Ulcerative Colitis: Bauer JJ

Cohen Z, Senagore AJ, Dayton MT, Koruda MJ, Beck DE, Wolff BG, Fleshner PR, Thirlby RC, Ludwig KA, Larach SW, Weiss EG, Bauer JJ, Holmdahl L. · Department of Surgery, Mount Sinai Hospital, University of Toronto, Toronto, Canada. · Dis Colon Rectum. · Pubmed #15868230 No free full text.

Abstract: INTRODUCTION: Postoperative abdominal adhesions are associated with significant morbidity and mortality, placing a substantial burden on healthcare systems worldwide. Development of a bioresorbable membrane containing up to 23 percent glycerol and chemically modified sodium hyaluronate/carboxymethylcellulose offers ease of handling and has been shown to provide significant postoperative adhesion prevention in animals. This study was designed to assess the safety of glycerol hyaluronate/carboxymethylcellulose and to evaluate its efficacy in reducing the incidence, extent, and severity of postoperative adhesion development in surgical patients. METHODS: Twelve centers enrolled 120 patients with ulcerative colitis or familial polyposis who were scheduled for a restorative proctocolectomy and ileal pouch-anal anastomosis with diverting loop ileostomy. Before surgical closure, patients were randomized to no anti-adhesion treatment (control) or treatment with glycerol hyaluronate/carboxymethylcellulose membrane under the midline incision. At ileostomy closure, laparoscopy was used to evaluate the incidence, extent, and severity of adhesion formation to the midline incision. RESULTS: Data were analyzed using the intent-to-treat population. Treatment with glycerol hyaluronate/carboxymethylcellulose resulted in 19 of 58 patients (33 percent) with no adhesions compared with 6 of 60 adhesion-free patients (10 percent) in the no treatment control group (P = 0.002). The mean extent of postoperative adhesions to the midline incision was significantly lower among patients treated with glycerol hyaluronate/carboxymethylcellulose compared with patients in the control group (P < 0.001). The severity of postoperative adhesions to the midline incision was significantly less with glycerol hyaluronate/carboxymethylcellulose than with control (P < 0.001). Adverse events were similar between treatment and no treatment control groups with the exception of abscess and incisional wound complications were more frequently observed with glycerol hyaluronate/carboxymethylcellulose. CONCLUSIONS: Glycerol hyaluronate/carboxymethylcellulose was shown to effectively reduce adhesions to the midline incision and adhesions between the omentum and small bowel after abdominal surgery. Safety profiles for the treatment and no treatment control groups were similar with the exception of more infection complications associated with glycerol hyaluronate/carboxymethylcellulose use. Animal models did not predict these complications.

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.

Nilubol N, Scherl E, Bub DS, Gorfine SR, Marion J, Harris MT, Kornbluth A, Lichtiger S, Rubin P, George J, Chapman M, Harpaz N, Present D, Bauer JJ. · Department of Surgery, The Mount Sinai Hospital, New York, New York, USA. · Dis Colon Rectum. · Pubmed #17429711 No free full text.

Abstract: PURPOSE: Inflammation, villous atrophy, colonic metaplasia, and dysplasia have been observed within the mucosa of ileal pelvic pouches after restorative proctocolectomy. This study was designed to determine the prevalence of mucosal dysplasia in ileal pouch and any associated risk factors. METHODS: Prospectively registered patients having restorative proctocolectomy were recruited. A cross-sectional study was performed using a questionnaire focusing on disease history, functional results, and pouchitis after surgery. Participants underwent screening endoscopic pouch examination using sigmoidoscopy. Mucosal biopsies were taken from six specific locations in the pouch from proximal ileal-pouch (inflow) to ileoanal anastomosis. All biopsies were performed under strict surveillance protocol regardless of patients' symptoms. Biopsies were interpreted by two pathologists unaware of each other's report. RESULTS: A total of 138 patients completed the protocol. Colectomy specimens from restorative proctocolectomy showed chronic ulcerative colitis in 118 (85.6 percent), familial adenomatous polyposis in 10 (7.2 percent), Crohn's colitis in 2 (1.4 percent), and indeterminate colitis in 8 (5.8 percent) patients. Twenty-two patients (18.3 percent) had dysplasia and eight (6.7 percent) had invasive cancer found in colectomy specimens after restorative proctocolectomy. Median interval between proctocolectomy and pouch biopsy was 5.4 years. Inflammatory changes were present in a majority of specimens, but these did not correlate with clinical history of pouchitis. No villous atrophy was identified. Pouch biopsies from only one patient were indefinite for dysplasia. Subsequent biopsies were negative. CONCLUSIONS: Clinical and microscopic evidence of ileal-pouch inflammation is common. Ileal-pouch mucosal dysplasia is uncommon, occurring in only 1 of 138 patients. Villous atrophy and colonic metaplasia were not observed in this series. Routine pouch surveillance with biopsies may not be warranted.

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.

Gorfine SR, Harris MT, Bub DS, Bauer JJ. · The Mount Sinai School of Medicine, Department of Surgery, New York, New York, USA. · Dis Colon Rectum. · Pubmed #15484353 No free full text.

Abstract: PURPOSE: Restorative proctocolectomy with ileal pouch-anal anastomosis is widely accepted as the procedure of choice for patients requiring surgery for chronic ulcerative colitis. The role of restorative proctocolectomy in the setting of chronic ulcerative colitis complicated by colorectal carcinoma is not clear. This study was undertaken to explore the clinical outcomes of chronic ulcerative colitis patients with coexisting colorectal carcinoma who underwent restorative proctocolectomy. METHODS: A total of 756 patients with chronic ulcerative colitis were followed prospectively after restorative proctocolectomy. Forty-five (5.9 percent) were found to have invasive carcinoma of the colon (n = 31) or rectum (n = 14). These patients were followed with special attention to cancer stage, adjuvant therapy, oncologic outcome, and functional results after restorative proctocolectomy. RESULTS: Twenty-one patients (45.6 percent) had staged surgery (colon, 14; rectum, 7). Twenty-seven patients received adjuvant chemotherapy (colon, 22; rectum, 5). Fourteen patients (51.8 percent) who received chemotherapy were not diverted during this treatment. Two node-positive rectal cancer patients had pelvic radiotherapy: one before restorative proctocolectomy and one after restorative proctocolectomy. Mean time to restoration of intestinal continuity among staged patients did not differ between cancer and noncancer patients. Six patients died of metastatic disease (colon, 3; rectum, 3). Five deaths occurred among patients with Stage III disease (colon, 3/13, 23.1 percent; rectum, 2/3, 66.7 percent). One patient with Stage I cancer at the time of restorative proctocolectomy died. Thirty-nine patients are alive without evidence of disease at a mean interval from surgery of 76.5 months. Thirty-six patients have functioning pelvic pouches. Bowel frequency, continence, and complication rates are similar among restorative proctocolectomy patients with and without cancer. CONCLUSIONS: Restorative proctocolectomy as a single or staged procedure is a viable therapeutic option for selected chronic ulcerative colitis patients with associated colorectal cancers. Prognosis seems to be related to cancer stage. Adjuvant chemotherapy can safely be given to nondiverted patients. Appropriate use of preoperative and postoperative radiotherapy for rectal cancer patients who are otherwise candidates for restorative proctocolectomy is unknown. Long-term functional results for cancer patients are similar to those seen in chronic ulcerative colitis patients without cancer.

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.

Ellozy SH, Harris MT, Bauer JJ, Gorfine SR, Kreel I. · Department of Surgery, The Mount Sinai School of Medicine, New York, New York, USA. · Dis Colon Rectum. · Pubmed #12352239 No free full text.

Abstract: PURPOSE: Early postoperative small-bowel obstruction is a common but poorly defined complication of abdominal surgery. This prospective cohort study was undertaken to examine a reproducible definition of early postoperative small-bowel obstruction, determine its incidence, evaluate potential risk factors for its development, and delineate management strategies. METHODS: Two hundred twenty-five patients undergoing 242 consecutive abdominal operations during a 9-month period were prospectively evaluated from the time of admission until Postoperative Day 30. Early postoperative small-bowel obstruction was present if, within 30 days of surgery, all of the following criteria were met after the return of intestinal function: development of crampy abdominal pain, vomiting, and radiographic findings consistent with intestinal obstruction. Patients with early postoperative small-bowel obstruction were followed up until discharge or reexploration. All patients with early postoperative small-bowel obstruction were initially treated with nasogastric decompression. RESULTS: Two hundred forty-two abdominal procedures were performed on 119 males and 123 females aged 13 to 98 (mean, 51) years. Ulcerative colitis (n = 70), malignancy (n = 59), and Crohn's disease (n = 41) were the most common diagnoses. One hundred nineteen patients (49.2 percent) had undergone previous laparotomy, and 45 patients (18.6 percent) had previously been diagnosed with intestinal obstruction. Early postoperative small-bowel obstruction occurred in 23 cases (9.5 percent). Patients with and without early postoperative small-bowel obstruction were similar with respect to diagnosis, preoperative immunosuppression, previous laparotomy or obstruction, surgery performed, and time to return of intestinal function. Twenty episodes (87 percent) resolved with nasogastric decompression alone; all but one resolved within six days or less. Three patients (13 percent) required relaparotomy; one required small-bowel resection. Two of three patients whose symptoms did not resolve with six days of nasogastric decompression required reexploration. There were no deaths and no major morbidity. CONCLUSIONS: Early postoperative small-bowel obstruction, defined by an objective data set, was observed in 9.5 percent of cases. No independent risk factors predisposing to early postoperative small-bowel obstruction were identified. Early postoperative small-bowel obstruction was safely and effectively managed by nasogastric decompression in the majority of cases, with low morbidity and no mortality. In general, reexploration should be reserved for those patients whose symptoms do not resolve within six days of nasogastric decompression.

Nilubol N, Taub PJ, Venturero M, Lichtiger S, Bauer JJ. · Department of Surgery, Mount Sinai School of Medicine, New York, NY, USA. · Mt Sinai J Med. · Pubmed #11687869 links to  free full text

Abstract: A 38-year-old woman with ulcerative colitis subsequently developed sarcoidosis. After ten years of recurrent episodes of colitis, she had presented with respiratory symptoms. The diagnosis of sarcoidosis was confirmed by mediastinal lymph node biopsy. Her respiratory symptoms gradually resolved without any specific treatment. Within the remission period of sarcoidosis, she underwent uneventful subtotal colectomy due to refractory colitis. Alterations in immune function and genetic susceptibility have been suggested to be present in both ulcerative colitis and sarcoidosis. However, the occurrence of both in the same patient has been rare. This is only the nineteenth case reported in the literature.

Gorfine SR, Bauer JJ, Harris MT, Kreel I. · The Mount Sinai Medical Center, New York, New York, USA. · Dis Colon Rectum. · Pubmed #11089596 No free full text.

Abstract: PURPOSE: Inflammatory bowel disease surveillance strategies are designed to identify patients at greater than average risk for the development of invasive colonic carcinoma. Colonoscopic detection of mucosal dysplasia is considered the best available surveillance tool. However, the usefulness of dysplasia as a marker for cancer is uncertain. Furthermore, when dysplasia is found some suggest immediate colectomy, whereas others opt for continued surveillance. The aim of this study is to determine whether an association between dysplasia grade and cancer exists in patients with chronic ulcerative colitis, to ascertain the sensitivity, specificity, and positive predictive value of dysplasia as a cancer marker, and to clarify what action to take once dysplasia is discovered. METHODS: The pathology reports of 590 patients who underwent total proctocolectomy or restorative proctocolectomy for chronic ulcerative colitis were reviewed for dysplasia, grade of dysplasia, presence of carcinoma, and tumor stage. One hundred sixty of these patients had undergone colonoscopic examination within the year before surgery. Findings from these studies were also reviewed. RESULTS: Seventy-seven specimens (13.1 percent) contained at least one focus of dysplasia. Invasive cancers were found in 38 specimens (6.4 percent). Cancers were significantly more common among specimens with dysplastic changes (33/77 vs. 5/513; P < 0.001). Specimens with dysplasia of any grade were 36 times more likely to harbor invasive carcinoma. Stage III disease was found in association with indefinite or low-grade dysplasia in 5 of 26 (19.2 percent) of cases. Tumor stage did not correlate with dysplasia grade. Preoperative colonoscopy identified neoplastic changes in 57 (69.5 percent) cases. Dysplasia, cancer or both were missed in 25 cases. Lesions were correctly identified in only 31 (39.7 percent) of cases. Colonoscopically diagnosed dysplasia as a marker for synchronous cancer had a sensitivity of 81 percent and a specificity of 79 percent. The positive predictive value of a finding of preoperative dysplasia of any grade was 50 percent. The positive predictive value of a finding of low-grade dysplasia was 70 percent. CONCLUSIONS: Dysplasia is an unreliable marker for the detection of synchronous carcinoma. However, when dysplasia of any grade is discovered at colonoscopy, the probability of a coexistent carcinoma is relatively high. Colonoscopic evidence of low-grade dysplasia has a higher positive predictive value than either dysplasia associated mass or lesion or high-grade dysplasia. Dysplasia grade does not predict tumor stage. Because advanced cancer can be found in association with dysplastic changes of any grade, confirmed dysplasia of any grade is an indication for colectomy.