Ulcerative Colitis: Sachar DB

Kornbluth A, Sachar DB, Anonymous00314. · The Henry D. Janowitz Division of Gastroenterology, The Department of Medicine, Mount Sinai School of Medicine, The Mount Sinai Medical Center, New York, NY 10128, USA. · Am J Gastroenterol. · Pubmed #15233681 No free full text.

Abstract: Guidelines for clinical practice are intended to indicate preferred approaches to medical problems as established by scientifically valid research. Double-blind placebo-controlled studies are preferable, but compassionate use reports and expert review articles are utilized in a thorough review of the literature conducted through Medline with the National Library of Medicine. When only data that will not withstand objective scrutiny are available, a recommendation is identified as a consensus of experts. Guidelines are applicable to all physicians who address the subject without regard to the specialty training or interests and are intended to indicate the preferable but not necessarily the only acceptable approach to a specific problem. Guidelines are intended to be flexible and must be distinguished from standards of care, which are inflexible and rarely violated. Given the wide range of specifics in any health-care problem, the physician must always choose the course best suited to the individual patient and the variables in existence at the moment of decision. Guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the Board of Trustees. Each has been extensively reviewed and revised by the Committee, other experts in the field, physicians who will use them, and specialists in the science of decision of analysis. The recommendations of each guideline are therefore considered valid at the time of their production based on the data available. New developments in medical research and practice pertinent to each guideline will be reviewed at a time established and indicated at the publication in order to assure continued validity.

Brown SJ, Ullman T, Sachar DB. · No affiliation provided · J Clin Gastroenterol. · Pubmed #16208106 No free full text.

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Sachar DB. · No affiliation provided · J Clin Gastroenterol. · Pubmed #12352289 No free full text.

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Harpaz N, Sachar DB. · Mount Sinai School of Medicine, New York, NY 10029, USA. · J Clin Gastroenterol. · Pubmed #16885696 No free full text.

Abstract: Segmental colitis associated with diverticular disease is an inflammatory disorder that bears close clinical and histopathologic similarities to idiopathic inflammatory bowel disease. Comparison with other inflammatory bowel disease-like disorders, such as blind-ended pouches in ulcerative colitis, chronic granulomatous appendicitis, and delayed-surgery appendicitis, affords intriguing analogies and potential clues to its pathogenesis.

Branco BC, Harpaz N, Sachar DB, Greenstein AJ, Tabrizian P, Bauer JJ, Greenstein AJ. · Department of Surgery, Mount Sinai School of Medicine, New York, NY, USA. · Inflamm Bowel Dis. · Pubmed #19177428 No free full text.

Abstract: BACKGROUND: For all the interest in the natural history of colorectal cancer (CRC) in ulcerative colitis (UC) and Crohn's disease (CD), surprisingly few data have been published regarding CRC in indeterminate colitis (IC). We present our experience with 15 cases of IC-associated CRC in order to assess their clinicopathological features and to determine their survival rates. METHODS: We retrospectively reviewed the medical records of patients with IC admitted to the Mount Sinai Hospital between 1994 and 2007 and who developed CRC. All patients were operated on and follow-up was complete for all patients to the closing date of study or to the time of death. RESULTS: A total of 19 adenocarcinomas were present in this series. There were 3 patients with multiple cancers; all cancers occurred in segments of colitis. The mean age at onset of IC was 28 years and the average time progression from the IC diagnosis to CRC was 19 years. Dysplasia was detected in 10 of the cases; 3 patients had mucinous tumors. Five patients had stage I tumors; 5 stage II; 4 stage III; 1 stage IV. There were 4 deaths due to CRC. The overall 5-year survival was 42%. CONCLUSIONS: CRC in IC shares most of the clinical and pathologic features as well as survival outcomes with CRC that occurs in the most prevalent forms of inflammatory bowel disease (IBD), UC and CD. Surveillance regimens currently used in the other forms of IBD seem applicable to IC patients as well.

Branco BC, Sachar DB, Heimann TM, Sarpel U, Harpaz N, Greenstein AJ. · Department of General Surgery, Mount Sinai School of Medicine, New York, New York 10029, USA. · Inflamm Bowel Dis. · Pubmed #19067409 No free full text.

Abstract: The occurrence of adenocarcinoma following ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) is an infrequent and but potentially lethal complication. We have seen 1 such case among 520 IPAAs performed in our group practice between 1978 and February 2008. We have added this case to a review of 25 previously reported cases of adenocarcinoma of the pouch or outflow tract following IPAA for UC. Our conclusions are 1) that post-IPAA cancer can occur following either mucosectomy or stapled anastomosis; 2) that this malignancy can occur after IPAA performed for UC either with or without neoplasia; and 3) that this complication is seen whether or not the initial cancer or dysplasia had involved the rectum.

Branco BC, Sachar DB, Heimann T, Sarpel U, Harpaz N, Greenstein AJ. · Department of Surgery, Mount Sinai School of Medicine, New York City, New York 10029, USA. · Colorectal Dis. · Pubmed #18662238 No free full text.

Abstract: This is a report of adenocarcinoma arising in an ileal pouch after restorative proctocolectomy (RPC) with rectal mucosal stripping performed by Cavitron Ultrasonic Surgical Aspirator (CUSA) for ulcerative colitis. The CUSA was introduced to simplify and optimize ileal pouch-anal anastomosis with mucosectomy and has been shown to shorten the operative time and reduce blood loss. Its use however, may increase the number of pathology specimens made uninterpretable on account of tissue ablation. In the present case, even though preoperative colonoscopy had clearly shown dysplasia, the surgical pathology report could not detect any neoplasia in the specimen; hence, the patient was not surveyed for pouch cancer. Six years later, the patient presented with intestinal obstruction caused by cancer. While protocols for universal pouch surveillance remain somewhat controversial, we conclude on the basis of this case and a review of the literature that in RPC with mucosectomy performed by CUSA, pouch cancer surveillance is particularly important because remnants of rectal epithelium may have been left behind and tissue ablation may have made the surgical pathology report uninterpretable.

Meier CB, Hegazi RA, Aisenberg J, Legnani PE, Nilubol N, Cobrin GM, Duerr RH, Gorfine SR, Bauer JJ, Sachar DB, Plevy SE. · Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA. · Inflamm Bowel Dis. · Pubmed #16239841 No free full text.

Abstract: BACKGROUND: Pouchitis is a frequent complication after ileal pouch-anal anastamosis (IPAA) for ulcerative colitis (UC). The aim of this study was to determine whether genetic polymorphisms in the innate immune receptors toll-like receptor (TLR)4 and caspase activation and recruitment domain family member 15 (CARD15) genes are associated with pouchitis. METHODS: From a retrospectively ascertained cohort of patients with UC 5 to 12 years after IPAA (n = 101), subjects were classified into 3 groups: no pouchitis (n = 52); 1 to 2 episodes per year (n = 11), and more than 2 episodes per year (n = 38). Single nucleotide polymorphisms in the tlr4 gene (D299G, T399I) were determined by a real-time polymerase chain reaction-based fluorogenic probe technique; and card15 polymorphisms (L1007fsinsC, R702W, G908R) were determined by pyrosequencing. RESULTS: Pouchitis affected 49% (49/101) of the study population. No correlation between pouchitis and the presence of TLR4 polymorphisms was found. The percentage of patients who harbored CARD15 mutations was significantly higher in patients with pouchitis than in patients without pouchitis (18% versus 8%; P < 0.05); 24% of pouchitis patients with more than 2 episodes per year harbored CARD15 mutations (P < 0.01 compared with the no pouchitis group). The CARD15 insertion mutation L1007fsinsC was present in 14% of patients with pouchitis and in 0% without pouchitis (P < 0.05). All patients who carried L1007fsinsC developed more than 2 episodes per year. CONCLUSIONS: CARD15 polymorphisms are seen in greater frequency in patients with pouchitis after IPAA for UC. These findings, if borne out in prospective analyses, suggest that CARD15 mutations, particularly L1007fsinsC, may predispose to the development of pouchitis after IPAA for UC.

Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein CN, Brant SR, Caprilli R, Colombel JF, Gasche C, Geboes K, Jewell DP, Karban A, Loftus Jr EV, Peña AS, Riddell RH, Sachar DB, Schreiber S, Steinhart AH, Targan SR, Vermeire S, Warren BF. · Mount Sinai Hospital, Toronto, Canada. · Can J Gastroenterol. · Pubmed #16151544 No free full text.

Abstract: The discovery of a series of genetic and serological markers associated with disease susceptibility and phenotype in inflammatory bowel disease has led to the prospect of an integrated classification system involving clinical, serological and genetic parameters. The Working Party has reviewed current clinical classification systems in Crohn's disease, ulcerative colitis and indeterminate colitis, and provided recommendations for clinical classification in practice. Progress with respect to integrating serological and genetic markers has been examined in detail, and the implications are discussed. While an integrated system is not proposed for clinical use at present, the introduction of a widely acceptable clinical subclassification is strongly advocated, which would allow detailed correlations among serotype, genotype and clinical phenotype to be examined and confirmed in independent cohorts of patients and, thereby, provide a vital foundation for future work.

Aisenberg J, Legnani PE, Nilubol N, Cobrin GM, Ellozy SH, Hegazi RA, Yager J, Bodian C, Gorfine SR, Bauer JJ, Plevy SE, Sachar DB. · Department of Gastroenterology, Mount Sinai Medical Center, New York, USA. · Am J Gastroenterol. · Pubmed #15056081 No free full text.

Abstract: OBJECTIVE: Pouchitis is the most frequent complication after ileal pouch-anal anastomosis for ulcerative colitis. This study aims to analyze the frequency and characteristics of pouchitis in long-term follow-up in a large population, and to determine whether a significant association exists between five immunogenetic markers and pouchitis. METHODS: From a population of over 500 ulcerative colitis patients who had undergone ileal pouch-anal anastamosis 5-12 yr earlier, 102 subjects participated in the study. Using clinical data obtained from interviews and chart reviews, patients were classified into three groups: no pouchitis; 1-2 episodes per year; and >2 episodes per year. Coded sera from the patients were analyzed for ulcerative colitis-associated perinuclear antineutrophil cytoplasmic antibodies and Crohn's disease-associated anti-saccharomyces cerevesiae antibodies. Interleukin-1 receptor antagonist, tumor necrosis factor (TNF), and lymphotoxin beta (lymphotoxin) polymorphisms were also analyzed. RESULTS: Pouchitis affected 49% of the study population. Antineutrophil cytoplasmic antibodies, anti-saccharomyces cerevesiae antibodies, and lymphotoxin-beta polymorphisms were not associated with pouchitis. Carriage of interleukin-1 receptor antagonist allele 2 was significantly greater among those without pouchitis than those with pouchitis. Patients without pouchitis had a significantly greater carriage rate of TNF allele 2. CONCLUSIONS: Perinuclear antineutrophil cytoplasmic antibodies and anti-saccharomyces cerevesiae antibodies are not correlated with pouchitis, but interleukin-1 receptor antagonist and TNF may play a role in its development. Further evaluation of these markers in pouchitis will require larger populations, long-term prospective observation, and studies that correlate polymorphisms with specific immunologic functions.

Sachar DB. · Mount Sinai School of Medicine, New York, USA. · Gut. · Pubmed #12427770 links to  free full text

This publication has no abstract.

Almogy G, Sachar DB, Bodian CA, Greenstein AJ. · Department of Surgery, Mount Sinai Hospital and the Mount Sinai School of Medicine, New York, NY, USA. · Arch Surg. · Pubmed #11735867 links to  free full text

Abstract: HYPOTHESIS: Medical therapy has changed the indications for surgery over the last 4 decades. Advances in perioperative care have significantly improved the outcome. DESIGN: The medical records of all patients 65 years and older who underwent surgery for ulcerative colitis during a 40-year period were analyzed retrospectively. SETTING: Tertiary referral center. PATIENTS: One hundred thirteen consecutive patients 65 years and older who underwent surgery for ulcerative colitis between January 1, 1960, and June 30, 1999. MAIN OUTCOME MEASURES: Changes in elective and urgent indications for surgery. Changes over time in outcome and the factors that brought about these changes. Predictors of poor outcome in an elderly population with ulcerative colitis. RESULTS: One hundred thirteen patients were divided into 3 cohorts of 38, 38, and 37 consecutive patients admitted to the hospital during the periods 1960 through 1984, 1985 through 1993, and 1994 through 1999, respectively. Indications for surgery and morbidity and mortality rates have changed with time. Dysplasia has replaced carcinoma as a major indication for elective surgery (P =.001). Toxic megacolon has become significantly less common as an indication for urgent surgery (P =.001). Surgery-associated adverse outcomes have decreased significantly from 50% (13% deaths, 37% major complications) to 27% (3% deaths, 24% major complications) (P =.04). Male sex, an albumin level of 2.8 g/dL or less, and urgent surgery were found to be independent predictors of poor outcome. CONCLUSIONS: In our referral center, the indications for urgent and elective surgery have changed during the past 4 decades from toxic megacolon and carcinoma, to disease refractory, to medical therapy and dysplasia, respectively. Morbidity and mortality have decreased dramatically over time. Urgent procedures, low levels of albumin, and male sex are all predictors of poor outcome.

Almogy G, Sachar DB, Gans WH, Greenstein AJ. · Department of Surgery, Mount Sinai Hospital, New York 10029, USA. · J Clin Gastroenterol. · Pubmed #11246356 No free full text.

Abstract: Inflammatory bowel disease is often associated with hematologic abnormalities such as anemia, leukocytosis, and thrombocytosis. We report for the first time an unusual case of ulcerative colitis complicated by thrombotic thrombocytopenic purpura. Severe lower gastrointestinal bleeding resolved with subtotal colectomy, but the thrombotic thrombocytopenic purpura proved unresponsive to medical treatment. Splenectomy and completion proctectomy were performed, ultimately resulting in a successful outcome.