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MicroRNAs (miRNAs) are small, non-coding RNA segments that regulate gene expression via post-transcriptional inhibition and have roles in cell differentiation, proliferation, and apoptosis. Expression differs between tumor and normal tissue in several malignancies. Most work has focused on tissue and cell expression with few reports of circulating miRNAs in colorectal cancer. Available biomarkers for colorectal cancer have limited sensitivity and specificity, thus there is a need for new markers.This study aimed to identify miRNAs that are differentially expressed in the blood of colorectal cancer patients compared to controls and to establish if this is specific to colorectal cancer and thus could be utilized as potential tumor markers.Blood samples were collected from 63 colorectal cancer patients and 45 controls. Expression of 7 target miRNAs (miR-143, miR-145, miR-21, miR-30a-3p, miR-31, miR-34a, and miR-92) was measured using RQ-PCR. Results were correlated with clinicopathological data and analyzed. Analysis of differentially expressed circulating miRNAs was expanded to include 62 patients with prostate, renal, breast, and melanoma cancers.Analysis of the relative quantification of the target miRNAs showed significantly reduced expression (P = 0.004) of miR-34a in colorectal cancer. MiR-34a was also significantly reduced in breast cancer (P = 0.019).This study demonstrates significantly reduced expression of circulating miR-34a in colorectal and breast cancer. This may have future application as part of a biomarker profile.

Following centralisation of breast cancer services, the National Cancer Control Programme (NCCP) introduced referral guidelines indicating which patients require urgent, early and routine review. This study prospectively analysed referrals to a symptomatic breast unit over 3 months to measure Primary Care Physician (GP) uptake of the NCCP referral guidelines, compare triage patterns of GP and consultant breast surgeon and evaluate the efficacy of the guidelines at identifying patients with breast cancer. 1044 consecutive referrals were categorised according to NCCP guidelines. 637 (61%) were referred using the NCCP form. GP referrals correlated well with consultant breast surgeon for patients requiring urgent review (r = 0.71, p0.001; Pearson). Patients categorised as "urgent" were more likely to have a breast biopsy compared to those categorised as "routine" (p0.0001; Chi2). The overall cancer incidence was 34 (3.3%) and significantly higher in the "urgent" group at 10.5%. NCCP guidelines were 91% sensitive for triaging breast cancer patients into the correct (urgent) category. The NCCP guidelines are accurate and should be considered the gold-standard for referral to the symptomatic breast service. Consideration should be given to a GP-delivered service to patients outside the "urgent" category.

The use of surgical drains in patients undergoing thyroid surgery is standard surgical teaching. Life-threatening complications, arising from post-operative haematomas, mandates their utilization. There is increasing evidence to suggest that this is an outdated practice. This paper determines whether thyroid surgery can be safely performed without the routine use of drains. A retrospective review of patients undergoing thyroid surgery, over a three year period was performed and post-operative complications documented. One hundred and four thyroidectomies were performed. 63 (60.6%) patients had a partial thyroidectomy, 27 (25.9%) had a total thyroidectomy and 14 (13.5%) had a sub-total thyroidectomy. Suction drains were not inserted in any patient. A cervical haematoma did not develop in any patient in this series and no patient required re-operation. There is no evidence to suggest the routine use of surgical drains following uncomplicated thyroid surgery reduces the rate of haematoma formation or re-operation rates and indeed is now unwarranted.

The identification of a second estrogen receptor (ER-beta) has significant implications for therapeutic strategy in breast cancer management arising from the potential agonist effect of Tamoxifen at estrogen receptor sites and as such, antiestrogen therapy may be inappropriate in patients with a dominance of ER-beta.To determine the proportion of breast cancer patients who may be so at risk, we developed a novel multiplexed RT-PCR technique to establish the relative ER-alpha and ER-beta levels in 53 primary breast cancers, 11 normal breast tissues and six cell lines. We further assessed the prognostic significance of receptor status relative to the Nottingham prognostic index (NPI). The ER-alpha and ER-beta status was also determined by immunohistochemistry using previously published and 'in-house' scoring systems.Using RT-PCR analysis, 46 tumours were hormone receptor positive (ER+) with 42 displaying ER-alpha predominance. Comparison with immunohistochemistry demonstrated 44/53 (ER-alpha) and 27/50 (ER-beta) concordance rates. There was no significant difference in the NPI between ER-alpha and ER-beta predominant cohorts or between ER+ and ER- cohorts.This study identifies the existence of a subgroup of ER+ patients in whom Tamoxifen therapy may be inappropriate and has significant implications for adjuvant therapy of primary breast cancer.

Breast cancer is characterised by a number of genetic aberrations. Our purpose was to use comparative genomic hybridisation (CGH) to screen breast carcinomas for copy number changes: 44 ductal and 8 lobular carcinomas were studied and a large number of genetic aberrations identified. Many of these showed similarity to previous CGH results, however, a number of loci not previously shown to have undergone frequent change were identified. This included copy number gains affecting chromosomes 1p, 4q, 5q, 6q and 13q. Furthermore, we have identified 2 regions of copy number change, the gain on 5p and deletion of 16q, which correlated with lobular carcinomas. Our results highlight several areas of the genome that may be important in the molecular genetics of breast cancer.

Tamoxifen is currently the first-line therapy for treatment of hormone-dependent breast cancer. However, despite initial benefits, most patients eventually relapse. Two groups of patients were identified: (a) a tamoxifen-sensitive group (n = 8); and (b) a tamoxifen-resistant group (n = 9). Using reverse transcription-PCR, the relative expression of mRNA for both estrogen receptor (ER) beta and transforming growth factor beta1 was determined in each patient group and quantified against a known reference standard. ER-beta mRNA was significantly up-regulated in the tamoxifen-resistant group as compared with the tamoxifen-sensitive group (P = 0.001 by Fisher's exact test), and, consistent with previous findings, transforming growth factor beta1 was also up-regulated in the tamoxifen-resistant cohort (P = 0.02). The importance of ER-beta in tamoxifen resistance was validated using tamoxifen-sensitive and -resistant cell lines, in which it was demonstrated that ER-beta mRNA was significantly up-regulated in the resistant cells. These results lend further support to a role for ER-beta as a poor prognostic factor in breast cancer.

The cloning of a second estrogen receptor (ER), ER beta, has prompted a reevaluation of the role of ERs in breast cancer. The aim of this study was to determine the expression of both ER isoforms in normal (n = 23) and malignant (n = 60) human breast tissue by reverse transcription-PCR and correlate this information with known prognostic factors including tumor grade and node status. In normal breast tissue, expression of ER beta predominated, with 22% of samples exclusively expressing ER beta; this was not observed in any of the breast tumor samples investigated. Most breast tumors expressed ER alpha, either alone or in combination with ER beta. Interestingly, those tumors that coexpressed ER alpha and ER beta were node positive (P = 0.02; Fisher's exact test) and tended to be of higher grade. Because antiestrogens are agonists when signaling through the AP1 element, overexpression of ER beta in tumors expressing both ER subtypes may explain the failure of antiestrogen therapy in some breast cancer patients. Thus, ER beta may be a useful prognostic factor in patients with breast cancer.

Small intestinal malignancies are rare and may have a delayed presentation owing to insidious growth. We have reviewed the case notes of 25 patients presenting with primary small bowel tumours over a 10-year period. Abdominal pain, weight loss and vomiting were the most common symptoms. The median duration of symptoms was 6 months. Physical examination was normal in 24% of patients. An abdominal mass was present in 46% of cases. Emergency laparotomy was undertaken in 28% of patients. Lymphomas were identified in 72% and adenocarcinomas were present in 16%. The predominance of small bowel lymphoma is an unusual finding and may be related to the high incidence of coeliac disease in the region. The median survival in the lymphoma group was 36 months, which compares favourably with reported series.

Carcinoma of the breast is characterized by a variable course with prognosis dependent on disease stage at presentation. Paradoxically, some patients with early malignancy demonstrate disease progression within a short time. The role of tumor markers in the management of carcinoma of the breast is controversial. While CA15-3 is the most widely used tumor marker in carcinoma of the breast, its role in the management of patients with early disease is controversial.Since 1986, all patients presenting to our unit with carcinoma of the breast have had serial CA15-3 levels measured. This study evaluates the role of serial CA15-3 levels in the management of a consecutive series of 168 patients with Stage I disease at presentation.The mean preoperative CA15-3 levels at presentation were significantly elevated in patients with Stage I disease compared with patients with benign disease. Sixteen patients had either locoregional (five patients) or metastatic recurrence (11 patients). CA15-3 levels were not elevated in patients with locoregional disease and were significantly elevated in patients with bony metastases and gave a mean lead time of 6.3 months over bone scintigraphy.Serial CA15-3 measurements are an efficient and cost-effective method of monitoring disease progression and have advantages over conventional investigations in patients with early carcinoma of the breast.

Although smoking has been identified as an independent risk factor in peripheral vascular disease, smokers do not accurately report their habit. Therefore, a cheap, non-invasive, objective method of measuring smoking behaviour in vascular surgical units is desirable. The value of end-expiratory carbon monoxide monitoring, which is both simple and inexpensive, was compared with two well-established, validated techniques (serum thiocyanate and blood carboxyhaemoglobin levels). Some 33 surgical patients with peripheral vascular disease provided samples of expired air for measurement of carbon monoxide and blood for carboxyhaemoglobin and thiocyanate levels. Carboxyhaemoglobin was the most sensitive test (90%) and had a high specificity (100%). Expired carbon monoxide was the least sensitive (60%) but had a high specificity (100%). The carbon monoxide and carboxyhaemoglobin levels correlated significantly (r = 0.829; P = 0.0001). Serum thiocyanate was relatively sensitive (80%) but had a lower specificity (70%). Conventional methods for assessing smoking behaviour have not gained widespread use because they are time-consuming, relatively invasive and require technical support. Non-invasive measurement of carbon monoxide gives immediate accurate results and is a useful inexpensive method for measuring cigarette smoking in patients attending a follow-up vascular unit.

Of 271 patients with primary colorectal cancer, 70 (26%) had detectable hepatic metastases. A primary tumour resection was possible for 225 (83%) of patients overall. Of the 46 patients with non resectable tumours, 38 (82%) had hepatic metastases. 23 (33%) of the patients with Dukes' D tumours died perioperatively relative to 13 (6%) of those with localised tumours (p.001). Seventeen (70%) of the twenty three patients with Dukes' D cancers who died perioperatively had locally advanced disease but were not obstructed and had neither a resection or a stoma performed. Perioperative mortality is unacceptably high in patients with hepatic metastases but may be reduced by more specialised investigation of patients with suspected advanced disease to assess the degree of local dissemination and liver seeding prior to considering laparotomy.

We report the first case of rupture of a false aneurysm of the iliac artery due to retrograde passage of a ureteric stent.