Scott A. Strong

Long-Term Functional Outcome and Quality of Life After Stapled Restorative Proctocolectomy

OBJECTIVE To evaluate prospectively long-term quality of life and functional outcome after restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis, and to evaluate and validate a novel quality-of-life indicator in this group of patients. SUMMARY BACKGROUND DATA Restorative proctocolectomy with ileal pouch-anal anastomosis is now the preferred option when total proctocolectomy is required for ulcerative colitis or familial adenomatous polyposis, but long-term data on functional outcome and quality of life after the procedure are lacking. METHODS Patients (n = 977) who underwent RPC with stapled anastomosis for colitis or polyposis coli and who were followed for > or =12 months were included. Quality of life, fecal incontinence, and satisfaction with surgery were prospectively evaluated by structured interview or questionnaire for 1 to 12 years after surgery (median 5.0). Quality of life was scored using the Cleveland Global Quality of Life (CGQL) instrument (Fazio Score). This is a novel score developed over the past 15 years by the senior author. Quality of life was also evaluated in a subgroup of patients with the Short Form 36 (SF-36). The CGQL was validated by determining its reliability, responsiveness, and validity as well as its correlation with the SF-36 score. RESULTS Postoperative quality of life as measured by SF-36 was excellent and compared well with published norms for the general U.S. population. The CGQL was found to be reliable, responsive, and valid, and there was a high correlation with the SF-36 scores. Using the CGQL, quality of life was shown to increase after the first 2 years after surgery, and there was no deterioration thereafter. The prevalence of perfect continence increased from 75.5% before surgery to 82.4% after surgery, and although this deteriorated somewhat >2 years after surgery, it was no worse than preoperative values. Ninety-eight percent of patients would recommend the surgery to others. CONCLUSIONS Long-term quality of life after ileal pouch surgery is excellent and the level of continence is satisfactory. This surgery is an excellent long-term option in patients requiring total proctocolectomy. The CGQL is a simple, valid, and reliable measure of quality of life after pelvic pouch surgery and may well be applicable in many other clinical conditions.

Mononuclear Leukocytes Bind to Specific Hyaluronan Structures on Colon Mucosal Smooth Muscle Cells Treated with Polyinosinic Acid:Polycytidylic Acid : Inter-α-Trypsin Inhibitor Is Crucial to Structure and Function

Inflammatory bowel disease (IBD) is a chronic disorder whose etiology is linked to triggering events, including viral infections, that lead to immunoregulatory dysfunction in genetically susceptible people. Characteristic pathological changes include increased mononuclear leukocyte influx into the intestinal mucosa as well as mucosal smooth muscle cell (M-SMC) hyperplasia. Virus infection or viral mimic [polyinosinic acid:polycytidylic acid (polyI:C)] treatment of human colon M-SMCs in vitro increases cell surface hyaluronan (HA), and nonactivated mononuclear leukocytes bind to virus-induced HA structures by interactions that involve the HA-binding receptor CD44. In this study, confocal microscopy reveals increased HA on poly I:C-treated M-SMC surfaces within 3 hours, arrayed in coat-like structures. By 17 hours, novel, lengthy cable structures are evident, and these are primarily responsible for mediating leukocyte adhesion. Immunohistochemical staining demonstrates components of the inter-alpha-trypsin inhibitor (IalphaI) complex in both coat-like and cable structures. M-SMCs co-treated with polyI:C and a polyclonal antibody to IalphaI display HA in coats but with diminished cables, and they bind significantly fewer leukocytes than M-SMCs treated with polyI:C alone. Western blot data suggest that heavy chains of IalphaI are specifically associated with cable structures. Staining of tissue sections from patients with IBD demonstrates the presence of HA in inflamed colon tissue, and shows that HA-associated IalphaI staining increases in the mucosa of inflamed IBD specimens compared to noninflamed sections from the same patient, establishing a probable link between the observations in vitro and the progression of the inflammatory process in IBD.

Effect of resection margins on the recurrence of Crohn's disease in the small bowel: A randomized controlled trial

OBJECTIVE The authors assess the effect of surgical margin width on recurrence rates after intestinal resection of Crohns Disease (CD). BACKGROUND The optimal width of margins when resecting DC of the small bowel is controversial. Most studies have been retrospective and have had conflicting results. METHODS Patients undergoing ileocolic resection for CD (N = 152) were randomly assigned to two groups in which the proximal line of resection was 2 cm (limited resection) or 12 cm (extended resection) from the macroscopically involved area. Patients also were classified by whether the margin of resection was microscopically normal (category 1), contained nonspecific changes (category 2), were suggestive but not diagnostic for CD (category 3), or were diagnostic for CD (category 4). Recurrence was defined as reoperation for recurrent preanastomotic disease. RESULTS Data were collected on 131 patients. Median follow-up time was 55.7 months. Disease recurred in 29 patients: 25% of patients in the limited resection group and 18% of patients in the extended resection group. In the 90 patients in category 1 with normal tissue, recurrence occurred in 16, whereas in the 41 patients with some degree of microscopic involvement, recurrence occurred in 13. Recurrence rates were 36% in category 2, 39% in category 3, and 21% in category 4. No group differences were statistically at the 0.01 level. CONCLUSION Recurrence of CD is unaffected by the width of the margin of resection from macroscopically involved bowel. Recurrence rates also do not increase when microscopic CD is present at the resection margins. Therefore, extensive resection margins are unnecessary.

Prospective, Age-Related Analysis of Surgical Results, Functional Outcome, and Quality of Life After Ileal Pouch-Anal Anastomosis

Objective To evaluate how age affects functional outcome and quality of life after ileal pouch anal anastomosis (IPAA). Summary Background Data Because of the limited number of older patients undergoing IPAA, it has been difficult to assess functional outcome and quality of life stratified by age. Methods IPAA was performed in 1895 patients. Patients were stratified by age into <45 (n = 1410), 46–55 (n = 289), 56–65 (n = 154), and more than 65 years (n = 42). Outcome was assessed prospectively. Results are presented at 1, 3, 5, and 10 years after surgery. Results Patients were followed for 4.6 ± 3.7 years (maximum, 17 years). Pouch failure occurred in 4.1% (pouch excision or permanent diversion). Incontinence and night time seepage were more common in older patients. There were minor differences in the quality of life, health, energy and happiness between age groups, with a slight benefit for those under 45 years. Fourteen percent or fewer patients experienced social, sexual or work restrictions. Overall, 96% of patients were happy to have undergone their surgery, and 98% recommended it to others. Although the respective figures were 89% and 96% in the over-65 age group, the difference was not significant. Conclusions These data provide a unique assessment of outcome after IPAA at multiple time points. Although functional outcome after IPAA is not as good in older patients, appropriate case selection confers acceptable function and quality of life to patients of all ages.

Pan-colonic decrease in interstitial cells of Cajal in patients with slow transit constipation

Background: Interstitial cells of Cajal (ICC) are required for normal intestinal motility. ICC are found throughout the human colon and are decreased in the sigmoid colon of patients with slow transit constipation. Aims: The aims of this study were to determine the normal distribution of ICC within the human colon and to determine if ICC are decreased throughout the colon in slow transit constipation. Patients: The caecum, ascending, transverse, and sigmoid colons from six patients with slow transit constipation and colonic tissue from patients with resected colon cancer were used for this study. Methods: ICC cells were identified with a polyclonal antibody to c-Kit, serial 0.5 μm sections were obtained by confocal microscopy, and three dimensional software was employed to reconstruct the entire thickness of the colonic muscularis propria and submucosa. Results: ICC were located within both the longitudinal and circular muscle layers. Two networks of ICC were identified, one in the myenteric plexus region and another, less defined network, in the submucosal border. Caecum, ascending colon, transverse colon, and sigmoid colon displayed similar ICC volumes. ICC volume was significantly lower in the slow transit constipation patients across all colonic regions. Conclusions: The data suggest that ICC distribution is relatively uniform throughout the human colon and that decreased ICC volume is pan-colonic in idiopathic slow transit constipation.

Platelets trigger a CD40-dependent inflammatory response in the microvasculature of inflammatory bowel disease patients

BACKGROUND & AIMS Platelets circulate in an activated state in patients with inflammatory bowel disease (IBD), but their role in the pathogenesis of IBD is unclear. The recent demonstration that activated platelets express CD40 ligand (L) provides a mechanism of interaction with CD40-positive endothelial cells, inducing them to produce proinflammatory mediators. We investigated whether platelets from patients with IBD express enhanced levels of CD40L and induce human intestinal microvascular endothelial cells (HIMEC) to up-regulate cell adhesion molecule (CAM) expression and secrete chemokines. METHODS CD40L expression was assessed in resting and thrombin-activated platelets by flow cytometry and in mucosal microthrombi by confocal microscopy. Platelet-HIMEC cocultures were used to study CAM up-regulation, and interleukin (IL)-8 and RANTES production by HIMEC. RESULTS IBD platelets expressed significantly higher CD40L levels than those of healthy subjects, and CD40L-positive platelets were detected in IBD-involved mucosa. Activated platelets up-regulated expression of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 as well as production of interleukin 8 by HIMEC in a CD40-dependent fashion. High levels of RANTES were present in platelet-HIMEC cocultures and platelets were identified as the source of this chemokine, which mediated T-cell adhesion to HIMEC. CONCLUSIONS These results show that platelets can actively contribute to mucosal inflammation and represent a previously unrecognized component of IBD pathogenesis.

Mononuclear Leukocytes Preferentially Bind via CD44 to Hyaluronan on Human Intestinal Mucosal Smooth Muscle Cells after Virus Infection or Treatment with Poly(I·C)

Pathological changes in inflammatory bowel disease include an increase in intestinal mucosal mononuclear leukocytes and hyperplasia of the muscularis mucosae smooth muscle cells (M-SMCs). Because virus infections have correlated with disease flare, we tested the response of cultured M-SMCs to respiratory syncytial virus, measles virus, and the viral analogue, poly(I·C). Adhesion of U937 cells and peripheral blood mononuclear cells was used to measure the leukocyte-interactive potential of M-SMCs. Untreated M-SMCs, only minimally adhesive for leukocytes, bound U937 cells after treatment with respiratory syncytial virus or measles virus. Mononuclear leukocytes also bound to poly(I·C)-treated M-SMCs. Although both vascular cell adhesion molecule-1 mRNA and protein increased 3–4-fold in poly(I·C)-treated M-SMC cultures, U937 cell adhesion was not blocked by an anti-vascular cell adhesion molecule-1 monoclonal antibody. However, hyaluronidase digestion of poly(I·C)- or virus-treated M-SMCs dramatically reduced leukocyte adhesion (∼75%). Fluorophore-assisted carbohydrate electrophoresis demonstrated a ∼3-fold increase in surface-bound hyaluronan on poly(I·C)-treated M-SMCs compared with untreated controls. In addition, pretreatment of mononuclear cells with a blocking anti-CD44 antibody, greatly decreased adhesion to poly(I·C)-treated M-SMCs. Recognition of this virus-induced hyaluronan/CD44 mechanism of mesenchymal cell/leukocyte interaction introduces a new avenue in the research of gut inflammation.

Dysplasia of the anal transitional zone after ileal pouch-anal anastomosis: results of prospective evaluation after a minimum of ten years.

AbstractPURPOSE: Stapling of the ileal pouch-anal anastomosis with preservation of the anal transitional zone remains controversial because of concerns about the potential risk of dysplasia and cancer. The natural history and optimal treatment of anal transitional zone dysplasia ten or more years after surgery are unknown. This study establishes the risk of dysplasia in the anal transitional zone and the outcome of a conservative management policy for anal transitional zone dysplasia, with a minimum of ten years’ follow-up after ileal pouch-anal anastomosis. METHODS: A total of 289 patients undergoing anal transitional zone–sparing stapled ileal pouch-anal anastomosis for inflammatory bowel disease between 1986 and 1990 were studied. Patients undergoing anal transitional zone–sparing ileal pouch-anal anastomosis who were studied with serial anal transitional zone biopsies for at least ten years postoperatively were included (n = 178). Median follow-up was 130 (range, 120–157) months. RESULTS: Anal transitional zone dysplasia developed in 8 patients 4 to 123 (median, 9) months after surgery. There was no association with gender, age, preoperative disease duration, or extent of colitis, but the risk of anal transitional zone dysplasia was significantly associated with cancer or dysplasia as a preoperative diagnosis or in the proctocolectomy specimen. Dysplasia was high grade in two patients and low grade in six. Two patients with low-grade dysplasia on two or more occasions after detection of low-grade dysplasia underwent completion mucosectomy and perineal pouch advancement with neo–ileal pouch-anal anastomosis. One patient with high-grade dysplasia on two occasions was to undergo completion mucosectomy, but this was not technically feasible. Partial mucosectomy with vigorous anal transitional zone biopsy was performed with close postoperative surveillance. Biopsies were negative for dysplasia. The second recently diagnosed patient with high-grade dysplasia underwent examination under anesthesia with negative anal transitional zone biopsies and will be kept under close surveillance. No cancer in the anal transitional zone was found during the study period. The 4 other patients with low-grade dysplasia on 1 or 2 occasions were treated expectantly and have been dysplasia free for a median of 119 (range, 103–133) months. CONCLUSIONS: Anal transitional zone dysplasia after stapled ileal pouch-anal anastomosis is infrequent and is usually self-limiting. Anal transitional zone preservation did not lead to the development of cancer in the anal transitional zone with a minimum of ten years of follow-up. Long-term surveillance is recommended to monitor dysplasia. If repeat biopsy confirms persistent dysplasia, mucosectomy with perineal pouch advancement and neo–ileal pouch-anal anastomosis is recommended.

Safety and longterm efficacy of strictureplasty in 314 patients with obstructing small bowel Crohn’s Disease

BACKGROUND Since its introduction in the early 1980s, strictureplasty (SXP) has become a viable option in the surgical management of obstructing small bowel Crohns disease. Questions still remain regarding its safety and longterm durability in comparison to resection. Precise indications and contraindications to the procedure are also not well defined. STUDY DESIGN A retrospective review of all patients undergoing SXP for obstructing small bowel Crohns disease at the Cleveland Clinic between 1984 and 1999 was conducted. A total of 314 patients underwent a laparotomy that included the index SXP The total number of SXPs performed was 1,124, with a median of two (range 1 to 19) per patient. Sixty-six percent of patients underwent a synchronous bowel resection. Recurrence was defined as the need for reoperation. Followup information was determined by personal interviews, phone interviews, or both. RESULTS The overall morbidity rate was 18%, with septic complications occurring in 5% of patients. Preoperative weight loss (p = 0.004) and older age (p = 0.008) were found to be significant predictors of morbidity. The surgical recurrence rate was 34%, with a median followup period of 7.5 years (range 1 to 16 years). Age was found to be a significant predictor of recurrence (p = 0.02), with younger patients having a shorter time to reoperation. CONCLUSIONS This large series of patients with longterm followup confirms the safety and efficacy of strictureplasty in patients with obstructing small bowel Crohns disease. The 18% morbidity and 34% operative recurrence rates compare favorably with reported results of resective surgery. Caution should be used in patients with preoperative weight loss, because they experienced higher complication rates. Although young patients seem to follow an accelerated course, SXP remains indicated as part of an overall strategy to conserve intestinal length.

Mucosectomy vs. stapled ileal pouch-anal anastomosis in patients with familial adenomatous polyposis: Functional outcome and neoplasia control

PURPOSE: The tradeoff of neoplasia control for better function represented by a stapled ileal pouch‐anal anastomosis is still controversial in patients with familial adenomatous polyposis. We compared outcomes after mucosectomy and hand‐sewn ileal pouch‐anal anastomosis with those after stapled ileal pouch‐anal anastomosis in 119 patients with familial adenomatous polyposis who underwent surgery since 1983. METHODS: Age, gender, length of follow‐up, complications, quality of life, incontinence, urgency, nighttime and daytime seepage, pad usage, necessity of ileostomy, and incidence of adenomas developing in pouch and anal transitional zone were recorded. RESULTS: There were 42 mucosectomy and 77 stapled patients who were followed up for an average of 5.8 and 3.6 years, respectively, with endoscopic surveillance. There was one postoperative death in the stapled group that prohibited long‐term follow‐up. Nine of 42 mucosectomy patients developed pouch adenomas vs. 8 of 76 in the stapled group. Six of 42 patients developed adenomas in the mucosectomized anal transitional zone in the mucosectomy group. Twenty‐one of 76 patients developed adenomas in the anal transitional zone in the stapled group. All were managed with local procedures or further surveillance. One of 76 patients developed cancer in the residual low rectum; this required further resection. Patients with stapled anastomosis had better outcomes in every category. Differences in incontinence, daytime and nighttime seepage, pad usage, and avoidance of ileostomy were statistically significant. All patients with mucosectomy required ileostomy vs. only 40 of 77 patients with stapled anastomosis. CONCLUSION: Familial adenomatous polyposis patients with stapled ileal pouch‐anal anastomosis have better functional outcome and can avoid temporary diversion. This should be balanced against a 28 percent incidence of adenomas in the anal transitional zone.PURPOSE: The tradeoff of neoplasia control for better function represented by a stapled ileal pouch-anal anastomosis is still controversial in patients with familial adenomatous polyposis. We compared outcomes after mucosectomy and hand-sewn ileal pouch-anal anastomosis with those after stapled ileal pouch-anal anastomosis in 119 patients with familial adenomatous polyposis who underwent surgery since 1983. METHODS: Age, gender, length of follow-up, complications, quality of life, incontinence, urgency, nighttime and daytime seepage, pad usage, necessity of ileostomy, and incidence of adenomas developing in pouch and anal transitional zone were recorded. RESULTS: There were 42 mucosectomy and 77 stapled patients who were followed up for an average of 5.8 and 3.6 years, respectively, with endoscopic surveillance. There was one postoperative death in the stapled group that prohibited long-term follow-up. Nine of 42 mucosectomy patients developed pouch adenomasvs. 8 of 76 in the stapled group. Six of 42 patients developed adenomas in the mucosectomized anal transitional zone in the mucosectomy group. Twenty-one of 76 patients developed adenomas in the anal transitional zone in the stapled group. All were managed with local procedures or further surveillance. One of 76 patients developed cancer in the residual low rectum; this required further resection. Patients with stapled anastomosis had better outcomes in every category. Differences in incontinence, daytime and nighttime seepage, pad usage, and avoidance of ileostomy were statistically significant. All patients with mucosectomy required ileostomyvs. only 40 of 77 patients with stapled anastomosis. CONCLUSION: Familial adenomatous polyposis patients with stapled ileal pouch-anal anastomosis have better functional outcome and can avoid temporary diversion. This should be balanced against a 28 percent incidence of adenomas in the anal transitional zone.