Crohn's disease and colorectal cancer.

The colorectal cancer risk in Crohn's disease eliminating all known biases was assessed in a cohort of 281 patients with Crohn's disease who resided in the West Midlands at the time of diagnosis, and were first seen within five years of onset of symptoms between 1945-1975. All patients were 15 years of age or more at onset and were followed up from 12-35 years (total 5213 person years at risk (PYR)). The colorectal cancer risk in the series compared with the risk in the general population was computed by applying sex and age specific PYRs to the date of death or end of the study period 31 December 1991. There were six colonic and two rectal cancers. Six of the eight colorectal cancers were diagnosed 20 or more years after the onset of Crohn's disease. The relative risk (RR) of colorectal cancer for the series as a whole was 3.4 (p < 0.001), with a fivefold excess in the colon, but no significant excess in the rectum. Patients with extensive colitis showed an 18-fold increase in risk (RR = 18.2, p < 0.001), which decreased with increasing age at onset. This study shows that there is a statistical excess risk of developing colorectal cancer in patients who develop their Crohn's disease at a young age of onset (less than 30 years of age).     

Reduction of colorectal cancer risk in patients with Crohn's disease

Patients with inflammatory bowel disease (IBD)-either Crohn's disease (CD) or ulcerative colitis (UC)-are at increased risk for developing cancers of the gastrointestinal tract, particularly colorectal cancer (CRC). Because of the relative rarity of IBD in the general population, it has been difficult to quantify this risk; nonetheless, within particular subsets of IBD patients, the cumulative risk of developing dysplasia and CRC may be substantial. Efforts to reduce this risk have included both prophylactic surgery and endoscopic screening programs. Despite the impact this disease has on quality of life and life expectancy, an optimal strategy for reducing the risk has yet to be defined. This article reviews the current literature relating to the risk of cancer for patients with IBD and methods available to help reduce this risk.     

Risks and clinical features of colorectal cancer complicating Crohn's disease in Japanese patients

Background and Aim: No reports on the relative risk of development of colorectal cancer (CRC) in Japanese patients with Crohn's disease (CD) have been published. The present study aimed to investigate the relative risk and the clinical features of CRC complicating CD among patients managed at Fukuoka University Chikushi Hospital, Fukuoka, Japan (a tertiary referral center for inflammatory bowel diseases). Methods: The clinical backgrounds were analyzed of 512 patients with CD who have been treated by our department during the last 20‐year period (1985–2005) (total 6212.6 person years at risk). The standardized incidence ratio (SIR) refers to the relative risk of CRC in the subjects as compared with that in a sex‐ and age‐matched healthy population. Results: There were six cases with CRC. The SIR was significantly higher (3.2‐fold higher; 95% confidence interval, 1.2–6.9 P < 0.05) in the CD group than in the healthy population. The significant risk factors identified were female sex, mixed small and large bowel type, observation period over 20 years, onset of CD at less than 25 years of age, presence of anal disease, and positive history of surgery. The prognosis for the six cases with CRC was very poor (five cases died within 1.5 years). Conclusion: The risk of CRC in longstanding CD in Japan was similar to that in Western countries. The necessity of surveillance in the management of CD would also need to be discussed in the near future, especially in CD patients with anal lesions or fistulae, and are particularly important in patients with a 20‐year or more history of CD.     

Interaction of the major inflammatory bowel disease susceptibility alleles in Crohn’s disease patients

AIM:To investigate the interaction of interleukin-23 receptor(IL23R)(rs1004819 and rs2201841),autophagy-related 16-like 1(ATG16L1)(rs2241880), caspase recruitment domain-containing protein 15 (CARD15)genes,and IBD5 locus in Crohn‘s disease(CD) patients. METHODS:A total of 315 unrelated subjects with CD and 314 healthy controls were genotyped.Interactions and specific genotype combinations of a total of eight variants were tested.The variants of IBD5locus(IGR2198a_1 rs11739135 and IGR2096a_1 rs12521868),CARD...     

Survival after colorectal cancer in patients with Crohn's disease: A nationwide population-based Danish follow-up study

BACKGROUND AND AIMS: Patients with Crohn's disease (CD) are at increased risk of colorectal cancer (CRC), but little is known about the impact of CD on CRC prognosis. Based on nationwide population-based registries, we compared survival among CRC patients with CD and CRC patients without CD. METHODS: We used the Danish Cancer Registry and the Danish Hospital Discharge Registry to identify all patients diagnosed with CRC, with and without CD, in Denmark between 1977 and 1999. We ascertained the stage distribution at the time of CRC diagnosis and 1- and 5-yr survival both for patients with Crohn-associated CRC and patients with non-Crohn CRC. Cox regression was used to compute hazard ratios (HRs), adjusting for gender, age, calendar year, and stage. RESULTS: We identified 100 CRC patients with CD and 71,438 CRC patients without CD. At the time of diagnosis, patients with CD were younger, but stage distributions were similar in the two groups. The overall HR for CRC with CD compared to CRC without CD was 1.82 (95% CI 1.36-2.43) after 1 yr of follow-up, and 1.57 (95% CI 1.24-1.99) after 5 yr of follow-up. Subanalyses showed that the effect of CD on CRC survival was more pronounced in the youngest patients (0-59 yr), in men, and in patients whose tumors had regional spread. CONCLUSIONS: We found that CD worsens the prognosis of CRC, particularly CRC with regional spread.     

Analysis of Ha-ras 1 allele frequencies in hereditary non-polyposis colorectal cancer.

Restriction enzyme digests of genomic DNA show multiple alleles of common, intermediate, and rare frequencies at the minisatellite locus of Ha-ras. It has been suggested that a higher frequency of rare alleles is associated with the presence of colorectal and other types of cancer. This study investigated the distribution of Ha-ras alleles in 40 members of hereditary non-polyposis colorectal carcinoma (HNPCC) families and in 34 cancer free subjects (spouses). There was no difference in rare allele frequency between the cancer group and cancer free group (chi2 = 0.25, not significant).     

Immunological studies in patients with Crohn's disease.

An investigation of immunological parameters was conducted in 38 patients with Crohn's disease. The immunological tests employed included skin tests with dinitrochlorobenzene and a battery of common skin test antigens, lymphocyte transformation with phytohaemagglutinin and pokeweed mitogen, serum immunoglobulins, and absolute lymphocyte counts. Crohn's disease patients were divided into two groups, those treated with immunosuppressive drugs and those not receiving immunosuppressive medications. The latter group was subdivided into patients with active and inactive disease. Immunosuppressed patients with Crohn's disease did not develop sensitivity to dinitrochlorobenzene and had mildly depressed skin test reactivity to common skin test procedures. Non-immunosuppressed patients with active Crohn's disease also reacted less frequently to common skin test antigens, but 16 of 17 such patients developed sensitivity to dinitrochlorobenzene. Lymphocyte transformation with phytohaemagglutinin and pokeweed mitogen was normal in all groups of patients with Crohn's disease. However, when suboptimal incubation periods were used with phytohaemagglutinin stimulation, there was a significant difference between Crohn's disease patients and controls. Serum immunoglobulin levels and absolute lymphocyte counts were normal in all Crohn's disease patients. We conclude that immunity in Crohn's disease is qualitatively normal.     

Risk of colorectal cancer in patients with hematologic disease

BACKGROUND AND AIMS: A relatively large number of patients with multiple myeloma have been reported to develop a secondary malignancy such as cancer of the breast, biliary system or bowel. METHODS: A retrospective study was perfomed in 734 patients with hematologic disease diagnosed at Nippon Medical School Hospital between May 1984 and September 1994 to determine the incidence of colorectal cancer in these patients based on a history review, colonoscopic findings, and surgical or autopsy data. RESULTS: Of the 734 patients, 14 (1.9%) had colorectal cancer; two of 11 patients (18.2%) had pure red cell aplasia; two of 25 patients (8%) had multiple myeloma; and three of 46 patients (6.5%) had aplastic anemia. Patients with pure red cell aplasia, multiple myeloma or aplastic anemia had colorectal cancer at a significantly higher rate compared to those with leukemia (P< 0.005, P< 0.02, P< 0.01, respectively). CONCLUSIONS: It is possible that a relatively large number of patients with pure red cell aplasia, multiple myeloma or aplastic anemia will develop a colorectal cancer.     

Intestinal cancer in patients with Crohn's disease. A population study in central Israel

A population study of Crohn's disease (CD) during the years 1970-1980 was performed in a defined area in central Israel with 1,400,000 inhabitants. Three hundred and sixty-five patients with definite CD were identified, and a complete follow-up was obtained with particular attention to intestinal cancer. The mean follow-up time was 9.95 years (range, 1-49 years). Forty-four per cent of the patients were operated on, but only a few had total colectomy or bypass operations. Only one patient developed colorectal cancer after 7 years of disease. The observed to expected ratio for this cancer was 1.14 at 10 years of disease and 0.73 at 20 years of disease. The incidence of colorectal cancer was not significantly different from the expected in the population. None of the patients developed small-bowel cancer. At least five patients had extraintestinal malignancies. A review of the literature showed conflicting results with regard to cancer risk in CD. The risk was not significantly increased in the two existing population studies, including the present one.     

Absorption of prednisolone in patients with Crohn's disease.

The absorption of prednisolone in patients with Crohn's disease was investigated. Seven patients with Crohn's disease and eight normal control subjects were given a tracer dose of tritiated prednisolone with 20 mg cold prednisolone by mouth. On a separate occasion they were given an intravenous injection of radiolabelled prednisolone. After oral ingestion only 53.4 +/- 11.7% of labelled material was excreted in the urine of Crohn's patients compared with 82.5 +/- 3.6% in the normal subjects. The oral/intravenous availability ratio was 0.61 +/- 0.14 in Crohn's patients and 0.89 +/- 0.07 in the normal group. Areas under plasma concentration-time curves were lower in patients than normal subjects and the oral/intravenous ratios were 0.6 +/- 0.2 and 0.86 +/- 0.09 respectively. Faecal excretion of radioactivity after oral ingestion was greater in Crohn's patients (19.3 +/- 2.5%, n = 3) than in normal subjects (7 +/- 2.8%, n = 4). The range for each type of measurement was much wider in the patient group than in the normal subjects. These data suggest that patients with Crohn's disease do not absorb prednisolone normally and that absorption varies between patients.     

Similarity of colorectal cancer in Crohn's disease and ulcerative colitis: implications for carcinogenesis and prevention.

Colorectal cancer is the most frequent malignant complication in patients with inflammatory bowel disease. Eighty patients with colorectal cancer complicating Crohn's disease (CD) or ulcerative colitis (UC) with median ages at diagnosis of colorectal cancer of 54.5 years and 43.0 years respectively were studied. The median duration of disease to the diagnosis of cancer was long (CD 15 years; UC 18 years). Most cancers developed after more than eight years of disease (CD 75%; UC 90%). Patients with multiple carcinomas at diagnosis were equally common (CD 11%; UC 12%). Carcinoma occurred in the area of macroscopic disease in most patients (CD 85%; UC 100%). Mucinous and signet ring histological features were equally common (CD 29%; UC 21%). Dysplasia was present with similar frequency in both diseases (CD 73%; UC 79%). The overall five year survival rates were also similar (CD 46%; UC 50%). These findings show that carcinomas complicating CD and UC have strikingly similar clinicopathological features and suggest that a common underlying process, such as chronic inflammation, maybe important in the pathogenesis of colorectal carcinoma.     

Anomalous leukopoiesis in two patients with Crohn's disease.

Crohn's disease is a major form of chronic inflammatory bowel disease in the western world. The molecular genetic basis of Crohn's disease is unknown. In this study, we present evidence for anomalous leukopoiesis-namely, the generation of a leukocyte subset characterized by aberrant expression of gammadelta T cell receptor (gammadeltaTCR) with or without CD19 on a myeloid background-in two patients with Crohn's disease. The aberrant cells of patient 1 have the surface phenotype gammadeltaTCR + CD19 - CD14 + CD64 +. The aberrant cells of patient 2 have the surface phenotype gammadeltaTCR + CD19 + CD14 - CD64 + CD16 + CD13 + CD33 +. The results presented here are significant both in light of recent speculation that a critical defect in Crohn's disease may be at the level of hematopoiesis and because the CD19 gene lies within the region on chromosome 16 that corresponds with the Crohn's disease susceptibility locus IBD1.     

Ulcerative colitis and Crohn's disease: a comparison of the colorectal cancer risk in extensive colitis.

The risk of developing colorectal cancer has been compared in two identically selected cohorts of patients with extensive Crohn's colitis (n = 125) and extensive ulcerative colitis (n = 486). In both groups the effects of selection bias have been reduced wherever possible. There was an 18-fold increase in the risk of developing colorectal cancer in extensive Crohn's colitis and a 19-fold increase in risk in extensive ulcerative colitis when compared with the general population, matched for age, sex, and years at risk. The absolute cumulative frequency of risk for developing colorectal cancer in extensive colitis was 8% at 22 years from onset of symptoms in the Crohn's disease group and 7% at 20 years from onset in the ulcerative colitis group. The relative risk of colorectal cancer was increased in both ulcerative colitis and Crohn's disease among those patients whose colitis started before the age of 25 years. Whether the absolute risk is greater in the younger age group or merely reflects that the expected number of carcinomas increases with age is uncertain. While there is an increased risk of developing colorectal cancer in extensive colitis the number of patients with Crohn's disease who actually develop colorectal cancer is small because many patients with extensive Crohn's colitis undergo colectomy early in the course of their disease to relieve persistent symptoms unresponsive to medical treatment.     

Colorectal cancer complicating Crohn's disease.

Some earlier studies have indicated that patients with inflammatory bowel disease, especially those with long-standing and extensive ulcerative colitis, have an increased risk of colorectal cancer. Moreover, others in tertiary care centres have suggested that patients with Crohn's disease also have a higher risk of colorectal cancer. Canadian data on colorectal cancer in Crohn's disease appear to be limited. For this investigation, a single clinician database of 877 patients with Crohn's disease was used. Altogether, there were six patients with colorectal cancer (ie, overall rate of 0.7%). All of these patients were men with an initial diagnosis of Crohn's disease established at a mean age of approximately 28 years, with either ileocolonic disease or colonic disease alone, but not with ileal disease alone. Although there was a predominance of women in the overall study population (ie, 56.1%), no women developed colorectal cancer. The clinical behaviour of Crohn's disease was classified as nonstricturing in all six patients with colorectal cancer, but in two patients, Crohn's disease was complicated by a perirectal abscess or a fistula. All cancers were located in the rectum and were diagnosed 30 years, 22 years, seven years, 18 years, 20 years and 40 years after Crohn's disease was initially diagnosed. In three patients, the cancer was detected in a residual rectal stump after a partial colon resection at least 10 years earlier. In five patients, localized extension of disease through the serosa, nodal or distant metastases (ie, liver, lung) was found at the time of cancer diagnosis; two patients have since died. The present study confirms that Crohn's disease involving the colon may be a possible risk factor for the development of colorectal cancer, at least in younger men, but, in this study, not in women. However, part of this increased risk in men may have been related to the presence of a rectal stump, rather than to Crohn's disease per se.     

Management of colorectal cancer in patients with inflammatory bowel disease

Background

This study evaluated the clinicopathological features and survival rates of patients with inflammatory bowel disease who developed colorectal cancer (CRC).

Methods

A retrospective review was performed on a prospectively maintained institutional database (1981–2011) to identify patients with inflammatory bowel disease who developed CRC. Clinicopathological parameters, management and outcomes were analysed.

Results

A total of 2,843 patients with inflammatory bowel disease were identified. One thousand six hundred and forty-two had ulcerative colitis (UC) and 1,201 had Crohn’s disease (CD). Following exclusion criteria, there were 29 patients with biopsy-proven colorectal carcinoma, 22 of whom had UC and 7 had CD. Twenty-six patients had a preoperative diagnosis of malignancy/dysplasia; 16 of these were diagnosed at surveillance endoscopy. Nodal/distant metastasis was identified at presentation in 47 and 71 % of the UC and CD group, respectively. Operative morbidity for UC and CD was 33 and 17 %, respectively. Despite the less favourable operative outcomes following surgery management of UC-related CRC, overall 5-year survival was significantly better in the UC group compared to the CD group (41 vs. 29 %; p = 0.04) reflecting the difference in stage at presentation between the two groups.

Conclusions

Patients who undergo surgery for UC-related CRC have less favourable short-term outcomes but present at a less advanced stage and have a more favourable long-term prognosis than similar patients with CRC and CD.