Systemic and tumor level iron regulation in men with colorectal cancer: a case control study

BACKGROUND: Increased cellular iron exposure is associated with colorectal cancer (CRC) risk. Hepcidin, a liver peptide hormone, acts as the primary regulator of systemic iron status by blocking iron release from enterocytes into plasma. Concentrations are decreased during low iron status and increased during inflammation. The role of hepcidin and the factors influencing its regulation in CRC remains largely unknown. This study explored systemic and tumor level iron regulation in men with CRC. METHODS: The participants were 20 CRC cases and 20 healthy control subjects. Colonic tissue (adenocarcinoma [cases] healthy mucosa [controls]) was subjected to quantitative PCR (hepcidin, iron transporters and IL-6) and Perls’ iron staining. Serum was analyzed using ELISA for hepcidin, iron status (sTfR) and inflammatory markers (CRP, IL-6, TNF-α). Anthropometrics, dietary iron intake and medical history were obtained. RESULTS: Cases and controls were similar in demographics, medication use and dietary iron intake. Systemically, cases compared to controls had lower iron status (sTfR: 21.6 vs 11.8 nmol/L, p < 0.05) and higher marker of inflammation (CRP: 8.3 vs 3.4 μg/mL, p < 0.05). Serum hepcidin was mildly decreased in cases compared to controls; however, it was within the normal range for both groups. Within colonic tissue, 30% of cases (6/20) presented iron accumulation compared to 5% of controls (1/20) (χ(2) = 5.0; p < 0.05) and higher marker of inflammation (IL-6: 9.4-fold higher compared to controls, p < 0.05). Presence of adenocarcinoma iron accumulation was associated with higher serum hepcidin (iron accumulation group 80.8 vs iron absence group 22.0 ng/mL, p < 0.05). CONCLUSIONS: While CRC subjects had serum hepcidin concentrations in the normal range, it was higher given their degree of iron restriction. Inappropriately elevated serum hepcidin may reduce duodenal iron absorption and further increase colonic adenocarcinoma iron exposure. Future clinical studies need to assess the appropriateness of dietary iron intake or iron supplementation in patients with CRC

Clinical Presentation of Acute Gastroenteritis in Children With Functional Abdominal Pain Disorders

Visceral hypersensitivity and abnormal coping are common in children with functional abdominal pain disorders (FAPDs). Thus, it would be expected that children with visceral hypersensitivity would report more pain if their gut is acutely inflamed. The aim of the study was to compare clinical symptoms and somatization of children with and without FAPDs at time of an episode of acute gastroenteritis. Seventy children with acute gastroenteritis and their parents completed the Rome III Diagnostic Questionnaire for Pediatric Functional GI Disorders and the Children's Somatization Inventory. Twenty-one percent of children were diagnosed with an FAPD. Children with FAPDs showed significantly more nongastrointestinal somatic symptoms than children without FAPDs. There were no significant differences in abdominal pain, nausea, vomiting, or school absenteeism between both groups at time of consultation

A comprehensive review of randomized placebo-controlled pharmacological clinical trials in children with functional abdominal pain disorders

OBJECTIVES: Abdominal pain-predominant functional gastrointestinal disorders (AP-FGIDs) are the most common cause of consultation to pediatric gastroenterology; however, no medications have been approved to treat this group of disorders in children. The Food and Drug Administration have published recommendations for clinical trials on AP-FGIDs in adults but not in children. The lack of methodological guidelines and accepted primary endpoints for clinical trials in children hampers the progress of the field, making the approval of new medications difficult. A necessary first step to determine the feasibility of clinical trials in children and provide recommendations on the best design for future trials is to review the methods, ability to recruit, attrition rate, and results of previous clinical trials. We designed a comprehensive review of pharmacological clinical trials in AP-FGIDs in children focused on study design. METHODS: Study eligibility was randomized controlled trials (RCTs) evaluating the efficacy of pharmacological interventions compared with that of placebo in children and adolescents with AP-FGIDs. RESULTS: There is no evidence to support the use of most commonly used drugs in children. Only 7 pharmacological RCTs on AP-FGIDs in children were found. Most studies were single center based and had a small sample size. The methods and outcomes were heterogeneous. Primary endpoints varied widely among studies. Many of the RCTs did not show a consistently significant benefit of the drug over placebo in some or all of the outcomes. We found a considerable risk of bias in most studies. None of the studies have considered minimal clinically important differences in their selection of primary endpoints. CONCLUSIONS: Few randomized clinical trials have been conducted. Most studies have methodological limitations and small sample size. There is an urgent need for well-designed randomized clinical trials using age-appropriate validated outcome measures

Construct validity of the pediatric Rome III criteria

Functional gastrointestinal disorders (FGIDs) are common. The diagnosis of FGIDs is based on the Rome criteria, a symptom-based diagnostic classification established by expert consensus. There is little evidence of validity for the pediatric Rome III criteria. The construct validity of the criteria, an overarching term that incorporates other forms of validity, has never been assessed. We assessed the construct validity of the Rome III criteria. Children from 2 schools in Colombia completed the Questionnaire on Pediatric Gastrointestinal Symptoms at baseline and weekly questionnaires of somatic symptoms and disability for 8 weeks (presence and intensity of gastrointestinal symptoms, nongastrointestinal symptoms, impact on daily activities). A total of 255 children completed at least 6 weekly surveys (2041 surveys). At baseline, 27.8% children were diagnosed as having an FGID. Prevalence of nausea (Δ 7.8%, 95% confidence interval [CI] 4.46-11.14), constipation (Δ 4.39%, 95% CI 1.79-6.99), diarrhea (Δ 6.69%, 95% CI 3.25-10.13), headache (Δ 7.4%, 95% CI 3.51-11.09), chest pain (Δ 9.04%, 95% CI 5.20-12.88), and limb pain (Δ 4.07%, 95% CI 1.76-6.37) and intensity of nausea (Δ 0.23, 95% CI 0.127-0.333), diarrhea (Δ 0.30, 95% CI 0.211-0.389), abdominal pain (Δ 0.18, 95% CI 0.069-0.291), headache (Δ 0.17, 95% CI 0.091-0.249), and limb pain (Δ 0.30, 95% CI 0.084-0.516) were higher in children with FGIDs (P < 0.001). Children with FGIDs had greater interference with daily activities (P < 0.001). Children with a Rome III diagnosis had significantly more gastrointestinal and nongastrointestinal complaints, and greater intensity of symptoms and disability than children without an FGID diagnosis. The study suggests that the Rome III pediatric criteria have adequate construct validit

Systemic and tumor level iron regulation in men with colorectal cancer: a case control study.

BackgroundIncreased cellular iron exposure is associated with colorectal cancer (CRC) risk. Hepcidin, a liver peptide hormone, acts as the primary regulator of systemic iron status by blocking iron release from enterocytes into plasma. Concentrations are decreased during low iron status and increased during inflammation. The role of hepcidin and the factors influencing its regulation in CRC remains largely unknown. This study explored systemic and tumor level iron regulation in men with CRC.MethodsThe participants were 20 CRC cases and 20 healthy control subjects. Colonic tissue (adenocarcinoma [cases] healthy mucosa [controls]) was subjected to quantitative PCR (hepcidin, iron transporters and IL-6) and Perls' iron staining. Serum was analyzed using ELISA for hepcidin, iron status (sTfR) and inflammatory markers (CRP, IL-6, TNF-α). Anthropometrics, dietary iron intake and medical history were obtained.ResultsCases and controls were similar in demographics, medication use and dietary iron intake. Systemically, cases compared to controls had lower iron status (sTfR: 21.6 vs 11.8&nbsp;nmol/L, p &lt; 0.05) and higher marker of inflammation (CRP: 8.3 vs 3.4&nbsp;μg/mL, p &lt; 0.05). Serum hepcidin was mildly decreased in cases compared to controls; however, it was within the normal range for both groups. Within colonic tissue, 30% of cases (6/20) presented iron accumulation compared to 5% of controls (1/20) (χ(2) = 5.0; p &lt; 0.05) and higher marker of inflammation (IL-6: 9.4-fold higher compared to controls, p &lt; 0.05). Presence of adenocarcinoma iron accumulation was associated with higher serum hepcidin (iron accumulation group 80.8 vs iron absence group 22.0&nbsp;ng/mL, p &lt; 0.05).ConclusionsWhile CRC subjects had serum hepcidin concentrations in the normal range, it was higher given their degree of iron restriction. Inappropriately elevated serum hepcidin may reduce duodenal iron absorption and further increase colonic adenocarcinoma iron exposure. Future clinical studies need to assess the appropriateness of dietary iron intake or iron supplementation in patients with CRC