Healing of the perineal wound after proctectomy in Crohn's disease patients: only preoperative perineal sepsis predicts poor outcome.

BACKGROUND: The aim of our study was to assess perineal wound healing in patients with Crohn's disease (CD) who undergo proctectomy or proctocolectomy with end ileostomy and to evaluate the influence of various factors including types of perineal dissection on eventual wound healing. METHODS: Data for patients with CD who underwent proctectomy or total proctocolectomy with end ileostomy from 1995 to 2012 were reviewed. The relationship between perineal wound healing and demographics, patient characteristics, and other factors was assessed using univariate and multivariate analyses. RESULTS: The perineal wound healed by 12 weeks in 72 (52.9%) out of 136 patients (63.2% female, mean age 41 ± 13 years); delayed healing occurred in 35 patients (25.7%), and in 29 patients (21.3%), there was non-healing. On multivariate analysis, the only factor associated with delayed healing and non-healing was preoperative perineal sepsis (p = 0.001). CONCLUSIONS: After proctectomy or proctocolectomy for CD, perineal wound healing is poor and poses a particular challenge for patients with preoperative perineal sepsis. These findings support a preoperative discussion regarding CD patients that examines potential outcomes and the consideration of measures such as the initial creation of defunctioning ostomy or control/drainage of local sepsis prior to proctectomy.

Measuring sexual and urinary outcomes in women after rectal cancer excision.

PURPOSE: This study was designed to investigate sexual and urinary dysfunction in women who underwent rectal cancer excision, and the influence of tumor and treatment variables on long-term outcomes. METHODS: Data were prospectively collected on 295 women who underwent rectal cancer excision at a tertiary referral colorectal center from 1998 to 2006. Sexual and urinary function was assessed preoperatively and at intervals up to five years after surgery. Functional outcomes were assessed by using univariate and multivariate regression analysis, chi-squared test for trend, or Kruskal-Wallis test. RESULTS: The mean age of the patients was 60.9 years. Anterior resection was performed in 222 patients (75.2 percent) and abdominoperineal resection in 73 patients (24.7 percent). Patients who underwent abdominoperineal resection were less sexually active (25 vs. 50 percent; P = 0.02) and had a lower frequency of intercourse than anterior resection patients at one year after surgery (anterior resection, 3 (0-5) (median interquartile range); abdominoperineal resection 0 (0-4); P = 0.029). The frequency of intercourse improved over time for abdominoperineal resection (4 months, 0 (0-0) median interquartile range; 5 years, 3 (0.25-4) median interquartile range; P = 0.028). Abdominoperineal resection was associated with increased dyspareunia (odds ratio, 5.75; 95 percent confidence interval (CI), 1.87-17.6; P = 0.002), urinary urgency (odds ratio, 8.52; 95 percent CI, 2.81-25.8; P < 0.001), incontinence (odds ratio, 2.41; 95 percent CI, 1.11-5.26; P = 0.026), poor stream (odds ratio, 5.64, 95 percent CI, 2.55-12.5; P

Complications and functional results after ileoanal pouch formation in obese patients.

OBJECTIVE: Ileoanal pouch formation (IPAA) can be technically challenging in obese patients, and there is little data evaluating results after the procedure in these patients. We compare outcomes for patients with a body mass index (BMI) > or =30 undergoing IPAA when compared with those for patients with BMI <30. METHODS: Retrospective analysis of prospectively accrued data for patients with BMI > or =30 undergoing IPAA. Patient and disease-related characteristics, complications, long-term function, and quality of life (QOL) using the Cleveland Global Quality of Life scale (CGQL) were determined for this group of patients (group B) and compared with those for patients with BMI <30 (group A). Kruskal-Wallis and Wilcoxon rank sum tests were used to compare quantitative or ordinal data and chi-square or Fisher's exact tests for categorical variables. Long-term mortality and complication rates were estimated using the Kaplan-Meier method with group comparisons performed using log rank tests. RESULTS: There were 345 patients (median BMI 32.7) in group B and 1,671 patients in group A. When the cumulative risk of complications over 15 years was compared, group B patients had a significantly higher chance of getting a complication (94.9% vs 88%, p = 0.006). The rates of pelvic sepsis (6.7% vs 5.3%, p = 0.3), pouchitis (58.1 vs 54.4%, p = 0.9), pouch failure (6% vs 4.5%, p = 0.9), and hemorrhage (5.6% vs 4.8%, p = 0.7) were similar for group B and group A. Group B patients, however, had a significantly higher risk of the development of wound infection (18.8% vs 8.1%, p < 0.001) and anastomotic separation (10.4% vs 5.4%, p < 0.001), whereas group A patients had a higher rate of development of obstruction over time (26.7% vs 22.3%, p = 0.02). Long-term outcome including QOL and function after 15 years was comparable between groups. CONCLUSIONS: Although technically demanding, IPAA can be undertaken in obese patients with acceptable morbidity. Good long-term functional results and QOL that is comparable to nonobese patients may be anticipated.

Risk factors associated with ileal pouch-related fistula following restorative proctocolectomy.

INTRODUCTION: Pouch-related fistula occurs in 5-10 per cent of patients after restorative proctocolectomy. The present study identified risk factors associated with the development of such fistulas. METHODS: Data on preoperative and postoperative risk factors were recorded from 1965 patients who underwent restorative proctocolectomy in a single tertiary centre between 1983 and 2001. Cox regression analysis was used to identify independent predictors of pouch-perineal, pouch-abdominal wall and pouch-vaginal fistula during follow-up. RESULTS: Median patient follow-up was 4.1 (range 0-19) years. By 15 years' follow-up, pouch-vaginal fistulas had occurred in 44 women (5.2 per cent). The prevalence of ileal pouch-perineal and pouch-abdominal wall fistula was 3.6 per cent (70 patients) and 1.5 per cent (30 patients) respectively. Independent predictors of pouch-related fistula identified by multivariate analysis were diagnosis of indeterminate colitis or Crohn's disease (hazard ratio (HR) 1.28 (95 per cent confidence interval (c.i.) 1.00 to 1.65) and 1.73 (95 per cent c.i. 1.07 to 3.48) respectively versus ulcerative colitis or familial adenomatous polyposis), previous anal pathology (HR 3.43 (95 per cent c.i. 2.43 to 4.84) and 4.02 (95 per cent c.i. 1.27 to 12.77) respectively for perineal abscess and fistula in ano versus no previous anal pathology), abnormal anal manometry (HR 4.29 (95 per cent c.i. 2.33 to 7.91)), patient sex (HR 0.74 (95 per cent c.i. 0.58 to 0.95) for men versus women) and pelvic sepsis (HR 3.79 (95 per cent c.i. 2.48 to 5.79)). CONCLUSION: This study suggests that Crohn's disease and the clinical signs that favour the diagnosis of Crohn's disease may contribute to the development of pouch-related fistula.

Analysis of the outcome of ileal pouch-anal anastomosis in patients with Crohn's disease.

PURPOSE: Ileal pouch-anal anastomosis has come to represent the procedure of choice for patients requiring surgery for mucosal ulcerative colitis. In contrast, a proven diagnosis of Crohn's disease is generally held to preclude ileal pouch-anal anastomosis. However, patients with ileal pouch-anal anastomosis for apparent mucosal ulcerative colitis who are subsequently found to have Crohn's disease have a variable course. We reviewed our experience in this scenario to determine whether selected patients with Crohn's disease may be candidates for ileal pouch-anal anastomosis. METHODS: A retrospective review of the prospectively maintained ileal pouch-anal anastomosis database was undertaken to identify patients with a diagnosis of Crohn's disease after ileal pouch-anal anastomosis. Clinical outcome and quality-of-life data were obtained from the database and chart review. End points were the development of recrudescent Crohn's disease, pouch failure, and quality of life and functional outcome at the time of data collection. Differences between groups were calculated using the chi-squared test. Cumulative incidence of recrudescent Crohn's disease and pouch loss were calculated by the Kaplan-Meier method. Factors predictive of development of recrudescent Crohn's disease and pouch loss were examined by univariate analysis. RESULTS: Sixty patients (32 females; median age, 33 (range, 15-74) years) who underwent ileal pouch-anal anastomosis for mucosal ulcerative colitis subsequently had that diagnosis revised to Crohn's disease. Median follow-up of all patients was 46 (range, 4-158) months at time of data collection by which time 21 patients (35 percent) had developed recrudescent Crohn's disease. No pre-ileal pouch-anal anastomosis factors examined were predictors of the development of recrudescent Crohn's disease on univariate analysis. Median follow-up of the latter group was 63 (range, 0-132) months from time of diagnosis, by which time six patients underwent pouch excision and another patient was permanently defunctioned. The overall pouch loss rate for the entire cohort was 12 percent and 33 percent for those with recrudescent Crohn's disease. Median daily bowel movements in those with ileal pouch-anal anastomosis in situ at the time of data collection was 7 (range, 3-20), with 50 percent of patients rarely or never experiencing urgency and 59 percent reporting perfect or near perfect continence. Median quality of life, health, and happiness scores were 9.9 and 10 of 10. CONCLUSIONS: The secondary diagnosis of Crohn's disease after ileal pouch-anal anastomosis is associated with protracted freedom from clinically evident Crohn's disease, low pouch loss rate, and good functional outcome. Such results only can be improved by the continued development of medical strategies for the long-term suppression of Crohn's disease. These data support a prospective evaluation of ileal pouch-anal anastomosis in selected patients with Crohn's disease.

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 microm 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.

Factors affecting local recurrence of colonic adenocarcinoma.

PURPOSE: The aim of this retrospective study was to determine which aspects of tumor morphology and histology influenced the incidence of local recurrence after curative resection of colonic adenocarcinoma. METHODS: Patients who had a curative resection for a primary colonic adenocarcinoma between 1980 and 1993 (inclusive) were identified from the colorectal cancer database in the Department of Colorectal Surgery. The charts of patients diagnosed with a local recurrence were then reviewed and their findings at operation and histologic assessment analyzed. Patients were followed up for at least five years or until death. RESULTS: Over the period of study, 1,031 patients had a curative resection for colonic adenocarcinoma. Local recurrences were detected in 32 patients (3.1 percent). The gender distribution of patients with local recurrence was 18 males (56.3 percent) and 14 females (43.7 percent) with a mean age of 63.4 years. The median time to local recurrence was 13 (range, 2-71) months. The distribution of primary tumors that recurred locally favored the cecum (n = 9; 28.1 percent) and sigmoid colon (n = 14; 43.7 percent) over other locations; these were, however, the most common sites of primary lesions. Less common sites included the ascending colon (n = 0; 0 percent), hepatic flexure (n = 2; 6.3 percent), transverse colon (n = 1; 3.1 percent), splenic flexure (n = 3; 9.4 percent), and descending colon (n = 3; 9.4 percent). Of the total number of tumors, 101 were found to be adherent to at least 1 other intra-abdominal viscus, and 12 (11.9 percent) recurred locally. Other factors associated with local recurrence were tumor perforation and fistulation. Overall, 30 tumors (2.9 percent) were perforated, and 6 (20 percent) recurred locally. Four tumors (0.4 percent) were fistulating; of these, 2 (50 percent) recurred locally. Advanced tumor stage was also associated with an increased rate of local recurrence (Stage I, 0 percent; Stage II, 2.05 percent; Stage III, 7.0 percent; and Stage IV, 6.1 percent). Similarly, tumor differentiation was related to local recurrence, with no instances in well-differentiated tumors, 2.8 percent in moderately differentiated tumors, and 6.8 percent in poorly differentiated tumors. CONCLUSIONS: The location of the primary tumor is not a factor in producing local recurrence. Fixity to another viscus, perforation or fistulation, advanced stage of disease, and differentiation of tumor appear to increase the chances of recurrence of curatively resected colonic carcinoma. Although the recurrence rate is higher in these groups than for tumors overall, definitive oncologic surgery prevents recurrence in the majority of cases. No colonic tumor that was T1 or T2 (N0, N1, or N2) or that was well differentiated recurred locally.

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.

Decreased Bax expression by mucosal T cells favours resistance to apoptosis in Crohn's disease.

BACKGROUND: Activated T cells are more susceptible to apoptosis than resting T cells. As intestinal T cells normally exhibit a higher state of activation, increased apoptosis may be necessary to maintain immune homeostasis in the specialised microenvironment of the mucosa. On the other hand, in Crohn's disease (CD) mucosal T cells are resistant to apoptosis, suggesting abnormal regulation of cell death mechanisms. AIMS: To investigate differences in expression of anti- and proapoptotic Bcl-2 family proteins, key regulators of apoptosis, between circulating and mucosal T cells, and possible alterations in CD. PATIENTS AND METHODS: Lamina propria T cells (LPT) were isolated from 10 control, seven CD, and eight ulcerative colitis (UC) patients, and peripheral blood T cells (PBT) from healthy volunteers. Purified T cells were stained intracellularly for Bcl-2, Bcl-x(L), and Bax, and mean fluorescence intensity measured by flow cytometry. RESULTS: Compared with PBT, the expression level of Bcl-2 and Bax, but not Bcl-x(L), was significantly greater in LPT, resulting in lower Bcl-x(L)/Bax ratios. In PBT, Bax expression was highly and significantly correlated with both Bcl-2 and Bcl-x(L), but correlation with Bcl-2 was absent in LPT. Bax expression in CD, but not UC, LPT was significantly lower than in control LPT, resulting in a significantly higher Bcl-x(L)/Bax ratio. The significant correlation of Bcl-x(L) to Bax was preserved in CD, but not UC, LPT. CONCLUSIONS: Regulation of Bcl-2 family protein expression differs between circulating and mucosal T cells, probably underlying diverse survival potentials. In CD LPT, a low Bax expression and a high Bcl-x(L)/Bax ratio favour resistance to apoptosis and may contribute to the chronicity of inflammation.

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 Crohn's 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 Crohn's 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 Crohn's 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.

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 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 ( approximately 75%). Fluorophore-assisted carbohydrate electrophoresis demonstrated a approximately 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.

Regulation of ICAM-1-mediated fibroblast-T cell reciprocal interaction: implications for modulation of gut inflammation.

BACKGROUND & AIMS: Immune-nonimmune cell interactions modulate mucosal immunity. We investigated the expression of adhesion molecules by intestinal fibroblasts, the effect of immune cell-derived factor on fibroblast binding of T cells, and the consequences of interfering with adhesion molecule expression on fibroblast-T cell interaction. METHODS: Expression of fibroblast intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 surface and messenger RNA (mRNA) was measured before and after exposure to immune cell-derived supernatants. Fibroblasts were treated with antibodies to ICAM-1 or VCAM-1, or ICAM-1 antisense oligonucleotide Isis 2302, before a T-cell adhesion assay. RESULTS: Fibroblast activation by immune cell-derived cytokines enhanced ICAM-1 and VCAM-1 surface expression and mRNA as well as adhesiveness for T cells. Blockade with neutralizing antibodies showed that binding was almost exclusively dependent on ICAM-1. Isis 2302 specifically reduced fibroblast ICAM-1 mRNA and dose-dependently inhibited ICAM-1 surface expression and T-cell binding. CONCLUSIONS: ICAM-1 is essential for intestinal fibroblast binding of T cells, a phenomenon that is efficiently and specifically disrupted by ICAM-1 antisense oligonucleotides. These observations emphasize the crucial regulatory role of fibroblasts in mucosal immunity and their potential as targets for therapeutic intervention in intestinal inflammation.

Is resection of pulmonary and hepatic metastases warranted in patients with colorectal cancer?

BACKGROUND: Conventional management of stage IV colorectal carcinoma is palliative. The value of resecting both liver and lung colorectal metastases that occur in isolation of other sites of metastasis is undetermined. OBJECTIVES: Our objectives were to (1) assess the efficacy of resecting both hepatic and pulmonary metastases, (2) investigate the influence of the sequence and timing of metastases, and (3) identify the profile of patients likely to benefit from both hepatic and pulmonary metastasectomy. PATIENTS AND METHODS: Of 48 patients identified with resection of colorectal cancer and, at some point in time, both liver and lung metastases, 25 patients underwent metastasectomy (resection group). The remaining 23 patients comprised the nonresection group. Risk factors for death were identified by multivariable analyses. RESULTS: Median survival was longer after the last metastatic appearance in the resection group (16 months) than in the nonresection group (6 months; P <.001). The pattern of risk also differed; it peaked at 2 years and then declined in the resection group but was constant in the nonresection group. In the resection group, patients with metachronous resections survived longer after colorectal resection (median, 70 months) than patients with synchronous (median, 22 months) or mixed resections (median, 31 months; P <.001). Risk factors for death included older age, multiple liver metastases, and a short disease-free interval. CONCLUSIONS: Younger patients with solitary metachronous metastases to the liver, then the lung, and long disease-free intervals are more likely to benefit from resection of both liver and lung metastases. Patients with risk factors also had better survival with resection than without resection.

Surgical treatment of inflammatory bowel disease.

Although laparotomy with resection remains the treatment of choice for most patients who require surgery for intestinal Crohn's disease, mounting evidence supports the safety and efficacy of less traditional approaches and procedures (ie, laparoscopy, stricture-plasty). In contrast to the approach to intestinal disease, many centers are advocating a more aggressive operative approach to perianal Crohn's disease. Over the past few years, restorative proctocolectomy with ileal pouch-anal anastomosis has emerged as the operation of choice for most patients requiring surgery for ulcerative colitis. As experience with the operation grows, patient selection, technical features, and management of postoperative complications are being more clearly defined and optimized.

Prognostic parameters of Crohn's disease recurrence.

Patients with Crohn's disease are haunted by the likelihood of recurrence following resection of their disease. In an effort to better counsel patients about their relative risk, many centres have evaluated a myriad of factors thought to be harbingers of recurrence. Insightful review of the numerous studies requires consideration of the definition of recurrence, length and manner of follow-up, and statistical tools used for analysis of the data. Factors that may possibly influence recurrence include: age of disease onset; gender; tobacco use; anatomical pattern of disease; clinical pattern of disease; extra-intestinal manifestations; duration of pre-operative symptoms; previous resections; operative indication; blood transfusion; extent of resection; faecal diversion; pathological features of resected bowel; and chemotherapy following resection. Unfortunately, the role that these factors play in disease recurrence remains poorly understood.

Proinflammatory cytokines differentially modulate their own expression in human intestinal mucosal mesenchymal cells.

BACKGROUND & AIMS: Intestinal homeostasis is coordinated through the response of different cell types, including the interaction of immune with nonimmune cells. This study investigated the effect of immune cell-derived proinflammatory cytokines on mesenchymal cell proliferation and gene product expression. METHODS: Primary cultures of human mucosal mesenchymal cells were activated with interleukin (IL)-1 beta, IL-6, and tumor necrosis factor alpha (TNF-alpha). Proliferation was measured by thymidine incorporation, messenger RNA (mRNA) expression was assessed by Northern blot analysis, and IL-1 receptor type was identified by reverse-transcription polymerase chain reaction. RESULTS: Mesenchymal cells dose-dependently proliferated in response to IL-1 beta, IL-6, and TNF-alpha. Each cytokine differentially induced mRNA expression in a dose-dependent and selective fashion: IL-1 beta was the most potent inducer, TNF-alpha was weaker, and IL-6 induced little or no mRNA; in contrast, IL-6 mRNA was the most abundantly induced, followed by IL-1 beta mRNA, whereas TNF-alpha mRNA was weakly and infrequently expressed. The IL-1 receptor antagonist inhibited cytokine mRNA expression, and mesenchymal cells expressed the type II, but not the type I, IL-1 receptor. CONCLUSIONS: The ability of intestinal mesenchymal cells to express proinflammatory gene products implicates them as regulators of local immune cells through immune-nonimmune interactions. Thus, mesenchymal cells should be considered as active regulators of intestinal immunity under normal and inflammatory conditions.

Factors associated with the occurrence of leaks in stapled rectal anastomoses: a review of 1,014 patients.

BACKGROUND: Despite improvement in surgical techniques and stapling devices during the last 10 years, colorectal anastomoses are still prone to leakage. The purpose of this study was to assess the performance and safety of stapled anastomoses in rectal surgery and to identify factors that influence the occurrence of anastomotic leaks. STUDY DESIGN: A review was undertaken of 1,014 patients who underwent stapled anastomoses to the rectum or anal canal for colorectal cancer or benign disease between 1989 and 1995 in a tertiary care institution. Indications for operations, comorbidities at admission, preoperative bowel preparation, stapler size, intraoperative events, associated surgical procedures, and clinical outcomes were tested for any association with anastomotic leak. RESULTS: A double stapled technique was used in 154 patients and a conventional single stapler technique was used in 860. Postoperative mortality was 1.6%, and the overall morbidity was 18.4%. Clinically apparent anastomotic leak developed in 29 patients (2.9%). Anastomotic dehiscence occurred in 22 of 284 patients (7.7%) after low stapling (within 7 cm from the anal verge) and in 7 of 730 patients (1%) after high stapling (p < 0.001). Diabetes mellitus, use of pelvic drainage, and duration of surgery were significantly related to the occurrence of anastomotic leak by the univariate analysis. Multivariate regression analysis identified an anastomotic distance from the anal verge within 7 cm as the only variable related to the occurrence of postoperative leak (p < 0.001). CONCLUSION: Low anastomoses were associated with a leak rate greater than with high colorectal anastomoses. We conclude that anastomoses to the rectum using the circular stapler can be done with low mortality and morbidity.

The risk of cancer and dysplasia among ulcerative colitis patients with primary sclerosing cholangitis.

BACKGROUND: Ulcerative colitis (UC) patients with primary sclerosing cholangitis (PSC) may have an increased risk for colonic dysplasia or cancer. They also may have higher levels of carcinogenic secondary bile acids and, thus, be more likely to develop cancer in the right side of the colon, where secondary bile acid concentrations are highest. METHODS: Since 1983, 1212 UC patients have undergone total proctocolectomy with ileal pouch-anal anastomosis at the Cleveland Clinic. All 27 patients with PSC were compared with the remaining 1185 patients in a historical cohort study. RESULTS: Dysplasia detected during cancer surveillance was the indication for surgery in 16 (59.5%) PSC patients and 136 (11.5%) controls [adjusted relative risk (RR), 6.9; 95% confidence interval (CI), 3.0-16.0]. Dysplasia or cancer was found in the resected specimen in 18 (66.7%) PSC patients and 145 (12.2%) controls (RR 10.4, CI 4.1-26.1). Right-sided cancers (proximal to the splenic flexure) were found in all four PSC patients with cancer and in 20 of 49 controls with cancer (RR 2.5, CI 1.3-5.4). CONCLUSIONS: UC patients with PSC are at a significantly increased risk for dysplasia or cancer. The high proportion of right-sided cancers supports the contention that secondary bile acids are carcinogenic and increase the likelihood of cancer in the proximal colon.

Guided imagery: a significant advance in the care of patients undergoing elective colorectal surgery.

PURPOSE: Guided imagery uses the power of thought to influence psychologic and physiologic states. Some studies have shown that guided imagery can decrease anxiety, analgesic requirements, and length of stay for surgical patients. This study was designed to determine whether guided imagery in the perioperative period could improve the outcome of colorectal surgery patients. METHODS: We conducted a prospective, randomized trial of patients undergoing their first elective colorectal surgery at a tertiary care center. Patients were randomly assigned into one of two groups. Group 1 received standard perioperative care, and Group 2 listened to a guided imagery tape three days preoperatively; a music-only tape during induction, during surgery, and postoperatively in the recovery room; a guided imagery tape during each of the first six postoperative days. Both groups had postoperative patient-controlled analgesia. All patients rated their levels of pain and anxiety daily, on a linear analog scale of 0 to 100. Total narcotic consumption, time to first bowel movement, length of stay, and number of patients with complications were also recorded. RESULTS: Groups were similar in age and gender distribution, diagnoses, and surgery performed. Median baseline anxiety score was 75 in both groups. Before surgery, anxiety increased in the control group but decreased in the guided imagery group (median change, 30; P < 0.001). Postoperatively, median increase in the worst pain score was 72.5 for the control group and 42.5 for the imagery group (P < 0.001). Least pain was also significantly different (P < 0.001), with a median increase of 30 for controls and 12.5 for the imagery group. Total opioid requirements were significantly lower in the imagery group, with a median of 185 mg vs. 326 mg in the control group (P < 0.001). Time to first bowel movement was significantly less in the imagery group (median, 58 hours) than in the control group (median, 92 hours; P < 0.001). The number of patients experiencing postoperative complications (nausea, vomiting, pruritus, or ileus) did not differ in the two groups. CONCLUSION: Guided imagery significantly reduces postoperative anxiety, pain, and narcotic requirements of colorectal surgery and increases patient satisfaction. Guided imagery is a simple and low-cost adjunct in the care of patients undergoing elective colorectal surgery.