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Biomedical subjects

D B Sachar

Publications and source records attributed to D B Sachar.

At least 19 recordsLinked to original sources
PubMed1995

Sialosyl-Tn antigen: initial report of a new marker of malignant progression in long-standing ulcerative colitis.

BACKGROUND & AIMS: Expression of the mucin-associated carbohydrate antigen sialosyl-Tn (STn) correlates with malignant transformation in sporadic colonic neoplasms. The aim of this study was to analyze STn antigen expression in patients with long-standing ulcerative colitis (UC). METHODS: STn antigen was assessed by immunohistochemistry in archival tissues. Study A was a retrospective chronological case-control study. Serial surveillance colonoscopic biopsy specimens without inflammation or dysplasia were analyzed in 7 patients who developed colon cancer and in 8 controls who did not develop colon cancer. Study B analyzed the anatomic distribution of STn expression in 17 cancer-bearing (case) and 6 cancer-free (control) colectomy specimens from patients with UC. In some colectomy specimens, STn was compared with aneuploidy, which was determined by flow cytometry. RESULTS: In study A, among the 7 patients with UC who developed cancer, 6 patients (86%) expressed STn in at least one prior nondysplastic surveillance biopsy specimen from the same site. Only 3 of 8 control patients (38%) expressed STn. In study B, STn was expressed in 40 of 82 specimens (49%) from cancer-bearing colons but only 8 of 62 specimens (13%) from cancer-free colons. STn was expressed in most aneuploid areas but was also found in diploid, nondysplastic mucosa. CONCLUSIONS: STn antigen seems to be a promising marker of cancer risk in patients with UC.

Aneuploidy↗
PubMed1995

Maintenance therapy in ulcerative colitis and Crohn's disease.

Aminosalicylates are of proven benefit in maintaining medically induced remissions of both ulcerative colitis and Crohn's disease. Even rectal 5-aminosalicylic acid has been found to be useful in maintaining long-term remissions of distal ulcerative colitis. Particularly noteworthy is the demonstrated efficacy of oral mesalamine in reducing recurrence rates of Crohn's disease following ileocecal resection, if introduced within the first few weeks after surgery. In all cases, the efficacy of the aminosalicylates is dose related, with little benefit demonstrable, at least in Crohn's disease, at oral doses < 2 g/day. In contrast to aminosalicylates, corticosteroids and cyclosporine are better suited to the induction of rapid remissions of acute disease than to the maintenance of long-term remissions. Antimetabolites, especially azathioprine and 6-mercaptopurine, are highly beneficial and relatively safe for long-term steroid-sparing therapy in both ulcerative colitis and Crohn's disease, at least for those patients whose initial remissions have already been induced by these agents.

Adjuvants, Immunologic↗
PubMed1994

Immunosuppressive drugs in Crohn's disease.

We review clinical experience with the immunosuppressive drugs 6-mercaptopurine (6-MP) and azathioprine, cyclosporine, and methotrexate in the management of patients with Crohn's disease. 6-MP and azathioprine are closely related structurally. Their exact mechanism of action is unknown, but both cause immunosuppression by interfering with nucleic acid metabolism in the immunological sequence that follows antigenic stimulation. 6-MP and azathioprine have proved most useful for two indications: reducing steroid requirements and healing fistulas. Among patients who are dependent on steroids for control of active inflammatory Crohn's disease, approximately 50% can be completely weaned from prednisone, and an additional 25% can tolerate a substantial dose reduction when treated with 6-MP or azathioprine. Likewise, 6-MP is effective in closing fistulas in approximately one third of patients and in reducing fistula drainage in an additional one third. However, the onset of action is slow and the results may be dose dependent. Cyclosporine, a selective immunosuppressant drug, inhibits T lymphocytes by inhibiting expression of interleukin-2 and its receptors. Its principal usefulness may be in patients with disabling fistulas or active steroid-refractory colitis who cannot tolerate the several months required for a remission induced by 6-MP or azathioprine. Methotrexate, a dihydrofolate reductase inhibitor, has antimetabolite and antiinflammatory properties. Methotrexate is only slightly, if at all, faster acting than 6-MP or azathioprine. Its principal usefulness may therefore be in cases when these other drugs have not been tolerated or are ineffective.(ABSTRACT TRUNCATED AT 250 WORDS)

Azathioprine↗
PubMed1992

Lymphoma in inflammatory bowel 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.

Adult↗
PubMed1992

Neuroleptic malignant syndrome induced by domperidone.

A 47-year-old woman with diabetic gastroparesis, on treatment with domperidone, a dopamine-receptor antagonist, was admitted to the hospital in coma, with high blood pressure and nonreactive pupils. She then developed high fever. Her condition progressively worsened for two days, when muscle rigidity was noted and creatine phosphokinase was greater than 2000 U/liter. A diagnosis of neuroleptic malignant syndrome was made, and the patient was given dantrolene with prompt and complete resolution of all signs and symptoms. Subsequent inquiry revealed a distant past history of positive muscle biopsy for malignant hyperthermia, obtained after the diagnosis had been made in a family member. This case suggests that domperidone may induce neuroleptic malignant syndrome and that patients with malignant hyperthermia are at increased risk for this complication.

Dantrolene↗
PubMed1992

Amyloidosis and inflammatory bowel disease. A 50-year experience with 25 patients.

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)

Adolescent↗
PubMed1992

Benign and malignant colorectal strictures in ulcerative colitis.

Colorectal strictures, either benign or malignant, are not uncommon in ulcerative colitis. Fifty nine of 1156 ulcerative colitis patients (5%) admitted to this hospital between 1959 and 1983 developed 70 separate colorectal strictures. Seventeen of the 70 strictures (24%) proved to be malignant and the other 53 benign. Nine patients developed more than one stricture. Three principal features distinguished the 17 malignant from the 53 benign strictures in this series: (1) appearance late in the course of ulcerative colitis (61% probability of malignancy in strictures that develop after 20 years of disease v 0% probability in those occurring before 10 years); (2) location proximal to the splenic flexure (86% probability of malignancy v 47% in sigmoid, 10% in rectum, and 0% in splenic flexure and descending colon); and (3) symptomatic large bowel obstruction (100% probability of malignancy v only 14% in the absence of obstruction or constipation). Moreover, cancer associated with strictures tends to be more advanced (76% stage D, 24% A and B) than that which does not produce strictures (18% stage D, 59% A and B).

Adolescent↗
PubMed1992

Malignant melanoma in inflammatory bowel disease.

Malignant melanoma occurred in 11 patients with inflammatory bowel disease (IBD). Six cases occurred in patients with ileocolitis, two in regional enteritis, one in granulomatous colitis, and two in patients with ulcerative colitis. The mean age at development of IBD was 24 yr, and at development of melanoma was 40 yr: the mean duration from onset of IBD to development of melanoma was thus 16 yr. All patients for whom complete information was available, except two, had received steroids and azulfidine for approximately a decade, as well as blood transfusions, usually multiple, and on repeated occasions. Six of the 11 patients had undergone one to seven prior operations (mean 3.5). All patients had wide radical excision of the melanoma, with or without concomitant or subsequent nodal dissection. Two patients (ages 25 and 36 yr) died rapidly from widely disseminated malignant melanoma. These cases may be coincidental, or else there may be an association between IBD and melanoma, related to immunosuppression either from the disease itself, from the medical and surgical therapy, and/or from x-ray exposure.

Adolescent↗
PubMed1991

Severe gastrointestinal hemorrhage in Crohn's disease.

Twenty-one of fifteen hundred twenty-six patients with Crohn's disease (CD) treated at The Mount Sinai Hospital between 1960 and 1986 developed severe gastrointestinal hemorrhage. There were 26 separate episodes of severe hemorrhage: 17 patients bled only once, three bled twice and one bled three times. The frequency of bleeding was significantly higher among patients with colonic involvement (17 of 929; 1.9%) than among those with small bowel disease alone (4 of 597; 0.7%) (p less than 0.001). Twelve patients required surgery on 13 occasions, which involved colon resection in all but one case. Eleven of these patients underwent surgery during their first hemorrhagic episodes, and 1 of 11 had a second operation for recurrent bleeding; the 12th patient, whose first hemorrhage had been treated medically, had surgery during a repeated episode of hemorrhage. The precise bleeding points could be located in only 2 of the 26 bleeding episodes, both at the ileocecal area. Three patients died, of whom two had not undergone surgery when they had bled a few weeks earlier. Primary bleeding episodes subsided without surgery in 10 of 21 cases, but 3 of these 10 patients (30%) rebled massively. By contrast primary excisional surgery was followed by recurrent hemorrhage in only 1 of 11 cases (9%). These differences in mortality and in recurrent bleeding rates, although not statistically significant, seem to favor removal of diseased bowel at the time of the first episode of massive hemorrhage.

Acute Disease↗
PubMed1991

Colorectal cancer in ulcerative colitis. Influence of anatomical extent and age at onset on colitis-cancer interval.

We have examined the age at onset of both ulcerative colitis and colitis-associated colorectal cancer in 100 patients seen at Mount Sinai Hospital between 1959 and 1988. There were 85 patients with extensive colitis and 15 with left sided colitis. There was a strong direct correlation between the age at onset of ulcerative colitis and age at diagnosis of cancer (p less than 0.0001); this correlation was found both in patients with extensive colitis (p less than 0.0001) and in those with left sided colitis (p less than 0.005). Patients with left sided colitis developed both their colitis and their cancers about a decade later than did those with extensive disease, but the mean duration of colitis before diagnosis of cancer was virtually the same (about 21 years) in both groups, irrespective of the age at onset of disease.

Adult↗
PubMed1991

Malignant colorectal strictures in Crohn's disease.

One hundred thirty-two of 980 patients (13.5%) with Crohn's disease (CD) involving the colon, admitted to The Mount Sinai Hospital between 1959 and 1985, developed 175 colonic strictures. Thirty-three patients developed more than one stricture. The frequency was twice as great in colitis (19%) as in ileocolitis (11%). Ten malignant strictures were identified in nine patients (three ileocolitis, six colitis). One of these patients had three strictures (two malignant, and one benign), and two had two strictures (one malignant and one benign). The frequency of cancer in patients with stricture (6.8%) was higher than in those without stricture (0.7%, six of 848, p less than 0.001). There were no differences in clinical symptoms between patients with benign and malignant stricture. Seventeen of 165 benign strictures (10.3%) were long, extending over more than one anatomical segment of colon, but all 10 malignant strictures were short (p less than 0.0001). The age at the diagnosis of stricture was higher in the nine patients with malignant stricture than in the 123 patients with benign stricture (mean age 57.2 vs. 41.4 yr, respectively, p less than 0.01). The proportion of strictures that were malignant increased with duration of disease from 3.3% with less than 20 yr of CD, to 11% with CD of 20 yr or more. All nine patients with malignant stricture were treated surgically, and four of the nine died of colon cancer during a mean follow-up of 4.3 yr. Prognosis was worse in six other nonstricture cancers in this series, with five colon cancer deaths during mean follow-up of 1.6 yr. In view of the high rate of malignancy, 6.8% in this series, colonoscopy with biopsy is essential in Crohn's disease patients with colonic strictures, and surgery must be considered when a stricture cannot be fully assessed during colonoscopy.

Adolescent↗
PubMed1990

Management of severe hemorrhage in ulcerative colitis.

Twenty-five patients with ulcerative colitis were treated between 1959 and 1986 at the Mount Sinai Hospital, with severe gastrointestinal hemorrhage as their major complaint. Twenty-two patients required operation, while three patients were treated medically. Total proctocolectomy with ileostomy was carried out in 5 patients, and subtotal colectomy accompanied by mucous fistula (14), Hartmann closure (2), or ileosigmoidostomy (1) was performed in 17 patients. Eleven of the patients who underwent operation had emergency colectomies, while the remaining 11 had semielective procedures. Subtotal colectomy was performed in 10 of the 11 emergency cases. Indications for emergency surgery were massive hemorrhage alone in seven patients and severe hemorrhage complicated by toxic megacolon in four patients. One patient died postoperatively of a perforated duodenal ulcer following emergency subtotal colectomy. There were two late deaths from leukemia in one surgically treated patient and one medically treated patient at 9 and 18 months, respectively. All 4 of the 25 patients with remaining intact rectums were alive and well at 3- to 12-year follow-up. Subtotal colectomy can be undertaken in patients with massive hemorrhage from ulcerative colitis for whom subsequent ileoanal anastomosis is planned, provided that one recognizes and is prepared for the approximately 12% risk of continued rectal hemorrhage.

Adolescent↗
PubMed1990

The problem of postoperative recurrence of Crohn's disease.

Most patients with Crohn's disease eventually require an operation and the overwhelming majority will ultimately experience a postoperative recurrence at the anastomotic site. Endoscopic lesions can be seen at the anastomosis in 85 per cent of patients by 3 years after surgery. While only 40 to 50 per cent of postoperative patients will ever undergo a second operation, clinical manifestations of recurrent disease develop at a cumulative rate of about 10 per cent per year. Postoperative recurrences of Crohn's disease are well recognized even after total proctocolectomy and ileostomy, but rates are higher following reanastomotic procedures. Evidence accumulated from published observations over the past 20 years, reinforced by new data from The Mount Sinai Hospital, suggests that Crohn's disease may follow at least two different patterns: "aggressive" disease characterized primarily by fistulae and abscesses, early requirement for surgery, and relatively rapid fistulizing-type recurrence; versus "indolent" disease characterized mostly by fibrotic stenosis and strictures, late requirement for surgery, and relatively slower obstructive-type recurrence. Pathophysiologic investigations and clinical trials alike should take into account this duality of clinical patterns. Regardless of the patterns of recurrence, however, surgery performed for proper indications is almost invariably rehabilitating for people disabled by the ravages and complications of Crohn's disease.

Crohn Disease↗
PubMed1990

Erythrocyte sedimentation as a measure of Crohn's disease activity: opposite trends in ileitis versus colitis.

To test our hypothesis that the erythrocytic sedimentation rate (ESR) correlates well with clinical activity in inflammatory disease of the colon, but not of the small bowel, we stratified 49 Crohn's disease patients according to their anatomic involvement and then measured the correlations between ESR and clinical activity within each of these anatomical subgroups. For 18 patients with Crohn's disease involving primarily the colon, there was a trend toward a direct correlation between clinical score and ESR (p = 0.15). In the 14 patients with Crohn's disease limited to the colon, this direct correlation was even more pronounced and statistically significant (p less than 0.02). By contrast, an opposite trend was observed for patients with small bowel disease. For the 26 patients with disease involving predominantly the small bowel, as well as for the 22 with disease limited to small bowel, there were statistically significant inverse correlations between clinical score and ESR (p less than 0.04). This difference between the directions of the correlations for Crohn's colitis versus ileitis was statistically significant (p less than 0.05). This study provides further evidence for the importance of analyzing putative indications of disease activity separately for each of the protean forms in which Crohn's disease occurs.

Blood Sedimentation↗