BACKGROUND:Current approaches to the detection of colorectal neoplasia associated with inflammatory bowel disease (IBD-CRN) are suboptimal.AIM:To test the feasibility of using stool assay of exfoliated DNA markers to detect IBD-CRN.METHODS:This investigation comprised tissue and stool studies. In the tissue study, gene sequencing and methylation assays were performed on candidate genes using tissue DNA from 25 IBD-CRNs and from 25 IBD mucosae without CRN. Mutations on p53, APC, KRAS, BRAF or PIK3CA genes were insufficiently informative, but several aberrantly methylated genes were highly discriminant. In the stool study, we evaluated candidate methylated genes (vimentin, EYA4, BMP3, NDRG4) in a prospective blinded study on buffered stools from 19 cases with known IBD-CRN and 35 age- and sex-matched IBD controls without CRN. From stool-extracted DNA, target genes were assayed using quantitative allele-specific real-time target and signal amplification method.RESULTS:IBD-CRN cases included 17 with ulcerative colitis (UC) and two with Crohn's disease (CD); nine had cancer and 10 had dysplasia. Controls included 25 with UC and 10 with CD. Individually, BMP3, vimentin, EYA4 and NDRG4 markers showed high discrimination in stools with respective areas under the ROC curve of 0.91, 0.91, 0.85 and 0.84 for total IBD-CRN and of 0.97, 0.97, 0.95 and 0.85 for cancer. At 89% specificity, the combination of BMP3 and mNDRG4 detected 9/9 (100%) of CRC and 80% of dysplasia, 4/4 (100%) of high grade and 4/6 (67%) of low grade.CONCLUSION:These findings demonstrate the feasibility of stool DNA testing for non-invasive detection of colorectal neoplasia associated with inflammatory bowel disease.

BACKGROUND:This study determined survival and recurrence rates following curative resection of rectal cancer without radiotherapy.METHODS:This was a retrospective review of the Mayo Clinic database of patients with rectal cancer treated with curative intent using surgery alone from 1990 to 2006. Patients who received neoadjuvant chemotherapy or radiation therapy and those who had any postoperative radiotherapy were excluded. Details were collected from the database and patient records using a protocol approved by the institutional review board.RESULTS:Some 655 consecutive patients with rectal cancer treated with curative intent using surgery alone were identified; 397 had stage I disease, 125 stage II and 133 stage III. Four hundred and nine patients underwent anterior resection (AR) and 246 abdominoperineal resection (APR). Median follow-up was 62 months. The 5-year rate of local recurrence was 4·3 per cent, disease-free survival 90·0 per cent and cancer-specific survival 91·5 per cent. Stage-specific and all-stage disease-free survival did not differ significantly between AR and APR. The 5-year cumulative local recurrence rate was lower following AR than APR (3·6 versus 5·5 per cent; P = 0·321). There were only two patients with positive margins and type of operation was not significant on multivariable analysis.CONCLUSION:Well-performed, standardized APRs have similar local recurrence to AR. Radiation therapy may not confer much additional benefit.

Background: The Crohn's Disease Activity Index (CDAI) has been used in medical trials with scores < 150 indicative of remission. Its value in assessing postoperative recurrence is unknown. The objective of this study was to explore the utility of the CDAI in determining the presence or absence of symptomatic disease recurrence in patients having previously undergone ileocolic resection for Crohn's disease.Methods: Ninety-three patients underwent clinical and colonoscopic evaluation within 12 months of ileocolic resection. Endoscopic appearance was assessed using the Rutgeerts score (i0-i4). Symptomatic disease recurrence was defined by the composite of symptom severity warranting therapy and an endoscopic score >= i2. CDAI scores were calculated. Comparisons were made using the receiver operator curve (ROC).Results: Thirty-nine (42%) patients had recurrent disease (22% symptomatic, 20% endoscopic only) at 12 months. Median CDAI for symptomatic recurrence was 198 (interquartile range [IQR]: 106-293), 80 for asymptomatic subjects (IQR 35-115). The area under the ROC curve for symptomatic disease and CDAI was 0.78 (95% confidence interval [CI] 0.64-0.91). Recurrence was best predicted by a CDAI of >= 148 (sensitivity 70%, specificity 81%). A strong linear relationship existed between the CDAI and Inflammatory Bowel Disease Questionnaire (r = 0.82).Conclusions: The CDAI performs reasonably well in the postoperative setting and 150 appears the best cutpoint for indicating symptomatic disease. However, it is likely not suitable for use as the primary outcome measure. These data suggest that a combination of symptom assessment plus endoscopic evidence of recurrence should remain the gold standard definition for assessing outcomes in postoperative CD trials.

BACKGROUND:The aim was to evaluate outcomes in patients with ulcerative colitis complicated by primary sclerosing cholangitis (PSC) who required ileal pouch-anal anastomosis (IPAA) and orthotopic liver transplantation (OLT).METHODS:A retrospective analysis was performed of 32 patients undergoing both IPAA and OLT between 1980 and 2006. Data were collected regarding demographics, indication for surgery, postoperative complications, and outcome of IPAA and OLT.RESULTS:Thirty-day mortality after either procedure was nil. The median preoperative Model for End-stage Liver Disease (MELD) score for the group with initial IPAA was 8 (range 6-20) and the postoperative score was 11 (range 6-19). At 1 and 10 years, 32 and 26 of the 32 liver grafts had survived, and 31 and 30 of the 32 pouches, respectively. Fourteen patients require daily medical therapy for chronic pouchitis. At a median follow-up of 3.6 (range 0.2-16.2) years after the second of two procedures, responding patients reported a median of 5.5 stools per day and 2 stools per night.CONCLUSION:IPAA and OLT are feasible and safe in patients requiring both procedures for ulcerative colitis and PSC. Functional outcomes are stable over time, despite an increased risk of chronic pouchitis.

PURPOSE:The aim of this study was to determine the optimal management of patients with colorectal cancer and abdominal aortic aneurysm in the elective situation.METHODS:All patients with a history of colorectal cancer and abdominal aortic aneurysm between 1986 and July 2000 were identified, and charts of those with concomitant disease were reviewed.RESULTS:A total of 435 patients with available charts were reviewed. Eighty-three patients with concomitant abdominal aortic aneurysm and colorectal cancer were identified. In 64 patients the colorectal cancer was treated first, and 44 of these patients had an abdominal aortic aneurysm less than 5 cm in diameter (average = 3.8 cm). No abdominal aortic aneurysm ruptured in the postoperative period. Median delay to colorectal cancer surgery from diagnosis was four days. Twenty patients with abdominal aortic aneurysm of 5 cm or greater (average = 5.4 cm) were treated for colorectal cancer first. In two of these patients (with abdominal aortic aneurysms sized 5 and 6.4 cm), the abdominal aortic aneurysm ruptured in the early postoperative period. Median delay to colorectal cancer resection was eight days. Twelve patients had both abdominal aortic aneurysm and colorectal cancer treated at the same time. The average size of the abdominal aortic aneurysm was 6.4 cm. Median delay from colorectal cancer diagnosis to resection was 15 days. No documented cases of graft infection occurred in this group; median follow-up was 3.2 years. Seven patients underwent abdominal aortic aneurysm repair before resection of colorectal cancer; in two patients, colorectal cancer was found at the time of resection. The average size of abdominal aortic aneurysm was 6 cm and median delay to treatment of colorectal cancer was 122 days, a statistically significant longer delay than in the other two groups (P < 0.0001).CONCLUSION:In patients with colorectal cancer and abdominal aortic aneurysm of 5 cm or more, treatment of colorectal cancer first may result in life-threatening rupture, whereas treatment of abdominal aortic aneurysm first may significantly delay treatment of colorectal cancer. Concomitant treatment seems to be a safe alternative. If anatomically suitable, the abdominal aortic aneurysm may be considered for endovascular repair followed by a staged colon resection. The presence of an abdominal aortic aneurysm less than 5 cm does not affect colorectal cancer treatment.

Soon after Crohn's disease was described in the early 1930s, surgeons began treating involved sections of bowel by resection and anastomosis.The point of reference at that time was bowel cancer, which also involved a focal segment of bowel and created enlarged lymph nodes in the mesentery.Of course this method of treating Crohn's disease by resection with `curative' intent, similar to that for bowel malignancy, was based on an erroneous assumption.This stemmed from a lack of understanding that the disease is a process that can affect any part of the gastrointestinal tract; it is not merely a focal problem affecting only one section of bowel.This background explains the early importance of proximal and distal margins in surgery for Crohn's disease.Time and surgical experience have shown that there is a high recurrence or relapse rate after resection for this condition.Some surgeons began to regard this relapse as almost inevitable, regardless of surgical technique.Others held that the problem was simply a result of inadequate clearance, and that a modi®cation of surgical technique would lead to lower recurrence rates.Such a difference of opinion engendered the great debate on the importance of surgical margins in the 1980s.Krause et al. 1 in 1985 reported a long-term follow-up study of 186 patients divided retrospectively into two groups, one with a `radical' resection of 10 cm or more of disease-free margins included in the resection specimen and the other with specimens with less than 10 cm of uninvolved bowel.Follow-up of more than 14 years showed that the group with the wider margins had a recurrence rate of 31 per cent and a better quality of life than the non-radical resection group which had a recurrence rate of 83 per cent.These dramatic results created much discussion and the study was criticized not only for being retrospective but also because the patient groups came from two different Swedish hospitals.Another retrospective study from Scandinavia provided a similar result in that patients with a margin of normal tissue of less than 4 cm (including those with histologically positive margins) had a recurrence rate that was ten times higher than that of a control group 2 .Nevertheless, a further retrospective study from the Uppsala region in Sweden, based on 353 patients undergoing a `curative' resection from 1969 to 1986, suggested that the length of the diseasefree resection margins did not in¯uence recurrence rates in univariate or multivariate analysis 3 .

The Whitehead technique of hemorrhoidectomy is not in widespread use. Complications such as stricture and ectropion discourage surgeons. A modification of the original technique with the use of various advancement flaps, however, preserves the anorectal skin and reestablishes the dentate line. The aim of this study was to compare and contrast the results of a modified Whitehead procedure with those of a conventional closed hemorrhoidectomy. A retrospective case-control study was carried out. The case notes of 110 patients who had undergone the modified Whitehead procedure were compared with age- and sex-matched controls. All patients underwent hemorrhoidectomy at the Mayo Clinic between 1984 and 1993. The two groups were well matched. Urinary retention was more common after modified Whitehead compared with closed hemorrhoidectomy. Suture line dehiscence occurred in 3% of the patients who underwent the modified Whitehead procedure. Wet anus or ectropion was not observed. Further hemorrhoidectomy was needed in 3% of the closed patients compared with none in the Whitehead group. In conclusion, a modified Whitehead hemorrhoidectomy can be carried out with low morbidity, comparable to that of the closed procedure, and with good long-term results.

Diverticular disease, and particularly diverticulitis, has an increasing incidence in Westernized countries because of low-fiber diet. Diverticular disease may be classified as asymptomatic, atypical, acute or uncomplicated, and complicated. Conservative or medical management is usually indicated for acute or uncomplicated diverticulitis, with elective surgical resection generally being recommended after two documented episodes. Complicated diverticulitis, because of the high rate of recurrent problems, is generally managed promptly with sigmoid resection. Sigmoid resection for diverticulitis, under appropriate circumstances, has one of the highest success rates of any of the common gastrointestinal procedures.

PURPOSE: This study examines the risk factors for developing perianal abscess or fistula formation after ileal pouch-anal anastomosis procedure for chronic ulcerative colitis or familial adenomatous polyposis. METHODS: A total of 1,457 patients with J-pouch, 1,304 (89.5 percent) with chronic ulcerative colitis and 153 (10.5 percent) with familial adenomatous polyposis who had a two-stage procedure without any evidence of previous perianal disease were included in the study. The effect of pouch-to-anal anastomosis type on perianal abscess or fistula formation was evaluated. RESULTS: A total of 108 patients (7.4 percent) had a perianal abscess or fistula after the ileal pouch-anal anastomosis procedure after at least one year of follow-up. No statistically significant difference was identified in fistula formation regarding the age and gender of the patients (P>0.05), nor did the risk of fistula formation differ significantly between the patients with handsewnvs. stapled anastomoses (P>0.05). However, patients with a diagnosis of chronic ulcerative colitis, compared with patients with familial adenomatous polyposis, had a statistically higher risk of developing abscess or fistula (P=0.012). CONCLUSION: The most important risk factor in developing perianal sepsis in long-term patients with ileal pouch-anal anastomosis is the initial disease type. After excluding patients without Crohn's disease, the risk of developing an abscess or fistula was found to be significantly greater in patients with chronic ulcerative colitis compared with patients with familial adenomatous polyposis, and this risk is independent of anastomotic technique.

PURPOSE: Virtually all untreated patients with familial adenomatous polyposis develop colorectal carcinoma. Thus, prophylactic colectomy is indicated. Detractors of ileal pouch-anal anastomosis prefer ileorectal anastomosis for teenagers because of the potential negative impact of ileal pouch-anal anastomosis on quality of life. The aim of this study was to assess the effects on quality of life of ileal pouch-anal anastomosis in teenagers with familial adenomatous polyposis. METHODS: Between 1981 and 1998, 48 teenagers underwent ileal pouch-anal anastomosis for familial adenomatous polyposis. One patient had proctectomy and ileal pouch-anal anastomosis after previous ileorectal anastomosis. A temporary diverting loop ileostomy was established in 42 patients (87.5 percent). One patient had colonic carcinoma diagnosed preoperatively. Two other patients were found to have unsuspected rectal cancer at surgery. Mean follow-up (± standard deviation) in 43 patients was 80.5 ± 42 months. RESULTS: There was no immediate postoperative mortality. Postoperative complications included pelvic sepsis (3 patients; 1 requiring reoperation) and bleeding (1 patient; no surgery required). One patient died of metastatic colonic carcinoma. Ten patients required reoperation, seven had bowel obstruction, one had portal hypertension, and two required an ileostomy. The mean (± standard deviation) daytime and nighttime stool frequency was 4 ± 1.5 and 1 ± 1, respectively. One patient reported daytime and nighttime incontinence, and two patients reported nighttime incontinence only. No patient experienced impotence or retrograde ejaculation. Social, sexual, sport, housework, recreation, family, travel, and work activities were improved or unchanged in 82.5, 87, 80, 90, 80, 92.5, 77.5, and 89 percent of patients, respectively. Three male patients fathered children, and three female patients had a total of six children after normal pregnancies and deliveries. CONCLUSION: The impact of ileal pouch-anal anastomosis on quality of life was favorable in the majority of teenagers. The risk of rectal cancer should be the major consideration before proposing an operation to teenagers with familial adenomatous polyposis.

: The role of a temporary defunctioning stoma in patients undergoing coloanal anastomosis remains controversial. Previous experimental studies have shown that the defunctioned colon is more resistant to neoplasia. The aim of this study was to investigate whether a defunctioning stoma was able to decrease complication rates and, also, to evaluate whether it had any impact on recurrence and survival rates in patients who underwent coloanal anastomosis. The records of 173 patients, 54 with benign rectal disease and 119 patients with cancer, operated on between 1980 and 1996, were retrospectively reviewed. Eighty-nine patients had a defunctioning stoma, 34 in the benign rectal disease and 55 in the cancer group. Mean age was 57.2 years (range 17–88). There were 126 men and 47 women. Follow-up was 57.2 month (range 17–88). There were 126 men and 47 women. Follow-up was done by clinical examination, telephone or mailed questionnaire. Mean time of follow-up was 3.8 years (range 0–13 years). There was no operative mortality. Non-stoma patients tended to have more early complications (pelvic sepsis and obstruction) and more probability of having a permanent stoma than the stoma group, but no significant differences could be found between the two groups ( P > 0.05). The probability of being free of stricture was greater in the non-stoma group (stoma 62.6%; non-stoma 78.5%; P < 0.05). Probability of disease-free survival, at 5 years, for rectal cancer patients, was 73.7% for the stoma group and 53.6% for non-stoma group ( P = 0.02). After coloanal anastomosis, defunctioning stomas may decrease postoperative complications, increase the likelihood of anastomosis structure and allow a greater disease-free survival.

OBJECTIVETo explore patients' perceptions of their participation in a randomized controlled trial.PATIENTS AND METHODSA 27-item questionnaire was mailed to all patients who participated in a randomized controlled trial that determined the effectiveness of mesalamine in preventing the recurrence of Crohn's disease postoperatively.RESULTSThe response rate was 66% (99 of 149). Fifty-five per cent of the patients felt that they received better medical care than they otherwise would have and 53% liked taking the medication. Sixty-eight per cent of the patients did not feel that annual colonoscopy was too frequent and 81% felt that the time commitment did not significantly interfere with their job or other activities. Seventy-five per cent and 62% of the patients would have liked more information and education, respectively, about Crohn's disease incorporated into the trial. Although 91% of the patients would agree to participate in a future randomized controlled trial comparing medical therapies, only 44% would agree to participate in a future randomized controlled trial comparing medical with surgical therapies.CONCLUSIONSThe majority of patients were satisfied with their participation in the trial. A large proportion of the patients would participate again but would like more information and education incorporated into the trial. Furthermore, post-trial questionnaires may be helpful in the design of future trials.

PURPOSE To assess the performance and potential clinical impact of a totally human monoclonal antibody, 88BV59 (HumaSPECT) (INTRACEL, Corp, Rockville, MD), in 202 assessable presurgical patients with recurrent, metastatic, or occult colorectal cancer. METHODS 88BV59, labeled with technetium Tc 99m (99mTc) (HumaSPECT-Tc), was injected intravenously, and planar and single photon emission tomography (SPECT) images were obtained 14 to 20 hours postinjection. Surgical and pathologic verification of tumor were used as the standard against which the performance of HumaSPECT-Tc imaging and computed tomography (CT) analysis were evaluated. RESULTS All patients entered onto the recurrent disease study had at least one tumor site defined on CT. The sensitivity of HumaSPECT-Tc in those CT-positive patients was 87%. The specificity of HumaSPECT-Tc was 57% compared with 17% for CT and the difference was statistically significant (P < .001). The diagnostic information provided by HumaSPECT-Tc significantly (P < .001) improved the accuracy of the identification of resectable and nonresectable disease over that of CT (80% v 62%). HumaSPECT-Tc scans resulted in a significant (P < .001) reduction versus CT in terms of the proportion of patients understaged (27% v 41%) and overstaged (4% v 26%). In patients with occult disease (increasing carcinoembryonic antigen [CEA] titer, negative diagnostic work-up, negative CT), HumaSPECT-Tc correctly identified disease in 15 of 22 (68%) patients. HumaSPECT-Tc images provided additional clinical data that would have affected patient management decisions in 40 of 202 (19.8%) patients. In 365 patients who received 88BV59, only a single detectable human anti-human antibody (HAHA) response (90 ng/mL) at 9 weeks postinfusion was observed. CONCLUSION HumaSPECT-Tc can provide important and accurate information about the presence and location of disease in patients with a high clinical suspicion of metastatic or recurrent colorectal cancer and either positive (known disease) or negative (occult disease) CT scans.

Coloanal anastomosis is a well-established technique for resecting very low rectal cancer The aim of this study is to determine whether the addition of a colonic pouch improves functional outcomes.Methods: The records of 104 patients with rectal cancer, in whom a coloanal anastomosis was performed between 1980 and 1993, were reviewed.A colonic pouch was constructed in 14%.Functional results were measured by determining patients' satisfaction.Follow-up was done by exam, telephone and/or questionnaire.Results: There was no operative mortality.Minor complications were present in 20%, and major complications in 47% of the patients who had a pouch.This difference was not statistically significant when compared with the group of patients without a pouch (p>0.05).Stool frequency was greater than three movements per day in only 11% of the patients with a pouch and in 52% of those with a straight coloanal anastomosis.This difference was statistically significant (p<0.05).Satisfactory continence was achieved by all the patients with a colonic pouch and by 85% without a pouch (p>0.05).Conclusion: Pouch coloanal anastomosis appears to improve defecatory function, without increased operative mortality and/or morbidity.