The lymph node ratio optimises staging in patients with node positive colon cancer with implications for adjuvant chemotherapy.

PURPOSE: The ratio of positive lymph nodes to total retrieved lymph nodes (lymph node ratio, LNR) has been proposed to be the superior prognostic score in colon cancer. This study aimed to validate LNR in a large, multi-centred population, focusing on patients that have undergone adjuvant chemotherapy. METHODS: Analysis of a prospectively collected database (The West of Scotland Colorectal Cancer Managed Clinical Network) with 1,514 patients with colonic cancer identified that had undergone elective curative surgical resection in the 12 hospitals in the West of Scotland from 2000-2004. Variables recorded were as follows: demographics, adjuvant chemotherapy, number of lymph nodes retrieved, lymph node retrieval ≥12, number of positive lymph nodes and LNR. Follow up continued until June 2009. Univariate and multivariate analyses were performed to determine the influence of LNR on overall survival. RESULTS: In 673 patients (44.5%), ≥12 lymph nodes were retrieved. Patients had a poorer long-term prognosis with increasing age, T stage and N stage. Retrieval of <12 lymph nodes and increasing LNR were both found to be significantly associated with poorer long-term survival, but on multivariable analysis, LNR was the only independently significant variable. In patients that had received adjuvant chemotherapy, only patients staged in the second lowest LNR group (0.05-0.19) had a significant improvement in long-term survival. CONCLUSION: Lymph node ratio is the optimal method of assessing lymph node status and highlights the heterogeneity of patients with node positive disease, altering patient stratification with implications for adjuvant chemotherapy.

Faecal haemoglobin concentration is related to detection of advanced colorectal neoplasia in the next screening round.

Objective To examine associations between faecal haemoglobin concentrations below the cut-off used in colorectal cancer screening and outcomes in the next screening round. Methods In the Scottish Bowel Screening Programme, faecal haemoglobin concentrations and diagnostic outcomes were investigated for participants with a negative result (faecal haemoglobin concentrations < 80.0 µg Hb/g faeces), followed by a positive result within two years. Results Of 37,780 participants with negative results, at the next screening round, 556 (1.5%) screened positive and 30,293 (80.2%) negative. Initial median faecal haemoglobin concentrations (2.1 µg Hb/g faeces, IQR: 0.0-13.2) were higher in those with subsequent positive results than those with subsequent negative results (0.0 µg Hb/g faeces, IQR: 0.0-1.4; p < 0.0001). Using faecal haemoglobin concentrations 0.0-19.9 µg Hb/g faeces as reference, logistic regression analysis showed high adjusted odds ratios for advanced neoplasia (advanced neoplasia: colorectal cancer or higher risk adenoma) detection at the next round of 14.3 (95% CI: 8.9-23.1) in those with initial faecal haemoglobin concentrations 20.0-39.9 µg Hb/g faeces, and 38.0 (95% CI: 20.2-71.2) with 60.0-79.9 µg Hb/g faeces. Conclusions A higher proportion of participants with faecal haemoglobin concentrations of ≥ 20 µg Hb/g faeces had advanced neoplasia detected at the next round than participants with lower faecal haemoglobin concentrations. Although most relevant when using high faecal haemoglobin concentrations cut-offs, studies of faecal haemoglobin concentrations and outcomes over screening rounds may provide strategies to direct available colonoscopy towards those at highest risk.

Primary invasive aspergillosis with disseminated intravascular coagulation as a presenting feature of non-Hodgkin's lymphoma.

Invasive aspergillosis (IA) is a life-threatening infection. IA is usually seen in severely immunocompromised patients. However, IA as a presenting feature of non-Hodgkin's lymphoma is rare. The patient we describe had no signs or symptoms of lymphoma prior to hospital admission. A. fumigatus was isolated from respiratory tract specimens on the day of admission and fungal elements were detected on autopsy. Isolation of Aspergillus in patients with severe sepsis should trigger a search haematological malignancy.

Faecal haemoglobin concentration is related to severity of colorectal neoplasia.

AIMS: Guaiac faecal occult blood tests are being replaced by faecal immunochemical tests (FIT). We investigated whether faecal haemoglobin concentration (f-Hb) was related to stage in progression of colorectal neoplasia, studying cancer and adenoma characteristics in an evaluation of quantitative FIT as a first-line screening test. METHODS: We invited 66 225 individuals aged 50-74 years to provide one sample of faeces. f-Hb was measured on samples from 38 720 responders. Colonoscopy findings and pathology data were collected on the 943 with f-Hb ≥ 400 ng Hb/ml (80 µg Hb/g faeces). RESULTS: Of the 814 participants with outcome data (median age: 63 years, range 50-75, 56.4% male), 39 had cancer, 190 high-risk adenoma (HRA, defined as ≥ 3 or any ≥ 10 mm) and 119 low-risk adenoma (LRA). 74.4% of those with cancer had f-Hb>1000 ng Hb/ml compared with 58.4% with HRA, and 44.1% with no pathology. Median f-Hb concentration was higher in those with cancer than those with no (p<0.002) or non-neoplastic (p<0.002) pathology, and those with LRA (p=0.0001). Polyp cancers had lower concentrations than more advanced stage cancers (p<0.04). Higher f-Hb was also found in those with HRA than with LRA (p<0.006), large (>10 mm) compared with small adenoma (p<0.0001), and also an adenoma displaying high-grade dysplasia compared with low-grade dysplasia (p<0.009). CONCLUSIONS: f-Hb is related to severity of colorectal neoplastic disease. This has ramifications for the selection of the appropriate cut-off concentration adopted for bowel screening programmes.

Clinical outcomes using a faecal immunochemical test for haemoglobin as a first-line test in a national programme constrained by colonoscopy capacity.

INTRODUCTION: Because of their many advantages, faecal immunochemical tests (FIT) are superseding traditional guaiac-based faecal occult blood tests in bowel screening programmes. METHODS: A quantitative FIT was adopted for use in two evaluation National Health Service (NHS) Boards in Scotland using a cut-off faecal haemoglobin concentration chosen to give a positivity rate equivalent to that achieved in the Scottish Bowel Screening Programme. Uptake and clinical outcomes were compared with results obtained contemporaneously in two other similar NHS Boards and before and after the evaluation in the two evaluation NHS Boards. RESULTS: During the evaluation, uptake was 58.5%. This was higher than in the same NHS Boards both before and after the evaluation, higher than in the other two NHS Boards and higher than the 53.7% achieved overall in Scotland. The overall positivity rate was higher in men than in women and increased with age in both genders. Positive predictive values for cancer (4.8%), high-risk adenoma (23.3%), all adenoma (38.2%) and all neoplasia (43.0%) in the two test NHS Boards were similar in all groups. CONCLUSIONS: In summary, this evaluation of the FIT supports the introduction of FIT as a first-line test, even when colonoscopy capacity is limited.

Natural antibiotic expression in celiac disease--correlation with villous atrophy and response to a gluten-free diet.

As infection influences the pathogenesis and presentation of celiac disease, we investigated the expression of natural antibiotics in this condition. Twenty-three adults were prospectively studied: 10 controls and 13 subjects with untreated celiac disease. Distal duodenal biopsies were taken at baseline and after 6 months of a gluten-free diet and assessed for the expression of natural antibiotics. Epithelial human beta-defensin 1 in subjects with celiac disease had a median of 0.02 unit at baseline, compared with 0.34 unit in controls (P < 0.001). It correlated negatively with the degree of villous atrophy (r = -0.64, P = 0.019) and rose to 0.04 unit on the gluten-free diet (P = 0.035 vs. baseline, P < 0.001 vs. controls). The expression of other antibiotics was unchanged. The expression of epithelial natural antibiotics is limited in celiac disease.