestine. The strong point the authors make is that even though there was a high rate of reoperation in this group with segmental disease, 81% of the patients retained intestinal continuity during the period of observation. This study is weakened by the very short follow-up period of 5.5 yr. In a disease that has so high a recurrence rate and begins often at a young age, clinicians must look past a 5-yr follow-up in planning their management. The small number of patients is also a cause of concern, but on the other hand permits a detailed examination of the individual procedures and courses of the patients. Recurrence rates should probably not be reported solely as crude recurrence rates as was done here, but as actuarial curves where the number of patients at risk is taken into consideration. A number of studies have shown a marked increase in recurrence rates when actuarial curves are used (N Engl J Med 1975;293:68590). The authors examine the average age at time of presentation of disease and then compare that age with the average age at recurrence; actuarial curves would give a better idea of the time to recurrence. The rate of recurrence of disease after total proctocolectomy and ileostomy is a controversial issue, which this study in part addresses. Recurrence rates for Crohn’s disease after a first operation are reported by actuarial analysis to be between 70% and 90% (N Engl J Med 1975;293:685-90, Gastroenterology 1985;88: 1826-33). The present study had an overall crude recurrence rate of 51%, which would likely be higher using actuarial data. However, the crude recurrence rate after total proctocolectomy and ileostomy was 20%. similar to what some have found [World J Surg 1980;4:173-82). Previous attempts to study this issue are possibly complicated by reoperations for stoma1 dysfunction being erroneously labeled as recurrence of disease. The patients in the present study who underwent this operation had panproctocolitis. It remains unclear whether the rate of recurrence in the small intestine would be similarly low if patients with limited segmental disease also had a total proctocolectomy rather than segmental resection. The answer to this issue depends on how often patients with segmental colonic disease experience recurrence in the small intestine, and this is not agreed upon. Furthermore, the figure of 20% may not be accurate when larger numbers of patients are examined over longer periods of time using actuarial methods. The issue of where in the bowel recurrences occur remains unclear. There is a trend in the literature to suggest that recurrence
generally
occurs
proximal
to the
anastomosis
(Gut
November
SELIXTED
1988
1972;13:973-5), although this is disputed by others (Dig Dis Sci 1981:26:528-31). In this study, there were recurrences in the rectum after ileorectal anastomosis and recurrences in the small intestine after segmental colonic resection. What seems indisputable is that the likelihood of a recurrence of disease after any operation besides proctocolectomy and ileostomy is at least 60%-70% if not >90% over a long follow-up period. The authors argue that the recurrence rates notwithstanding, the best procedure to do is segmental resection of diseased bowel. The justification for this is that the quality of life is improved by delaying the need for permanent ileostomy. This conclusion, although it seems reasonable, i.e., save as much large bowel as possible and avoid ileostomy for as long as possible, may not necessarily be the best course for all patients. If the price of maintaining intestinal continuity is steroid treatment, repeated colonoscopies. continued physician visits, and further operations, some patients might choose the more definitive procedure of proctocolectomy and take the 20% chance of a small bowel recurrence, assuming the 20% recurrence rate is accurate. Current practice seems to be in line with the authors’ suggestions that segmental resection and intestinal continuity should be the aim of surgery. More studies are needed from centers where large numbers of patients with Crohn’s colitis are operated upon. The issue of small bowel recurrence after either proctocolectomy or segmental colonic resection needs further study. A.M. MAGUN. M.D.
VASCULAR ADDRESSINS: TISSUESPECIFIC ANTIGENS THAT MAY CONTROL LYMPHOCYTE HOMING TO LYMPHOID TISSUES PR, Berg EL, Rouse BTN, Bargatze RF, Butcher EC (Department of Pathology, Stanford University School of Medicine, Stanford, California, and Veterans Administration Medical Center. Palo Alto, California) A tissuespecific endothelial cell molecule involved in lymphocyte homing. Nature 1988;331:41-6. Streeter
Lymphocytes home to and enter specific tissues by adhering to and migrating through high endothelial venules, which are specialized cuboidal endothelial cells. This provides a regulatory mechanism for the trafficking of lymphocytes from one organ to another via the bloodstream and allows the homing of distinct lymphocyte subsets with tissue specificity. Streeter and coworkers have now identified endothelial cell recognition elements involved in tissue-specific lymphocyte interactions with high endothelial venules by the production of monoclonal antibodies. They produced two monoclonal antibodies that defined an endothelial cell surface antigen present on high endothelial venules in mucosal tissues and that is absent from high endothelial venules in nonmucosal sites. Furthermore, this antigen functions as a mucosa-specific endothelial cell marker and recognition element that is required for the selective extravasation of lymphocytes in mucosal lymphoid tissues. The monoclonal antibodies were produced by immunizing rats with endothelial cells isolated from mouse mesenteric and peripheral lymph nodes. The resultant hybridomas were screened for monoclonal antibodies that would stain mouse high endothelial venules by immunohistologic staining techniques. Two antibodies (MECA-89 and
SUMMARIES
1427
MECA-367) stained high endothelial venules in mucosal lymphoid organs and Peyer’s patches, but not high endothelial venules in peripheral lymph nodes. Mesenteric lymph nodes revealed a heterogeneous staining pattern, indicating that some high endothelial venules express mucosa-associated antigens whereas others do not. Both large and small intestinal lamina propria contained venules that stained with the monoclonal antibodies. Furthermore, lactating mammary gland, which is a mucosal tissue into which mucosa-specific lymphoblast populations such as immunoglobulin A plasma cell precursors home, also had venules that stained positively with the monoclonal antibody. In contrast, skin did not stain with either of the monoclonal antibodies. The antigen against which the antibodies were directed was identified as a protein of -62,000 (58,000-66,000) molecular weight. Functional assays demonstrated the biologic capabilities of the mucosa-specific antigen. Frozen sections of tissue were used to assess the ability of lymphocytes to bind to high endothelial venules. MECA-367 but not MECA-89 resulted in a 92% reduction in the ability of Peyer’s patch high endothelial venules to bind lymphocytes. Similarly, MECA-367 but not MECA-89 inhibited lymphocyte binding to mesenteric lymph node high endothelial venules by 52%. In contrast, neither monoclonal antibody had any effect on lymphocyte binding to peripheral lymph node high endothelial venules. Pretreatment of high endothelial venules with the monoclonal antibody MECA-367 inhibited binding, whereas pretreatment of lymphocytes did not alter high endothelial venule binding capabilities. Streeter and coworkers then utilized cells capable of binding to high endothelial venules in a tissue-specific manner and found that MECA367 could completely block the binding of a mucosal high endothelial venule-specific binding cell line (TKl) to high endothelial venules in Peyer’s patches and mesenteric lymph nodes. In contrast, MECA-367 had no effect on the binding of the peripheral lymph node-specific cell line (38C13) to peripheral or mesenteric lymph node high endothelial venules. Thus, the monoclonal antibody MECA-367 was able to specifically interfere with lymphocyte recognition of high endothelial venules via a blocking of mucosa-specific recognition systems. In contrast, the monoclonal antibody MECA-89, although similar in its staining pattern and similar in the nature of the antigen being recognized, did not block adherence. Finally, Streeter and coworkers examined the physiologic effects of blockade of lymphocyte homing by injecting mice with MECA-367 monoclonal antibody. Chromium 51-labeled mesenteric lymph node cells were then injected into the mice 4 h later. Treatment with MECA.-367 resulted in nearly complete (97%) blockade of lymphocyte binding to Peyer’s patches and a partial (37%) reduction in homing and localization of lymphocytes into mesenteric lymph nodes. Comment. At least three independent lymphocyte, high endothelial venule recognition systems have been identified that are capable of mediating lymphocyte binding to high endothelial venules in either peripheral lymph nodes. mucosal lymphoid tissues, or the synovium of inflamed joints. The present important and excellent study by Streeter and coworkers defines antigens on