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Is irritable bowel syndrome a low-grade inflammatory bowel disease?

Irritable Bowel Syndrome (IBS) is multifactorial in its etiology and heterogeneous in its clinical presentation and pathogenesis. It is recognized that inflammation plays an important role in symptom generation, at least in a subset of patients with IBS. Previous gastroenteritis has been identified as the most important risk factor for IBS, and several studies reported that a substantial proportion of patients with gastrointestinal infection develops IBS symptoms,which can persist for several years. Recent studies have demonstrated that a proportion of IBS patients without any history of enteritis has signs of immune activation in the gut. There is clinical overlap between IBS and inflammatory bowel disease (IBD), with IBS-like symptoms frequently reported in patients before the diagnosis of IBD, and a higher than expected percentage reports of IBS symptoms in patients in remission from established IBD. Thus,these conditions may coexist with a higher than expected frequency, or may exist on a continuum, with IBS and IBD at different ends of the same spectrum. This article examines these relation-ships using immune activation and inflammation as a common pathogenic process to IBD and a subset of IBS patients.

Animals↗

A web-based patient education system and self-help group in Persian language for inflammatory bowel disease patients.

BACKGROUND AND AIMS: To study the use patterns of a Persian web-based patient education system for inflammatory bowel disease (IBD) patients in Iran. METHODS: A web-based patient education system was developed with Persian content in three sections: general, ulcerative colitis (UC), and Crohn's disease (CD). The website included a forum for patients to communicate as a self-help group. A customized web tracking system recorded web use statistics. Polls at the bottom of each page collected the visitors' opinion on the extent of helpfulness and readability of page contents. Web use data were analyzed for an 18-month period from October 2004 to April 2006. RESULTS: Having excluded page visits from search engine robots, the website's homepage was visited 4452 times (mean of monthly visits: 234, range: 102-330). The web pages titled Anatomy of gastrointestinal system, Nutrition in IBD, Diagnostic tests, How to cope with IBD, and IBD in women were the most favorite in general section. The web page titled IBD treatment was the most visited in both CD and UC sections followed by the web pages on cause of disease, diagnostic procedures and complications in CD section; and those titled symptoms, cause of disease and risk factors in the UC section. Overall, the content evaluation polls received 294 hits (from 186 unique visitors) of which, 196 (67%) were from patients, 30 (10%) from patients' relatives/friends, 21 (7%) from doctors, and 47 (16%) from other groups. During the 18-month period, 47 patients registered in the self-help forum, 24 threads were opened, and 97 posts (33 in CD and 64 in UC section) were sent. CONCLUSIONS: Considering the increasing trend of Internet use in developing countries like Iran, and the consequent increase in the proportion of Internet-using patients, and finally the time constraints gastroenterologists face answering patients' questions; similar websites seem to be effective ways of patient education in close future.

Humans↗

Genetic and Microbial Analysis of Invasiveness for Escherichia coli Strains Associated With Inflammatory Bowel Disease.

BACKGROUND & AIMS: The adherent-invasive Escherichia coli (AIEC) pathotype is implicated in inflammatory bowel disease (IBD) pathogenesis. AIEC strains are currently defined by phenotypic measurement of their pathogenicity, including invasion of epithelial cells. This broad definition, combined with the genetic diversity of AIEC across patients with IBD, has complicated the identification of virulence determinants. We sought to quantify the invasion phenotype of clinical isolates from patients with IBD and identify the genetic basis for their invasion into epithelial cells. METHODS: A pangenome with core and accessory genes (genotype) was assembled using whole genome sequencing of 168 E coli samples isolated from 13 patients with IBD. A modified assay for invasion of epithelial cells (phenotype) was established with consideration of antibiotic resistance phenotypes. Isolate genotype was correlated to invasiveness phenotype to identify genetic factors that cosegregate with invasion. RESULTS: Pangenome-wide comparisons of E coli clinical isolates identified accessory genes that can cosegregate with invasion phenotype. These correlations found the acquisition of antibiotic resistance genes in clinical isolates compromised the traditional gentamicin protection assays used to quantify invasion. Therefore, an alternate assay, based on amikacin resistance, identified genes cosegregating with invasion. These genes encode an arylsulfatase, a glycoside hydrolase, and genetic islands carrying propanediol utilization and sulfoquinovose metabolism pathways. CONCLUSIONS: This study highlights the importance of incorporating antibiotic resistance screening for invasion assays used in AIEC identification. Accurately screened invasion phenotypes identified accessory genome elements among E coli IBD isolates that correlate with their ability to invade epithelial cells. These results help explain why single genetic markers for the AIEC phylotype are challenging to identify.

Humans↗

Dual infection with Helicobacter bilis and Helicobacter hepaticus in p-glycoprotein-deficient mdr1a-/- mice results in colitis that progresses to dysplasia.

Patients with inflammatory bowel disease (IBD) are at increased risk for developing high-grade dysplasia and colorectal cancer. Animal IBD models that develop dysplasia and neoplasia may help elucidate the link between inflammation and colorectal cancer. Mdr1a-/- mice lack the membrane efflux pump p-glycoprotein and spontaneously develop IBD that can be modulated by infection with Helicobacter sp: H. bilis accelerates development of colitis while H. hepaticus delays disease. In this study, we determined if H. hepaticus infection could prevent H. bilis-induced colitis. Unexpectedly, a proportion of dual-infected mdr1a-/- mice showed IBD with foci of low- to high-grade dysplasia. A group of dual-infected mdr1a-/- animals were maintained long term (39 weeks) by intermittent feeding of medicated wafers to model chronic and relapsing disease. These mice showed a higher frequency of high-grade crypt dysplasia, including invasive adenocarcinoma, possibly because H. hepaticus, in delaying the development of colitis, allows time for transformation of epithelial cells. Colonic epithelial preparations from co-infected mice showed increased expression of c-myc (5- to 12-fold) and interleukin-1alpha/beta (600-fold) by real-time polymerase chain reaction relative to uninfected wild-type and mdr1a-/- animals. This animal model may have particular relevance to human IBD and colorectal cancer because certain human MDR1 polymorphisms have been linked to ulcerative colitis and increased risk for colorectal cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Helicobacter bilis infection accelerates and H. hepaticus infection delays the development of colitis in multiple drug resistance-deficient (mdr1a-/-) mice.

mdr1a-deficient mice lack P-glycoprotein and spontaneously develop colitis with age. Helicobacter spp. are gram-negative organisms that have been associated with colitis in certain mouse strains, but Helicobacter spp. have been excluded as contributing to the spontaneous colitis that develops in mdr1a-/- mice. We wished to determine whether infection with either H. bilis or H. hepaticus would accelerate the development of inflammatory bowel disease (IBD) in mdr1a-/- mice. We found that H. bilis infection induced diarrhea, weight loss, and IBD in mdr1a-/- mice within 6 to 17 weeks post-inoculation and before the expected onset of spontaneous IBD. Histopathology of H. bilis-induced IBD included crypt hyperplasia, inflammatory cell infiltrates, crypt abscesses, and obliteration of normal gut architecture. Reverse transcription-polymerase chain reaction and Taqman analysis from colonic tissue showed increased transcripts for interferon-gamma and interleukin-10 from H. bilis-infected colitic mdr1a-/- mice. Additionally, mesenteric lymph nodes had increased cellularity with expansion of CD4+ and CD8+ T cells and B cells and increased proliferation to soluble H. bilis antigens with elaboration of interferon-gamma, tumor necrosis factor-alpha and interleukin-10. In contrast, H. hepaticus infection of mdr1a-/- mice did not accelerate disease but rather delayed the onset of spontaneous colitis which was milder in severity. mdr1a-/- mice infected with Helicobacter spp. may provide a useful tool to explore the pathogenesis of microbial-induced IBD in a model with a presumed epithelial cell "barrier" defect.

ATP Binding Cassette Transporter, Subfamily B↗

Cytokine profiles differ in newly recruited and resident subsets of mucosal macrophages from inflammatory bowel disease.

BACKGROUND & AIMS: Most macrophages in the normal intestinal mucosa have a mature phenotype. In inflammatory bowel disease (IBD), a monocyte-like subset (CD14+ L1+) accumulates. The aim of this study was to characterize its potential with regard to cytokines. METHODS: Lamina propria mononuclear cells were adherence-separated, with or without depletion of CD14+ cells, and production of cytokines was investigated by bioassay, enzyme-linked immunosorbent assay, or immunocytochemistry. RESULTS: Tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), and IL-1 receptor antagonist were found mainly in cells positive for myelomonocytic L1. In undepleted IBD cultures, TNF-alpha, IL-1alpha and beta, and IL-10 were markedly up-regulated by pokeweed mitogen stimulation; IL-1alpha and beta and IL-10 were also up-regulated by stimulation of interferon gamma and lipopolysaccharide in combination. The latter stimulation had no effect on normal control or CD14-depleted IBD cultures. Indomethacin caused a marked increase of TNF-alpha, particularly in undepleted IBD cultures, whereas IL-10 and IL-4 decreased TNF-alpha and IL-1beta in both CD14+ and CD14 macrophages. CONCLUSIONS: In IBD mucosa, macrophages with a monocyte-like phenotype are primed for production of TNF-alpha and IL-1alpha/beta and may therefore be of significant pathogenic importance [corrected]. However, this CD14+ subset, as well as the mucosal resident macrophages, have preserved responsiveness to several down-regulatory factors such as the macrophage deactivators IL-10 and IL-4.

Adult↗

The C-X-C chemokine ENA-78 is preferentially expressed in intestinal epithelium in inflammatory bowel disease.

BACKGROUND & AIMS: Secretion of chemokines by epithelial cells may represent a crucial event in the pathogenesis of inflammatory bowel disease (IBD). Expression of the chemokine epithelial neutrophil-activating peptide 78 (ENA-78) was monitored in patients with IBD and normal controls. METHODS: In situ hybridizations were performed on 41 tissue specimens from 15 patients with IBD and 10 controls to detect ENA-78 messenger RNA (mRNA). Immunofluorescence stainings were used to localize ENA-78 protein. RESULTS: Intestinal epithelial cells expressing ENA-78 mRNA at detectable levels are found at comparable frequencies in patients with Crohn's disease and ulcerative colitis. Tissue specimens with mild to moderate histological signs of disease activity show slightly higher frequencies of ENA-78 mRNA-expressing epithelial cells than areas with signs of severe disease activity (P = 0.14). Immunofluorescence stainings showed presence of the ENA-78 protein in > 90% of preserved epithelial cells in IBD, in control tissues, ENA-78 mRNA was not detectable, and ENA-78 protein was detectable in 0%-30% of epithelial cells. CONCLUSIONS: The observations are in agreement with a role of the C-X-C chemokine ENA-78 in the pathogenesis of IBD.

Acute Disease↗

Bone mineral density assessment in children with inflammatory bowel disease.

BACKGROUND & AIMS: Children with inflammatory bowel disease (IBD) are at risk for osteoporosis because of undernutrition, delayed puberty, and prolonged corticosteroid use. The aim of this study was to compare bone mineral density (BMD) in children with IBD with that in normal children and to assess the effects of nutritional and hormonal factors and corticosteroid dosages on BMD. METHODS: One hundred sixty-two subjects (99 with IBD and 63 healthy sibling controls) were enrolled. Patients underwent anthropometric assessment, pubertal staging, bone age radiography, and BMD assessment by dual energy x-ray absorptiometry of the lumbar spine, femoral neck, and radius. Laboratory evaluations included serum calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone, osteocalcin, urinary N-telopeptides, albumin, insulin-like growth factor I, and testosterone or estradiol. Cumulative corticosteroid doses were calculated. RESULTS: BMD Z scores at the lumbar spine and femoral neck were lower in patients with IBD, and lower in those with Crohn's disease compared with those with ulcerative colitis. Low BMD persisted after correction for bone age in girls with Crohn's disease (lumbar spine, P = 0.004; femoral neck, P = 0.002). Cumulative corticosteroid dose was a significant predictor of reduced BMD. BMD did not correlate with measures of calcium homeostasis, except elevated serum phosphate and urine calcium levels in girls. CONCLUSIONS: Low BMD occurs in children with IBD (more in Crohn's disease than in ulcerative colitis), especially pubertal and postpubertal girls. Cumulative corticosteroid dose is a predictor of low BMD, but other factors in Crohn's disease remain undetermined.

Adolescent↗

Interleukin 15 activity in the rectal mucosa of inflammatory bowel disease.

BACKGROUND & AIMS: Interleukin (IL)-15 has been found to share many immunoregulatory activities in lymphocytes with IL-2. The aim of this study was to investigate IL-15 activity in organ cultures, localization of IL-15 messenger RNA (mRNA), and proliferation of lamina propria mononuclear cells (LPMCs) in response to recombinant IL-15 using the mucosal tissues obtained from patients with inflammatory bowel disease (IBD). METHODS: The contents of IL-15, tumor necrosis factor alpha, and IL-2 in the culture supernatant of the rectal mucosal tissues were determined by an enzyme-linked immunosorbent assay. Expression of IL-15 mRNA was analyzed by in situ hybridization, and proliferative response of LPMCs to recombinant IL-15 was determined by [3H]thymidine incorporation into DNA. RESULTS: Significantly greater IL-15 activity was detected in active IBD, and this elevation was also observed in inactive ulcerative colitis. In contrast, greater tumor necrosis factor alpha activity was observed only in active IBD, and IL-2 was not detected in organ cultures. In situ hybridization showed IL-15 mRNA in macrophages and epithelial cells in active IBD specimens, and recombinant IL-15 induced a dose-dependent proliferative response in LPMCs. CONCLUSIONS: Mucosal IL-15 may be involved in the pathogenesis of IBD as one of the important mediators in activation of mucosal immune cells.

Adolescent↗

Involvement of neutrophils and free radicals in the potentiating effects of passive cigarette smoking on inflammatory bowel disease in rats.

BACKGROUND & AIMS: Cigarette smoking is associated with inflammatory bowel diseases (IBDs), particularly Crohn's disease, in humans. The aim of this study was to examine whether passive cigarette smoking aggravates experimental IBD in rats and to clarify the underlying mechanisms. METHODS: Rats were exposed to cigarette smoke (CS) for 1 hour once daily for 4 days before induction of IBD by 2,4, 6-trinitrobenzene sulfonic acid (TNBS)-ethanol enema and were then killed at 2, 6, or 24 hours later. RESULTS: Preexposure to CS significantly potentiated colonic damage induced by TNBS. TNBS-ethanol enema caused a pronounced increase in colonic myeloperoxidase activity, leukotriene B(4) level, and also inducible nitric oxide synthase activity, its protein, and messenger RNA expression. These parameters were all significantly increased further by exposure to CS. In contrast, increased colonic superoxide dismutase activity after TNBS-ethanol enema was attenuated by CS exposure. The potentiating effects of CS exposure on TNBS-induced IBD were significantly alleviated after pretreatment with cyclosporin A (an immunosuppressant), N (G)-nitro-L-arginine methylester (a nitric oxide synthase inhibitor), and dimethyl sulfoxide (a hydroxyl radical scavenger). CONCLUSIONS: The results show that promotion of neutrophil infiltration and free radical production contributed significantly to the potentiating effect of passive cigarette smoking on experimental IBD.

Animals↗

Inflammatory bowel disease in African-American children living in Georgia.

We describe the clinical characteristics of inflammatory bowel disease (IBD) African-American compared with non-African-American children. We identified 172 children with IBD; forty-nine (29%) were African-American. Median symptom duration before IBD diagnosis in African-American children (6 months) was shorter than that of non-African-American children (10 months). The most frequent presenting symptom was hematochezia (ulcerative colitis) and abdominal pain (Crohn's disease) in both racial groups. The estimated incidence of Crohn's disease in African-Americans ranged from 7 per 100,000 to 12 per 100,000, whereas the observed incidence in those with ulcerative colitis was between 5 and 7 per 100,000 during the 10 years of the study. Our pilot study suggests that IBD may be more common in African-American children than previously reported. Prospective population-based studies would be useful to determine whether inheritable factors linked with ethnicity are associated with IBD.

Adolescent↗

Inflammatory bowel disease in older patients.

The onset of UC and CD may occur later in life. Although making the diagnosis of IBD in the elderly can be challenging, the clinical course, natural history, and response to treatment are similar for older and younger patients. In fact, both UC and CD tend to be less extensive in older patients, a feature that may contribute to the overall favorable prognosis for elderly patients with IBD. Overall mortality rates for both UC and CD appear to be similar to that of the general population except for those few patients that present with severe initial disease. Typical features of IBD in the elderly are summarized in Table 3. The differential diagnosis of IBD in the elderly includes infectious causes of enterocolitis, ischemic colitis, and diverticular disease as well as several other mimics of IBD. Awareness of the possibility of late-onset disease and the unique manifestations of disease in the elderly contributes to accurate diagnosis and timely treatment.

Aged↗

[TNF-alpha inhibitors in inflammatory bowel disease].

Inflammatory bowel disease (IBD) is a chronic immunoinflammatory response to an stimulus that activates a chain of cellular mediators causing intestinal damage. One of the most well recognized proinflammatory mediators involved in the pathogenesis of IBD is tumor necrosis factor alpha (TNFalpha). The treatment of IBD has advanced in parallel to the improvement of the knowledge of its physiopathology, leading to the development of biological therapies. An example of this kind of treatment is the use of substances that antagonize TNFalpha, such as monoclonal antibodies infliximab, adalimumab, natalizumab, etanercept or onercept, with infliximab being the unique approved for use in IBD. Several studies have demonstrated that inhibition of TNFalpha is useful in the treatment of Crohn's disease (CD). In CD, infliximab induces the remission of relapses which are refractory to the conventional treatment, prevents more relapses and induces a closure of enterocutaneous and perianal fistula that do not respond to first line treatment. However, infliximab is not useful in ulcerative colitis. Infliximab treatment has some drawbacks, such as the development of anti-infliximab antibodies, which cause a loss of efficacy of the treatment and hypersensitivity reactions. Other reported adverse effects of infliximab are the development of autoimmunity, such as that related with antinuclear or anti-DNA antibodies, or the reactivation of infections such as tuberculosis. In fact, a screening for tuberculosis is necessary before administration of infliximab. To reduce the adverse effects due to infliximab immunogenicity, several trials with humanized or completely human agents, such as adalimumab or onercept, are under way. Until the precise stimulus that triggers IBD is identified, biological therapies have a great future and the selective antagonism of TNFalpha is already a reality.

Antibodies, Monoclonal↗

The platelet count as a simple measure to distinguish inflammatory bowel disease from infective diarrhoea.

A total of 212 adult patients with infective diarrhoea and 27 with inflammatory bowel disease (IBD), admitted consecutively to an infectious disease unit, were studied in order to determine whether clinical features and laboratory measurements performed on admission identified cases of IBD. Long-standing diarrhoea, blood in the faeces, anaemia, leucocytosis, thrombocytosis, raised ESR and a reduced concentration of serum albumin were more common in patients with IBD (P less than 0.05). The most striking difference was in the platelet count with 59% patients with IBD and 1.6% patients with infective diarrhoea having platelet counts greater than 450 x 10(9)/l. A raised platelet count in a patient admitted to hospital with 'acute gastro-enteritis' suggests IBD.

Adult↗

Differential alterations in tachykinin NK2 receptors in isolated colonic circular smooth muscle in inflammatory bowel disease and idiopathic chronic constipation.

Inflammatory bowel disease (IBD) and idiopathic chronic constipation (ICC) are intestinal disorders which disrupt normal colonic motility. Enteric tachykinins are well-recognised to play a role in the motor control of the gut, and increased colonic levels of substance P are seen in IBD, whereas decreased levels have been reported in ICC. In this investigation, we have characterised the tachykinin receptor population of normal human colonic circular smooth muscle and examined any changes that occur in IBD and ICC. The selective tachykinin NK2 receptor agonist, [beta-Ala8]neurokinin A(4-10), caused concentration-dependent contractions in healthy tissues; neither NK1 receptor-selective nor NK3 receptor-selective agonists were contractile. In diseased preparations also, only [beta-Ala8]neurokinin A(4-10) caused contractions with EC50 values similar to health. The maximum contractile responses (Emax), however, were significantly decreased in both forms of IBD but significantly increased in ICC. The muscarinic acetylcholine receptor agonist, carbachol, also caused contractions in diseased tissues, but EC50 and Emax values were not significantly different from health. The differential changes in contractility found in IBD and ICC are specific to NK2 receptors, and may reflect the altered levels of substance P or other tachykinins found in these intestinal disorders.

Adult↗

[Frequent Internet use among Catalan patients with inflammatory bowel disease].

UNLABELLED: No data are available on the use of the Internet by Spanish patients with chronic diseases. AIM: To determine the extent to which patients with inflammatory bowel disease (IBD) in Barcelona (Spain) make use of the Internet and the relationship between Internet use and demographic characteristics. METHOD: A questionnaire on Internet use was administered to 200 patients attending an information session on IBD organized by the Gastroenterology Department of a university referral hospital in the city of Barcelona. RESULTS: Replies were received from 86% of those surveyed. The mean age was 40 years and 60% were women. Sixty-eight percent had home computers and 49% had an Internet connection. Forty-four percent sporadically or regularly obtained information on IBD from the web. A positive correlation was found between availability and Internet use and young age and higher educational level. No differences were found between men and women. Eighty-four percent expressed interest in having a web site on IBD supported by the physicians of their referral center and 65% were prepared to pay a subscription for this service. CONCLUSION: Patients with IBD from Barcelona frequently looked for information on their disease on the Internet and were receptive to initiatives concerning electronic information from physicians of their local referral center.

Adolescent↗

Prostate brachytherapy in patients with inflammatory bowel disease.

PURPOSE: There are minimal data to support the perceived contraindication of radiation therapy in patients with inflammatory bowel disease (IBD). Because of widespread concern about the possibility of radiation-related morbidity in IBD patients, the posttreatment course for 6 patients with a history of IBD who were treated with 125I prostate implantation for early stage prostate cancer are reported here. MATERIALS AND METHODS: Six patients with a prior history of IBD and Stage T1c-T2c prostatic carcinoma underwent 125I prostate brachytherapy from 1991-1996. Three patients had Crohn's disease and three had ulcerative colitis. The treatment plans were designed to treat the preimplant prostatic margin, as defined on planning CT scan, to 150 Gy. No special effort was made to minimize the rectal surface dose. Detailed records were available for all patients, and all patients were interviewed for this report. Follow-up ranged from 1 to 6 years (median: 3.7 years). RESULTS: None of the 6 patients experienced unusual or significant gastrointestinal side effects following implantation. All 6 patients remain free of GI complications. The rectal surface area that received > 100 Gy was kept below 10 mm2 in all patients, in accordance with previously published guidelines. CONCLUSIONS: Based on the limited information available, it appears that prostate brachytherapy is safe in patients with a history of IBD.

Adult↗

Rectal cancer and inflammatory bowel disease: natural history and implications for radiation therapy.

PURPOSE: There exists little information concerning the natural history of rectal cancer in patients with inflammatory bowel disease (IBD). In addition, the tolerance of pelvic irradiation in these patients is unknown. We analyzed the largest series of patients with IBD and rectal cancer in order to determine the natural history of the disease as well as the effect and tolerance of pelvic irradiation. METHODS AND MATERIALS: A retrospective analysis of 47 patients with IBD and rectal cancer treated over a 34-year period (1960-1994) was performed. Thirty-five patients had ulcerative colitis and 12 patients had Crohn's disease. There were 31 male patients and 16 female patients. The stage (AJC) distribution was as follows: stage 0 in 5 patients, stage I in 13 patients, stage II in 7 patients, stage III in 13 patients, and stage IV in 9 patients. Surgical resection was performed in 44 patients. In two of these patients, preoperative pelvic irradiation was given followed by surgery. Twenty of these patients underwent postoperative adjuvant therapy (12 were treated with chemotherapy and pelvic irradiation and 8 with chemotherapy alone). Three patients were found to have unresectable disease and were treated with chemotherapy alone (2 patients) or chemotherapy and radiation therapy (RT) (1 patient). Radiation complications were graded using the RTOG acute and late effects scoring criteria. Follow-up ranged from 4 to 250 months (median 24 months). RESULTS: The 5-year actuarial results revealed an overall survival (OS) of 42%, a disease-free survival (DFS) of 43%, a pelvic control rate (PC) of 67% and a freedom from distant failure (FFDF) of 47%. DFS decreased with increasing T stage with a 5-year rate of 86% for patients with Tis-T2 disease compared to 10% for patients with T3-T4 disease (p < 0.0001). The presence of lymph node metastases also resulted in a decrease in DFS with a 5-year rate of 67% for patients with NO disease compared to 0% for patients with N1-N3 disease (p < 0.0001). DFS decreased with increasing histopathologic grade with 5-year DFS rates of 71%, 52%, and 24% for grades 1, 2, and 3 respectively (p = 0.03). The T and N stages showed a statistically significant effect on pelvic control, with 5-year PC rates of 60% for Tis-2 versus 26% for T3-4 (p = 0.002) and 79% for NO versus 51% for N1-3 (p = 0.007). The histopathologic grade of the tumor did not significantly affect pelvic control. An analysis of high-risk patients (30) with T3-T4 or N1-N3 disease revealed at 5 years an OS of 9%, a DFS of 10%, a PC rate of 26%, and FFDF of 20%. In this subset of patients, there was a trend toward improved pelvic control in patients receiving RT (14 patients) with a 5-year PC of 60% compared to a rate of 23% for those patients not irradiated (16 patients). Acute complications (grade 3 or >) were noted in three patients (20%) receiving pelvic irradiation +/- chemotherapy and these included two cases of grade 3 skin reactions and one case of grade 4 gastrointestinal toxicity. Two patients (13%) developed small bowel obstruction at 2 and 4 months, respectively, postirradiation which were managed conservatively. There were no long-term complications in patients irradiated. CONCLUSION: Treatment results are comparable to those historically reported for non-IBD-related rectal cancer although the subset of high-risk patients appeared to have a poorer outcome. In light of this finding and the ability of these patients to tolerate chemotherapy and pelvic irradiation, aggressive adjuvant therapy should be given to IBD-associated rectal cancer patients with high-risk features.

Adolescent↗