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PURPOSE: There is a difference of opinion concerning the role of ileal pouch-anal anastomosis in Crohn's disease, even in the absence of small-bowel or perianal disease. One view is that ileal pouch-anal anastomosis should never be entertained, the other is that ileal pouch-anal anastomosis, like ileoproctostomy, can be justified sometimes, because it allows young people a period of stoma-free life. The aim of this study was to examine the outcome of ileal pouch-anal anastomosis and to contrast it with ileoproctostomy in patients with Crohn's disease without small-bowel or perianal disease. METHODS: Ileal pouch-anal anastomosis was performed in 23 patients with Crohn's disease (12 of whom had evidence of Crohn's disease at the time of operation and 11 who were eventually found to have Crohn's disease as a result of complications) and ileoproctostomy in 35. Patients were matched for age, gender, follow-up, and medication, but all ileoproctostomy cases had relative rectal sparing. Thus, the groups were not comparable and the reasons for ileal pouch-anal anastomosis and ileoproctostomy were therefore quite different. RESULTS: The outcome in ileal pouch-anal anastomosis at a mean follow-up of 10.2 years was pouch excision, 11 (47.8 percent); proximal stoma, 1 (4.3 percent; patient preference); average small-bowel resection, 65 cm; persistent perineal sinus, 8 of 11 having pouch excision (73 percent); and mean time in hospital, 37 (range, 8–108) days. Of those in circuit having ileal pouch-anal anastomosis (n=12), 24-hour bowel frequency was 6, with no incontinence or urgency, but 6 (50 percent) were on medication. When ileal pouch-anal anastomosis was done for Crohn's disease in the resection specimen, only 4 of 12 (33 percent) were excised compared with 7 of 11 (64 percent) in whom the diagnosis was made as a result of complications. The outcome in ileoproctostomy at a mean follow-up of 10.9 years was rectal excision in 3 (8 percent), proximal stoma in 1 (3 percent), average small-bowel resection was 15 cm, persistent perineal sinus in 1 (3 percent), and time in hospital was 21 (range, 8–36) days. Of those in circuit (n=32), 24-hour bowel frequency was 5, 2 had incontinence, 3 had urgency, and 12 (36 percent) were taking medication. CONCLUSIONS: These results indicate that the overall outcome of ileal pouch-anal anastomosis is inferior to that of ileoproctostomy, especially if Crohn's disease was diagnosed as a result of complications. Nevertheless, the functional results of those with a successful outcome are comparable.

In diffuse jejunoileal Crohn's disease, resectional surgery may lead to short-bowel syndrome. Since 1980 strictureplasty has been used for jejunoileal strictures. This study reviews the long-term outcome of surgical treatment for diffuse jejunoileal Crohn's disease.The cases of 46 patients who required surgery for diffuse jejunoileal Crohn's disease between 1980 and 1997 were reviewed.Strictureplasty was used for short strictures without perforating disease (perforation, abscess, fistula). Long strictures (20 cm) or perforating disease was treated with resection. During an initial operation, strictureplasty was used on 63 strictures in 18 patients (39%). After a median follow-up of 15 years, there were 3 deaths: 1 from postoperative sepsis, 1 from small-bowel carcinoma, and 1 from bronchogenic carcinoma. Thirty-nine patients required 113 reoperations for jejunoileal recurrence. During 75 of the 113 reoperations (66%), strictureplasty was used on 315 strictures. Only 2 patients experienced the development of short-bowel syndrome and required home parenteral nutrition. At present, 4 patients are symptomatic and require medical treatment. All other patients are asymptomatic and require neither medical treatment nor nutritional support.Most patients with diffuse jejunoileal Crohn's disease can be restored to good health with minimal symptoms by surgical treatment that includes strictureplasty.

PURPOSE: This study examined risk factors for intra-abdominal sepsis after surgery in Crohn's disease. METHODS: We reviewed 343 patients who underwent 1,008 intestinal anastomoses during 566 operations for primary or recurrent Crohn's disease between 1980 and 1997. Possible factors for intra-abdominal sepsis were analyzed by both univariate (chi-squared test) and multivariate (multiple regression) analyses. RESULTS: Intra-abdominal septic complications, defined as anastomotic leak, intra-abdominal abscess, or enterocutaneous fistula, developed after 76 operations (13 percent). Intra-abdominal septic complications were significantly associated with preoperative low albumin level (

PURPOSE: The aim of this study was to study the natural history of perforating and nonperforating ileocecal Crohn's disease. METHODS: One hundred sixty-five cases of primary ileocecal Crohn's disease operated on between 1975 and 1995 were reviewed. Perforating disease was defined as acute free perforation, subacute perforation with an abscess, or chronic perforation with an internal or external fistula. RESULTS: Perforating disease was identified in 72 patients (44 percent); 11 with acute free perforation, 18 with abscess formation, and 43 with fistulas. Postoperative complications occurred in 29 percent of perforating and in 23 percent of nonperforating disease (not a significant difference). There was no significant difference in the cumulative reoperation-free rate for recurrence at the ileocolonic anastomosis (perforating, 78 percentvs. nonperforating, 73 percent at 5 years and perforating, 61 percentvs. nonperforating, 55 percent at 10 years), or in the median time interval from the primary to the secondary operation (perforating, 49vs. nonperforating, 37 months). Seventy percent of perforating disease re-presented with perforating recurrence. Likewise, 83 percent of nonperforating disease re-presented with nonperforating (P

This study was undertaken to assess the clinicopathologic features and management of gastroduodenal Crohn disease.The medical records of 54 patients with gastroduodenal Crohn disease treated between 1958 and 1997 were reviewed.Gastroduodenal Crohn disease occurred in association with disease elsewhere in 52 patients (96%). The commonest pathology was stricture (n = 41), followed by ulceration (n = 4) and duodenocutaneous fistula (n = 2). Medical treatment was initially attempted in 31 patients, of whom 12 required no surgical treatment for gastroduodenal disease. Nineteen patients required surgery for gastroduodenal obstruction or fistula despite medical treatment. Overall, 33 patients (61%) required surgery; the indication was obstruction in 30, duodenocutaneous fistula in 2, and bleeding in 1. There was one postoperative death because of persistent bleeding and intraabdominal sepsis after oversewing of a bleeding ulcer. In obstructive disease 16 patients were treated by bypass surgery, 10 by strictureplasty, and 4 by gastrectomy. After surgery for obstructive disease anastomotic leak developed in three patients, and persistent gastric outlet obstruction was seen in six patients. In the long term 11 patients required reoperation for anastomotic obstruction (n = 9) or stomal ulceration (n = 2). For duodenocutaneous fistula one patient underwent simple closure of fistula, and the other patient duodenojejunostomy. Both of these patients developed an intra-abdominal abscess without evidence of leak. There has been no fistula recurrence.Gastroduodenal Crohn disease is a complex and difficult problem that is associated with serious complications and need for reoperation.

Objective : To assess the changing distribution of disease within the large bowel in patients presenting with ulcerative proctitis or proctosigmoiditis. To evaluate the influence of clinical exacerbations, smoking, parity and family history in disease extension. Design : Retrospective single-centre study in a university hospital. Methods : Case records of patients presenting over a 40-year period were examined to evaluate the clinical course and disease distribution from initial presentation to final follow-up. For each patient whose disease extended to the more proximal colon, an age- and sex-matched control patient was identified whose disease remained confined to the original site. Patients completed a questionnaire to provide information on family history, smoking and parity. The differences in clinical exacerbations, family history, smoking and parity were then compared between the two groups. Results : Among 145 patients presenting with proctitis or proctosigmoiditis followed prospectively for a median period of 10.9 years, the disease extended in 53 patients. Using actuarial methods the disease progressed beyond the rectosigmoid area in 16% of patients at 5 years and 31% at 10 years. Among the patients whose disease progressed, progression was preceded in 68% of cases by a clinical exacerbation of the colitis. When patients whose disease progressed were compared with those whose disease remained confined to the original site, no differences were detected in the number of clinical exacerbations, smoking habit, family history or parity. Conclusions : The factors that are associated with the extension of colitis are probably different from those that predisposed an individual to develop inflammatory bowel disease initially.

The clinical course of 44 patients undergoing elective proximal fecal diversion for Crohn's disease of the colon is reported. Sustained disease remission was obtained in 31 patients (70 percent). Diversion was associated with a significant reduction in steroid requirements (P

Azathioprine (AZA) is an effective treatment for inflammatory bowel disease. The measurement of thiopurine methyltransferase (TPMT) activity levels helps to identify the one in 300 patients who are at risk of profound myelosuppression with standard doses of AZA. Thus, it is important that the measurement of TPMT activity is accurate. We report a case of misclassification of TPMT phenotype caused by prior blood transfusion. The patient appeared to have an intermediate level of TPMT enzyme activity as measured after the blood transfusion. However, following severe myelosuppression soon after starting AZA, her genotype was determined, which showed that she was homozygous for low TPMT activity. This report reviews some of the limitations in determining both the phenotype and the genotype of TPMT, especially following recent blood transfusion. The dilemma of whether or not to wait for the TPMT activity result before starting AZA is also discussed.

Background Smoking increases the risk of recurrent Crohn's disease (CD). Methods We examined the impact of smoking, quitting smoking, and other factors on reoperation for recurrent CD. We distributed questionnaires to 584 patients from a surgical database whom had undergone a surgical operation for ileocecal CD to assess history of smoking, medical, behavioral, and demographic information. Results Two hundred sixty-seven patients completed the questionnaire (46% response). Smokers were more likely to have undergone 1, 2, and 3 reoperations for recurrence at any site (relative incidence rates [RIR] 1.32, 95% confidence interval [CI]: 1.10 to 1.60; RIR 1.55, 95% CI: 1.09 to 2.20; and RIR 1.77, 95% CI: 1.02 to 3.06, respectively) and were more likely to have undergone one reoperation for recurrent ileocecal CD (RIR 1.48, 95% CI: 1.18 to 1.86). Patients who quit smoking were less likely to have undergone 1, 2, and 3 reoperations for recurrence at any site (RIR 0.25, 95% CI: 0.15 to 0.41; RIR 0.30, 95% CI: 0.16 to 0.57; and RIR 0.25, 95% CI: 0.10 to 0.71, respectively) and were less likely to have undergone one reoperation for recurrent ileocecal CD (RIR 0.27, 95% CI: 0.15 to 0.47). Conclusions This study indicates that patients with ileocecal CD who stop smoking reduce the risk of reoperation for recurrent CD.

The role of fecal diversion alone for perianal Crohn's disease remains unclear. This study was undertaken to assess its role in perianal Crohn's disease and to examine predictive factors for outcome. Thirty-one patients who underwent fecal diversion alone for perianal Crohn's disease between 1970 and 1997 were reviewed. The principal indications for fecal diversion were severe perianal sepsis in 13 patients, recurrent deep anal ulcer in 3, complex anorectal fistula in 9, and rectovaginal fistula in 6. Twenty-five patients (81%) went into early remission, and six (19%) failed to respond. Of the 25 early responders, 17 relapsed at a median duration of 23 months after fecal diversion. By contrast, 8 patients (26%) went into complete remission and required no further surgery at a median duration of 81 months after the diversion. Altogether, 22 patients required surgery at a median duration of 20 months after fecal diversion: proctectomy in 21 and repeated drainage of anal sepsis in 1. At present, intestinal continuity has been restored in only three patients (10%). The following parameters were compared in patients with and without complete remission after fecal diversion: age, gender, duration of disease, steroid use, smoking, coexisting Crohn's disease, preoperative blood indices, and Crohn's disease activity index. None of these parameters affected the outcome. In conclusion, fecal diversion alone is effective in selected patients with perianal disease, but the prospect of restoring intestinal continuity is low. There were no parameters to identify those in whom a successful outcome is likely.

PURPOSE: This study was undertaken to review our overall experience of single-stage proctocolectomy for Crohn's disease. METHODS: One hundred three patients who underwent single-stage proctocolectomy for Crohn's disease between 1958 and 1997 were reviewed. Factors affecting the incidence of recurrence were examined using a multivariate analysis. RESULTS: Principal indications for proctocolectomy were chronic colitis (49 percent), acute colitis (37 percent), and anorectal disease (14 percent). The commonest postoperative complication was delayed perineal wound healing (n=36; 35 percent), followed by intra-abdominal sepsis (17 percent) and stomal complications (15 percent). In 23 patients the perineal wound healed between three and six months after proctocolectomy, whereas in 13 patients the wound remained unhealed for more than six months. There were two hospital deaths (2 percent) caused by sepsis. The 5-year, 10-year, and 15-year cumulative reoperation rates for small-bowel recurrence were 13, 17, and 25 percent, respectively, after a median follow-up of 18.6 years. From a multivariate analysis, factors affecting reoperation rate for recurrence were gender (male; hazard ratio 2.4vs. female;P=0.03) and age at operation (≤30 years; hazard ratio 2.6vs. >30 years;P=0.04). The following factors did not affect the reoperation rate: duration of symptoms, smoking habits, associated perforating disease, coexisting small-bowel disease, postoperative complications, and medical treatment. CONCLUSIONS: Proctocolectomy for Crohn's disease is associated with a high incidence of complications, particularly delayed perineal wound healing. Proctocolectomy carries a low recurrence rate in the long term. However, young male patients are at high risk of recurrence.

After resection for ileocecal or ileocolonic Crohn's disease anastomotic recurrence is common, and many patients require further surgery. This study reviews our overall experience of surgery for ileocolonic anastomotic recurrence of Crohn's disease so we can propose a strategy for management. A series of 109 patients who underwent surgery for anastomotic recurrence after ileocecal or ileocolonic resection for Crohn's disease between 1984 and 1997 were reviewed. Ileocolonic recurrence was treated by strictureplasty in 39 patients and resection in 70 (with sutured end-to-end anastomosis, 48; stapled side-to-side anastomosis, 22). Stapled anastomosis has been frequently used between 1995 and 1997. Short recurrence was mainly treated by strictureplasty, and long or perforating disease was resected. Coexisting small bowel disease was more common in the patients having strictureplasty. Septic complications (leak/fistula/abscess) related to the ileocolonic procedure occurred in 1 of 39 patients (3%) after strictureplasty, in 6 of 48 (13%) after resection with sutured anastomosis, and in none of 22 after resection with stapled anastomosis. The median duration of follow-up was 90 months after strictureplasty, 105 months after resection with sutured anastomosis, and 22 months after resection with stapled anastomosis. Altogether 18 of 39 patients (46%) after strictureplasty, 22 of 48 (46%) after resection with sutured anastomosis, and none of 22 after resection with stapled anastomosis required further surgery for suture line recurrence. In conclusion, strictureplasty is useful for short ileocolonic recurrence in patients with multifocal small bowel disease or previous extensive resection. Stapled side-to-side anastomosis was associated with a low incidence of complications, and early recurrence was not observed, although the duration of follow-up was short.

Between 1960 and 1996, 70 patients (27 men) with Crohn’s colitis were treated by colectomy and ileorectal anastomosis, of whom five had previously undergone subtotal colectomy and end ileostomy. The cumulative proportion with a functioning ileorectal anastomosis was calculated using the Kaplan‐Meier method. Factors affecting the cumulative proportion with a functioning ileorectal anastomosis were analysed using univariate and multivariate methods: log rank test and Cox’s proportional hazard model respectively. P < 0·05 was considered to be statistically significant.

PURPOSE: The aim of this study was to review the long-term outcome of strictureplasty for small-bowel Crohn's disease. METHODS: We reviewed 111 patients who underwent 285 primary strictureplasties (Heineke-Mikulicz, 236; Finney, 49) between 1980 and 1997. RESULTS: Eighty-seven patients (78 percent) had had previous bowel resections. Forty-six patients (41 percent) required synchronous resection for perforating disease (abscess or fistula) or long strictures (>20 cm). The mean number of strictureplasties was three (range, 1–11). There were no operative deaths. Septic complications (fistula or intra-abdominal abscess) related to strictureplasty developed in eight patients (7 percent), of whom two required a proximal ileostomy. Abdominal symptoms were relieved in 95 percent of patients. The majority (95 percent) of patients with preoperative weight loss gained weight (median gain, +2 kg; range, −6 to +22.3 kg). After a median follow-up of 107 months, symptomatic recurrence occurred in 60 patients (54 percent). In 11 patients symptomatic recurrence was successfully managed by medical treatment. Forty-nine patients (44 percent) required reoperation for recurrence: strictureplasty alone in 22 patients, resection alone in 19 patients, strictureplasty and resection in 6 patients, and ileostomy alone in 2 patients. Eighteen patients (16 percent) required a third operation. One patient died from a small-bowel carcinoma which developed in the vicinity of a previous stricture-plasty. Two of 19 patients with diffuse jejunoileal disease developed short-bowel syndrome, and were receiving long-term parenteral nutrition. Two other patients were taking corticosteroids for recurrent symptoms. All other patients were asymptomatic, receiving neither medical treatment nor nutritional support. CONCLUSIONS: Strictureplasty is a safe and efficacious procedure for small-bowel Crohn's disease in the long-term.

PURPOSE: Persistent perineal sinus is a source of morbidity after proctocolectomy for Crohn's disease. This study examined the factors responsible for persistent sinus after proctocolectomy for Crohn's disease. We also assessed the outcome of surgical treatment for persistent perineal sinus. METHODS: The records of 145 patients who underwent proctocolectomy for Crohn's disease between 1970 and 1997 were reviewed. RESULTS: Persistent sinus occurred in 33 (23 percent) patients after proctocolectomy. Factors associated with a significantly greater risk of perineal sinus were younger age (P=0.006), rectal involvement (P=0.02), perianal sepsis (P=0.0005), high fistulas (P=0.04), extrasphincteric excision (P=0.0004), and fecal contamination at operation (P=0.0003). Multivariate analyses showed that age (P=0.0001), rectal involvement (P=0.007), and fecal contamination (P=0.009) were significant independent predictive factors for perineal sinus. Fifty-six operations, including 24 radical excisions, two rectus abdominis flaps, four gracilis transpositions, and two omentoplasties were performed in 24 patients with persistent sinus, but only 9 achieved healing. Long sinuses (>10 cm) and sinuses presenting late (>12 weeks after proctocolectomy) were seldom cured by surgical treatment. CONCLUSION: Persistent perineal sinus is more likely to occur if an extrasphincteric dissection is needed because of extensive anorectal disease or if fecal contamination occurs at operation. Attempted surgical eradication of perineal sinus is often ineffective.

Background The outcome of strictureplasty for duodenal Crohn's disease has not been critically documented. The aim of this study was to assess the outcome of strictureplasty for duodenal Crohn's disease. Methods A retrospective review was undertaken of 13 patients who underwent strictureplasty (including four pyloroplasties) for obstructive duodenal Crohn's disease between 1974 and 1997. Results Ten patients underwent strictureplasty as the primary procedure, and in three strictureplasty was used as a revision procedure after previous bypass surgery. Two patients developed anastomotic breakdown and were treated either by Roux-en-Y duodenojejunostomy or partial gastrectomy. Symptoms of obstruction persisted in four patients after strictureplasty; three eventually resolved after prolonged nasogastric aspiration, but the other required gastrojejunostomy. In the long term, six patients developed restricture at the previous strictureplasty site. Five required repeat strictureplasty and the other patient underwent duodenojejunostomy. One patient who had repeat strictureplasty required a further strictureplasty because of restricture at the previous strictureplasty site. Overall nine of 13 patients required further surgery because of early postoperative complications or restricture at the strictureplasty site. Conclusion Strictureplasty for duodenal Crohn's disease is associated with a high incidence of postoperative complications and restricture.

We have determined the outcome of a defined policy for the management of distal ileal Crohn's disease using a prospective computer-based analysis of 139 patients diagnosed between 1970 and 1988 with a mean follow-up of 10 years. The policy in outline consists of conservative treatment for acute obstructive episodes, resection or strictureplasty for recurrent obstructive episodes, surgical treatment for abscess and fistula formation and specific medical treatment (corticosteroids, immuno-suppressive therapy or metronidazole) for symptomatic non-obstructive disease. Twenty-nine patients had a benign course without resection. The remainder were treated surgically at some time but only 28 of these patients had specific treatment before operation. Thirty-three needed more than one resection and five needed more than three surgical procedures. Immediate, early or delayed surgical treatment did not affect the reoperation rates or the long-term outcome. Eleven patients died, ten of causes unrelated to Crohn's disease. Of the 128 living patients, 114 are fit and well, and only two are currently taking specific medication. Fourteen are unwell of whom six either need or have refused further surgery which could restore them to good health. This management policy has achieved excellent long-term results in nearly all patients, and our findings suggest that the timing of surgery and its nature are more important in determining outcome than specific medical therapy.

We have reviewed our experience with, and management of, entero-enteric fistula in Crohn's disease between 1970 and 1980 (inclusive). Thirty-three patients (20 of them female) came to our unit with entero-enteric fistulas, representing one-third of all Crohn's fistulas seen during those years. Entero-enteric fistulas gave few symptoms and their precise identification was not important in clinical management. The presence of the fistula itself is not an indication for operation and treatment should be directed towards the active or stenotic disease and not to the entero-enteric fistula. Therefore, radiological examination is important only to identify the extent of underlying disease.

From January 1971 to December 1984, fifty-three patients presented with severe acute colitis, defined clinically as a temperature above 38°C., a pulse above 100/min, and bloody diarrhea more than 5 times/day. Twenty-eight patients (12 male) had ulcerative colitis, 25 patients (13 male) had Crohn's colitis. The severe attack occurred earlier in the course of the disease in Crohn's colitis. The mean age for those with Crohn's disease was 31 years (range 17–58) and 41 years (range 17–70) for those with ulcerative colitis. All patients were managed on a combined medical and surgical gastrointestinal unit. The initial treatment was medical; 49 patients received corticosteroids, 40 salazopyrine, and 7 antibiotics. Twenty-seven patients settled on medical treatment in a mean of 11 days (range 3–30). Of these, 3 required resection later. Twenty-six patients required urgent operation (panproctocolectomy in 9, total colectomy and ileorectal anastomosis in 11, and colectomy with retention of rectum in 6). Ten patients developed toxic megacolon, 9 requiring urgent surgery. The other one initially settled but had a colectomy later on during the admission. There were no deaths in this series. Postoperative complications were uncommon. No factors on admission could predict the need for an operation. We believe that with close cooperation between experienced physicians and surgeons, mortality and morbidity from severe, fulminating colitis can be avoided.

Seventy-four patients have had a one-stage proctocolectomy for the management of Crohn's disease. Indications for operation were: acute colitis 28 percent, chronic colitis 39 per cent, perianal disease 13 per cent, proctitis and perianal disease 8 per cent, bleeding 5 per cent, coexisting colonic malignancy 7 per cent. There were two hospital deaths (2·7 per cent), both associated with sepsis. Late deaths (n = 13) were most commonly associated with reoperations for recurrent disease (n = 3), cardiovascular disease (n = 4) and colorectal carcinoma (n = 1). Postoperative complications were principally associated with sepsis. Cumulative reoperation rates at 5 and 10 years were 19 and 24 per cent respectively. Recurrence was unrelated to the age of the patients, the duration of disease, or the presence of ileal disease at the time of colectomy.

Recently, in a mathematics curriculum class of mine, we had an opportunity to critically evaluate an article by Harold M. Ness, Jr., entitled “Another Look at Fractions” (January 1973). It was the general consensus of the class that the pedagogical ideas put forth in the article deserved a written reaction. Specific criticisms follow.

A prospective double-blind placebo controlled trial was performed to test the value of 24-h cover with metronidazole and gentamicin in 57 patients requiring elective resections for inflammatory bowel disease (phase 1). The short term antimicrobial cover was not associated with a reduction in the incidence of postoperative sepsis. A further group of 30 patients who received metronidazole and gentamicin cover for 5 days (phase 2) was therefore studied and the results were compared with phase 1. There was a significant reduction in the incidence of sepsis in the patients receiving 5-day postoperative antibiotic cover compared with the placebo group.

A 10 year follow-up of 109 patients with histologic Crohn's disease and anal lesions is reported. Fourteen patients (13 percent) have died, 7 from unrelated disorders. Ten required excision of the rectum, but only 5 for perianal disease (4.5 percent). Of the remaining 85 patients, 61 have been followed up to proctoscopy and rectal biopsy. Anal skin tags were still evident in 25 of 37 patients (68 percent), but new tags have appeared in only 2 patients. Ten of 53 fissures (19 percent) were still present at 10 years, and there were no new fissures. Seven of 21 patients (33 percent) still had fistulas but were asymptomatic; the remainder of the fistulas had healed spontaneously (8) or after operation (6). New fistulas have appeared in five patients. None of the patients have been incontinent. These results indicate that perianal manifestations of Crohn's disease pursue a relatively benign course and are rarely an indication for proctectomy.

Forty-four patients seen between 1975 and 1985 with anorectal strictures complicating Crohn's disease have been reviewed to determine the natural history and outcome of surgical treatment. Proctitis was present in 98 per cent, and 93 per cent of patients had severe perianal disease. The site of strictures was rectal in 22, anal in 15 and anorectal in 11 (4 patients had a stricture at 2 sites). Initial treatment was by rectal excision alone in 6, dilatation in 33, and 5 needed no treatment at all. Single dilatation was effective in 15, 8 required two dilatations and in 10 repeated dilatation was necessary. Proctocolectomy was eventually required in 19 patients, 2 have a loop ileostomy and I has an ileostomy with a rectal stump in situ. Only 21 remain asymptomatic while 3 continue to need dilatation. Perineal wound healing was delayed in 9 of 19 patients having a proctocolectomy and in 3 the perineal wound has never healed.

The metabolism of Pte-Glu* has been extensively studied in rats and a breakdown process demonstrated (Murphy et al., 1976; Connor et al., 1979). However, previous studies in human volunteers have produced incomplete, conflicting results. In the present study the metabolism of PteGlu was investigated in hospital in-patients, who gave their informed consent. Patients with malignant disease were compared with a control group suffering from other disorders. Fourteen patients were given an oral dose of a mixture of [2-"C]and [3',5',7,9-3H]-PteGIu (0.5, 1.0 or 5.0mg of PteGlu). Urine was collected on to sodium ascorbate for the following time periods: 0-6h, 6-12h and 12-24h after administration. In some cases, faeces were collected for 0-48 h. Total radioactivity in urine and faeces was determined as described previously (Barford et al., 1978; Connor et al., 1979). Urine samples were sequentially chromatographed on DEAEcellulose. Sephadex G-15 and paper (Barford et al., 1977; Connor et al., 1979). In all cases this revealed a number of radioactive components and the following metabolites were identified by co-chromatography with authentic standards; PteGlu, 5 -methyltetrahydropteroylglutamate, 10formylpteroylglutamate, p-acetamidobenzoyl-L-glutamate and p-acetamidobenzoate. 'H,O and at least one species labelled Abbreviation: PteGlu, pteroylglutamic acid. principally with I4C were also detected. At the 5mg dose, quantitative analysis shows some differences between patients suffering from malignancies and control subjects, 34.0% of 3H and 28.4% of 14C and 15.9% of 'H and 13.0% of I4C of the dose being excreted in the urine in 24 h by the control subjects and cancer patients respectively. In every case an excess of 'H over I4C was observed in the urine. The urinary recovery of the individual cancer patients shows a correlation between the total urinary recovery and the size of the tumour. The urinary recovery decreased as the approximate size and extent of the tumour mass increased, indicating a larger requirement for folate in malignant disease. Up to 10.3% of 3H and 26.6% of 14C of the dose was recovered in the faeces examined, an excess of "C over .'H being present, as observed in the rat (Pheasant 8c Blair, 1979). The relative amounts of metabolites excreted in urine is shown in Table 1. The cancer patients tended to excrete less unchanged PteGlu and the ratio between PteGlu and 5-methyltetrahydropteroylglutamate decreased considerably with time, whereas it remained relatively constant in the control group. p-Acctamidobenzoyl-L-glutamate excretion was maximal in the first time period and decreased thereafter, whereas p-acetamidobenzoate shows a reciprocal pattern. It was not present in the 0-6 h urine sample of either group, appeared in the 6-12h urine sample of the cancer patients and in the 12-24h collection in both groups. In general, the excretion of scission products relative to intact folates increased with time. Control and cancer patients receiving 1 mg of PteGlu excreted 5.3% of 3H and 3.5% of I4C and 2.5% of 3H 1.7% of I4C of the dose in the urine in 24h respectively; the values for those receiving 0.5mg of PteGlu were 3.4% of 3H and 2.3% of "C

Summary A total of 105 patients have been treated with colectomy and ileorectal anastomosis from 1958 to 1978 in Birmingham, England (48) and in Leiden, Netherlands (57). At the end of 1978 the mean follow-up was 7.6 years (6 months–20 years). Mild or moderate degrees of proctitis were not considered as contraindications for ileorectal anastomosis. The presence or absence of ileal disease or perianal disease at the time of ileorectal anastomosis did not affect the long term prognosis but patients with sigmoidoscopic proctitis appeared to fare less well (69 per cent still functioning) than those with an apparently normal rectum (87 per cent). However, no statistical significance was obtained. The risk of reoperation for recurrence of Crohn's disease after ileorectal anastomosis calculated by actuarial methods shows a 50 per cent cumulative reoperation rate after 16–20 years. This result suggests that ileorectal anastomosis is a safe and useful procedure for most patients with Crohn's colitis who do not have severe proctitis.

We have undertaken a prospective randomized trial of one month's antimicrobial therapy for patients with symptomatic relapse of Crohn's disease. Criteria for entry included two major symptoms: fever, abdominal pain, diarrhea, weight loss, abdominal mass or complications (excluding perianal disease); and two hematologic abnormalities: hemoglobin, ESR, albumin, C reactive protein, iron, or total iron binding capacity. Patients were monitored for the aforementioned clinical and hematologic (hemoglobin, albumin, CRP) parameters over six weeks and for changes in fecal flora. Randomization was to four groups: metronidazole alone (M), cotrimoxazole alone (C), metronidazole and cotrimoxazole (C plus M), or double placebo (P). Seventy-two patients entered the study (18 = M, 16 = C, 21 = C plus M, 17 = P). After two weeks, improvement was reported as follows: M = 67 percent, C = 17 percent, C plus M = 71 percent, P = 35 percent. In the metronidazole group, two patients required surgery and one had troublesome side effects. In the cotrimoxazole group, two had side effects. In the combined group (C plus M), four had troublesome side effects and two of the placebo group (P) required operation. By four weeks, there was no difference in response among the groups: (M = 44 percent, C = 62 percent, C plus M = 57 percent, P = 41 percent). Antimicrobials had no effect on fecal flora or hematologic parameters. These results indicate that antimicrobials have little therapeutic potential for relapse of intestinal Crohn's disease.

Summary A randomized trial has compared the results of brush cytology before or after biopsy in patients with solitary gastric lesions. One hundred and eleven carcinomas were identified in 324 patients. False positive histological reports were recorded in 2 patients but there were no false positive cytology results. The cumulative accuracy of biopsy and cytology in patients with carcinoma was 97 per cent, which was significantly better than biopsy alone (83 per cent, P < 0.001) or cytology alone (87 per cent, P < 0.001). The cumulative results of brushing before biopsy were significantly better than results obtained by brushing after biopsy (P < 0.05) and indicate that brush cytology should normally be performed before biopsy.

The cumulative probability of reoperation for recurrent ileal Crohn's disease at five years was: 17 percent following ileocecal resection, 19 percent following proctocolectomy, and 28 percent after ileorectal anastomosis. At ten years, the rate of ileal recurrence was significantly less after proctocolectomy; 24 percent as compared with 43 percent for ileorectal anastomosis (P less than 0.01), whereas ileocecal resection assumed an intermediary position with 35 percent.

A patient with Crohn's disease underwent resection for internal fistulas. Later a rectovaginal fistula developed that persisted with minimal symptoms for 10 years before causing pain and induration in the posterior vaginal wall, due to carcinoma developing within the fistula.