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Biomedical subjects

D B Sachar

Publications and source records attributed to D B Sachar.

At least 37 records · Page 2Linked to original sources
PubMed1996

Colorectal adenocarcinoma in Crohn's disease.

OBJECTIVE: The authors' aim was to review the clinical features and estimate the long-term survival of patients with colorectal carcinoma complicating Crohn's disease. SUMMARY BACKGROUND DATA: Recent studies have demonstrated a significantly increased risk of colorectal carcinoma in patients with Crohns disease. METHODS: The authors reviewed retrospectively the medical records of 30 patients with Crohn's disease admitted to The Mount Sinai Hospital between 1960 and 1989 in whom colorectal adenocarcinoma developed. All patients were operated on and follow-up was complete for all patients to 10 years after operation, to the time of death, or to the closing date of the study in December 1989. RESULTS: The 30 patients in the series had 33 colorectal adenocarcinomas; three patients (10%) presented with two synchronous cancers. The patients were relatively young (mean age, 53 years) and had long-standing Crohn's disease (duration >20 years in 87%). The 5-year actuarial survival was 44% for the overall series: 100% for stage A, 86% for stage B, 60% for stage C. All five patients with excluded bowel tumor died of large bowel cancer within 2.4 years; by contrast, the actuarial 5-year survival for patients with in-continuity tumors was 56%. CONCLUSIONS: The incidence, characteristics, and prognosis of colorectal carcinoma complicating Crohn's disease are similar to the features of cancer in ulcerative colitis, including young age, multiple neoplasms, long duration of disease, and greater than a 50% 5-year survival rate (without excluded loops). These observations suggest the advisability of surveillance programs for Crohn's disease of the colon similar to those for ulcerative colitis of comparable duration and extent.

Adenocarcinoma↗
PubMed1996

Patterns of postoperative recurrence in fistulizing and stenotic Crohn's disease. a retrospective cohort study of 71 patients.

To compare the time course of clinical recurrences and reoperations following primary resections for fistulization versus fibrostenotic obstruction in ileal Crohn's disease, we performed a retrospective cohort study of 71 patients undergoing their first resection at The Mount Sinai Hospital between 1961 and 1984. Among these 71 patients, 35 were classified as fistulizing and 36 as fibrostenotic. Follow-up was 93% complete through 1990, with a median follow-up of 73 months to reoperation and 105 months to last contact. The fistulizing and fibrostenotic patients experienced virtually identical numbers of clinical recurrences: 25 from the former group and 24 from the latter. The recurrences appeared very slightly earlier among the fistulizing than among the fibrostenotic group, but the difference did not approach statistical significance. Only 18 patients came to reoperation during follow-up: 12 from the fistulizing and 6 from the fibrostenotic group. The earliest reoperation in the fistulizing group occurred at 14 months and in the fibrostenotic group at 44 months. There was a trend for earlier reoperation in the fistulizing group, but the difference was not statistically significant. Different clinical patterns of Crohn's disease have yet to be correlated with distinctive subclinical biologic markers.

Adult↗
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

Enterolithiasis, refractory anemia, and strictures of Crohn's disease.

In Crohn's disease, multiple areas of small bowel stenosis are relatively common, but there are only 11 reported cases with stenosis complicated by enterolithiasis. We describe three patients with multiple strictures, enterolithiasis, and refractory iron deficiency anemia. The chronic anemia was severe, requiring multiple transfusions in two patients. One patient developed a perforation, and a second had cancer within one of the saccular dilatations between strictures. Management of this stricture-enterolith-anemia triad requires removal of the enteroliths and correction of the strictures by strictureplasty and/or resection. If the operation of choice is strictureplasty, however, meticulous inspection and biopsy of each proposed site of enteroplasty is essential to rule out carcinoma.

Adult↗
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↗
PubMed1993

Survival with colorectal cancer in ulcerative colitis. A study of 102 cases.

OBJECTIVE: This study was undertaken to correlate postoperative survival of patients with ulcerative colitis-associated colorectal cancer with the stage, configuration, size, and mucin content of the tumor. SUMMARY BACKGROUND DATA: The factors influencing prognosis in colorectal cancer in the general population are well accepted, but less is known about their influence in cases of colorectal cancer associated with ulcerative colitis. METHODS: The authors reviewed the records of 102 patients with ulcerative colitis-associated colorectal cancer admitted to The Mount Sinai Hospital between 1959 and 1988. Tumors were classified on independent pathologic review according to histologic stage, configuration, size, and mucin content. Comparisons among survival curves were tested by the generalized Wilcoxon test. Cox regression models were used to examine the joint effects of selected clinicopathologic features on postoperative survival rates. RESULTS: Complete follow-up was obtained for 93 patients (92%). Overall 5-year actuarial survival was 52%. When factors were analyzed one at a time, survival was significantly poorer among patients with advanced cancer stage, larger tumor size, infiltrating and ulcerating configuration, and high mucin concentration. On multivariate analysis by the Cox regression model, however, only cancer stage emerged as a factor independently predicting survival. CONCLUSIONS: For colitis-associated colorectal cancers, as for noncolitic cancers, histologic stage is the most important variable determining postoperative survival. The distribution of stages in our series and the survival rates within each stage did not differ appreciably from the distributions and survival rates reported for noncolitic colorectal cancers.

Adult↗
PubMed1993

Refractory pouchitis: does it reflect underlying Crohn's disease?

Typical 'pouchitis' is a well recognised complication of ileal pouches in ulcerative colitis. Infrequently, a refractory pouchitis (RP) presents with certain clinical, endoscopic, and pathological features resembling Crohn's disease and is often ascribed to misdiagnosis of the initial colitis. To test that hypothesis and to identify risk factors for RP, this study reviewed cases of presumed ulcerative colitis with ileal pouches constructed at The Mount Sinai Hospital between 1973 and 1986. Twenty four cases with RP (16 Kock pouches and eight pelvic pouches) and 21 controls were compared for eight clinical variables. The original colectomy slides from 15 RP and 18 control cases were reviewed blindly, classified into five histological categories (corresponding to definite ulcerative colitis, definite Crohn's disease, and three indeterminate groups), and scored for 23 histological features. There were no significant clinical differences between RP and control cases except for more frequent extraintestinal manifestations (38% v 5%) and male preponderance (79% v 43%) in RP. There were also no significant differences between the distributions of RP cases and controls among the five histological categories or in the 23 histological features studied. Refractory pouchitis therefore does not seem to reflect underlying Crohn's disease, but may be linked to immunological mechanisms that are manifested clinically as extraintestinal complications.

Adult↗
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↗