McCune Albright Syndrome: Gastrointestinal Polyps and Platelet Dysfunction over 12 Years.

BACKGROUND AND OBJECTIVE: Gastrointestinal (GI) polyps with unknown malignant potential and a platelet storage pool deficiency that increases the risk of severe intraoperative and other types of bleeding have been identified in McCune-Albright syndrome (MAS). The natural course of these disorders has not been well characterized. The aim of this study was to report the follow-up of GI polyps and platelet dysfunction (PD) in a cohort of 28 patients with MAS. METHODS: Twenty-eight patients with MAS (15 females) were included. Endoscopic screening for GI polyps was undertaken in 14 subjects and 19 were tested for PD. RESULTS: Six subjects (5 males) were diagnosed with GI polyps at a median age of 23 (range 15-43) years, and were monitored for a median period of 8 (range 4.5-11.5) years. At endoscopic follow-up, the 4 patients with hamartomatous polyps at first endoscopy had either normal findings (n = 2), or duodenal gastric metaplasia (n = 2). Two patients with caecal polyps were identified. Of 8 subjects with a platelet storage pool deficiency, 5 required transfusions during surgery, and subsequent platelet cover in 2 markedly reduced intraoperative blood loss. CONCLUSIONS: New polyps with uncertain malignant potential are diagnosed after long term follow-up in MAS. Platelet cover reduces the need for red blood cell transfusion during orthopaedic surgery and may be useful to reduce non-operative bleeding events. We recommend regular upper and lower endoscopy and screening for PD in all MAS patients.

Elevated serum triglyceride and low-density lipoprotein cholesterol promotes the formation of colorectal polyps.

BACKGROUND: Hyperlipidaemia may be a potential risk factor for the occurrence of intestinal polyps. This study aimed to evaluate correlation between lipidaemia and the formation of colorectal polyps. METHODS: One hundred and fourteen patients with colorectal polyps and forty-eight healthy controls were included in this study. Colonoscopies were performed for all patients and controls within 1 week before blood samples were taken. The concentrations of serum lipids and lipoproteins were measured simultaneously using an automatic biochemical analyser. The colorectal lesions were classified based on pathological characteristics, and four types were identified in the study: hyperplastic polyp (HP), tubular adenoma (TA), tubulovillous adenoma (TVA) and adenoma with high-grade dysplasia (A-HGD). Advanced adenoma was classified according to the number, size and histological type of polyps. RESULTS: The value of low-density lipoprotein cholesterol (LDL-C) was significantly higher in the group with advanced adenoma than in the controls (p < 0.05). Moreover, the LDL-C values in the HP and TA groups were higher when compared to that of controls (p < 0.05). Obesity, age, and increased TG and LDL-C were independent risk factors for the formation of colorectal polyps. The cut-off values of triglyceride (TG) and LDL-C to distinguish polyp patients from healthy controls were 0.96 mmol/L (AUC = 0.604, p = 0.036) and 3.05 mmol/L (AUC = 0.654, p = 0.002). The combined use of increased LDL-C and TG levels to distinguish polyp patients was effective, with a sensitivity of 50.0% and a specificity of 89.6% (AUC = 0.733, p < 0.01). CONCLUSIONS: Colorectal polyps are more often found in obese and older patients. Increased LDL-C and TG were correlated with the occurrence of polyps. Combination of the two serum indicators was useful to assess risk of colorectal lesions, maybe more effective in screening hyperplastic polyp, tubular adenoma and advanced adenoma.

Heart Failure Stimulates Tumor Growth by Circulating Factors.

BACKGROUND: Heart failure (HF) survival has improved, and nowadays, many patients with HF die of noncardiac causes, including cancer. Our aim was to investigate whether a causal relationship exists between HF and the development of cancer. METHODS: HF was induced by inflicting large anterior myocardial infarction in APCmin mice, which are prone to developing precancerous intestinal tumors, and tumor growth was measured. In addition, to rule out hemodynamic impairment, a heterotopic heart transplantation model was used in which an infarcted or sham-operated heart was transplanted into a recipient mouse while the native heart was left in situ. After 6 weeks, tumor number, volume, and proliferation were quantified. Candidate secreted proteins were selected because they were previously associated both with (colon) tumor growth and with myocardial production in post-myocardial infarction proteomic studies. Myocardial gene expression levels of these selected candidates were analyzed, as well as their proliferative effects on HT-29 (colon cancer) cells. We validated these candidates by measuring them in plasma of healthy subjects and patients with HF. Finally, we associated the relation between cardiac specific and inflammatory biomarkers and new-onset cancer in a large, prospective general population cohort. RESULTS: The presence of failing hearts, both native and heterotopically transplanted, resulted in significantly increased intestinal tumor load of 2.4-fold in APCmin mice (all P<0.0001). The severity of left ventricular dysfunction and fibrotic scar strongly correlated with tumor growth ( P=0.002 and P=0.016, respectively). We identified several proteins (including serpinA3 and A1, fibronectin, ceruloplasmin, and paraoxonase 1) that were elevated in human patients with chronic HF (n=101) compared with healthy subjects (n=180; P<0.001). Functionally, serpinA3 resulted in marked proliferation effects in human colon cancer (HT-29) cells, associated with Akt-S6 phosphorylation. Finally, elevated cardiac and inflammation biomarkers in apparently healthy humans (n=8319) were predictive of new-onset cancer (n=1124) independently of risk factors for cancer (age, smoking status, and body mass index). CONCLUSIONS: We demonstrate that the presence of HF is associated with enhanced tumor growth and that this is independent of hemodynamic impairment and could be caused by cardiac excreted factors. A diagnosis of HF may therefore be considered a risk factor for incident cancer.

Global and targeted serum metabolic profiling of colorectal cancer progression.

BACKGROUND: Patients with colorectal adenoma polyps (PLPs) are at higher risk for developing colorectal cancer (CRC). However, the development of improved and robust biomarkers to enable the screening, surveillance, and early detection of PLPs and CRC continues to be a challenge. The aim of this study was to identify biomarkers of progression to CRC through metabolomic profiling of human serum samples with a multistage approach. METHODS: Metabolomic profiling was conducted with the Metabolon platform for 30 CRC patients, 30 PLP patients, and 30 control subjects, and this was followed by the targeted validation of the top metabolites in an additional set of 50 CRC patients, 50 PLP patients, and 50 controls with liquid chromatography-tandem mass spectrometry. Unconditional multivariate logistic regression models, adjusted for covariates, were used to evaluate associations with PLP and CRC risk. RESULTS: For the discovery phase, 404 serum metabolites were detected, with 50 metabolites showing differential levels between CRC patients, PLP patients, and controls (P for trend < .05). After validation, the 3 top metabolites (xanthine, hypoxanthine, and d-mannose) were validated: lower levels of xanthine and hypoxanthine and higher levels of d-mannose were found in PLP and CRC cases versus controls. A further exploratory analysis of metabolic pathways revealed key roles for the urea cycle and caffeine metabolism associated with PLP and CRC risk. In addition, a joint effect of the top metabolites with smoking and a significant interaction with the body mass index were observed. An analysis of the ratio of hypoxanthine levels to xanthine levels indicated an association with CRC progression. CONCLUSIONS: These results suggest the potential utility of circulating metabolites as novel biomarkers for the early detection of CRC. Cancer 2017;123:4066-74. © 2017 American Cancer Society.

[Expression and significance of serum microRNA-135a-5p level in colorectal cancer].

Objective: To explore the expression level of serum miR135a-5p and its diagnostic value in colorectal cancer (CRC). Methods: Serum samples were randomly collected from 60 primary CRC patients, 40 patients with intestinal polyps and 50 healthy controls, and the serum concentrations of miR135a-5p, CEA and CA199 were detected. The relationships between serum miR135a-5p level and clinicopathological parameters were analyzed by Mann-Whitney U test. The correlation of serum miR135a-5p level and serum concentrations of CEA or CA199 was analyzed by Pearson's correlation test.Receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to evaluate the diagnostic efficacy of miR135a-5p, CEA and CA199 as diagnostic indicators. Results: The serum level of miR135a-5p in CRC patient was 2.451 (1.107, 4.413), significantly higher than 0.946 (0.401, 1.942) in the patients with intestinal polyps and 0.949 (0.194, 1.415) in the healthy controls (U = 351.0 and U = 313.0, respectively, P<0.001). The serum level of miR135a-5p in CRC patients was associated with both histological differentiation and clinical stage (P<0.05 for both), however, not correlated with the serum concentration of CEA (r2 = 0.023, P = 0.293) or CA199 (r2 = 0.067, P = 0.068). The AUC of serum miR135a-5p level in CRC patients was 0.832 (0.730-0.930) when compared to the patients with intestinal polyps and was 0.875 (0.800-0.950) when compared with the healthy controls. Conclusions: The serum level of miR135a-5p in CRC patients is significantly higher than that in patients with intestinal polyps and healthy controls, and might be an important diagnostic marker of CRC.

Treatment with anti-interleukin-6 receptor antibody ameliorates intestinal polyposis in Apc(Min/+) mice under high-fat diet conditions.

The prevalence of colorectal malignancies is increasing in the world. The parallel increase of metabolic syndrome gives a speculation between these two conditions, although the precise mechanism is still unclear. Interleukin-6 (IL-6) is a cytokine known to correlate with obesity and serve as a proinflammatory adipokine. In the present study, we investigated the effect of IL-6 signaling blockade on intestinal polyp formation in obesity using a mouse model of adenomatous polyposis coli (Apc). Male C57BL/6J-Apc(Min/+) mice were fed a high-fat diet from 5 weeks of age, and the overweight mice thus obtained were given a weekly intraperitoneal injection of anti-mouse IL-6 receptor antibody (MR16-1) from 6 to 15 weeks of age, while control mice received IgG or phosphate-buffered saline (PBS). The total number of intestinal polyps was significantly decreased in the MR16-1-injected group (53.1 ± 6.8) relative to the control groups (PBS-injected, 81.3 ± 6.1; rat IgG-injected, 74.7 ± 4.8, p = 0.01), and in particular the number of polyps larger than 2 mm in diameter was markedly decreased. In addition, the mean diameter of polyps in the MR16-1-injected group was significantly smaller than that in the control groups. On the other hand, no significant differences in body weight, epididymal fat pad mass, or the plasma levels of glucose, insulin and triglyceride were observed among the three groups. Thus, treatment with anti-IL-6 receptor antibody suppressed polyp growth in obese Apc(Min/+) mice fed the high-fat diet. We suggest that IL-6 signaling may be responsible for the obesity-associated colorectal tumorigenesis.

Metabolomics of ApcMin/+ mice genetically susceptible to intestinal cancer.

BACKGROUND: To determine how diets high in saturated fat could increase polyp formation in the mouse model of intestinal neoplasia, ApcMin/+, we conducted large-scale metabolome analysis and association study of colon and small intestine polyp formation from plasma and liver samples of ApcMin/+ vs. wild-type littermates, kept on low vs. high-fat diet. Label-free mass spectrometry was used to quantify untargeted plasma and acyl-CoA liver compounds, respectively. Differences in contrasts of interest were analyzed statistically by unsupervised and supervised modeling approaches, namely Principal Component Analysis and Linear Model of analysis of variance. Correlation between plasma metabolite concentrations and polyp numbers was analyzed with a zero-inflated Generalized Linear Model. RESULTS: Plasma metabolome in parallel to promotion of tumor development comprises a clearly distinct profile in ApcMin/+ mice vs. wild type littermates, which is further altered by high-fat diet. Further, functional metabolomics pathway and network analyses in ApcMin/+ mice on high-fat diet revealed associations between polyp formation and plasma metabolic compounds including those involved in amino-acids metabolism as well as nicotinamide and hippuric acid metabolic pathways. Finally, we also show changes in liver acyl-CoA profiles, which may result from a combination of ApcMin/+-mediated tumor progression and high fat diet. The biological significance of these findings is discussed in the context of intestinal cancer progression. CONCLUSIONS: These studies show that high-throughput metabolomics combined with appropriate statistical modeling and large scale functional approaches can be used to monitor and infer changes and interactions in the metabolome and genome of the host under controlled experimental conditions. Further these studies demonstrate the impact of diet on metabolic pathways and its relation to intestinal cancer progression. Based on our results, metabolic signatures and metabolic pathways of polyposis and intestinal carcinoma have been identified, which may serve as useful targets for the development of therapeutic interventions.

Real-time polymerase chain reaction quantification of free DNA in serum of patients with polyps and colorectal cancers.

BACKGROUND: Colorectal cancer (CRC) is one of the most frequent causes of cancer related deaths worldwide. Recently, the use of cell-free DNA as diagnostic tools to identify cancer has been investigated. The aim of this work was to assess whether circulating DNA could be considered a useful marker for detection of early stage CRC and polyps. METHODS: A total of 118 patients with CRC were included in the study along with 49 patients with colorectal polyps and 26 control subjects. Cell-free DNA was quantified using a real-time TaqMan-polymerase chain reaction assay. Non-parametric tests (Mann-Whitney test and Spearman correlation) were utilized for statistical analysis. RESULTS: Serum DNA concentrations were significantly higher in CRC patients and patients with polyps (median value 105.0 ng/mL and 40.0 ng/mL) compared with controls (median value 14.0 ng/mL; p<0.05). Although carcinoembryonic antigen was above the cut-off in only 13/66 (19.7%) patients with early stage CRC, serum free DNA showed values above the threshold identified using receiver operator characteristic (ROC) curve analysis in 53/66 (80.3%) patients. CONCLUSIONS: Our data confirm that serum DNA concentrations are significantly increased in CRC patients with early stage disease and in patients with polyps. This marker might be useful for identifying high-risk individuals.

Unexplained iron deficiency anaemia: Is it worthwhile to perform capsule endoscopy?

BACKGROUND: In around 30% of iron deficiency anaemia (IDA) cases a definite diagnosis cannot be made. AIM: To investigate the role of capsule endoscopy (CE) in detecting lesions in patients with unexplained IDA after a negative endoscopic, serologic and haematologic diagnostic work up and its possible role in influencing clinical outcome. METHODS: 138 patients suffering from IDA were identified among 650 consecutive patients undergoing CE at our unit. RESULTS: CE revealed the following positive findings in 91/138 patients: angiodysplasias in 51 patients; jejunal and/or ileal micro-ulcerations in 12; tumours/polyps in 9; erosive gastritis in 4; Crohn's disease in 5; jejunal villous atrophy in 5; a solitary ileal ulcer in 1 and active bleeding in the last 4 patients. Follow up data were available for 80/91 patients (87.9%). In 15 out of 46 patients with angiodysplasias IDA spontaneously resolved without any treatment; 9 patients required iron supplementation; 10 patients healed after lanreotide administration; APC was performed in 9 out of 46 patients and 3 patients underwent regular blood transfusion without any success on IDA. 10 out of the 12 patients with small bowel micro-ulcers spontaneously recovered from IDA whilst 2 patients after iron supplementation. All 9 patients affected by tumours/polyps were surgically addressed. In all erosive gastritis cases, patients recovered from IDA after PPI and Helicobacter pylori eradication. Four patients with Crohn's disease diagnosis restored to health with medical therapy. One out of the 4 patients with jejunal villous atrophy and the sole patient with a solitary ileal ulcer spontaneously healed. In 1 out of 3 patients with active bleeding IDA resolved without further treatment after blood transfusion whilst 2 patients were referred for surgical treatment. At follow up, complete resolution of IDA was achieved in 96.25%. CONCLUSIONS: Small bowel investigation is a matter of great importance in IDA patients after negative upper and lower gastrointestinal endoscopy.

Inter-test agreement and quantitative cross-validation of immunochromatographical fecal occult blood tests.

Immunochromatographical fecal occult blood tests were shown to have higher sensitivity for detecting colorectal neoplasms than the commonly used guaiac-based test. However, positivity rates, sensitivity and specificity vary widely. We aimed to assess the reasons for this heterogeneity. Six dichotomous (qualitative) immunochromatographical tests were used in the same stool samples, taken before cathartic bowel preparation, from 1,330 participants of the German colonoscopy screening program. Positivity rates were determined, and inter-test agreement beyond chance was quantified by kappa coefficients (kappa). In addition, kappa coefficients were expressed in relation to their maximum possible values given differences in test positivity rates (kappa/kappa(max)). Furthermore, the distribution of fecal hemoglobin concentration was assessed by an additional quantitative test in participants classified as clearly positive, borderline positive or clearly negative according to the qualitative tests. Positivity rates strongly varied from 6.4 to 46.8%. As a result, overall agreement between tests was only poor to moderate, with kappa ranging from 0.14 to 0.61. However, apart from the different positivity rates, agreement was mostly very high, with kappa/kappa(max) ranging from 0.53 to 1.00, and exceeding 0.70 in 12 of 15 cases. Distribution of fecal hemoglobin concentrations in the various categories strongly varied across tests. The observed patterns suggest that the strongly different positivity rates essentially reflect different cutoff levels of tests with otherwise very high inter-test agreement. Definition of cutoffs is a critical issue in the application of immunochromatographical tests and should be redefined for several of these tests.

Identifying mutations for MYH-associated polyposis.

Polyposis associated with mutations in the gene MYH is an autosomal recessive syndrome characterized by the development of colorectal adenomas and cancer. Two common mutations, p.Tyr165Cys (exon 7) and p.Glu382Asp (exon 13), have been shown to account for the majority of the mutations occurring in individuals of Caucasian ancestry. Other mutations have been found throughout the gene and many have been shown to have very low frequencies. Ethnic differences in the mutation spectrum have also been observed. Thus, in order to achieve the highest clinical sensitivity, it is necessary to perform whole-gene sequencing of the MYH gene. The sequencing protocol described allows one to identify mutations throughout the MYH gene.

Soluble CD26 levels and its association to epidemiologic parameters in a sample population.

INTRODUCTION: Previous studies have suggested the use of soluble CD26 (sCD26) as a tumour marker for the detection of colorectal cancer (CRC) and advanced adenomas. The aim of this study was to assess the sCD26 concentration in a large cohort to evaluate its association to epidemiologic parameters and CRC-related symptoms/pathologies. SUBJECTS AND METHODS: Serum samples were collected from 2,754 putatively healthy individuals with ages ranging from 30-65 years, and with personal or familial history of polyps, CRC and/or CR symptoms. sCD26 levels were measured by ELISA. RESULTS: No association was found between the sCD26 concentration and age (< 50 and 50), the personal or familial history of polyps or CRC, rectal bleeding, haemorrhoids or diverticula. However, sCD26 was related to non-inflammatory benign pathologies (excluding rectal bleeding, changes in bowel habits, haemorrhoids, diverticula) and to inflammatory benign pathologies. DISCUSSION: Our results confirm that the sCD26 can be easily offered and evaluated in a large cohort. Additionally, the validation of sCD26 as a tumour marker for screening and case-finding purposes requires a further comparison with an established non-invasive test like the faecal occult blood.

Risk of colorectal neoplasm in patients with acromegaly and its relationship with serum growth hormone levels.

OBJECTIVES: Acromegalics have been reported to be at an increased risk of colorectal neoplasm. However, the magnitude of the risk is still controversial and the mechanism has not been fully investigated. In this study, we attempted to determine the magnitude of the association between acromegaly and colorectal lesions after taking into account age, gender, smoking status, and treatment status. In addition, we assessed the relationship between colorectal lesions and serum growth hormone (GH) levels in acromegalics. METHODS: We conducted a case-control study by using 19 consecutive untreated patients (male:female = 11:8) who were newly diagnosed with acromegaly between 1990 and 2000. All patients underwent colonoscopy and received a histological diagnosis of colorectal lesions. Prevalence of hyperplastic polyp, adenoma, and carcinoma were compared with the prevalence in 76 controls matched for gender, age, and smoking status. Serum GH levels were compared between acromegalic patients with and without each type of colorectal lesion. RESULTS: The prevalence of hyperplastic polyp, adenoma, and carcinoma were significantly higher in the acromegalic patients compared to the controls (p < 0.05, odds ratios; 8.3, 4.2, and 9.8, respectively). In acromegalics, the presence of hyperplastic polyps and carcinomas were significantly associated with higher serum GH levels after adjusting for the other lesions and age (p < 0.05). CONCLUSIONS: After controlling for age, gender, smoking status, and treatment status, acromegaly was associated with significantly higher prevalence of colorectal hyperplastic polyp, adenoma, and carcinoma. High serum GH levels may be associated with the presence of hyperplastic polyp and carcinoma.

Multiple somatostatin- and gastrin-containing carcinoids of the duodenum: report of a case treated by pancreas-sparing duodenectomy.

A 59-year-old Japanese man was incidentally discovered to have multiple polyps in the duodenum by endoscopy during a health checkup. Laboratory studies showed an elevated level of serum somatostatin. The mutation of the MEN1 gene was not observed. An endoscopic examination revealed multiple polypoid lesions in the bulbus and in the second portion of the duodenum. An upper gastrointestinal series also showed the multiple polypoid lesions in the bulbus, and in the descending and horizontal portions of the duodenum. The biopsy specimen showed small monotonous cells with round nuclei compatible with a carcinoid tumor. The tumor cells were positive for somatostatin and gastrin. Based on the clinical diagnosis of multiple carcinoids of the duodenum, a pancreas-sparing duodenectomy was performed. Macroscopic findings showed about 30 polypoid lesions throughout the duodenum. The biggest one was not over 10 mm in size. A histological examination revealed well-demarcated carcinoid tumors located in the submucosal layer. Immunohistochemically, the tumors were diffusely positive for somatostatin and were scatteringly positive for gastrin. The patient's postoperative course of treatment was uneventful and his postoperative serum somatostatin went down to normal range. The pancreas-sparing duodenectomy is a safe and effective treatment in patients with multiple carcinoids of the duodenum, that are smaller than 1 cm in size.

Decrease in serum levels of vitamin A and zeaxanthin in patients with colorectal polyp.

OBJECTIVE: Several retrospective and prospective epidemiological investigations have demonstrated that a diet rich in carotenoids could prevent the development of pre-cancerous and neoplastic lesions of the digestive tract. The aim of this examination was to analyse the correlation between colorectal polyps with different histological classifications and serum carotenoid levels. DESIGN AND METHODS: A 10 ml blood sample was taken from all of the patients after the colonoscopic diagnosis. The serum levels of vitamin A, lutein, zeaxanthin, alpha- and beta-cryptoxanthin, alpha- and beta-carotene were measured in patients with adenomatous colorectal polyp (n = 59, 35 males, 24 females) by high-pressure liquid chromatography (HPLC) and compared with those in healthy subjects (n = 20, 10 males, 10 females). The patients were separated into four groups depending on their histological findings. RESULTS: The serum levels of vitamin A and zeaxanthin were significantly lower in all patients with polyps (vitamin A: 0.913 +/- 0.112 micromol/l, zeaxanthin: 0.071 +/- 0.012 micromol/l) than in the control healthy group (vitamin A: 2.036 +/- 0.354 micromol/l, zeaxanthin: 0.138 +/- 0.048 micromol/l). The lowest levels were found in patients with focal adenocarcinoma in the polyp. There were no significant differences in the serum levels of other carotenoids. The serum levels of cholesterol, haemoglobin, total protein and albumin were normal in these patients. CONCLUSIONS: There are close and inverse correlations between the serum level of carotenoids and colorectal polyps with different histological grades. The low mean carotenoid levels in patients with adenocarcinoma in the polyp indicate that deficiency of carotenoids may be an important factor in the development of colorectal cancer.

Plasma ferritin, iron intake, and the risk of colorectal polyps.

High iron exposure has been associated with colorectal neoplasia in several studies. The authors investigated plasma ferritin, an indicator of iron stores, and iron intake as risk factors for adenomatous polyps, intermediate markers for colorectal cancer. During 1991-1993, they collected fasting blood samples from and administered questionnaires to men and women 50-75 years old who visited free sigmoidoscopy clinics at a health maintenance organization. Data from 965 subjects (467 cases, 498 controls) were analyzed. Compared with those who had low-normal plasma ferritin concentrations (73-141 micrograms/liter), those with elevated concentrations ( > 289 micrograms/liter) had a multivariate-adjusted odds ratio of 1.5 (95% confidence interval (CI) 1.0-2.3) after excluding subjects with possible non-iron-related elevations in ferritin. Compared with subjects consuming an adequate amount of iron (11.6-13.6 mg/day), multivariate-adjusted odds ratios were 1.6 (95% CI 1.1-2.4) for < 11.6 mg/day and 1.4 (95% CI 0.9-2.0) for > 27.3 mg/day. These results provide further support for a weak positive association between iron exposure and colorectal polyps.

Effect of bowel cleansing and colonoscopy on serum CEA levels.

A group of patients being investigated for various forms of colonic pathology showed an apparent rise in serum carcinoembryonic antigen (CEA) level following bowel cleansing at the time of colonoscopy, as compared with the 'resting' level. The rise was particularly marked in a small group of patients with colonic polyps or previous colonic resection for carcinoma, suggesting a need for careful timing in the taking of blood samples. The findings may also have diagnostic importance in identification of patients at higher risk of malignant disease of the colon.

Double immunochemical screening test (hemoglobin and albumin) for the detection of occult intestinal bleeding.

The authors have developed a combined electrophoretic-immunoprecipitation technique suitable for the simultaneous demonstration of two blood proteins, i.e., hemoglobin and albumin, in the feces. The analytical sensitivity of the method is 2 micrograms hemoglobin and albumin/ml. The technique is simple, inexpensive, and suitable for the reliable demonstration of occult intestinal bleeding for either inpatients or mass screening. This technique is an aid not only to the fact that bleeding can be detected, but to its intensity, as well. This new technique improves the diagnostic accuracy of early detection of carcinomas and polyps, presumably without raising significantly the number of "false-positive" reactions.

An association between hypocholesterolaemia and colorectal carcinoma in an Irish population.

A group of 114 Irish patients with primary adenocarcinoma of the large bowel had significantly lower serum cholesterol concentrations than an age and sex matched group drawn from the general population. The hypocholesterolaemiac trait was manifest in male and female patients. Rigorous control procedures established that it was neither an artefact of nutritional compromise nor of preoperative bowel preparatory protocols. The data suggested that the appreciable hypocholesterolaemia observed was not influenced by the pathological stage or degree of differentiation of the tumour.