Biomedical subjects
Publications and source records attributed to B I Korelitz.
This article provides the current state of knowledge on the interrelations between ulcerative colitis and Crohn's disease and pregnancy and its multiple concerns, including inheriting inflammatory bowel disease, fertility, influence of inflammatory bowel disease activity on pregnancy and vice versa, the safety of drug therapy, and risk factors. The author provides some conclusions and his recommendations.
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Steroid therapy is often avoided in the Crohn's disease patient with a palpable abdominal mass, for fear of dissemination of infection, should the mass prove to contain an abscess. In the present study, 24 patients with Crohn's disease and a palpable abdominal mass were treated with high dose steroids. In 15, the mass resolved completely and, in another nine, it decreased in size by at least 50%. Fourteen of 24 patients eventually required resection for persistence or recurrence of Crohn's disease activity with or without the abdominal mass, but in all the operation was performed electively. At least eight patients never required resection during a mean follow-up period of 40 months. In 13 patients, the mass was later proved to actually contain an abscess cavity. No complications attributable to steroid therapy were seen in either the operative or nonoperative group. Clinicians should not fear using high dose ACTH/corticosteroids to treat severe Crohn's disease with an abdominal mass, if indicated, as it is both safe and effective whether an abscess cavity is present or not.
Activation of c-Ki-ras by point mutation within exon 1 was studied in 33 specimens of dysplastic gastrointestinal lesions or of cancers presumed to arise from dysplasia. Samples were obtained from patients with underlying ulcerative colitis or Barrett's esophagus, two diseases associated with dysplasia and increased rates of colonic or esophageal adenocarcinoma, respectively. Genomic DNA was amplified using primers bounding this exon in the polymerase chain reaction. Polymerase chain reaction products were analyzed by direct dideoxy sequencing. Three point mutations in codon 13 of c-Ki-ras were found, all in colonic specimens (two high-grade dysplasias and one adenocarcinoma arising in ulcerative colitis). No point mutations were observed in the second exon of c-Ki-ras or in and around codons 12, 13, and 61 of c-N-ras and C-Ha-ras in a partial sampling of the specimens. These data indicate that ras family protooncogene activation is an uncommon event at this level of malignant progression in these disease states. Carcinogenesis in ulcerative colitis and Barrett's esophagus may proceed via different pathways than in sporadic colon cancer, perhaps involving loss or inactivation of suppressor genes.
Patients with ulcerative colitis are at greater risk of developing carcinoma of the colon than the general population even if the exact risk cannot be determined. Thus, an effort must be made to find the carcinoma at its inception or better still before it occurs. Dysplasia serves as a premalignant marker in some cases, and a surveillance program serves to find either dysplasia or the carcinoma. Until more specific premalignant changes are identified, endoscopic surveillance with multiple biopsies offers the best protection for the patient with longstanding ulcerative colitis against carcinoma. There is now sufficient evidence that this also pertains to Crohn's disease of the colon.
Serial sections of 812 rectal biopsy specimens from 356 Crohn's disease patients were analysed for mucosal epithelial dysplasia. Dysplasia was found in 18 patients (5%), with four showing dysplasia on repeat biopsy specimen. In these 22 biopsy specimens the dysplasia was mild in 13, moderate in nine, and severe in none. Subsequently, three patients (17%) developed neoplasms including carcinoma in two and an adenomatous polyp in one. In colectomy specimens which showed dysplasia, significantly more dysplastic changes were found in seven patients who underwent colonic resection than in 10 others who underwent operation but had no prior dysplasia (p less than 0.001). Thirteen patients still have their rectum in situ and remain at risk of developing colonic cancer. Four carcinomas developed in patients with Crohn's disease who did not have dysplasia on rectal biopsy specimen.
We report our observations over 18 years (1970-1988) on 81 compliant patients with resistant ulcerative colitis who received 91 courses of treatment with 6-mercaptopurine (6-MP) for at least 4 months. These represent 172 patient years of 6-MP therapy and 308 years of observation after initiating 6-MP. In all patients, treatment with sulfasalazine and steroids had failed; most (96%) were dependent on systemic steroids and still symptomatic. The mean treatment period with 6-MP was 1.8 yr. In 42 out of 87 courses (48%) of 6-MP steroids could be eliminated, and in another 11 (13%) could be significantly reduced, for a total response rate of 61%. When four patients not on steroids were included, the response rate was 63%. The steroids were discontinued after a mean treatment time of 10 wk, and the 42 patients remained steroid free for the remainder of 6-MP treatment. Follow-up data after discontinuing 6-MP in 29 patients from this group show the mean time to relapse was 21 months with a median time of 12.5 months. We conclude that 6-MP is effective in inducing remission, eliminating steroids, and maintaining remission in many patients with refractory ulcerative colitis. Patients should be made aware of this option before colectomy is recommended.
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We assess toxicity related to 6-mercaptopurine in the treatment of inflammatory bowel disease by reporting our experience with 396 patients (120 patients with ulcerative colitis, 276 with Crohn disease) observed over 18 years. Follow-up data for a mean period of 60.3 months were obtained for 90% of the patients. Toxicity directly induced by 6-mercaptopurine included pancreatitis in 13 patients (3.3%), bone marrow depression in 8 (2%), allergic reactions in 8 (2%), and drug hepatitis in 1 (0.3%). These complications were reversible in all cases with no mortality. Most cases of marrow depression occurred earlier in our experience, when the initial drug doses used were higher. Infectious complications were seen in 29 patients (7.4%), of which 7 (1.8%) were severe, including one instance of herpes zoster encephalitis. All infections were reversible with no deaths. Twelve neoplasms (3.1%) were observed, but only 1 (0.3%), a diffuse histiocytic lymphoma of the brain, had a probable association with the use of 6-mercaptopurine. Our data, showing a low incidence of toxicity in 396 patients, coupled with the previously demonstrated efficacy of 6-mercaptopurine in the treatment of inflammatory bowel disease, indicate that the drug is a reasonable alternative in the management of patients with intractable inflammatory bowel disease.
We reviewed the course of 500 patients with Crohn's disease to document the incidence, the nature, and the results of management of fistulas to the bladder. Seventeen patients (14 men and three women) had developed enterovesical fistulas: 16 had pneumaturia. The barium radiographs demonstrated the fistula in only 37%. All had received sulfasalazine, and most were treated with corticosteroids and antibiotics intermittently; two had successful control of their urinary symptoms on this regimen. Eight patients who received 6-mercaptopurine (6-MP) in addition tolerated the urinary fistula well, so that we encourage a trial of 6-MP for this complication of Crohn's disease. Six patients continue on medical therapy alone after a mean of 5.3 years. There were no instances of pyelonephritis during 60 patient years. Eleven patients eventually underwent bowel resection, but in only two was persistence of the enterovesical fistula the primary indication for elective surgery, and in both, it was the patient's choice. Visualization of the fistula on barium enema radiograph or presence of a connection between the sigmoid and the bladder were not associated with adverse outcome. An enterovesical fistula in Crohn's disease rarely leads to serious complications and can often be treated successfully with medical therapy alone: by itself, it need not serve as an indication for surgery.
Amebic colitis can mimick Crohn's disease of the colon and ulcerative colitis. Inflammatory bowel disease (IBD) patients can also be carriers of amebae. Since steroids can provoke amebic activity and even cause a fulminating colitis, it is necessary to determine that amebae do or do not exist. Furthermore, amebae can be easily eliminated by drug therapy but it is hard to eradicate IBD. Despite the above, diagnostic modalities for IBD are as effective as those for amebiasis, particularly for Crohn's disease with ileal involvement. Problems in differential diagnosis arise with IBD grossly limited to the colon. In these cases, false negative stool studies are increased by diarrhea and preparation for examinations, and both stool studies and serologies are compromised by steroids. If the clinical course of IBD is downhill, the clinician is justified in starting steroids even if evaluation for amebiasis incomplete. If, however, the index of suspicion is high, concomitant treatment with Metronidazole would be reasonable.
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Thirteen of 43 patients (30%) with inflammatory bowel disease referred for psychiatric consultation were found to be drug dependent, most commonly on oral narcotics. Drug dependence was more frequent in patients with Crohn's disease than ulcerative colitis and many had a borderline personality disorder. The study suggests that drug dependence is not recognized often enough in patients with inflammatory bowel disease and that patients with certain psychiatric disorders are at higher risk of developing it. Recognition of drug dependence is aided by interviewing family members. It is best prevented by seeking and treating the specific cause of pain and by having only one physician assigned to prescribe and manage narcotics.
A 21-year-old woman with duodenal Crohn's disease developed pancreatitis many years after radiographic evidence of duodenopancreatic reflux. We review the 17 previously reported cases of non-drug-induced recurrent pancreatitis associated with Crohn's disease and discuss possible pathogenetic mechanisms. Pancreatitis should be considered in any Crohn's disease patient with filling of the pancreatic duct on barium study of the upper gastrointestinal tract.
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Conventional sigmoidoscopy and rectal biopsy are very useful in the diagnosis, differential diagnosis, and management of inflammatory bowel disease. The rectal biopsy is particularly important in establishing the diagnosis of Crohn's disease when the rectal mucosa is grossly normal. The sigmoidoscopy and biopsy serve to assess the response to medical therapy in inflammatory bowel disease and are important adjuncts to colonoscopy in surveillance for dysplasia and carcinoma in patients with ulcerative colitis. Sigmoidoscopy is quick, requires no preparation, is cost effective, and the biopsies are extremely safe with the use of the cupped bronchoscopic forceps.
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