Serum Selenium Concentration as a Potential Diagnostic Marker for Early-Stage Colorectal Cancer: A Comparative Study.

BACKGROUND Selenium deficiency is an established risk factor for colorectal cancer. The aim of the present study was to determine selenium levels in blood samples obtained from colorectal cancer patients compared with the levels of this element in the blood of patients who had undergone hernia repair and cholecystectomy. MATERIAL AND METHODS The study group consisted of 49 patients diagnosed with colorectal cancer at our institution. The comparison group consisted of 29 and 26 patients undergoing hernia repair and cholecystectomy, respectively. The histological staging level was evaluated on a 4-grade scale. Serum selenium concentration was quantified by inductively coupled mass spectrometry using methane to reduce polyatomic interference. RESULTS Colorectal cancer patients had significantly lower serum selenium concentration than the comparison patients (67.24±15.55 µg/L vs 78.81±12.93 µg/L; P<0.001), and selenium concentration was below the reference range in a high percentage of colorectal cancer patients. However, among the colorectal cancer patients, no significant difference in cancer grading was observed according to selenium concentration (P=0.235). Serum selenium concentration in the patients was evaluated on the basis of 5 independent variables (R=0.6250): age (P=0.011), number of leukocytes (P=0.010), family history of cancer (P=0.045), dietary supplements (P=0.023), and exposure to chemical factors (P=0.057). CONCLUSIONS This study supports findings from previous studies that low serum selenium levels are associated with colorectal cancer and that selenium deficiency may be a risk factor for colorectal cancer.

Surgical removal of Aquafilling localized to different sites.

<b><br>Introduction:</b> Aquafilling, a widely used soft-tissue filler since 2005, shows multiple adverse effects, necessitating the development of effective methods for its removal. We present a surgical method for removal of Aquafilling present in the breasts, breasts with migration to the chest and/or the abdomen, and the buttocks, and elaborate and discuss the advantages of this method.</br> <b><br>Aim:</b> The aim of this study was to present a surgical method for removal of Aquafilling (soft-tissue filler) present in the breasts, breasts with migration to the chest and/or the abdomen, and the buttocks, and to elaborate the advantages of this proposed technique.</br> <b><br>Materials and methods:</b> The surgical Aquafilling removal method described here was used in 25 patients (age, 21-53 years). The technique was used to remove Aquafilling present in the breasts (14 patients), breasts with migration to the chest and/or the abdomen (7 patients), and the buttocks (3 patients). The detailed course of Aquafilling removal surgery and postoperative treatment for these three types of cases is described.</br> <b><br>Results:</b> Surgical removal of Aquafilling with the described method did not cause any of the previously described ailments in each patient, excluding one patient who only showed significant pain reduction in both breasts preceding each menstruation cycle.</br> <b><br>Conclusions:</b> The method described herein can be recommended for removal of Aquafilling present in the breasts, breasts with migration to the chest and/or the abdomen, and buttocks, since it allowed thorough Aquafilling removal and decreased the local inflammatory state and the risk of potential carcinogenesis.</br>.

Evaluation of CD10 expression as a diagnostic marker for colorectal cancer.

Aim: We aimed to determine the potential of CD10 as a marker for the early diagnosis of adenocarcinoma of the colon. Background: Adenocarcinoma is diagnosed in one out of 20 individuals in the USA and western European countries. Its prognosis and treatment depend largely on the severity of the disease at the time of diagnosis. Additional new biological markers are being sought that can help diagnose colon cancer at an early stage. One such marker present in both serum and tumor tissue is CD10. Methods: CD10 concentrations were tested by ELISA and immunohistochemistry in serum and tissue samples, respectively, from 113 patients diagnosed histopathologically and treated for adenocarcinoma of the colon. Additionally, the ROC curve with optimal cut-off point based on Youden's criterion was calculated for CD10. Results: Serum concentrations of CD10 and its tissue expression in patients diagnosed with adenocarcinoma of the colon correlate with cancer staging based on the Astler-Coller-Dukes classification. To ascertain the optimal cut-off point for CD10 as a predictor of belonging to the study group, ROC curve was prepared for CD10. Optimal cut-off point for CD10 was 0.57, with prediction of belonging to the study group for CD10 ≥ 0.57. Conclusion: CD10 can be a useful marker in the early diagnosis of adenocarcinoma of the colon.

Crohn's Disease Susceptibility and Onset Are Strongly Related to Three NOD2 Gene Haplotypes.

The genetic background and the determinants influencing the disease form, course, and onset of inflammatory bowel disease (IBD) remain unresolved. We aimed to determine the NOD2 gene haplotypes and their relationship with IBD occurrence, clinical presentation, and onset, analyzing a cohort of 578 patients with IBD, including children, and 888 controls. Imaging or endoscopy with a histopathological confirmation was used to diagnose IBD. Genotyping was performed to assess the differences in genotypic and allelic frequencies. Linkage disequilibrium was analyzed, and associations between haplotypes and clinical data were evaluated. We emphasized the prevalence of risk alleles in all analyzed loci in patients with Crohn disease (CD). Interestingly, c.2722G>C and c.3019_3020insC alleles were also overrepresented in ulcerative colitis (UC). T-C-G-C-insC, T-C-G-T-insC, and T-T-G-T-wt haplotypes were correlated with the late-onset form of CD (OR = 23.01, 5.09, and 17.71, respectively), while T-T-G-T-wt and C-C-G-T-wt were prevalent only in CD children (OR = 29.36, and 12.93, respectively; p-value = 0.001). In conclusion, the presence of c.3019_3020insC along with c.802C>T occurred as the most fundamental contributing diplotype in late-onset CD form, while in CD children, the mutual allele in all predisposing haplotypes was the c.2798 + 158T. Identifying the unique, high-impact haplotypes supports further studies of the NOD2 gene, including haplotypic backgrounds.

Multifocal colorectal cancer in ulcerative colitis patient with sclerosing cholangitis - case report.

<b>Introduction:</b> U lcerative colitis (CU) is an inflammatory disease predisposing to colorectal cancer. Colorectal cancer in ulcerative colitis is more often metachronous or synchronous. <br><b>Case report:</b> In this case report we present a patient with multifocal colorectal cancer in the course of CU and operative treatment that was implemented. Additionallyprimary sclerosing cholangitis was diagnosed in this patient post-operatively.

MicroRNA regulation in colorectal cancer tissue and serum.

Colorectal cancer is recognized as the fourth leading cause of cancer-related deaths worldwide. Thus, there is ongoing search for potential new biomarkers allowing quicker and less invasive detection of the disease and prediction of the treatment outcome. Therefore, the aim of our study was to identify colorectal cancer specific miRNAs expressed in cancerous and healthy tissue from the same patient and to further correlate the presence of the same miRNAs in the circulation as potential biomarkers for diagnosis. In the current study we detected a set of 40 miRNAs differentially regulated in tumor tissue when comparing with healthy tissue. Additionally, we found 8 miRNAs differentially regulated in serum of colorectal cancer patients. Interestingly, there was no overlap in miRNAs regulated in tissue and serum, suggesting that serum regulated miRNAs may be not actively secreted from colorectal tumor cells. However, four of differentially expressed miRNAs, including miR-21, miR-17, miR-20a and miR-32 represent the miRNAs characteristic for different tumor types, including breast, colon, lung, pancreas, prostate and stomach cancer. This finding suggests important groups of miRNAs which can be further validated as markers for diagnosis of tumor tissue and regulation of carcinogenesis.

The relationship between the symptom of fatigue and the functioning of patients with inflammatory bowel diseases after surgery.

INTRODUCTION: The occurrence of fatigue in patients suffering from inflammatory bowel diseases (IBD) is influenced by pain, frequent bowel movements, stress associated with symptoms and time of their occurrence reaction of surroundings, fear for their own health, sleep disturbances, side effects of pharmacological treatment, physical and mental exhaustion, hindered social contacts and difficulties at work. AIM: To evaluate the fatigue and the assessment of functioning of patients with IBD, who were treated surgically. MATERIAL AND METHODS: To evaluate the functioning of patients, a Polish version of the Inflammatory Bowel Disease Questionnaire was used. To evaluate the occurrence of fatigue in studied subjects, a Polish version of the Functional Assessment of Chronic Illness Therapy - Fatigue Scale was used. The activity of disease was evaluated with the use of the Crohn's Disease Activity Index for patients with Crohn's disease (CD) and the Clinical Activity Index for patients with ulcerative colitis (UC). RESULTS: Before surgery, there was no significant difference between CD and UC patients, with regard to the mean FACIT-F (28.76 for CD and 28.76 for UC, p = 0.72). Also, after surgery, there was no significant difference between CD and UC patients, with regard to the mean FACIT-F (14.8 for CD and 16.0 for UC, p = 0.71). The IBD patients who underwent surgery for CD and UC had significantly lower FACIT-F scores compared to the patients before the surgery (p = 0.001 and p = 0.0001, respectively). IBD patients who underwent surgery for CD and UC had significantly better functioning and higher IBDQ total scores compared to the patients before the surgery. CONCLUSIONS: Surgical treatment significantly reduces the fatigue symptom in patients with IBD. The severity of fatigue correlates with disease activity and functioning in the respective areas.

The influence of rifaximin on diverticulitis rate and quality of life in patients with diverticulosis.

Diverticulosis, its associated symptoms and complications are one of the most common pathologies of the gastrointestinal tract in more economically developed countries. Presence of diverticuli and their clinical consequences can be divided into four categories: 1) diverticulosis, i.e. an asymptomatic presence of diverticuli that are usually found by accident 2) symptomatic uncomplicated diverticulosis 3) diverticulitis (acute uncomplicated diverticulitis) 4) complications of diverticulitis (conditions requiring hospital stay). The aim of this study was to retrospectively analyze the efficacy of rifaximin in preventing diverticulitis in patients visiting proctology clinics. The diagnostic criterium for diverticulosis was confirmation by colonoscopy, barium enema or CT colography (virtual colonoscopy) as well as history of at least one documented episode of diverticulosis. History of diverticulosis was evaluated based on medical records, clinical symptoms, elevated level of CRP (>5.0) and/or diagnostic imaging (ultrasound, CT). After setting strict exclusion criteria, 248 patients were qualified for the study out of 686, and they were later divided into two groups: control group (group I - 145 patients) and studied group (group II - 103 patients receiving rifaximin prophylaxis). Diverticulitis rate was comparable in both groups over a period of 6 months before study (p = 0.1306) and 6 months of treatment (p=0.3044). Between the 6th and 12th month of treatment, a significantly lower rate of diverticulitis was noted in the group receiving rifaximin compared to control group (p<0.0001). Patients receiving rifaximin reported higher quality of life (which was assessed using the VAS scale) compared to control group after 12 months. The results confirmed the efficacy of riaximin in prevention of diverticulitis, even in the scheme of repeated courses every 3 months. Not only did application of rifaximin lower the rate of diverticulitis and its complications in patients after an episode of diverticulitis, but also it improved the patients' quality of life. It seems that diverticulitis prophylaxis based on rifaximin can be economically efficient, however, it requires further research.

Health-related quality of life assessment among patients with inflammatory bowel diseases after surgery - review.

Aim of the work was to review systematically the published literature addressing whether quality of life (QoL) and health-related QoL (HRQoL) are influenced by surgery among patients with inflammatory bowel disease (IBD). Electronic databases and published articles were searched to identify relevant studies published in the years 1990-2015. Then, a multistep selection was undertaken to identify articles that met specific selection criteria, such us specific key-words (IBD, HRQoL, ulcerative colitis (UC), Crohn's disease (CD), and surgery), and the population was assessed (studies concerning patients < 18 years old were excluded). The review included 27 studies that were evaluated in the context of the influence of surgery on QoL and HRQoL. Concluding, with the increase in the incidence of IBD, monitoring of QoL is an important indicator of the health effects at each stage of the surgical treatment.

Checklist in colorectal surgery - proposal of experts of the Polish Club of Coloproctology and National Consultant in general surgery.

A checklist is a collection of information that helps reduce the risk of failure due to limitations in human memory and attention. In surgery, the first Surgical Safety Checklist (SSC), created under the supervision of WHO (World Health Organization), was established in 2007 and covers three stages related to the patient's stay in the operating theater and operation: 1. Prior to initiation (induction) of anesthesia; 2. before cutting the skin; 3. before the patient leaves the operating room Colorectal surgery is particularly at high risk for complications and relatively high mortality. Elimination or, more likely, reducing the risk of complications by standardizing perioperative procedures may be particularly important in this group. The introduction of "dedicated" colorectal checklist surgery seems to be justified. The checklist proposed by the authors in colorectal surgery is divided into four stages, in which conscientious completion of checklists is intended to reduce the potential risk of complications due to hospitalization and surgical treatment. The presented checklist is obviously not closed, as a new publications or recommendations appear, some points may be modified, new issues may be added to the checklist. At present, however, it is a tool considering the well-known and confirmed elements of intraoperative procedures, the compliance of which may significantly reduce the rate of adverse events or surgical complications.

Significance of intratissue estrogen concentration coupled with estrogen receptors levels in colorectal cancer prognosis.

Dysregulation of estrogen related pathways is implicated colorectal cancer (CRC) development. However, significance of intratissue concentration of estrone (E1) and 17ß-estradiol (E2) in relation to estrogen receptor (ESR) expression level was not addressed so far. Herein, we measured E1 and E2 intratissue concentration using liquid chromatography electrospray ionization tandem mass spectrometry (ESI LC/MS) and mRNA levels of ESR1 and ESR2 using RT-qPCR in cancerous and histopathologically unchanged tissue from 75 and 110 CRC patients, respectively. The obtained results were associated with clinicopathological factors, expression of estrogen dependent genes (CTNNB1, CCND1) and prognostic significance. We found no statistically significant differences in E1 or E2 concentration between cancerous tissue and histopathologically unchanged counterparts. Moreover, mRNA levels of ESR1 and ESR2 were significantly decreased in cancerous tissue compared with histopathologically unchanged (p=0.00001). Log rank analysis revealed no benefit of low E1 to E2 ratio, high E1, E2 concentration or ESR1, ESR2 mRNA level for patients' overall (OS) and disease free survival (DFS). Interestingly, we have observed that patients with low ESR1 mRNA level coupled with low E1 intratissue concentration had a significant decrease in DFS compared with group of patients with high ESR1 mRNA level and high E1 concentration (HR=0.16, 95% CI 0.02-1.05; p=0.06). Furthermore, patients with low E1 concentration and low ESR1 transcript had significantly higher CTNNB1 and CCND1 mRNA level compare with subgroup with high level of both grouping factors. Our study indicates a potential value of estrogen intratissue concentration and its receptor expression level for CRC patients' prognosis.

Effect of DNA methylation profile on OATP3A1 and OATP4A1 transcript levels in colorectal cancer.

Epidemiological studies indicate that 17ß-estradiol (E2) prevents colorectal cancer (CRC). Organic anion transporting polypeptides (OATPs) are involved in the cellular uptake of various endogenous and exogenous substrates, including hormone conjugates. Because transfer of estrone sulfate (E1-S) can contribute to intra-tissue conversion of estrone to the biologically active form -E2, it is evident that the expression patterns of OATPs may be relevant to the analysis of CRC incidence and therapy. We therefore evaluated DNA methylation and transcript levels of two members of the OATP family, OATP3A1 and OATP4A1, that may be involved in E1-S transport in colorectal cancer patients. We detected a significant reduction in OATP3A1 and a significant increase in OATP4A1 mRNA levels in cancerous tissue, compared with histopathologically unchanged tissue (n=103). Moreover, we observed DNA hypermethylation in the OATP3A1 promoter region in a small subset of CRC patients and in HCT116 and Caco-2 colorectal cancer cell lines. We also observed increased OATP3A1 transcript following treatment with 5-aza-2-deoxycytidine and sodium butyrate. The OATP4A1 promoter region was hypomethylated in analyzed tissues and CRC cell lines and was not affected by these treatments. Our results suggest a potential mechanism for OATP3A1 downregulation that involves DNA methylation during colorectal carcinogenesis.

Familial Adenomatous Polyposis; 30-Year Observation of a Female Patient - Case Report.

Familial adenomatous polyposis (FAP) is a colorectal cancer syndrome caused by a germline mutation inherited in an autosomal-dominant pattern with a 100% penetrance. Our detailed case report presents a history of a 55-year-old FAP female patient who had been under constant clinical observation for 30 years. The disease was diagnosed at the age of 22. The patient underwent restorative proctocolectomy with ileal pouch-anal anastomosis (PRC-IPAA). During our follow-up extra-colonic manifestations occurred such as a desmoidtumour, fundic gland polyps in the stomach and duodenal polyps also in the periampullary region. Apart from disease-related symptoms the patient manifested other complications such as small bowel adhesive obstruction, benign breast tumours, uterine myomas, cholelithiasisand thyroid nodules. Our analysis of the above case presents advantages of a long-term medical observation of a FAP patient carried out by a specialist surgical medical centre.

Transcriptional changes between uninflamed ulcerative colitis and familial adenomatous polyposis pouch mucosa can be attributed to an altered immune response.

A total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is considered the surgery of choice for definitive management of familial adenomatous polyposis (FAP) and some patients with ulcerative colitis (UC). However, this surgical treatment is often associated with pouchitis, a long-term complication that occurs mostly in UC patients. The purpose of this study was to better define the molecular background of pouchitis. A microarray-based survey was performed using pouch mucosal samples collected from 28 and 8 patients undergoing surgery for UC and FAP, respectively. There were 4,770 genes that significantly differentiated uninflamed from inflamed mucosal samples, and their functional features were represented mostly by metabolic and cell proliferation pathways. In contrast, functional analyses of aberrantly expressed genes between UC and FAP samples, irrespective of mucosal inflammation status, revealed multiple pathways and terms that were linked to changes in immune response. Interestingly, the comparison of uninflamed UC and FAP samples identified a set of 29 altered probe sets, including an inflammation-related transcript encoding a Charcot-Leyden crystal (CLC) protein. The most distinct changes in gene expression profiles differentiating uninflamed UC and FAP pouch mucosal samples were attributed to the Gene Ontology category innate immune response. Our study confirmed that alterations in immune responses can be found between patients who underwent surgery for UC and FAP, independent of the pouch inflammation status. This observation may be important when managing IPAA patients.

Clinical significance of DNA methylation mRNA levels of TET family members in colorectal cancer.

PURPOSE: Ten eleven translocation (TET) enzyme activity is essential for active DNA demethylation in biological processes, and their altered expression has been observed in various malignancies. Therefore, we investigated DNA methylation and mRNA levels of all TETs in colorectal cancer (CRC) patients. METHODS: TET mRNA levels were evaluated using quantitative RT-PCR in primary cancerous and histopathologically unchanged colorectal tissues from patients who underwent radical surgical colon resection (n = 113). DNA methylation levels of the TET CpG island were assessed using bisulfite DNA sequencing and high-resolution melting analysis. RESULTS: We found reduced transcript levels of TET1, TET2 and TET3 in cancerous tissue compared with their histopathologically unchanged counterparts (p = 0.000011; p = 0.000001; p = 0.00031, respectively). Importantly, multivariate Cox regression analysis revealed favorable overall survival (OS) and disease-free survival (DFS) outcomes for patients with high TET2 mRNA levels in histopathologically unchanged tissue (HR(OS) = 0.091, 95 % CI 0.011-0.77, p = 0.028; HR(DFS) = 0.21, 95 % CI 0.04-1.06, p = 0.059). Moreover, we found no DNA methylation in the TET2 and TET3 promoter regions in cancerous and histopathologically unchanged tissue. In contrast, we reported TET1 DNA hypermethylation in a small fraction of patients (n = 12/113). CONCLUSION: To best of our knowledge, our study is the first to investigate TET mRNA levels in a cohort of CRC patients and correlate them with patients' prognosis. Present study provides the evidence that TET2 mRNA expression may be an independent prognostic factor for disease recurrence and outcome. Additionally, our findings initially indicate the importance of DNA methylation in regulating TET1 expression.

Management of traveller's diarrhoea with a combination of sodium butyrate, organic acids, and A-300 silicon dioxide.

INTRODUCTION: Traveller's diarrhoea (TD), defined by UNICEF/WHO as three or more unformed stools with or without other symptoms, imposes a considerable burden on travellers from developed countries. Various efforts have focused on decreasing the prevalence and severity of this condition. AIM: To assess the efficacy of a combination of sodium butyrate, organic acids, and A-300 silicon dioxide in treatment providing symptomatic relief of TD. MATERIAL AND METHODS: The study was conducted in accordance with a protocol presented to the Bioethical committee of Poznan University of Medical Sciences. A total of 278 patients travelling to countries with higher risk of diarrhoea for at least 10 days were divided into a study arm being administered, in case of TD, a combination of sodium butyrate, organic acids, and A-300 silicon dioxide (n = 139) and a placebo arm (n = 139) with placebo administration. RESULTS: Forty-seven patients completed the study (22 in the study arm and 25 in the placebo arm). The diarrhoea occurrence after initiation of treatment at first symptoms was significantly lower in the study arm as compared to the placebo arm (9% vs. 36%, p = 0.041). Also, subjects from the study arm more frequently reported that the regimen administered had been efficient for their symptoms in comparison to the placebo arm (72.7% vs. 32%, p = 0.008). No adverse effects of the administered medication were noted during the study. CONCLUSIONS: Sodium butyrate, organic acids, and A-300 silicon dioxide can be successful in decreasing symptoms of TD. Because of its efficacy and lack of observed side effects it has a strong potential in the treatment of patients with TD.

Quality of life in patients with ulcerative colitis treated surgically.

INTRODUCTION: Ulcerative colitis belongs to the group of inflammatory bowel diseases. The specific symptoms and chronic nature of the disease significantly affect the quality of patients' lives. Quality-of-life assessment helps to define its determining factors as well as the efficiency of surgical procedures. AIM: Quality-of-life evaluation of patients with ulcerative colitis treated surgically. MATERIAL AND METHODS: A retrospective review was carried out on 35 patients with ulcerative colitis, who were treated surgically in the Clinic of General and Colorectal Surgery, University of Medical Sciences in Poznan. The research tools used to assess the quality of life consisted of: the Inflammatory Bowel Disease Questionnaire, a Polish version of the Short Form Health Survey-36, and a questionnaire. RESULTS: The mean of the IBDQ scale was 152.51, and the median was 161. In this scale, a higher score indicates better quality of life. The situation in the subjective SF-36 scale is reversed: a lower score indicates better quality of life. The mean of the SF-36 was 115.94, and the median was 58. Many discrepancies in the field (e.g. the influence of determining factors) create a niche for further studies. CONCLUSIONS: Moreover, quality-of-life evaluation may lead to better patient care, understanding their problems or treatment modifications, and finally may become a kind of therapy efficiency parameter.

Prognostic potential of DNA methylation and transcript levels of HIF1A and EPAS1 in colorectal cancer.

UNLABELLED: Hypoxic conditions during the formation of colorectal cancer may support the development of more aggressive tumors. Hypoxia-inducible factor (HIF) is a heterodimeric complex, composed of oxygen-induced HIFα and constitutively expressed HIFß subunits, which mediates the primary transcriptional response to hypoxic stress. Among HIFα isoforms, HIF1α (HIF1A) and endothelial PAS domain-containing protein 1 (EPAS1) are able to robustly activate hypoxia-responsive gene signatures. Although posttranslational regulation of HIFα subunits is well described, less is known about their transcriptional regulation. Here, molecular analysis determined that EPAS1 mRNA was significantly reduced in primary colonic adenocarcinoma specimens compared with histopathologically nonneoplastic tissue from 120 patients. In contrast, no difference in HIF1A mRNA levels was observed between cancerous and noncancerous tissue. Bisulfite DNA sequencing and high-resolution melting analysis identified significant DNA hypermethylation in the EPAS1 regulatory region from cancerous tissue compared with nonneoplastic tissue. Importantly, multivariate Cox regression analysis revealed a high HR for patients with cancer with low EPAS1 transcript levels (HR, 4.91; 95% confidence interval, CI, 0.42-56.15; P = 0.047) and hypermethylated EPAS1 DNA (HR, 33.94; 95% CI, 2.84-405.95; P = 0.0054). Treatment with a DNA methyltransferase inhibitor, 5-Aza-2'-deoxycytidine (5-aza-dC/Decitabine), upregulated EPAS1 expression in hypoxic colorectal cancer cells that were associated with DNA demethylation of the EPAS1 regulatory region. In summary, EPAS1 is transcriptionally regulated by DNA methylation in colorectal cancer. IMPLICATIONS: DNA methylation and mRNA status of EPAS1 have novel prognostic potential for colorectal cancer.