Enhanced recovery in colorectal resections: a systematic review and meta-analysis.

OBJECTIVE: The study aimed to produce a comprehensive up-to-date meta-analysis exploring the safety and efficacy of enhanced recovery (ER) programmes after colorectal resection. METHOD: Key-word and MESH-heading searches of MEDLINE, EMBASE and the Cochrane Databases from 1966 to February 2007 were used to identify all available randomized and clinical controlled studies. Two independent reviewers assessed studies for inclusion and exclusion based on methodological quality criteria prior to undertaking data extraction. Summary estimates of treatment effects using a fixed effect model were produced with RevMan 1.0.2, using weighted means for length-of-stay data and relative risks of morbidity, mortality and readmission rates. RESULTS: Analysis of four papers including 376 patients demonstrated primary and total length-of-stays (primary + readmission length-of-stay) to be significantly reduced (P < 0.001) with ER programmes [weighted mean differences of -3.64 days (95% confidence interval, 95% CI -4.98 to -2.29) and -3.75 days (95% CI-5.11 to -2.40)]. Analysis of controlled clinical trial data showed morbidity rates to be reduced and readmission rates increased. These trends were not seen amongst the randomized controlled trial data. There were no differences in mortality rates. CONCLUSION: Enhanced recovery programmes after colorectal resections reduce length-of-stay and may reduce 30 days morbidity and increase 30 days readmission without increasing mortality.

Direct polymerase chain reaction amplification of formalin-fixed, paraffin-wax-embedded tissue after automated sequential laser microdissection and pressure catapulting.

A robust method to facilitate rapid laser microdissection and pressure catapulting (LMPC) coupled with direct polymerase chain reaction (dPCR) to eliminate the need for extraction of DNA before a PCR-based assay is described. This sequential LMPC-dPCR method is rapid and decreases the number of processing steps, reducing the chance of tissue loss and contamination.

Recurrence rates after DCE-MRI image guided planning for breast-conserving surgery following neoadjuvant chemotherapy for locally advanced breast cancer patients.

BACKGROUND: Neoadjuvant therapy results in a significant increase in breast-conserving surgery. However, traditional imaging methods are unable to accurately predict the extent of viable residual disease leading to uncertainty in surgical planning and some previous studies have shown a disproportionately high incidence of locoregional recurrence. Dynamic contrast enhanced-MRI (DCE-MRI) has been shown to provide a potentially more accurate prediction of residual disease. RESULTS: Patients undergoing neoadjuvant chemotherapy for breast cancer in our unit are staged with the DCE-MRI of the breast performed at 1.5 T before, during and after treatment and the final result was used to plan surgery. Two hundred and four patients with breast cancer were treated with neoadjuvant chemotherapy between 1996 and April 2005. Eighteen of these patients had distant metastases at the time of initial diagnosis and so were excluded from the present study. Following neoadjuvant chemotherapy, 186 patients underwent surgical treatment. Of these, 68 patients had breast-conserving surgery. At a median follow up of 30 months (range: 5.6-72 months) 21 patients in this group developed subsequent recurrence (21/68 - 30%) of whom 9 (9/68 - 13%) had locoregional recurrence, 7 had local recurrence (7/68 - 10%), and 17 (17/68 - 25%) had distant recurrence. Logistic regression analysis revealed only vascular invasion (p=0.006) of the tumour to be significantly associated with overall recurrence. None of the pathological factors (ER, PR status, vascular invasion, lymph node metastases, pathological complete response to neoadjuvant chemotherapy) showed a significant association with locoregional recurrence. CONCLUSION: Breast-conserving surgery with DCE-MRI planning after neoadjuvant chemotherapy provides an acceptable level of local recurrence without the need for mastectomy.

A point prevalence survey of wounds in north-east England.

OBJECTIVE: To review current wound-care practice and the standard of wound care in Hull and East Yorkshire; obtain information on prevalence, treatment and outcomes; provide a basis for estimating the extent of the problem, treatment modalities used, service provision and future needs; highlight areas of care in need of improvement; highlight areas with excellent wound practices and gain information for future research projects within the population of the region. METHOD: Point prevalence interface audit of community and acute trusts. RESULTS: The cumulative wound prevalence for the region was 12%. Community nurses were involved in caring for 70.1% of patients with wounds, with 52.7% of wounds being treated in the patient's home. The largest proportion of wounds were surgical wounds (n=699, 41.5%), followed by leg and foot ulcers (n=629, 37.3%) and pressure ulcers (n=294, 17.4%). Diabetes and cancer were related to 15.1% and 9.7% of the wounds respectively. 41.9% of the wounds were on the lower leg. The primary and secondary dressings used the most were low/non-adherent dressings at 25.9% and 27.3% respectively.Almost half of the patients with a venous leg ulcer (46%) did not receive multilayer compression and 7% of patients with an arterial ulcer did; 23.6% of the leg and foot wounds were not assessed with a Doppler. CONCLUSION: Wounds represent a significant cause of morbidity in the general population.A systematic focus is necessary on effective and timely diagnosis, on ensuring treatment is appropriate to the cause and condition of the wound and on active measures to prevent complications.A number of initiatives have commenced in order to provide a effective and efficient wound care.

A pilot study on the effect of topical negative pressure on quality of life.

OBJECTIVE: To discover the impact of topical negative pressure (TNP) on quality of life. METHOD: An exploratory prospective cohort study was conducted on 26 patients undergoing TNP. The Cardiff Wound Impact Schedule (CWIS), a wound-specific tool, was used to investigate quality-of-life scores before therapy and four weeks after therapy or at wound closure. Wound dimensions were measured at both assessments, and the values for the CWIS domains (physical symptoms, social functioning, well-being and overall quality of life) were investigated using parametric and non-parametric tests. RESULTS: The mean duration of TNP therapy was 3.3 +/- 1.7 weeks. Topical negative pressure therapy helped to achieve complete wound closure in 14 patients (54%), and there was a mean reduction in wound surface area from 52.2 cm2 (range 4-150) to 26.8 cm2 (0-120). While there was no significant change in quality of life in patients whose wounds healed (1 +/- 11.9), the physical-functioning domain improved in obese patients (20 +/- 21, p < 0.05) and worsened in ambulatory patients (-3 +/- 13, p < 0.05). The portableTNP system had no significant impact on quality of life (-3 +/- 16), while the global quality-of-life score worsened with surgical intervention (-0.5 +/- 2, p < 0.05). CONCLUSION: Although TNP aids wound closure in patients with complex wounds, in selected cases their quality of life can worsen. This is the first exploratory cohort study of its kind, and has identified an urgent need to validate the use of patient-based outcome measures in TNP therapy. Such data can be useful in allocating resources and justifying funding in wound care.

Patient demographics and treatment for early breast cancer: an observational study.

This study aims to examine relationships between demographic factors and treatment choice for early breast cancer (T2/N<1). Two hundred and two patients were offered modified radical mastectomy (MRM), breast conserving therapy (BCT) or MRM and reconstruction and interviewed at a University Hospital and oncology centre in South Wales. Median age at treatment was 57 (32-90) years. Seventy-one patients (35%) choose MRM, 10 (5%) MRM and reconstruction and 121 (60%) BCT. Median age of women choosing MRM was 61 and 55 for BC (P<0.0001). Single women (P=0.009) and those with no family history of breast cancer (P=0.02) were more likely to choose MRM. There was no difference between treatment choice and method of cancer detection and the age at which the patient left education (P=0.065). Mean histological tumour diameter was smaller for women choosing BC (15 mm) than for women choosing mastectomy (17 mm; P=0.014). There was no association between tumour grade and treatment choice.

Differentiation of benign from malignant breast disease associated with screening detected microcalcifications using dynamic contrast enhanced magnetic resonance imaging.

Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) is an effective diagnostic modality for symptomatic breast disease. However, its role in evaluating clinically occult disease associated with mammographically detected microcalcification remains unclear. Women recalled following screening mammography with microcalcification had DCE-MRI examination of the breast. The data were evaluated subjectively and objectively using both empirical and 2-compartment pharmacokinetic modelling techniques to evaluate signal intensity parameters. Eighty-eight patients aged 50-75 years (median 58) were recruited. Comparing malignant and benign lesions, the mean values in arbitrary units for the enhancement index at 1 min in the most enhancing 9-pixel square +/-1 standard deviation were 0.61+/-0.40 vs. 0.22+/-0.26 p=<0.001 with sensitivity, specificity, PPV, NPV and accuracy of 80.0%, 82.4%, 57.1%, 93.3% and 81.8%, respectively. The corresponding values attained by the radiologist were 75.0%, 89.7%, 68.2%, 92.4% and 86.4%. DCE-MRI is able to differentiate malignant from benign clinically occult lesions associated with microcalcification and may therefore offer an alternative to open surgical biopsy for women with equivocal findings following initial triple assessment for microcalcification in the breast.

Potential prognostic and therapeutic roles for cytokines in breast cancer (Review).

Cytokines are known to have both stimulatory and inhibitory effects on breast cancer growth depending on their relative concentrations and the presence of other modulating factors in the tumour microenvironment. Certain cytokines appear to prevent an effective immune response being mounted, permitting cancer growth, whereas others promote the immune system's anti-tumour capability. Furthermore, the systemic levels of certain cytokines, e.g. IL-6 and IL-18, independently show promising correlations with disease stage and progression. With advances in methods for delivery of cytokines to a tumour site, the enhanced induction of anti-tumour immunity by targeted cytokine release is becoming a realistic option. Here, we review the role of cytokines in the immune response against breast cancer and assess their potential as prognostic indicators and/or use in immune therapy. A literature search was conducted using Medline, restricted to articles published in the English language, using combinations of the following MeSH terms: cytokines, breast cancer, immunology, immunotherapy and interleukins. Focused searches using keywords relevant to the role of cytokines in breast cancer immunology yielded >200 references.

Effects of bilateral breast reduction on anxiety and depression: results of a prospective randomised trial.

We assessed the effects of bilateral breast reduction on anxiety and depression in women with mammary hypertrophy (macromastia). Seventy-three consecutive women referred for consideration for breast reduction were recruited. They were randomised to have either early operation (within six weeks of initial assessment) or delayed operation (within six months of recruitment). The Hospital Anxiety and Depression Score was given before randomisation and four months later. All 73 patients completed the study. The mean (SD) age was 39 (12) years. The groups were matched for age, smoking, social class, and educational achievement. There were highly significant improvements (p<0.001) in symptoms of anxiety and depression. Reduction mammaplasty significantly improved symptoms of clinical depression in women with macromastia.

MRI and conservative treatment of locally advanced breast cancer.

AIMS: The objectives of this study were to compare the efficacy of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the response of primary breast carcinoma to neoadjuvant chemotherapy compared to conventional imaging modalities, and to see how surgical outcome was influenced as a result of these findings. METHODS: Thirty-four patients with locally advanced primary breast cancer underwent conventional imaging and DCE-MRI following six cycles of neoadjuvant chemotherapy prior to surgery. Changes in surgical management based on the post-chemotherapy DCE-MRI findings were recorded. RESULTS: Prior to neoadjuvant chemotherapy, 22 of the 34 patients were assessed as requiring mastectomy and the remaining 12 were considered inoperable. Following chemotherapy two patients were still considered inoperable. In 11 of the 34 patients, the final decision to proceed to either mastectomy or non-surgical management was based primarily on pre-treatment disease status or patient choice. DCE-MRI findings, therefore, contributed to the operative decision in 21 of 34 patients. Two of these 21 patients were spared surgery as DCE-MRI demonstrated complete response to chemotherapy and one declined surgery. The remaining 18 were able to undergo wide local excision, with only two patients subsequently requiring mastectomy for involved margins. CONCLUSIONS: DCE-MRI is able to accurately predict those patients suitable for breast conserving surgery following neoadjuvant chemotherapy and should be the imaging modality of choice in assessing the response of patients with primary breast carcinoma to neoadjuvant chemotherapy.

Karyotypic variation between independently cultured strains of the cell line MCF-7 identified by multicolour fluorescence in situ hybridization.

The breast cancer cell line MCF-7 is a widely used model in breast cancer research however a number of conflicting reports have been published regarding its biological properties. We hypothesised that there will be significant in vitro mutation and genotypic evolution over time in this cell line. To assess the genetic divergence of MCF-7 at the chromosomal level, we analysed MCF-7 cell lines grown independently at three different laboratories using M-FISH and CGH. In addition, MCF-7 cells from our own laboratory were also analysed at two time points 18 months apart. Several common chromosomal translocations were identified in all variants of the cell lines. In addition, a significant number of unique abnormalities were identified, characterising each of the variants studied. Genotypic differences between cell lines grown independently in different laboratories would significantly alter the phenotypic characteristics of each cell line rendering biological properties inconsistent between laboratories.

Prognostic factors: guidelines for investigation design and state of the art analytical methods.

The proliferation of putative prognostic factors, derived prognostic indices and computerised prediction of outcome in surgical oncology has led to some confusion over the exact methods available for deriving clinically significant prognostic factors. The realisation that the interaction between factors is often complex and non-linear has led to the development of new statistical techniques. The aim of this article is to review the currently available methods of analysis. A review of the relevant literature available from statistical, medical and computer science sources was performed. Information has been conveyed at a level aimed at producing a practical understanding of the techniques involved rather than their underlying mathematical basis. There are now clear guidelines for the investigation of putative prognostic factors (Table 1). The established role of linear statistical models and prognostic indices remains vitally important for the majority of diseases with many derived prognostic indices having been validated in a prospective fashion. However, in order to improve the delineation of prognostic factors other more complex methods of analysis are now being utilised. Furthermore, the recognition of complex dynamic non-linearity within biological systems has led to the increasing use of non-linear statistical techniques and artificial intelligence. As such it is incumbent upon the modern clinician to be able to understand the basic assumptions required for multivariate analysis and also to realise when alternative statistical techniques should be employed.

Inflammatory breast carcinoma.

Inflammatory breast cancer (IBC) is a rare subtype of breast cancer traditionally associated with an extremely poor prognosis. The appearance of the effected breast can be misleading, with the incorrect diagnosis of an infective process, rather than a malignant disease, further delaying treatment. Compared with the results achieved by monotherapy with either surgery, radiotherapy or chemotherapy; multimodality treatments have achieved significant improvements in both disease-free and overall survival. The purpose of this article is to provide a comprehensive review of the current literature and highlight those areas where potential advances in the overall management of IBC have been made.

Radioresistance in carcinoma of the breast.

Radiotherapy plays an important role in the management of breast cancer. Whilst its role in achieving local control following surgery in patients with early stage cancer is well established, there is still unclear evidence to explain the factors governing radioresistance in patients who develop recurrences both in the breast and axilla. Radiotherapy induces damage to the DNA. Various cell cycle damage check points and DNA damage repair pathways have been demonstrated. Ataxia telangiectasia mutant (ATM) kinase, which is a member of phosphatidylinositol-3 kinase (PI-3K) family appears to play a central role in DNA damage check point pathways. Over-expression of Insulin like growth factor-I receptor (IGF-IR), Human Epidermal Growth factor receptors (HERS), Vascular Endothelial growth factor (VEGF) on the cell surface and increased concentration of Epidermal Growth factor in the extracellular fluid have been associated with radioresistance. Specific genes such as p53, BRCA, Bcl-2 and chromosomal characteristics like telomere lengths have also been identified as playing significant roles in radiation responsiveness of a cell. This article reviews the current data on general principles of radiotherapy, the cellular mechanisms that operate in response to radiation damage and various molecular markers, intranuclear and extranuclear which have been demonstrated to influence radiation sensitivity in breast cancer cells.

Gynaecomastia and the plant product "Tribulis terrestris".

Gynaecomastia is the commonest benign breast condition seen in men. It is well recognised that certain drugs that alter the normal sex hormonal profile in the body can induce gynaecomastia. Recently, an increasing use of androgenic-anabolic steroids among young men especially body-builders has increased the incidence of gynaecomastia. We report a case of a young weight-trainer who developed gynaecomastia due to oral intake of a herbal tablet which he used as a steroid alternative for body-building.

Pancolitis associated with docetaxel: a rare cause of megacolon.

The toxic effects of chemotherapy have been noted to cause a range of acute necrotizing colonic inflammatory disorders but until recently these have not been associated with docetaxel chemotherapy. Here we report a case of pancolitis presenting as megacolon following the administration of docetaxel for recurrent breast cancer.

Combined wide excision and mastopexy/reduction mammoplasty for inframammary hidradenitis: a novel and effective approach.

Hidradenitis suppurativa is a rare chronic skin condition involving the apocrine glandular zones, which are found predominantly in the axilla and inguinoperineal regions, but have been described at other sites, including the inframammary fold. Treatment requires complex surgical intervention with wide excision of involved tissue. Inframammary hidradenitis tends to affect young women and can prove resistant even to this radical form of surgery, which often results in marked scarring and breast deformity. We therefore decided to adopt a novel approach by incorporating the wide excision of inframammary skin currently necessary in a reduction mastopexy procedure. This enables primary closure with ptosis correction and should improve cosmesis. The reduction in the depth of the inframammary fold also makes hygiene easier in the long term. During a 6-year period, five patients (mean age 27 years) have been treated by this method. All patients had long-standing hidradenitis (mean 12 years), and had been treated with several courses of antibiotics. A modified Wise pattern reduction incision was used with a minimum amount of breast tissue being removed. In each case histology was consistent with hidradenitis. All wounds healed well and to date there have been no inframammary recurrences. The success of this operation in curing inframammary hidradenitis has had a dramatic affect on the lives of these young women and underlines the need for this rare condition to be treated in a specialist centre.

Dynamic contrast enhanced magnetic resonance imaging aids the surgical management of invasive lobular breast cancer.

AIMS: Infiltrating Lobular Carcinoma (ILC) accounts for 5-10% of all breast cancers and is associated with subtle clinical and mammographic changes. It is also frequently multifocal and traditional diagnostic methods are unable to reliably detect this preoperatively. The aim of the study was to evaluate the efficacy of current imaging modalities compared with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the evaluation of ILC. METHODS: Data from women with ILC treated between 1996 and 2000 who had undergone preoperative triple assessment and DCE-MRI was analysed. The diagnostic accuracy and the detection of multifocal disease for each modality was assessed and any changes in clinical management following DCE-MRI were recorded. RESULTS: Twenty-one women (mean age 57, range 43-72 years) were recruited. The sensitivity of X-ray mammography, ultrasound, clinical assessment, fine needle aspiration cytology or core biopsy and DCE-MRI was 90.5, 87.5, 76.2, 85.7 and 95.2% respectively. DCE-MRI identified all the patients with subsequently histologically proven multifocal disease (n=11) with PPV and NPV of 100 and 95.2% respectively. X-ray mammography and ultrasound combined identified only 27% (n=3/11) with PPV and NPV of 100 and 55.6% respectively. Management was changed in 24% (5/21) of the cases following DCE-MRI. CONCLUSION: DCE-MRI has a higher sensitivity than other imaging modalities and is able to accurately delineate multifocal disease not evident on conventional imaging. DCE-MRI should therefore be used for accurate staging prior to surgery for invasive lobular breast cancer.

Molecular prognostic indicators in breast cancer.

Here we review a panel of oncogene products, proteases and markers of proliferation that have shown potential as prognostic indicators in primary breast cancer. The relative merits of specific genetic mutations as well as alterations at the protein level are discussed. Finally an assessment is made of the transfer of knowledge from the laboratory to the bed-side.