Colorectal polyp outcomes after participation in the seAFOod polyp prevention trial: Evidence of rebound elevated colorectal polyp risk after short-term aspirin use.

BACKGROUND: The seAFOod polyp prevention trial was a randomised, placebo-controlled, 2 × 2 factorial trial of aspirin 300 mg and eicosapentaenoic acid (EPA) 2000 mg daily in individuals who had a screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP). Aspirin treatment was associated with a 20% reduction in colorectal polyp number at BCSP surveillance colonoscopy 12 months later. It is unclear what happens to colorectal polyp risk after short-term aspirin use. AIM: To investigate colorectal polyp risk according to the original trial treatment allocation, up to 6 years after trial participation. METHODS: All seAFOod trial participants were scheduled for further BCSP surveillance and provided informed consent for the collection of colonoscopy outcomes. We linked BCSP colonoscopy data to trial outcomes data. RESULTS: In total, 507 individuals underwent one or more colonoscopies after trial participation. Individuals grouped by treatment allocation were well matched for clinical characteristics, follow-up duration and number of surveillance colonoscopies. The polyp detection rate (PDR; the number of individuals who had ≥1 colorectal polyp detected) after randomization to placebo aspirin was 71.1%. The PDR was 80.1% for individuals who had received aspirin (odds ratio [OR] 1.13 [95% confidence interval 1.02, 1.24]; p = 0.02). There was no difference in colorectal polyp outcomes between individuals who had been allocated to EPA compared with its placebo (OR for PDR 1.00 [0.91, 1.10]; p = 0.92). CONCLUSION: Individuals who received aspirin in the seAFOod trial demonstrated increased colorectal polyp risk during post-trial surveillance. Rebound elevated neoplastic risk after short-term aspirin use has important implications for aspirin cessation driven by age-related bleeding risk. ISRCTN05926847.

The Cytotoxic Effect of Isolated Cannabinoid Extracts on Polypoid Colorectal Tissue.

Purified cannabinoids have been shown to prevent proliferation and induce apoptosis in colorectal carcinoma cell lines. To assess the cytotoxic effect of cannabinoid extracts and purified cannabinoids on both colorectal polyps and normal colonic cells, as well as their synergistic interaction. Various blends were tested to identify the optimal synergistic effect. Methods: Biopsies from polyps and healthy colonic tissue were obtained from 22 patients undergoing colonic polypectomies. The toxicity of a variety of cannabinoid extracts and purified cannabinoids at different concentrations was evaluated. The synergistic effect of cannabinoids was calculated based on the cells' survival. Isolated cannabinoids illustrated different toxic effects on the viability of cells derived from colorectal polyps. THC-d8 and THC-d9 were the most toxic and exhibited persistent toxicity in all the polyps tested. CBD was more toxic to polypoid cells in comparison to normal colonic cells at a concentration of 15 µM. The combinations of the cannabinoids CBDV, THCV, CBDVA, CBCA, and CBGA exhibited a synergistic inhibitory effect on the viability of cells derived from colon polyps of patients. Isolated cannabinoid compounds interacted synergistically against colonic polyps, and some also possessed a differential toxic effect on polyp and adjacent colonic tissue, suggesting possible future therapeutic value.

Metformin Use Is Inversely Associated with Prevalent, but Not Incident Colorectal Adenomas.

BACKGROUND: Chemoprevention for colorectal neoplasia has attracted growing interest, with multiple medications investigated. Metformin may decrease the overall incidence of cancer in patients with diabetes and may decrease the incidence of colorectal cancer. AIMS: We aimed to determine the impact of metformin use on the behavior of colorectal adenomas in a US veteran population. METHODS: All patients with at least two high-quality colonoscopies between January 1997 and December 2013 at Veterans Affairs New York Harbor Healthcare System were identified. Outpatient prescription records were used to determine metformin exposure, and colonoscopy findings were recorded. Multivariable logistic regression was used to determine factors associated with adenoma detection on baseline and interval colonoscopy. RESULTS: In total, 1869 patients with two successive colonoscopies (median 4.5 years) were included. Four hundred and sixty patients had metformin exposure prior to baseline and/or interval colonoscopy. Overall adenoma detection rate was 59.7% at baseline and 45.9% at interval colonoscopy. On multivariable analysis, metformin use was associated with decreased adenoma prevalence at baseline (OR 0.68; 95% CI 0.51-0.92; p = 0.015). Metformin did not impact adenoma incidence at interval colonoscopy whether prescribed before baseline (OR 1.26; 95% CI 0.60-2.67), after baseline (OR 1.25; 95% CI 0.91-1.72), or before and after baseline (OR 1.14; 95% CI 0.82-1.58). CONCLUSIONS: In this retrospective analysis of an average-risk cohort, metformin use was associated with a decreased prevalence of colorectal adenomas at baseline colonoscopy. This inverse association did not persist on interval colonoscopy. Prospective studies are needed to evaluate potential chemoprotective effects of metformin over time.

Circulating 27-hydroxycholesterol and Risk of Colorectal Adenomas and Serrated Polyps.

The oxysterol 27-hydroxycholesterol (27-OHC) is an endogenous selective estrogen receptor modulator implicated in breast cancer etiology. It is unknown whether circulating 27-OHC is associated with colorectal neoplasia risk. Circulating 27-OHC was measured using LC/MS in fasting plasma collected at baseline from participants of the Vitamin D/Calcium Polyp Prevention Study, a completed randomized clinical trial. Participants were between 45 and 75 years old, recently diagnosed with ≥1 colorectal adenoma, and followed for new colorectal polyps during colonoscopic surveillance. Adjusted risk ratios (RR) with 95% confidence intervals (CI) of new colorectal polyps were estimated for quartiles of circulating 27-OHC using log-linear regression for repeated outcomes. Polyp phenotypes included any adenomas, advanced adenomas, hyperplastic polyps, and sessile serrated adenomas/polyps. Circulating 27-OHC was measured at baseline for 1,246 participants. Compared with participants with circulating 27-OHC below the first quartile (<138 ng/mL), those with circulating 27-OHC at or above the fourth quartile (≥201 ng/mL) had 24% higher risk of adenomas (RR, 1.24; 95% CI, 1.05-1.47) and 89% higher risk of advanced adenomas (RR, 1.89; 95% CI, 1.17-3.06). Stronger associations were observed among participants with advanced adenomas at baseline. Circulating 27-OHC was not associated with risk of hyperplastic polyps (RR, 0.90; 95% CI, 0.66-1.22) or sessile serrated adenomas/polyps (RR, 1.02; 95% CI, 0.50-2.07). Circulating 27-OHC may be a risk factor for colorectal adenomas but not serrated polyps. PREVENTION RELEVANCE: This study found that plasma concentration of 27-hydroxycholesterol, a metabolite of cholesterol that regulates lipid metabolism and acts as a selective estrogen receptor modulator, is associated with the risk of developing precursor lesions for colorectal cancer.

Topical aloe vera for the treatment of cetuximab-related acneiform rash in colorectal cancer: A case report.

INTRODUCTION: Colorectal cancer is one of the most common cancers in the world. Cetuximab is an epidermal growth factor receptor (EGFR) inhibitor which provides survival benefit when combined with chemotherapy in RAS wild type metastatic colorectal cancer. Cutaneous toxicities associated with cetuximab have a significant impact on patient quality of life, treatment continuation and healthcare resource utilization. CASE REPORT: A 60-year-old male patient presented with fatigue, weight loss and abdominal pain. Two closely located malignant polypoid lesions were detected in the sigmoid colon, and pathological examination revealed colonic adenocarcinoma.Management and outcome: Thorax, abdominal and pelvic computed tomography showed metastases. FOLFOX chemotherapy and cetuximab were started. The patient developed acneiform rash firstly in his face, although prophylactic vitamin K1 0.1% containing cream was given. He was given mild potency topical corticosteroid and doxycycline. The lesions progressed to his front and back body. He did not want to use topical vitamin K1 cream, topical steroid and doxycycline tablets. Instead, he wanted to use aloe vera extract which he produced from the leaves of the plant. Patient's lesions were regressed significantly. DISCUSSION: The most common and earliest skin toxicity is acneiform rash which affects 60 to 80% of the patients. In this case, cetuximab-related severe acneiform rash was effectively treated by topical aloe vera. Topical aloe vera may be used in the management of cetuximab-related cutaneous toxicities without any side effect.

The efficacy and safety of sulindac for colorectal polyps: A protocol for systematic review and meta-analysis.

BACKGROUND: Sulindac has been used for treating colorectal polyps widely. However, the efficacy and safety of sulindac for colorectal polyps are unclear. This study aims to evaluate the efficacy and safety of sulindac for colorectal polyps. METHODS: Randomized controlled trials of sulindac in the treatment of colorectal polyps will be searched in PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, the Chongqing VIP Chinese Science, and Technology Periodical Database, and China biomedical literature database (CBM) from inception to August, 2020. And Baidu Scholar, Google Scholar, International Clinical Trials Registry Platform, and Chinese Clinical Trials Registry will be searched to obtain more relevant studies comprehensively. Two researchers will perform data extraction and risk of bias assessment independently. Statistical analysis will be conducted in RevMan 5.3. RESULTS: This study will summarize the present evidence by exploring the efficacy and safety of sulindac in the treatment of colorectal polyps. CONCLUSION: The findings of the study will provide helpful evidence for the efficacy and safety of sulindac in the treatment of colorectal polyps, facilitating clinical practice and further scientific studies. ETHICS AND DISSEMINATION: The private information from individuals will not publish. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/N5GDH.

Sulindac plus a phospholipid is effective for polyp reduction and safer than sulindac alone in a mouse model of colorectal cancer development.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and sulindac are effective for colorectal cancer prevention in humans and some animal models, but concerns over gastro-intestinal (GI) ulceration and bleeding limit their potential for chemopreventive use in broader populations. Recently, the combination of aspirin with a phospholipid, packaged as PL-ASA, was shown to reduce GI toxicity in a small clinical trial. However, these studies were done for relatively short periods of time. Since prolonged, regular use is needed for chemopreventive benefit, it is important to know whether GI safety is maintained over longer use periods and whether cancer prevention efficacy is preserved when an NSAID is combined with a phospholipid. METHODS: As a first step to answering these questions, we treated seven to eight-week-old, male and female C57B/6 Apcmin/+ mice with the NSAID sulindac, with and without phosphatidylcholine (PC) for 3-weeks. At the end of the treatment period, we evaluated polyp burden, gastric toxicity, urinary prostaglandins (as a marker of sulindac target engagement), and blood chemistries. RESULTS: Both sulindac and sulindac-PC treatments resulted in significantly reduced polyp burden, and decreased urinary prostaglandins, but sulindac-PC treatment also resulted in the reduction of gastric lesions compared to sulindac alone. CONCLUSIONS: Together these data provide pre-clinical support for combining NSAIDs with a phospholipid, such as phosphatidylcholine to reduce GI toxicity while maintaining chemopreventive efficacy.

Protective effect of Matricaria chamomilla extract against 1,2-dimethylhydrazine-induced colorectal cancer in mice.

Background Colorectal cancer (CRC) is a major public health problem, with almost 1.8 million newly diagnosed cases and about 881,000 deaths annually. Chamomile (Matricaria chamomilla) is a well-documented medicinal herb that possesses anti-inflammatory and anti-carcinogenic properties. This study aimed to unravel the effect of aqueous chamomile extract against 1,2-dimethylhydrazine(DMH)-induced CRC in mice. Methods Male Balb/c mice received a weekly intraperitoneal injection of DMH (20 mg/kg body weight) for 12 weeks. Chamomile extract (150 mg/kg body weight/5 days/week p.o.) was administered at the initiation and post-initiation stages of carcinogenesis. Polyps count, histopathological analysis, real-time polymerase chain reaction (RT-PCR) analysis of Wnt signaling genes, ELISA of cyclooxygenase-2 (COX-2), and enzyme assay for inducible nitric oxide synthase (iNOS) were performed. Results Chamomile extract modulated the Wnt pathway in colonic tissues, where it significantly downregulated Wnt5a, ß-catenin, T cell factor (Tcf4), lymphoid enhancer factor 1 (Lef1), c-Myc and Cyclin D1 expression levels, while it upregulated adenomatous polyposis coli (APC) and glycogen synthase kinase (GSK3ß) expression levels. This extract significantly reduced COX-2 levels and iNOS activities. Polyps count and histopathological analysis provided supportive evidence for the biochemical and molecular analyses. Conclusions Chamomile can act as a potent dietary chemopreventive agent against DMH-induced CRC.

Comparison of the efficacy of cyclosporine and leflunomide in treating inflammatory colorectal polyps in miniature dachshunds.

Inflammatory colorectal polyps (ICRPs) are frequently observed in miniature dachshunds in Japan and treated by prednisolone and immunosuppressive drugs such as cyclosporine and leflunomide. The purpose of this retrospective study was to compare the treatment efficacy, such as response rate, response interval, recurrence rate, and adverse events between cyclosporine and leflunomide. While the response rates were significantly higher in dogs treated with leflunomide, no significant differences were observed in the response interval or recurrence rate. Two of the 11 dogs treated with leflunomide showed hematological or gastrointestinal adverse events, while no dog treated with cyclosporine showed any adverse events. A case-controlled prospective study to compare the treatment efficacy of leflunomide with that of cyclosporine should be conducted.

Regresión de pseudopólipo gigante en paciente con enfermedad de Crohn del colon tras tratamiento con infliximab / Regression of a giant pseudopolyp in a patient with colonic Crohn's disease after therapy with infliximab

Los pseudopólipos inflamatorios gigantes (> 15 mm) son una complicación infrecuente de la enfermedad inflamatoria intestinal (EII). Es difícil el diagnóstico diferencial con adenomas y carcinomas. Aunque suelen ser asintomáticos, debido a su tamaño pueden ocasionar obstrucción o invaginación intestinal. El manejo habitual se realiza con biopsias de la lesión y extirpación endoscópica de la misma en casos seleccionados, reservando la cirugía para complicaciones inherentes a su tamaño o bien ante la duda anatomopatológica. Presentamos el caso de una paciente de 43 años con enfermedad de Crohn (EC) de colon en remisión clínica y sin tratamiento específico para la enfermedad en la que en una colonoscopia de cribado se identificó un pseudopólipo gigante (40 mm). Se inició tratamiento con infliximab y azatioprina para intentar reducir tamaño y permitir resección endoscópica posteriormente. Tras dosis de inducción, en las semanas 0, 2 y 6 se realizó una nueva colonoscopia que evidenció una clara reducción de tamaño de la lesión. Se intentó resección mucosa pero no fue posible por la intensa fibrosis que impedía elevación de la lesión tras inyección en su base. Una nueva colonoscopia de control a los tres meses confirmó, sin embargo, la desaparición completa de la lesión. Los datos en la literatura respecto al manejo terapéutico de los pseudopólipos gigantes son escasos, pero se ha publicado que es poco frecuente que desaparezcan con tratamiento médico, requiriendo resección quirúrgica o endoscópica

Giant inflammatory pseudopolyps (> 15 mm) are an uncommon complication of inflammatory bowel disease (IBD) and a differential diagnosis with adenomas and carcinomas is challenging. Although usually asymptomatic, they may result in intestinal obstruction or intussusception due to their size. The standard management involves lesion biopsies and endoscopic excision for selected cases; surgery is usually reserved for size-associated complications or an uncertain pathology. We report the case of a 43-year-old female patient with Crohn's disease (CD) in clinical remission, with no specific treatment at the time. A giant pseudopolyp of 40-mm was found during a screening colonoscopy. Therapy was initiated with infliximab and azathioprine in an attempt to reduce the size of the polyp and allow an endoscopic resection. Additional colonoscopies were performed following induction doses at weeks 0, 2, and 6, which revealed a reduced lesion size. Mucosal resection was attempted but failed due to severe fibrosis, which prevented base injections from lifting up the polyp. However, a follow-up colonoscopy three months later showed that the lesion had completely disappeared. The evidence in the literature regarding giant pseudopolyp management is scarce, but reports indicate that they rarely disappear with medical therapy alone and usually require surgery or endoscopic resection

Neuroendocrine tumor associate with inflammatory bowel disease: two cases report.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) have a higher risk of developing gastrointestinal tumors, the adenocarcinoma is the most frequently associated, and neuroendocrine tumor (NET) the most rare. CLINICAL CASES: We present two patients, one with Crohn's disease and the other with ulcerative colitis, who present nonspecific symptoms, and after resection of an intestinal lesion, a gastrointestinal NET (GINET) is diagnosed. DISCUSSION AND CONCLUSION: The GINET have an insidious clinic and these can be confused with those of the IBD. There could be an association between both pathologies; an important role of the chronic intestinal inflammatory process is suggested. The best treatment for GINET is the resection.

INTRODUCCIÓN: Los pacientes con enfermedad inflamatoria intestinal (EII) tienen mayor riesgo de desarrollar neoplasias gastrointestinales y el adenocarcinoma es el relacionado con más frecuencia y el tumor neuroendocrino (TNE) el más raro. CASO CLÍNICO: Se presentan los casos de dos pacientes, uno con enfermedad de Crohn y otro con colitis ulcerosa, que cursan con clínica inespecífica, y tras resección de la lesión intestinal se diagnostica un TNE gastrointestinal (TNEGI). DISCUSIÓN Y CONCLUSIONES: Los TNEGI tienen una clínica insidiosa y pueden confundirse con los de la EII. Es posible un nexo entre ambas entidades, lo que sugiere un papel importante del proceso inflamatorio crónico intestinal. El tratamiento de elección de los TNEGI es la resección.

Regression of a giant pseudopolyp in a patient with colonic Crohn's disease after therapy with infliximab.

Giant inflammatory pseudopolyps (> 15 mm) are an uncommon complication of inflammatory bowel disease (IBD) and a differential diagnosis with adenomas and carcinomas is challenging. Although usually asymptomatic, they may result in intestinal obstruction or intussusception due to their size. The standard management involves lesion biopsies and endoscopic excision for selected cases; surgery is usually reserved for size-associated complications or an uncertain pathology. We report the case of a 43-year-old female patient with Crohn's disease (CD) in clinical remission, with no specific treatment at the time. A giant pseudopolyp of 40-mm was found during a screening colonoscopy. Therapy was initiated with infliximab and azathioprine in an attempt to reduce the size of the polyp and allow an endoscopic resection. Additional colonoscopies were performed following induction doses at weeks 0, 2, and 6, which revealed a reduced lesion size. Mucosal resection was attempted but failed due to severe fibrosis, which prevented base injections from lifting up the polyp. However, a follow-up colonoscopy three months later showed that the lesion had completely disappeared. The evidence in the literature regarding giant pseudopolyp management is scarce, but reports indicate that they rarely disappear with medical therapy alone and usually require surgery or endoscopic resection.

Safety of Cold Snare Polypectomy in Patients Receiving Treatment with Antithrombotic Agents.

BACKGROUND: With the aging of the population and rising incidence of thromboembolic events, the clinical use of antithrombotic agents is also increasing. There are few reports yet on the management of antithrombotic agent use in patients undergoing cold snare polypectomy (CSP). AIMS: The aim of this study was to evaluate whether continued administration of antithrombotic agents in patients undergoing CSP would be associated with an increased rate of delayed post-polypectomy bleeding (DPPB). METHODS: A total of 1177 colorectal polyps in 501 patients were resected at Omori Red Cross Hospital between October 2017 and March 2018. The polyps were divided into two groups depending on whether the patients received antithrombotic agent treatment or not: the antithrombotic group (911 polyps) and the no-antithrombotic group (266 polyps). RESULTS: Among the 1177 polyp resections, there was no case of DPPB, including in the antithrombotic group. Immediate bleeding occurred in a total of 63 (5.4%) cases. Polyp location in the rectum (OR (95% CI) 2.64 (1.223-5.679); p = 0.013), polyp size ≥ 6 mm (OR (95% CI) 4.64 (2.719-7.933); p < 0.001), polypoid growth pattern (OR (95% CI) 2.78 (1.607-4.793); p < 0.001), and antithrombotic agent use (OR (95% CI) 2.98 (1.715-5.183); p < 0.001) were identified as significant risk factors of immediate bleeding. CONCLUSIONS: Continued use of antithrombotic agents does not increase the risk of DPPB, even in those receiving multiple antithrombotic agents. Thus, it is safe to perform CSP even in multiple agent users. Prospective, randomized studies are necessary to confirm our results.

Underutilization of Aspirin in Patients With Advanced Colorectal Polyps.

BACKGROUND: Colorectal cancer is the third-most common cause of cancer deaths in the United States, and advanced colorectal polyps are a major risk factor. Although there are no large-scale individual trials designed a priori to test the hypothesis, in meta-analyses of trials in primary prevention of cardiovascular disease, aspirin reduces risk of colorectal cancer. The US Preventive Services Task Force used a microsimulation model, including baseline risk factors, and concluded that aspirin reduces risk of colorectal cancer by 40%. Their guidelines suggest that without a specific contraindication, clinicians should routinely prescribe aspirin to patients with advanced colorectal polyps. METHODS: Written informed consent was obtained, and brief telephone interviews were conducted by trained interviewers for 84 men and women with biopsy-proven advanced colorectal polyps from 55 clinical practices. RESULTS: Of the 84, 39 (46.4%) were men. The mean age was 66 with a range from 41 to 91 years. Among the 84, 36 (42.9%) reported taking aspirin. CONCLUSIONS: These data suggest underutilization of aspirin by patients with advanced colorectal polyps. These data pose major challenges that require multifactorial approaches by clinicians and their patients, which include therapeutic lifestyle changes, adjunctive drug therapies, and screening. Lifestyle changes include treating overweight status and obesity and engaging in regular physical activity; adjunctive drug therapies include aspirin. These multifactorial approaches will be necessary to achieve the most good for the most patients with regard to prevention, as well as, early diagnosis and treatment of colorectal cancer in patients with advanced colorectal polyps.

Dysbiosis-Associated Polyposis of the Colon-Cap Polyposis.

Cap polyposis is a rare gastrointestinal disease characterized by multiple inflammatory polyps located between the distal colon and the rectum. Despite the lack of clarity regarding its pathogenesis, mucosal prolapse, chronic inflammatory responses, and Helicobacter pylori infection are considered key contributors to the development of this disease entity. Although it is now generally accepted that dysbiosis of gut microbiota is associated with intestinal and extra-intestinal diseases, alterations of intestinal microbiota have been poorly defined in cap polyposis. Here, we report a patient with H. pylori-negative cap polyposis who was successfully treated with antibiotics and exhibited dramatic alterations in intestinal microbiota composition after antibiotic treatment. The patient was treated with oral administration of ampicillin and metronidazole and showed regression of cap polyposis 6 months after antibiotic treatment. Fecal microbiota analysis using the next-generation sequencing technology revealed a significant alteration in the intestinal microbiota composition following antibiotic treatment-a marked reduction of Blautia, Dorea, and Sutterella was observed concomitant with a marked increase in Fusobacterium. These data suggest that cap polyposis may originate from dysbiosis and that microbiome-targeted therapy may be useful in this disorder.

Combination Chlorambucil/Firocoxib or Chlorambucil/Prednisolone Treatment for Inflammatory Colorectal Polyps in Miniature Dachshunds.

Inflammatory colorectal polyps (ICRP), which are more commonly recognized in miniature dachshunds, are thought to represent an immune-mediated disease. This retrospective case series describes six miniature dachshunds with refractory ICRP, who were treated with chlorambucil (CLB) combined with firocoxib or prednisolone. Improvement in clinical manifestations was seen in five of the six dogs by the end of the study period; four were treated with CLB/firocoxib and one with CLB/prednisolone. One dog had nonregenerative anemia after 23 mo of treatment with CLB, but whether there was a causative relationship was unclear. No severe adverse events were observed during treatment in the remaining five dogs. CLB in combination with firocoxib or prednisolone appears to be an effective alternative treatment for ICRP in dogs. Further studies are needed to confirm the effectiveness and long-term complications of CLB treatment for ICRP in dogs.