Interaction between azathioprine and aminosalicylates: an in vivo study in patients with Crohn's disease.

BACKGROUND: The inhibition of thiopurine methyltransferase activity, one of the enzymes responsible for azathioprine metabolism, by aminosalicylates has been described in an in vitro study. This could result in a higher risk of bone marrow depression when using the two drugs together. AIM: To investigate the in vivo interaction between azathioprine and aminosalicylates in quiescent Crohn's disease by measuring 6-thioguanine nucleotide levels, thiopurine methyltransferase activity and the plasma levels of the acetylated metabolite of 5-aminosalicylic acid. METHODS: Sixteen patients taking a stable dose of azathioprine, plus sulfasalazine or mesalazine, were enrolled and completed the study. They were not taking any drugs interfering with azathioprine metabolism. Four visits every 4 weeks were held over a 3-month period. Aminosalicylate administration was withdrawn after the second visit. At each visit, the blood cell count, inflammatory parameters, levels of 6-thioguanine nucleotide and the acetylated metabolite of 5-aminosalicylic acid and thiopurine methyltransferase activity were determined. RESULTS: After aminosalicylate withdrawal, mean 6-thioguanine nucleotide levels decreased significantly from 148 pmol (57-357 pmol) to 132 pmol (56-247 pmol) per 8 x 10(8) red blood cells (P=0.027), without significant changes in thiopurine methyltransferase activity or biological parameters. CONCLUSIONS: This in vivo study favours the existence of an interaction between azathioprine and aminosalicylates through a mechanism which remains unclear. This drug-drug interaction should be taken into account when using azathioprine and aminosalicylates simultaneously.

Assessment of the new immunological test Hemoblot for detecting occult blood in faeces.

Hemoblot, a new immunological faecal occult blood test, produced by Gamma, Angleur, Belgium, was characterized and compared with another immunological test (HemeSelect, SmithKline Diagnostics, USA) and with a guaiac test (Hemoccult II, SmithKline Diagnostics). The analytical sensitivity of Hemoblot is 0.15 mg haemoglobin/g faeces and the test is specific for human haemoglobin. In addition, 135 symptomatic patients who had to undergo a colonoscopy were tested using the three tests. Two criteria were considered for the analysis: (1) the blood criterion: any pathology likely to cause colorectal or other bleeding; and (2) the precancerous-cancerous criterion: the pathology being either a colorectal polyp > 0.5 cm or a colorectal cancer. Considering both criteria, the sensitivity of Hemoblot was significantly higher than the sensitivity of Hemoccult: 38% and 23%, respectively, for the blood criterion; and 54% and 29% for the precancerous-cancerous criterion. Sensitivity and specificity did not differ statistically between Hemoblot and HemeSelect but Hemoblot was faster and simpler to perform. It could be widely used in mass screening.

Chronic idiopathic constipation with outlet obstruction.

Defecatory difficulties may be a source of great distress to patients. Normal defecation requires the coordination of abdominal and pelvic muscles. Throughout the last decade, many studies have demonstrated various and often mixed abnormalities of these mechanisms. Pathophysiological studies are able to determine, in a specific patient, the most probable causes of the obstructive symptom. Progress in the management of such disorders can only be achieved by understanding their pathophysiology.

[Anal surgery in Crohn's disease. Clinical and functional results]. / Chirurgie anale dans la maladie de Crohn. Résultats cliniques et fonctionnels.

The aim of this study was to evaluate the results of anal surgery performed in 105 patients for perianal symptomatic complications of Crohn's disease. The patients were divided into 3 groups: group I: 45 patients with simple fistulae; group II: 53 patients with complex fistulae; group III: 7 patients with other symptomatic perianal lesions. All patients underwent a resection of their perianal lesions. Complete wound healing was obtained in 95 patients after a mean interval of 11 weeks. Satisfactory results persisted during a mean follow-up of 5 years. The functional results were clinically evaluated in 100 patients: 90 patients were asymptomatic, 6 patients complained of soiling and 4 patients noticed occasional incontinence for flatus and liquid stools. Anorectal function was studied by manometry in the last 31 patients who underwent surgery. Before surgery, the resting anal pressure and the maximal voluntary squeezing pressure were significantly lower than in control subjects. After surgery, there was no statistical difference between the pre- and postoperative results for both parameters. In conclusion, anal surgery in Crohn's disease is hazardous because of the complexity of lesions and preoperative anorectal dysfunction. However, the clinical and functional results obtained in our patients were satisfactory.

[Solitary lesions of the rectum caused by suppositories combining acetylsalicylic acid and paracetamol]. / Lésions solitaires du rectum dues à des suppositoires associant acide acétylsalicylique et paracétamol.

The reports of 8 female patients who, because of recurrent headache, were using analgesic suppositories containing acetylsalicylic acid and paracetamol (Perdolan) for more than two years are analyzed. Symptoms were nonspecific: anal pain, rectal tenesmus or bleeding. The lesions were located within 8 cm from the anal verge and consisted of superficial ulcerations, fibrotic scar tissue and rectal stenosis. Biopsies showed non-specific inflammation, limited to the rectum. Rectal prolapse or intussusception was not associated. By discontinuing the use of suppositories, symptoms usually resolved; rectal stenoses required anorectal dilatations and in 2 cases surgical resection. When solitary rectal lesions are observed in the absence of rectal prolapse, chemical aggression of the rectal mucosa by use of suppositories containing acetylsalicylic acid should be considered.

[Ileo-anal anastomosis in hemorrhagic-ulcerative rectocolitis and familial adenomatous polyposis: is it mandatory to perform resection of the endo-anal mucosa?]. / L'anastomose iléo-anale dans la rectocolite ulcéro-hémorragique et la polypose adénomateuse familiale: faut-il faire une mucosectomie endo-anale de principe?

The aim of this study was to assess the clinical outcome after ileal pouch-anal anastomosis with mucosectomy for ulcerative colitis and for familial adenomatous polyposis, and to characterize the histology of the stripped endoanal mucosa with particular reference to the ulcerative colitis activity, adenomatous polyps and dysplasia. Twenty-eight patients were operated, 16 for ulcerative colitis (group I) and 12 for familial adenomatous polyposis (group II). In group I, there were no intraoperative complications, but mucosectomy was tedious in 10 patients (62%) and the anastomosis was performed under some degree of tension in 10 patients (62%). In group II, there was a direct injury of the internal sphincter by a posterior tear during the mucosal stripping in one case. Mucosectomy was easy to perform in 8 patients (67%) and 10 anastomoses (84%) were performed under tension. In both groups, there were no postoperative complications related to the mucosectomy or to the anastomosis itself. Functional results were good, with a normal continence in 80% of ulcerative colitis patients and 92% of familial adenomatous polyposis patients. Review of histological sections of the stripped anal mucosa in group I showed chronic active ulcerative colitis in 8 patients (50%), chronic non-active ulcerative colitis in 4 (25%) and quiescent ulcerative colitis in 4 (25%). There was only one case of moderate dysplasia in a patient with a Dukes A carcinoma. In group II, anal mucosa showed micropolyps in all cases with mild dysplasia in 3 cases (25%) and moderate dysplasia in 9 (75%).(ABSTRACT TRUNCATED AT 250 WORDS)

[Anal surgery in Crohn disease]. / Chirurgie anale dans la maladie de Crohn.

For twenty years, opinions concerning local surgery of anal lesions in Crohn's disease have changed in practice and in the literature. We have reviewed 209 patients, usually in remission of disease, with at least 6 months' follow-up, who underwent local surgery for various anal lesions from 1974 to 1992. In this study, our indications and results are discussed and compared to the literature. Results of partial haemorrhoidectomy are successful. In anorectal stenosis, with rectal involvement, surgery improves the symptoms and can avoid or delay proctectomy. Results of surgery for simple fistulas appear to be identical in cases with or without Crohn's disease. In complex and suprasphincteric fistulas, seton management improves chronic suppuration, occasionally cures the lesion and reduces the number of tracts. After seton drainage, transanal rectal advancement flaps can be performed, but the results of this procedure have yet to be confirmed.

[Etiopathogenesis of colonic diverticular disease; role of dietary fiber and therapeutic perspectives]. / Etiopathogénie de la maladie diverticulaire colique; rôle des fibres alimentaires et perspectives thérapeutiques.

The authors review the literature about the aetiopathogenesis, the epidemiology and the treatment of uncomplicated diverticular disease of the colon. The influence of dietary fibre deficiency explaining the increasing prevalence in industrialized countries and the variable geographical distribution are explained, as well as the effects of dietary fibres on colonic functions. Progressive elastosis of the taeniae may explain the influence of age on the incidence of diverticulosis. The rationale for the introduction of dietary fibre into the treatment is based on the observation that a high fibre diet such as coarse bran is lowering the colonic pressure and therefore may prevent the development of new diverticula and complications, although an effect on symptoms is not always obtained.

Coombs-positive autoimmune hemolytic anemia complicating ulcerative colitis. A case report.

We report the case of a 41-year-old woman with a 5-year history of left-sided ulcerative colitis easily controlled by sulfasalazine. She was admitted because of severe anemia, in the absence of any exacerbation of the colitis. A Coombs-positive (IgG type) hemolytic anemia was diagnosed and high-dose corticosteroid therapy was started, which proved to be unsuccessful. A splenectomy was then performed but the hemolytic anemia failed to subside. The patient was subsequently treated with a corticosteroid-azathioprine association with a sustained favourable effect on the anemia. The prevalence and pathophysiology of hemolytic anemia in ulcerative colitis is reviewed and a specific therapeutic approach is proposed.

[Impact of endoscopy in Crohn's disease]. / Apport de l'endoscopie dans la maladie de Crohn.

Two types of endoscopic lesions are observed in Crohn's disease (CD): active lesions or scars, frequently associated. Following their localization at different sites of the digestive tract, they are defining the type of disease. Ileo-colonoscopy is an important step of the initial characterization of the lesions, completed with biopsies helful for the differential diagnosis between CD and ulcerative colitis or infectious colitis An endoscopy is only repeated in front of a new clinical problem or when a change of treatment is required. In case of severe colitis, colonoscopy may detect septic lesions as well as deep ulcers indicating severe evolution with a bad prognosis. After surgery, in most of the cases ileocolonoscopy detects recurrent lesions whose severity is linked to an unfavourable clinical evolution and permits therapeutic adaptation. Since the risk of colorectal cancer in CD predominant in the colon is probaly underestimated, a systematic colonoscopy after 8 to 10 years of evolution should be performed for the screening of malignant lesions. Colonoscopy is also useful for the treatment of complications of CD, i. e. dilatation of benign strictures, as well as localization and treatment of distal bleeding. Upper digestive tract endoscopy, endosonography, enteroscopy, videocapsule and endoscopic retrograde cholangio-pancreatography are other contributive methods within the field of correct indications.

[Hemorrhoids. Review]. / La maladie hémorroïdaire. Revue.

Correct definition of haemorrhoidal disease allows the estimation of the incidence and the therapeutic choices. The term "haemorrhoidal disease" should be used specifically for symptoms secondary to abnormalities of the intern haemorrhoidal plexus. The classification of severity is useful but difficult to apply to individual cases. The aetiopathogenesis remains unclear. Many arguments are in favour of a progressive degeneration of the fibromuscular structure of the internal haemorrhoidal plexus responsible for his prolapse in the anal canal. Most patients suffering from haemorrhoids are relieved by simple dietary advice. Moderate prolapsing haemorrhoids are significantly improved by rubber band ligation. Surgical haemorrhoidectomy remains the procedure of choice in patients with advanced prolapsing haemorrhoids.

Anal fissure: correlation between symptoms and manometry before and after surgery.

The study compared symptoms and manometric results in 76 patients (42 men and 34 women; median age: 45 years) before and at long-term follow-up (median time: 54 months) after fissurectomy with posterior midline sphincterotomy for anal fissure. The fissure healed in all cases. Sporadic loss of continence for flatus or for liquid stool occurred in 21 patients (27.6%) and soiling was present in 7 other patients (9.2%). Preoperative maximum resting anal pressure was significantly greater in the study group compared with 40 control subjects (p less than 0.001). Postoperative resting anal pressure fell significantly (p less than 0.001) and remained low on long-term assessment. Postoperative maximal squeeze pressure remained unchanged. No correlation could be found between preoperative and postoperative clinical symptoms (including continence) and anorectal manometry.

[Acute dilatation of the colon]. / Les dilatations aiguës du côlon.

Dilated colon is provoked by obstructing lesions, toxic megacolon or colonic pseudoobstruction. The obstructing lesions of the colon are colonic volvulus, inflammatory bowel disease with stenosis or colonic cancer. Toxic megacolon is more often caused by I.B.D. and rarely by infectious diseases. Etiological diagnosis is possible after clinical and radiological evaluation. Colonoscopy is always indicated, except in toxic megacolon. Balloon dilatation of strictures, palliative treatment of colonic carcinoma by Laser procedures, reduction of colonic volvulus and aspiration of colonic pseudoobstruction are the principal indications of therapeutic colonoscopy in the non surgical treatment of dilated colon.

Perianal condylomata acuminata.

Anal and perianal condylomata acuminata are warts caused by infection with the human papillomavirus (HPV). The annual incidence of genital warts seems to have increased during the past few decades. Approximately 1.5 million consultations per year take place in the United States with this condition (1). Papillomavirus is a sexually transmitted disease, and is associated with several other venereal infections as well as with intraepithelial neoplasia and invasive squamous carcinoma. Only certain genotypes of HPV are carcinogenic, and can be precisely identified by in situ hybridisation techniques. There are many therapeutic alternatives, possibly reflecting the wide variability in treatment response.

Colonic angiodysplasia. Follow-up of patients after endoscopic treatment for bleeding lesions.

Endoscopic electrocoagulation or photocoagulation is now the method of choice for treating colonic angiodysplasia. Follow-up of such patients has not been extensive. The authors report 26 patients with typical and symptomatic lesions who have been treated endoscopically. Follow-up (mean duration, 29.3 months) revealed that 21 patients remained symptom-free after a single procedure. Two patients needed a second procedure before being considered cured. In two others, the need for transfusions was lessened considerably after treatment. The last patient died of terminal cardiac failure. No complications occurred during treatment. Endoscopic treatment is a safe and efficient method for treating bleeding colonic angiodysplasia.

[Risk of recurrence of colorectal polyps following endoscopic resection]. / Risques de récidive des polypes colo-rectaux après résection endoscopique.

From 1976 to 1985, 1063 patients (614 men, 449 women, mean age: 63 years) underwent the excision of 1887 adenomatous or villous colonic or rectal polyps. Regular controls by barium enema or total colonoscopy have been proposed to these patients. A first control, performed in 715 patients (67%) after a mean of 27 months, revealed the presence of polyps in 162 of them (23%). A second control performed in 331 of the 535 controllable patients (61%), was positive (presence of polyps) in 82 of them (24%). During the follow-up period, 16 cancerous lesions were observed. Comparing the initial status of the patients with the results of the different controls, 3 risk factors for developing a new colonic or rectal polyp emerged: 1) male sex, 2) the presence of multiple lesions at the initial examination, 3) a recurrence at a previous control.

[Villous tumors of the rectum. Endoscopic treatment using monopolar coagulation]. / Tumeurs villeuses du rectum. Traitement endoscopique par coagulation monopolaire.

UNLABELLED: Many methods are used to treat villous adenomas of the rectum. The best choice between these methods is not well established. Ninety-six patients (47 men, 49 women) treated with endoscopic monopolar coagulation were studied. The mean age was 66 years (range 37-84). The lesions were located in the lower third of the rectum in 27 cases, in the middle third in 35 cases and in the upper third in 34 cases. The circumferential extent of the lesions was less than 1/3 in 70 cases (C1), greater than 1/3-less than 2/3 in 23 (C2) and greater than 2/3 in 3 cases (C3). The follow-up of 2 patients (1 C1 and 1 C2) was not sufficient. Healing was not achieved in 8 of the 94 evaluated patients. Eighty-six patients were totally healed: 68 C1, 16 C2 and 2 C3 with a follow-up of 2 to 132 months (median: 36 months). The treatment was achieved after a mean of 2.1 sessions per patient (range 1-13). CONCLUSIONS: 1) Endoscopic monopolar coagulation of villous adenoma of the rectum is a simple and efficient treatment. 2) This method is complementary to surgery for extensive lesions (C3).

[Villous tumors of the rectum. Endoscopic treatment using photocoagulation]. / Tumeurs villeuses du rectum. Traitement endoscopique par photocoagulation.

We report the results of endoscopic photocoagulation in the treatment of villous adenomas of the rectum in 49 consecutive patients (26 males, and 23 females, mean age: 74 years). Twenty-six patients were treated with a high-power Nd-Yag laser (80 W/sec). After a mean of 3.4 laser sessions, all the small-sized adenomas (C1) and 88% of the intermediate-sized adenomas (C2) were healed. No extensive villous adenoma (C3) could be eradicated. Complications occurred in 5 patients. Recurrence was observed in 3 C2 patients who are still on maintenance laser therapy. Twenty-three patients were treated with another Nd-Yag laser (maximal power output: 45 W/sec). After a mean of 6.4 laser sessions, 85% of the C1 patients were healed, while eradication of villous tissues was obtained in 60% of C2 and C3 patients. No complications were noted. A recurrence was observed in three C1 patients with secondary healing after reinstitution of laser therapy in 2 cases. Moreover, two C3 patients also relapsed and laser eradication was again obtained in 1 patient. In conclusion, these results confirm the efficacy of laser therapy in small- and intermediate-sized villous adenomas of the rectum. The number of laser sessions required for eradicating a villous tumour was lower using a high-power Nd: Yag laser, but the risk of complications was increased.

The clinical [corrected] background of familial adenomatous polyposis. History, epidemiology, diagnosis and treatment.

Familial adenomatous polyposis (FAP) is a dominantly inherited genetic disorder predisposing to colon cancer through the early development of multiple adenomatous polyps in the large bowel. FAP is not restricted to the colon and rectum, but is a more complex disease which can potentially affect almost any organ not only with benign tumours but also with life threatening carcinomas. Desmoid tumours and gastroduodenal polyps and cancer are the two more worrying extracolonic manifestations of FAP. Recent advances in FAP knowledge, such as the report of congenital hypertrophy of the retinal pigment epithelium (CHRPE) or the APC gene identification, are very useful for screening and long-term follow-up of the patients through regional or national registries. Nutritional and pharmacological intervention trials are under way to assess potential new medical treatments of FAP. Surgery is still the only effective treatment for colorectal cancer prevention in FAP. The choice of a surgical procedure is controversial, but the introduction of total proctocolectomy with ileal pouch-anal anastomosis can be considered as a major advance in surgical treatment of FAP during the last decade.