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Systemic amyloidosis is caused by a variety of different diseases and frequently involves the gastrointestinal tract. Each type of amyloid affects the gastrointestinal tract differently. This article reviews the unique pathogenesis, pattern of gastrointestinal disposition, diagnosis, and treatment of the five systemic amyloidoses, and discusses the gastrointestinal diseases that cause systemic amyloidosis: inflammatory bowel disease and familial Mediterranean fever.

Since 1939, a series of clinical reports and laboratory investigations have suggested that the intestinal fecal stream may play a significant part in the pathogenesis of Crohn's disease (CD). The beneficial effect of exclusion of the stream by ileostomy was followed by improvement in patients with CD of the ileum and colon despite little change in the histopathology of the excluded loop, even to the point of allowing restoration of intestinal continuity in some patients. End ileostomy lowers the risk of recurrence of CD compared with anastomotic operations. Ileostomy effluent can reactivate the clinical activity of quiescent bypassed bowel and some of its biochemical processes, and may be related to an ultrafilterable constituent > 5 microns. Experimental models of inflammatory bowel disorders in immunologically altered rodents (transgenic, knockout, or spontaneous) require the presence of normal luminal bacteria, especially of the Bacteroides species, and respond to antibiotic (metronidazole) therapy. Thus, many but not all of the well-recognized clinical features of CD are compatible with a pathogenetic role of the fecal stream. Although difficult to quantitate, this concept opens the way to a variety of testable research lines, and allows some speculation regarding its clinical implications.

Summary: Five children with ulcerative colitis for whom surgery was recommended were treated with cyclosporine. The five had received corticosteroids for 1–24 months. The group included two patients with acute-onset ulcerative colitis and three with acute exacerbations of intractable corticosteroid-dependent chronic ulcerative colitis. The average age at initiation of cyclosporine therapy was 13.8 years (range, 11.5–16); all five patients were boys. Cyclosporine was initiated in the hospital by continuous i.v. infusion. Trough levels of 400–600 ng/dl (measured by radioimmunoassay) were achieved, at which point oral cyclosporine was given and oral dosage was adjusted to similar levels. Significant hypertension requiring medical attention was seen in one patient. Of the two recently diagnosed acute cases, one failed to respond and required subtotal colectomy after 2 weeks of treatment, and the other, despite an initial response, had a subtotal colectomy 10 months later. Of the three corticosteroid-dependent children, none was able to be weaned from corticosteroids and all underwent subtotal colectomy. Our experience emphasizes that the appropriate role of cyclosporine as therapy for children with ulcerative colitis is yet to be determined. Cyclosporine was not effective as an alternative to surgery in our patients.

We have conducted a meta-analysis of 16 placebo-controlled trials of single drug therapy in ulcerative colitis (UC) for both induction (11 trials) and maintenance of remission (five trials). A total of 468 and 343 patients, respectively, was studied. Various clinical criteria of success were analyzed. The Dersimonian-Laird method for meta-analysis was used to calculate the risk difference. Therapeutic advantage, defined as the difference between drug and placebo response, was also determined. Using various criteria of success, single drug therapy for the induction of remission conferred a therapeutic advantage of 37-48% over placebo. In trials for maintenance of remission, the therapeutic advantage at 6 months was 21%, whereas at 12 months the therapeutic advantage rose to 46% because of a decline in placebo responders with time. In conclusion, meta-analysis has established a standard of reference against which future drug trials can be compared. This standard of reference for drug and placebo rates, as well as the corresponding therapeutic advantages, can help determine the relative value of newer agents in the therapy of UC.

This article deals with the dilemmas in the definition, diagnostic work-up, and treatment of patients with the irritable bowel syndrome. The data presented are a blend of scientific insight to date and more than four decades of clinical experience with this disorder.

Medicine in the late plays of Shakespeare evolves into something rich and strange. The physician, transformed into a magus enlightened through his ‘secret studies’, becomes capable of invoking supernatural forces in his cure of souls and bodies as the magic of his invocations is infused with the magic of music. The magic of this therapist has been much discussed1,2, but this paper is directed to the role of the magic of music in the romances of Shakespeare. The contribution of music to the magus's magic is best viewed in the context of the revival of the tradition of the ancient occult philosophy which was promulgated by the Neoplatonists at the Medici Court of Florence. This was stimulated by the recovery of the texts of Plato and the Corpus Hermeticum in the translation of Marcilio Ficino (1433-1499) and his follower Pico della Mirandola (1463-1494). The addition of music to the magic of the old occult tradition was elevated by Ficino, son of a physician and himself a practising physician. Two strands were involved in the development of the magic of music in the growth of magic itself: one was the concept of the music of the spheres, the harmony of the universe; the other the concept of the power of music to influence the human mind and soul. The one part, the philosophical basis of music's power, was derived from Pythagoras' observations (born c 580 BC) based on the relation of the length of strings of instruments to the musical notes which they produced when vibrating. From this he had evolved the idea that the explanation of the universe is to be sought not in matter but in musical numbers and their relationships. The other part of the concept, of music as therapy, followed in part from Ficino's writings influenced by Plotinus, the third century Neoplatonist. Ficino had accepted the Stoic notion which postulated a cosmic affect (spiritus mundi) permeating the entire universe and furnishing a pathway between the heavens and the world. At the same time the spirit was an instrument of the incorporeal soul. Sound affected the spirit more than sight because it transmitted movement and itself was moving, whereas sight merely reproduced the static surface of things. In this way, Agrippa in De Occulta Philosophia (1533) united the two strands: ‘Thus no songs, sounds and instrumental music are stronger in moving the emotions of man and in inducing magical impression than those composed in number, measure, and proportion as likenesses of the heavens’3. Music is effective in so far as it mirrors the harmony of the music of the spheres.

In the nearly 20 yr since collagenous colitis was first recognized, the results of therapies have not been systematically described in substantial numbers of patients. We have therefore conducted a retrospective analysis of 26 patients treated in this institution during the years 1991-1994.Twenty-nine cases of collagenous colitis were obtained by review of biopsy specimens collected between 1991 and 1994 at The Mount Sinai Hospital. Each chart was reviewed for patient demographics, symptoms, coexisting conditions, specific therapies, and therapeutic outcomes. Additional data were obtained from telephone calls to patients when deemed necessary. Three patients were exeluded from the study because of lack of follow-up. Therapeutic outcomes were defined as follows: Complete Remission (CR): normalization of bowel function; Partial Remission (PR): 50% reduction in frequency of bowel movements; Failure:50% reduction in frequency of bowel movements; or Relapse: return of symptoms after cessation of treatment. Median follow-up was 58 wk from time of diagnosis, with a range of 22-376 wk.The 26 patients (25 women, one man) had a mean age of 62 yr (range, 22-85 yr) at diagnosis. Of 26 patients, 22 responded to some form of therapy and one had spontaneous remission. Six of the responders ultimately remained in CR with no therapy. Twelve are maintained on 5-aminosalicylic acid (5-ASA) and or antidiarrheals to control symptoms. An additional six required prednisone throughout the follow-up period to remain in CR or PR. Two patients failed all therapy.Collagenous colitis is a treatable condition in most patients. We recommend initial therapy with antidiarrheals, followed by a trial of 5-ASA agent. A trial of 5-ASA in combination with prednisone should be attempted in patients refractory to 5-ASA alone, with subsequent attempts in the responders to taper prednisone and maintain remission with no therapy, if possible, or with 5-ASA and/or antidiarrheal agents if necessary.

I have conducted an experiment in medical subspecialty education during the last 10 years in the division of gastroenterology of the Mount Sinai School of Medicine in the form of 3-month preceptorships during the second year of the fellowship. I recognized that our training program, along with other subspecialty training programs, was no longer a purely hospital affair, but its future lay as well in the outpatient setting. I wanted to have the fellows participate in the daily care of patients in the realistic setting of practice. I hoped to offer them the excitement, as well as the problems, of daily gastroenterology practice. By seeing new and established patients with gastrointestinal problems in four daily sessions, and caring for hospitalized patients, including those being operated on, the fellows were to participate in every aspect of a busy office. The flavor of reality was to be heightened by their exposure to the preceptor's uncensored discussions with the patient, the family, the radiologists, endoscopists, and referring physicians. Here I report what the fellows and I have learned from experience, and I address the problems we all must face in the era of managed care, with the ongoing reduction in the number of specialists. I also consider who will do the teaching and who will pay them to protect the time they need.

Although the etiology of inflammatory bowel disease remains unknown, current evidence favors the interplay of genetic predisposition with environmental factors. Clustering of inflammatory bowel disease in spouses had been described, and supports a role for an environmental agent. We describe three unrelated, unmarried men all attorneys who enjoyed a close, sustained friendship in college, and who within a decade of their contact developed inflammatory bowel disease. We describe the nature of their college contact, the course of their inflammatory bowel disease, and relate our cluster to the scanty literature on clustering in inflammatory bowel disease. Physicians should report similar observations to illuminate the roles of genetics and environment in the development of these illnesses.

Amyloidosis is a rare but serious complication of inflammatory bowel disease (IBD), especially Crohn's disease (CD). It occurred in 15 of our 1709 patients with CD (0.9%) (706 with ileocolitis, 310 with colitis, and 693 with enteritis), but in only 1 of our 1341 patients with ulcerative colitis (UC) (0.07%), admitted to The Mount Sinai Hospital between 1960 and 1985. Eleven of the patients with CD who had amyloidosis had ileocolitis, 2 colitis, and 2 ileitis; these figures represent a frequency within each group of 1.6%, 0.6%, and 0.3%, respectively. Amyloidosis was thus associated 4.4 times more often with CD of the colon than with pure small bowel disease. We have added to this group of 15 patients the 5 cases of CD that were originally reported by Werther et al in 1960, plus another 4 (2 with UC and 2 with CD) who have been seen since 1985, making a total of 25 patients in this series, 22 with CD and 3 with UC. There was a striking male preponderance, 16 of 22, among patients with CD, although 2 of the 3 patients with UC were female. Amyloid disease was diagnosed at a mean age of 40 years, 15 years (range, 1-42) after the onset of CD. Six major forms of amyloidosis occurred: nephropathy, enteropathy, cardiomyopathy, hepatosplenomegaly, thyroid mass, and generalized amyloidosis. Renal disease with proteinurea and/or renal insufficiency occurred in 18 of the 22 patients with CD and in all 3 with UC. Nephropathy was by far the most common lethal manifestation of IBD-associated amyloidosis in this series. Nephrotic syndrome developed in 15 patients with CD and was accompanied by renal failure, the major contributor to mortality, in 10 of the 13 patients who died. Amyloidosis may be associated with suppurative or other extraintestinal manifestations of IBD. Fifteen of the 22 patients with CD who had amyloidosis also had suppurative complications of their bowel disease, although the other 7 had no recognizable suppuration. Extraintestinal manifestations were also common in this series, occurring in 12 of 22 patients with CD and in 2 of the 3 patients with UC; 6 of the 18 patients with nephrotic syndrome also had arthritis. However, there is no evidence that patients with IBD with amyloidosis have extraintestinal manifestations more frequently than do IBD patients without amyloidosis. Earlier reports of amyloid associated with IBD came from autopsy series. In recent years, biopsy has allowed diagnosis to be made during life.(ABSTRACT TRUNCATED AT 400 WORDS)

We have conducted a meta-analysis of 12 placebo controlled trials to determine the efficacy of single drug therapy in Crohn's disease for both induction (seven trials) and maintenance (five trials) of remission. A total of 767 and 796 patients were studied, respectively. Various clinical criteria of success were analyzed. The Dersimonian-Laird method for meta-analysis was used to calculate the risk difference (RD). Therapeutic advantage, defined as the difference between drug and placebo response, was also determined. Using various criteria of success, we found that single drug therapy conferred an 11-29% therapeutic advantage (RD = 0.13-0.33) over placebo for the induction of remission. In trials for maintenance, no therapeutic advantage was found for single drug therapy over placebo. All forms of maintenance therapy followed nearly identical linear rates of relapse over time, showing an approximately 90% maintenance of remission rate at 3 months, which decreased to 25% at 36 months. In conclusion, meta-analysis has established a standard of reference against which future drug trials can be compared. This standard of reference for drug and placebo rates, as well as the corresponding risk differences and therapeutic advantages can help determine the relative value of newer agents in the therapy of Crohn's disease.

Nine patients with lymphoma occurring in association with inflammatory bowel disease were admitted to The Mount Sinai Hospital between 1960 and 1983. Five (two men and three women) occurred among 1156 patients (0.43%) with ulcerative colitis (UC) and four (men), among 1480 patients (0.27%) with Crohn's disease (CD), a strong male preponderance in the latter group. In all four of the patients with CD and in four of the five patients with UC, the lymphomas were extraintestinal. The mean age of onset of UC in these patients was late (46 years, 19 years older than in our overall series), with lymphomas occurring a mean of only 12 years later. By contrast, patients with CD had bowel disease much younger (mean age, 26 years), and their lymphomas appeared after a longer disease duration (mean, 24 years). The risk factors for the one patient with colonic lymphoma were similar to those with colitis-associated colorectal carcinoma: extensive and long-standing colitis and relatively young age when malignant disease developed. Four of the patients with lymphoma had associated colonic carcinoma; in three of them, the carcinoma appeared within the first decade of colitis, an unusual occurrence. A second malignant lesion also occurred in three patients with UC.

We evaluated the efficacy of fish oil n--3-omega-fatty acids, inhibitors of leukotriene synthesis, in the treatment of ulcerative colitis. An open trial of 10 patients with mild to moderate ulcerative colitis who had either failed (n = 9) or refused (n = 1) conventional therapy was performed. Patients received 15 MAX-EPA capsules containing a total of 2.7 g of eicosapentanoic acid in three divided doses daily for 8 weeks. The activity of ulcerative colitis and response to therapy was based upon daily stool diaries, sigmoidoscopy, and symptomatic response. All patients tolerated the fish oil and showed no alteration in routine blood studies. Seven patients had moderate to marked improvement; steroid dose could be reduced in four of the five patients on prednisone. Three patients had little or no improvement. No patient worsened. These results of our open study appear to justify a double-blind trial of this dietary supplement in ambulatory patients with ulcerative colitis.

It appears well established that the recurrence rates following operations for Crohn's disease of ileum and colon are higher after anastomotic operations than after an end ileostomy. To obtain further information regarding the rate of recurrence following end ileostomy we reviewed the charts of 182 patients: 117 with involvement of the ileum as well as the colon, and 65 with Crohn's colitis only, who were operated upon at the Mt. Sinai Hospital during 1952-1984. They were followed until death or the first ileostomy revision or the last contact. Of the ileocolitis group, 50 patients (43%), and of the colitis group, nine patients (14%) required an ileostomy revision. Of the 50 with ileocolitis, 34 (29%) and four of the colitis group (6.2%) had revisions done primarily for recurrent Crohn's disease at or near the stoma. The estimated overall cumulative probability of recurrence was 50% twenty years following ileostomy, and was significantly higher in the ileocolitis group than in the colitis group (64% vs. 15%; p < 0.001), with mean follow-up durations of 6.5 and 7.5 years, respectively. The probability of ileostomy revision for any reason was also significantly higher for patients with ileocolitis (74% vs. 34%; p < 0.001). We conclude that the site of initial Crohn's disease plays a role in the recurrence of disease in an end ileostomy, with a better outlook for patients with colonic involvement alone.

The case histories of 1961 patients with inflammatory bowel disease (IBD), 1227 with Crohn's disease (CD) and 734 with ulcerative colitis (UC), have been studied for the incidence of extraintestinal malignant neoplasms. There were 54 extraintestinal cancers in 51 patients: 28 patients with CD and 23 with UC; 25 men and 26 women. There were 9 breast, 7 skin, 15 reticuloendothelial, 11 genitourinary, 3 lung, 3 perianal, 2 pancreatic islet cell, and several miscellaneous cancers. The number of patient-years from the onset of disease to the last date of follow-up was calculated for men and women with each form of IBD. The observed number (O) of neoplasms was recorded. The expected number (E) of neoplasms was derived from the Department of Health, Education, and Welfare (DHEW) incidence figures for the same neoplasms that occurred in a standard age- and sex-matched population. The O/E ratio was then calculated for each type of cancer as well as for the entire series. There were no statistically significant increases in overall O/E ratios of extraintestinal cancers for either CD (0.76) or UC (1.32). On the other hand, several specific types of cancer did appear to occur with a frequency that was significantly greater than expected. These cancers were classified into two groups. The first group included reticuloendothelial neoplasms. There was an excess of leukemias in UC (P less than 0.005) and an excess of lymphomas in both UC and CD (P less than 0.005). The second group included three squamous cell cancers of the perianal region, an incidence 30 times greater than expected, and two squamous cell cancers of the vagina, also in excess of the expected number. Lymphoma, leukemia, and squamous cell cancers have been reported to occur in excess in immunosuppressed or irradiated patients. It may therefore be speculated that the apparently increased incidence of these neoplasms in the patients with ileitis and colitis might be related to immunologic deficiencies associated with IBD, to the long-term administration of steroids or other immunosuppressive medications that were given to most of the patients or, possibly, to increased exposure to ionizing radiation. The apparently increased incidence of perianal and vaginal cancers of the squamous variety might be a consequence of the combined effects of chronic inflammatory disease involving these areas and primary immune suppression.

SummaryThe leukocyte migration technique was employed to study in vitro cell-mediated immune responses to purified CEA in patients with Crohn's disease and active ulcerative colitis and in those with colonic and pancreatic carcinoma.No significant inhibition of leukocyte migration was demonstrated by CEA, with the exception of one patient with pancreatic carcinoma. Thus, with the leukocyte migration technique, no consistent in vitro cell-mediated immunity to CEA was demonstrated supporting the hypothesis that CEA is not the antigen toward which cell-mediated host response phenomena are directed.The authors wish to thank Jacques Vandevoorde, of the Hoffmann-La Roche Research Division, Nutley, NJ, for performing the radioimmunoassays for CEA and Carlos Pereira for skillful technical assistance.These studies were supported under U.S.P.H.S. Grant No. Al 09857, a N.I.H. Training Grant (AM-05126), and Mount Sinai Clinical Genetics Center Grant No. GM 19-443.

We describe two cases of universal ulcerative colitis in which toxic megacolon was complicated by the unusual occurrence of air tracking retroperitoneally through the diaphragm and the mediastinum, without signs of free intraperitoneal air, and ultimately presenting as subcutaneous emphysema in the neck. Physicians should remain alert to this unusual presentation of air leakage from the colon in toxic ulcerative colitis, in order to appreciate the potential gravity of the situation.

Cancer occurred in 28 of 579 patients (4.8%) with Crohn's disease (CD) and in 30 of 267 (11.2%) with ulcerative colitis (UC) admitted to the Mount Sinai Hospital between 1960--1976. The proportion of cancers that were extraintestinal was greater in CD than in UC (43 vs. 12%), as was the proportion of gastrointestinal cancers that arose in apparently normal bowels (33 vs. 4%). The incidence of gastrointestinal cancer increase with duration of disease in both CD and UC, but the absolute rates were three times higher in UC. For extraintestinal cancer, on the other hand, there was less correlation with increasing duration of disease, and no higher frequency in UC than in CD. Mortality from gastrointestinal cancer was 82% in CD and 50% in UC, but occurred only within two years of tumor diagnosis; survival beyond two years seemed to indicate a favorable prognosis.

To evaluate the pathogenetic significance of impaired cellular immunity in inflammatory bowel disease (IBD), we have measured the cutaneous responsiveness to dinitrochlorobenzene (DNCB) among 58 patients with IBD, 33 with Crohn's disease and 25 with ulcerative colitis, 63 of their clinically normal relatives, 24 additional ileitis and colitis patients who had undergone resection of all visibly diseased bowel, and 23 control subjects. Cutaneous anergy to DNCB was demonstrated among 70% of the patients with CD and 48% of those with UC, as against only 9% of the controls (p less than 0.001). There was no increased incidence of anergy among either 44 first-degree relatives (7%) or 19 spouses (3%), nor was there any special proclivity toward anergy among six pairs of patients with familial inflammatory bowel disease. In Crohn's disease, anergy was still present after bowel resection in six of 10 patients (60%), while in ulcerative colitis anergy was found after colectomy in only two of 14 patients (14%). Our data suggest that the immune defect in patients with inflammatory bowel disease may be a secondary phenomenon. In ulcerative colitis, the defect appears to reverse after colectomy, but in Crohn's disease it persists despite resection. This finding is consistent with the observed tendency of Crohn's disease, but not ulcerative colitis, to inexorable postoperative recurrence.

The authors estimated cancer risk among 589 patients hospitalized with Crohn's disease between 1960-1976 by calculating the ratios of observed number of cancers (O) in our hospital sample to the expected number of cancers (E) based on the age- and sex-specific cancer rates of a standard population. The authors then compared these O/E ratios with the O/E ratios similarly calculated among 267 patients hospitalized with ulcerative colitis. The risk of colorectal cancer was significantly increased in Crohn's disease (O/E = 6.9, P less than 0.001). This increase was similar in magnitude to that found in left-sided ulcerative colitis (O/E = 8.6, P less than 0.001) but was much less than that found in universal ulcerative colitis (O/E = 26.5, P less than 0.001). The incidence of small bowel cancer was greatly increased in the combined group of regional enteritis and ileocolitis (O/E = 85.8, P less than 0.001), and even more so in the regional enteritis group alone (O/E = 114.5, P less than 0.001). The incidence of extraintestinal cancer did not increase in any of the patient groups.

Sixty-six outpatients with active ulcerative colitis who were intolerant of sulfasalazine were treated in a double-blind randomized trial. They received placebo or olsalazine sodium in daily doses of 0.75, 1.5, or 3 g. Overall, 35% of patients receiving olsalazine improved clinically, compared to 16% of patients receiving placebo. When the colitis activity at study entry was compared with that observed at the completion of the study period, statistically significant or nearly significant improvement was demonstrated within the combined olsalazine group (p = 0.01) and within patient groups receiving olsalazine at daily doses of 1.5 g (p = 0.04) and 3 g (p = 0.055). A dose-response relationship was suggested because 16%, 29%, 27%, and 50% of patients improved in the placebo and 0.75-, 1.5-, and 3-g olsalazine groups, respectively, (p = 0.04). A similar pattern of improvement was seen when sigmoidoscopic criteria were used, although a dose-response relationship was not demonstrated. There were no differences between the treatment and placebo groups for any of the adverse effects or laboratory variables reported at baseline or during the trial period. Four patients were withdrawn because of adverse reactions: 2 developed a skin rash while receiving olsalazine and 2 had diarrhea, one while on olsalazine and the other while on placebo. The data suggest that olsalazine is effective for the treatment of ulcerative colitis and is well tolerated among patients intolerant to sulfasalazine.

A young woman who developed acute pancreatitis coincident with Crohn's disease is presented. The pancreatitis was documented by pancreatic hyperamylasemia, elevated urine amylase activity, abdominal sonogram, computed tomography, and laparotomy. A cause-and-effect relationship has not been established, however; no etiology other than the Crohn's disease, which was confined to the ileum and colon, could be identified. Surgical removal of the severely involved ileum led to the resolution of the pancreatitis. A possible relationship between acute pancreatitis and Crohn's disease is proposed, although potential pathophysiologic mechanisms are unknown. The diagnosis of pancreatic involvement in such cases may make an important contribution to therapy.

Operations for intraabdominal abscess were performed in 46 (20 percent) of 230 patients with Crohn's colitis and ileocolitis treated at the Mount Sinai Hospital during the decade 1964 to 1974. Internal and external fistulas, intestinal obstruction, and abdominal mass occurred significantly more often in patients with intraabdominal abscess, while only overt bleeding was significantly less common. Abscesses were equally divided between 23 patients who had undergone previous surgery and 23 cases of spontaneous onset. In ileocolitis, the most frequent site of origin was the terminal ileum with right lower quadrant abscess, as opposed to a sigmoid origin in colitis with presentation in the left lower quadrant. There was no mortality among 24 patients treated with simple drainage, usually for superficial abscess, but enterocutaneous fistulas persisted in 5 of these patients (21 percent). Four of 11 patients (35 percent) died after undergoing bypass or ileostomy diversion. Among the 31 patients surviving either of these procedures, 18 (60 percent) required subsequent resection of the diseased bowel. By contrast, among 11 patients treated with primary en bloc resection plus drainage, there was only 1 death (9 percent) and no abscess recurrence or chronic enterocutaneous fistula formation during a follow-up period of 1 to 4 years. The high mortality rate after bypass may be explained by the more serious nature of the disease and the preexisting deep intraabdominal abscess and postoperative sepsis. Simple extraperitoneal drainage is a safe procedure associated with an extremely low mortality; however, when feasible, resection of the diseased bowel seems to be the treatment of choice for abscess in patients with Crohn's colitis and ileocolitis.

Sixty-six patients hospitalized for ulcerative colitis were treated in a prospective, double-blind, clinical trial. They received either 120 U/day of intravenous corticotropin or 300 mg/day of intravenous hydrocortisone. Patients were randomized within strata defined by whether they had received oral corticosteroids continuously for at least 30 days before the study (group A, 35 patients), or whether they had received no such prior treatment (group B, 31 patients). Twenty-eight of the 66 patients (42%) achieved remission. In group B, the proportion of patients entering remission was greater with corticotropin than with hydrocortisone (63% vs. 27%, 0.025

it is a diarrheal disease with relatively infrequent bleeding, associated with fever, abdominal masses, anal and perianal lesions, and growth retardation in the young. Enteric fistulas and sinus tracts are characteristic. The involved gut displays linear ulcerations, deep fissures, and enlarged regional lymph nodes. Histologically, the inflammation may spare the mucosa but involves all other layers, especially the submucosa. It is characterized by the aggregation of chronic inflammatory cells, especially histi­ ocytes and macrophages, and by the presence of sarcoid-like non-caseating granulo­ mas, which may extend throughout the entire thickness of the bowel wall and be present in the regional lymph nodes. We assume that Crohn's disease is one disease wherever it occurs, and urge that it should be separated from other "nonspecific" inflammatory diseases of the bowel, although we grant that this may not be possible in all cases.

A retrospective study of 267 patients with ulcerative colitis admitted to The Mount Sinai Hospital during the period 1960--1976 revealed 26 (9.7%) with adenocarcinoma of the colon. Twenty-one cases of colorectal cancer were observed among 158 patients with universal colitis (13%), and 5 occurred among 109 patients with left-sided disease (5%). Patients with left-sided disease tended to develop cancer at least a decade later than patients with universal disease. The median duration from onset of colitis to diagnosis of cancer was 20 yr for those with universal colitis, and 32 yr for those with left-sided colitis. The decade incidence of colorectal carcinoma increased from 0.4% in the first decade to 7.4% in the second, 15.9% in the third, and 52.6% in the fourth decade of follow-up. The estimated cumulative probability of developing cancer reached 34% at 30 yr and 64% at 40 yr. Cancer risk was positively correlated with duration and anatomic extent of colitis, but did not appear to be increased by early age at onset of disease.

Clostridium difficile toxin, the presumed mechanism of antibiotic-associated pseudomembranous colitis, has been suggested as a contributory factor to mucosal injury in inflammatory bowel disease. We evaluated its incidence and apparent role in 65 consecutive patients with diarrheal and inflammatory bowel diseases. Toxin was demonstrated in 3 of 18 patients with ulcerative colitis (17%), 1 of 26 with Crohn's colitis (4%), and 5 of 21 with a variety of diarrheal illnesses (24%). Toxin appeared only in those who had been exposed to antimicrobials within 2 mo. In inflammatory bowel disease, presence of toxin was not correlated with disease severity. We conclude that Clostridium difficile toxin appears only in patients exposed to antimicrobials and is unlikely to be a significant contributory factor in inflammatory bowel disease.

To identify potential risk factors that influence postoperative recurrence rates of Crohn's disease, the postoperative recurrence-free survival of 93 patients who underwent their first resections at The Mount Sinai Hospital between 1964 and 1973 has been examined. Features analyzed individually and jointly were age, sex, anatomic location, operative procedure, and preoperative disease duration. In patients with Crohn's colitis, recurrence rates appeared somewhat lower among 11 patients with ileostomy than among 5 patients with anastomosis. In the entire series, recurrence rates were lowest in patients with longest preoperative durations (p = 0.02). This same tendency was especially marked among the 68 patients without ileostomies (p = 0.005). Likewise, among the 38 patients with ileitis, the relative risk of recurrence was significantly lower for those with disease duration exceeding 10 yr (p = 0.01). Relative risk of recurrence in the entire series for patients with 2-yr duration was 1.5 compared with those who had 10-yr duration. This inverse association between preoperative disease duration and postoperative recurrence rate may reflect persisting differences between inherently more aggressive versus more indolent forms of Crohn's disease.