Adaptive responses to air pollution in human dermal fibroblasts and their potential roles in aging.

The damaging effects of air pollution on the skin are becoming increasingly researched and the outcomes of this research are now a major influence in the selection and development of protective ingredients for skincare formulations. However, extensive research has not yet been conducted into the specific cellular defense systems that are being affected after exposure to such pollutants. Research investigating the affected systems is integral to the development of suitable interventions that are capable of augmenting the systems most impacted by air pollutant exposure. The following studies involved exposing primary human dermal fibroblasts to different concentrations of particulate matter and analyzing its effects on mitochondrial complex activity, nuclear factor erythroid 2-related factor 2 localization using immunocytochemistry and protein expression of electron transport chain complex proteins, sirtuin-1 (SIRT1), and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) using western blotting. Particulate matter-induced alterations in both mitochondrial complex protein and activity, indicating oxidative stress, which was also complimented by increased expression of antioxidant proteins GSTP1/2 and SOD2. Particulate matter also seemed to modify expression of the proteins SIRT1 and PGC-1α which are heavily involved in the regulation of mitochondrial biogenesis and energy metabolism. Given the reported results indicating that particulate matter induces damage through oxidative stress and has a profound effect on mitochondrial homeostasis, interventions involving targeted mitochondrial antioxidants may help to minimize the damaging downstream effects of pollutant-induced oxidative stress originating from the mitochondria.

Exposing human primary dermal fibroblasts to particulate matter induces changes associated with skin aging.

With a large proportion of the world's population living in areas where air quality does not meet current WHO guidelines, combined with the knowledge that pollutants can interact with human skin, it is now of even greater importance that the effects of air pollutant exposure on human skin be investigated. To evaluate the damaging effects of a known component of air pollution (particulate matter) on human primary dermal fibroblasts. These studies were undertaken by exposing primary human dermal fibroblasts to different concentrations of particulate matter and analyzing the effects over time using resazurin reduction assays. Immunofluorescence microscopy was used to determine if particulate matter caused activation of the aryl hydrocarbon receptor, and phosphorylation of histone H2AX, a known marker of double-strand DNA breaks. Dot blotting was also used to analyze expression changes in secreted MMP-1, MMP-3, and TGFß. Particulate matter was found to dose-dependently increase cellular viability, activate the aryl hydrocarbon receptor, increase double-strand DNA breaks, and increase the expression of MMP-1, MMP-3, and TGFß. With the potential of air pollutants such as particulate matter to not only modulate the expression of proteins implicated in skin aging, but also affect cells at a genetic level, brings a pressing need for further investigation so protective strategies can be implemented.

Comparing long-term local recurrence rates of surgical and non-surgical management of close anterior margins in breast conserving surgery.

PURPOSE: While it is known that histologically involved margins lead to a higher local recurrence rate, re-excision of anterior margins is less common than that of radial margins. However, there are minimal long-term data on the oncological safety of non-surgical management of anterior margins. PATIENTS AND METHODS: A retrospective study was performed of all patients who underwent breast conserving surgery for breast cancer between 2000 and 2008 at two tertiary referral centres. A close margin was defined as disease within two mm of the resection margin (including disease at the margin). RESULTS: 6922 patients underwent surgery for invasive or in situ breast cancer of whom 277 patients had a close anterior margin alone after breast conserving surgery. Two hundred and twenty patients had non-surgical management of their margins, while 57 had re-excision surgery. Overall, there were 4/57 local recurrences in the surgical management group and 12/220 in the non-surgical management group. The local recurrence-free survival rate at 5 years was 98.2% (1 recurrence, 95% CI 87.8-99.7) in the surgical management group and 97.2% (6 recurrences, 95% CI 93.8-98.7) in the non-surgical management group. At 10 years, the rates were 92.2% (4 recurrences, 95% CI 80.3-97.0) in the surgical management group and 93.9% (12 recurrences, 95% CI 89.4-96.5) in the non-surgical management group. There was no significant difference found in the local recurrence rate between management groups (HR 1.24, 95% CI 0.40, 3.85; p = 0.71). CONCLUSIONS: Local recurrence rates are acceptable and similar in both the surgically and non-surgically managed groups. Non-surgical management of close anterior margins appears oncologically safe when combined with appropriate adjuvant therapy.

Radioactive seed localization compared with wire-guided localization of non-palpable breast carcinoma in breast conservation surgery- the first experience in the United Kingdom.

OBJECTIVE: In the UK, guidewires have traditionally been used for localization of non-palpable breast lesions in patients undergoing breast conservation surgery (BCS). Radioactive seed localization (RSL) using Iodine-125 seeds is an alternative localization method and involves inserting a titanium capsule, containing radioactive Iodine-125, into the breast lesion. We aim to demonstrate feasibility of RSL compared with guidewire-localization (GWL) for BCS in the UK. METHODS: Data were collected on 100 patients with non-palpable unifocal invasive carcinoma of the breast undergoing GWL WLE prior to the introduction of RSL and the first 100 patients treated with RSL WLE. Statistical comparisons were made using Χ2-squared analysis or unpaired two-sample t-test. Significance was determined to be at p ≤ 0.05. RESULTS: Mean total tumour size was 19.44 mm (range: 5-55) in the GWL group and 18.61 mm (range: 3.8-59) in the RSL group (p = 0.548), while mean total specimen excision weight was significantly lower in the RSL group; 31.55 g (range: 4.5-112) vs 37.42 g (range: 7.8-157.1) (p = 0.018). Although 15 patients had inadequate surgical resection margins in the GWL group compared the 13 in the RSL group (15 vs 13%, respectively, p = 0.684), 10 of the patients in the GWL group had invasive carcinoma present resulting in at least one positive margin compared with only 3 patients in the RSL group (10 vs 3%, respectively, p = 0.045). CONCLUSION: In this study, RSL is shown to be non-inferior to the use of GWL for non-palpable carcinoma in patients undergoing BCS and we suggest that it could be introduced successfully in other breast units. Advances in knowledge: Here we have demonstrated the use of RSL localization results in significant lower weight resection specimens of breast carcinoma when compared with a matched group using GWL, without any significant differences in oncological outcome between the groups.

The Internet: What are our patients exposed to when considering breast reconstruction following mastectomy?

BACKGROUND: The exponential increase in internet use has transformed the healthcare provider-patient relationship. There is a need to guide patients. This study analyses the information available, clinicians approach and patients' experiences. METHODS: An internet search, "breast reconstruction after mastectomy" was performed on Google and Bing search engines. The first 100 sites on each search were analysed. Target audience, provider and readability were assessed. Modified Health on the Net criterion was used to assess quality. Additionally clinicians and patients were surveyed about their experiences. RESULTS: Private companies dominated, accounting for 67% of sites, the majority advertised private healthcare groups. Of "information pages", 16% were government sites and 9% were from professional bodies but 28% were private. Blogs had high rates of surreptitious advertising. Patients wanted guidance on which sites to use. Endorsed sites were commonly recommended and used despite only accounting for 13 of the 100 sites. CONCLUSION: The internet is a powerful tool for disseminating information. There is a wide variety of information presented on breast reconstruction following mastectomy from a range of providers with different interests. Patients should not only be provided with a list of internet resources but also counselled on the types of information they may encounter.

Synchronous gastric and colonic metastases of invasive lobular breast carcinoma: case report and review of the literature.

Breast cancer is the most common malignancy in women and the main cause of cancer death in the UK. Gastrointestinal (GI) tract metastasis and carcinomatosis from primary breast cancer are rare but breast cancer is the second most common primary malignancy to metastasise to the GI tract after malignant melanoma. The metastatic patterns of invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) have been shown to differ considerably. Liver, lung and brain metastases are more common in IDC. Most series report a greater prediliction for lobular carcinoma to metastasise to the GI tract, gynaecological organs or peritoneum. The presentation of GI metastasis due to breast cancer is typically vague and the clinical, radiological, endoscopic and histopathologic findings are often difficult to distinguish from primary gastric carcinoma. Such a patient is more likely to present to a luminal surgeon or gastroenterologist than a breast surgeon. Therefore a high index of clinical suspicion with early endoscopy in those with non-specific symptoms and a past history of breast cancer, particularly ILC, are recommended. It is imperative to differentiate between metastatic breast cancer and primary gastric carcinoma as treatment strategies differ hugely. Therefore, correlation of endoscopic biopsy histology with the primary breast cancer histology is essential. Treatment modalities are limited to appropriate systemic therapy, which may have a palliative effect in up to 50%. Surgical intervention is nearly always limited to palliative bypass only. Prognosis is consistent with the median survival of all women with metastatic disease secondary to breast cancer.

An unusual case of chronic anal pain--a pin in the bum?

We report the case of a 70-year-old woman who had previously undergone anterior resection in 2001 for a diverticular stricture. Bleeding from pelvic veins intra-operatively necessitated the use of two thumbtacks to aid haemostasis. Over the next 7 years, she presented repeatedly with anal pain, bleeding and mucus discharge per rectum. Multiple lower gastrointestinal endoscopies failed to make a definitive diagnosis until a single thumbtack was found eroding through the rectal mucosa. This was removed and she has been subsequently asymptomatic. This condition was clearly difficult to diagnose and requires a high index of suspicion in those patients who have previously undergone pelvic surgery.

Should chest drains be put on suction or not following pulmonary lobectomy?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether the use of suction applied to chest drains in patients undergoing lobectomy reduces the incidence of prolonged air leak. Altogether 391 papers were found using the reported search, of which 6 represented the best evidence on this topic, including 5 well conducted prospective randomised controlled trials. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses were tabulated. We conclude that of the 6 studies presented, no studies found in favour of suction to reduce the incidence of air leak, 2 studies found no difference between the two strategies, and 4 studies found evidence that water seal drainage without suction reduced the incidence of air leak. Five of the 6 studies used a short period of suction in the immediate post-operative period and the one study looking at immediate water seal drainage found no differences in outcome. Exceptions to the water seal strategy may be patients with a large air leak, or a large pneumothorax on CXR.