scholarly journals Effects of oral bovine lactoferrin on a mouse model of inflammation associated colon cancer

Author(s):  
Hajime Tanaka ◽  
Sivagami Gunasekaran ◽  
Dina Mourad Saleh ◽  
William Theodore Alexander ◽  
David Bedell Alexander ◽  
...  

Both ulcerative colitis and colonic Crohn's disease patients have a significantly increased risk of developing colorectal cancer. bLF is reported to inhibit the development of colon cancer in rats and mice, and in a placebo controlled trial, ingestion of bLF inhibited the growth of intestinal polyps. In addition, in a case study a Crohn's disease patient was reported to have remained in remission for over 7 years while ingesting 1 gram of bLF daily. Thus, bLF has an inhibitory effect on colon carcinogenesis, and it may also promote remission of Crohn's disease. The purpose of the present study was to begin to investigate the effect of bLF on a mouse model of IBD-related colorectal cancer. Azoxymethane (AOM) was used to initiate intestinal cancer and dextran sulfate sodium (DSS) was used to induce IBD-like inflammation in the intestine of C57BL/6 mice. Mice were divided into 4 groups: untreated, bLF alone, AOM+DSS, and AOM+DSS+bLF. At the end of the study, mice given AOM+DSS+LF had a better fecal score, less wounding in the colon, and less weight loss than mice in the AOM+DSS group. However, there were no statistically significant differences between the two groups in tumor burden.

2021 ◽  
Vol 10 (20) ◽  
pp. 4663
Author(s):  
Hyunil Kim ◽  
Ji Hoon Kim ◽  
Jung Kuk Lee ◽  
Dae Ryong Kang ◽  
Su Young Kim ◽  
...  

We investigated the risk of colorectal cancer (CRC) in patients with Crohn’s disease (CD) using the claims data of the Korean National Health Insurance during 2006–2015. The data of 13,739 and 40,495 individuals with and without CD, respectively, were analyzed. Hazard ratios (HRs) were calculated using multivariate Cox proportional hazard regression tests. CRC developed in 25 patients (0.18%) and 42 patients (0.1%) of the CD and non-CD groups, respectively. The HR of CRC in the CD group was 2.07 (95% confidence interval (CI), 1.25–3.41). The HRs of CRC among men and women were 2.02 (95% CI 1.06–3.87) and 2.10 (95% CI, 0.96–4.62), respectively. The HRs of CRC in the age groups 0–19, 20–39, 40–59, and ≥60 years were 0.07, 4.86, 2.32, and 0.66, respectively. The HR of patients with late-onset CD (≥40 years) was significantly higher than that of those with early-onset CD (<40 years). CD patients were highly likely to develop CRC. Early-onset CD patients were significantly associated with an increased risk of CRC than matched individuals without CD. However, among CD patients, late-onset CD was significantly associated with an increased risk of CRC.


2002 ◽  
Vol 16 (11) ◽  
pp. 779-784 ◽  
Author(s):  
Hugh J Freeman

A variety of malignant complications occur in Crohn’s disease, and previous studies have recorded an increased intestinal cancer risk. The present investigation tabulated myeloid and lymphoid malignancies compared with intestinal cancers in 1000 consecutively evaluated patients with Crohn’s disease who were followed over an extended period by a single clinician. Myeloid and lymphoid neoplasms were present in 0.5% of patients, while cancer in the intestinal tract was detected in 1%. Most of these patients with a malignancy had Crohn’s disease for a prolonged period of more than 20 years and had negative outcomes, including death or presentations with advanced disease. In this cohort, lymphoma was not detected in a single patient after definition of Crohn’s disease, possibly reflecting the limited use of immunosuppressives or infused biological agents in this clinical practice. Bypassed rectal ‘stumps’ were associated with subsequent colorectal cancer in half of all males with colon cancer in this series, suggesting an important risk factor following colectomy in Crohn’s disease. Epithelial dysplasia was detected in only a single male patient before colorectal cancer, implying that this histopathological marker may be a poor predictor of subsequent colon cancer development in Crohn’s disease, an inflammatory bowel disease process that is typically patchy or focal in distribution in the intestinal tract.


1995 ◽  
Vol 9 (1) ◽  
pp. 23-26 ◽  
Author(s):  
Anders M Ekbom

There is an increased risk of cancer in both ulcerative colitis and Crohn's disease. In 3121 patients with ulcerative colitis, 225 cases of cancer were diagnosed compared with 142.1 expected (standardized incidence ratio [SIR] 1.6, 95% CI 1.4 to 1.8), and in 1655 patients with Crohn's disease, 58 cases of cancer were detected compared with 47.1 expected (SIR 1.2, 95% CI 0.9 to 1.6). After excluding colorectal cancer the observed number of malignancies was very close to that expected for ulcerative colitis (SIR 1.0, 95% CI 0.9 to 1.2) and for Crohn's disease (SIR 1.1, 95% CI 0.8 to 1.5). Thus, the increased risk of cancer in inflammatory bowel disease is confined to colorectal cancer. In Crohn's disease 12 cases of colorectal cancer were observed (SIR 2.5, 95% CI 1.3 to 4.3). The increased risk was confined to those with colonic involvement and young age at diagnosis. In patients with colonic involvement and younger than age 30 years at diagnosis, the SIR was 20.9 (95% CI 6.8 to 48.7) versus 2.2 for those older than 30 years at diagnosis (95% CI 0.6 to 5.7). In ulcerative colitis 91 cases of colorectal cancer were observed with an SIR of 5.7 (95% CI 4.6 to 7.0). Extensive disease and young age at diagnosis were independent risk factors. Pancolitis at diagnosis resulted in an SIR of 14.8 (95% CI 11.4 to 18.9), 2.8 in left-sided colitis (95% CI 1.6 to 4.4) and 1.7 in proctitis (95% CI 0.8 to 3.2). There is great variation in the risk estimates in different studies worldwide. Different treatment strategies could be an explanation, a hypothesis that was substantiated in a study of 102 cases of colorectal cancer among patients with ulcerative colitis compared with 196 controls. Pharmacological therapy with sulfasalazine entailed a strong protective effect against colorectal cancer (relative risk of 0.34, 95% CI 0.190 to 0.62).


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S013-S014
Author(s):  
O Olen ◽  
R Erichsen ◽  
M C Sachs ◽  
L Pedersen ◽  
J Halfvarson ◽  
...  

Abstract Background Crohn’s disease (CD) is a risk factor for colorectal cancer (CRC). Earlier studies reflect older treatment and surveillance strategies, and most have studied incident CRC without addressing potential lead-time and surveillance biases. Such bias can be reduced by examining tumour stage-adjusted CRC incidence and CRC mortality. We aimed to assess risks of CRC mortality and incident CRC among patients with CD compared with the general population. Methods Nationwide register-based cohort study during 1969–2017 of 47,035 patients with CD in Denmark (n = 13,056) and Sweden (n = 33,979), compared with 463,187 general population reference individuals, matched for sex, age, calendar year, and place of residence. We used Cox regression to estimate hazard ratios (HRs) for incident CRC and CRC mortality. In a multistate model, assessing competing events during follow-up (CRC diagnosis, CRC death, other death), we also took a tumour stage into account. Results During 1969–2017, 499 patients with CD developed CRC, corresponding to an adjusted HR of 1.40 [95% confidence interval (CI) 1.27–1.53]. We observed 296 (0.47/1000 person-years) deaths from CRC in patients with CD compared with 1968 (0.31/1000) in reference individuals [HR 1.74 (95% CI 1.54–1.96)]. CD patients diagnosed with CRC were at increased risk of CRC mortality compared with reference individuals also diagnosed with CRC [HR = 1.30 (95% CI 1.06–1.59)] and tumour stage at CRC diagnosis did not differ between groups (p = 0.27). CD patients who had 8 or more years of follow-up or who were diagnosed with primary sclerosing cholangitis (PSC) and hence were potentially eligible for CRC surveillance had an increased overall risk of CRC death [HR 1.41 (95% CI 1.18–1.69)] or CRC diagnosis [HR = 1.12 (95% CI = 0.98–1.28)]. However, in patients potentially eligible for CRC surveillance, we only found significantly increased risks in patients with CD onset &lt;40 years, disease activity in the colon only, or with PSC (Figure 1). Conclusion CD patients are at increased risk of a CRC diagnosis and CRC death. Despite repeated colonoscopies during follow-up, CD patients are not diagnosed earlier (less severe tumour stage) with CRC than reference individuals. Nevertheless, CD patients with CRC have higher mortality than non-CD patients also diagnosed with CRC. CRC surveillance could likely be improved and should be focussed on CD patients &lt;40 years at CD onset, patients with colon inflammation, and patients who have PSC.


2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S068-S069
Author(s):  
B Sensi ◽  
J Khan ◽  
W Janindra ◽  
L Siragusa ◽  
Y Panis ◽  
...  

Abstract Background There is a recognized increased risk for colorectal cancer (CRC) in patients with Crohn’s disease (CD). CD patients with CRC might also show a higher prevalence of synchronous and metachronous cancers. On this basis, current guidelines recommend pan-proctocolectomy (PPC) as a treatment. Aim of this study was to evaluate oncologic outcomes and the actual risk of developing metachronous cancers in CD patients undergoing segmental colectomy (SC) for CRC. Methods All CRC CD patients undergoing surgery in select European and U.S. tertiary referral centres were enrolled. Short and long-term results of SC were compared with those of patients undergoing extended colectomies: total colectomy (TC) and panproctocolectomy (PPC). Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes were postoperative complications, 30 days mortality, re-admission, length of stay, incidence of synchronous and metachronous lesions. Results 91 patients were included: 50 (54%) did not have Crohn’s colitis or had cancer developed in a non-involved segment; cancer developed in inflamed colic segment in 41 (46%). Patients without colitis were more often treated with SC (84%). 62 patients underwent segmental colectomies and 29 extended colectomies (EC): 19 PPC and 10 TC. Patients in the SC group were older (p 0.0429), harboured more metastases at diagnosis (p 0.0219) and were less likely to suffer from CD pancolitis (p 0.0022). Incidence of major complications was comparable in SC (8.6%) vs EC (3.45%) (p 0.06602). There was no perioperative mortality and no difference in specific complications, re-admission or length of stay. 28 patients (30%) suffered disease progression: 22 (35%) after SC and 6 (21%) after EC. Of the 19 cancer related deaths (20%), 16 (25%) were in SC and 3 (10%) in EC groups. There was no difference in unadjusted PFS between SC and EC (0.64 vs 0.79 respectively, Wilcoxon p 0.1029) nor in OS (0.74 vs 0.89, Wilcoxon p 0.1591), after a median follow up of 42 months (55.76 vs 31.13 months respectively). Multivariate analysis confirmed no difference in PFS (HR 1.582, p 0.4964) or OS (HR1 428, p 0.4758). 6 synchronous lesions were found in the 29 patients undergoing EC: 3 low grade dysplasia (10%), 1 high grade dysplasia (3.4%) and 2 preoperatively diagnosed cancers (6.8%). 1 patient (1,61%) developed a metachronous colon cancer of the 62 who had SC and none of the 10 TC. Conclusion CRC in CD is a complex situation and choice of procedure is multifaceted. Incidence of synchronous and metachronous cancers appears much lower than previously described. SC offers similar long-term outcomes to more extensive surgery. Current guidelines for the treatment of CRC in CD patients may need to be reconsidered.


2001 ◽  
Vol 15 (4) ◽  
pp. 231-236 ◽  
Author(s):  
Hugh J Freeman

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.


2015 ◽  
Vol 2015 ◽  
pp. 1-4
Author(s):  
Youssef Botros ◽  
Mary Mathews ◽  
Hiren Patel ◽  
Nihar Shah ◽  
Walid Baddoura ◽  
...  

Hepatocellular carcinoma (HCC) usually occurs in patients with underlying risk factors such as liver cirrhosis and chronic hepatitis B. Although patients with Crohn’s disease (CD) are at an increased risk to develop malignancies such as colon cancer, the incidence of HCC in this population is extremely rare. We report a case of 62-year-old male with long history of CD treated with azathioprine (AZA) and aminosalicylic acid (ASA) who was incidentally diagnosed with HCC, for which left hepatectomy was done. Four years later during routine follow-up, patient had another hepatic lesion and underwent resection of the mass. The mechanism of occurrence of HCC in patient with CD is still controversial and may include immune mediated changes and medication related complications. AZA was reported in all case reports of CD that developed HCC. Through this report we hope to explore the complex pathophysiological mechanisms contributing to the development of HCC in the Crohn’s disease patient population.


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