A clinical experience of the supraclavicular flap used to reconstruct head and neck defects in late-stage cancer patients

The supraclavicular island flap has been widely used in head and neck reconstruction, providing an alternative to the traditional techniques like regional or free flaps, mainly because of its thin skin island tissue and reliable vascularity. Head and neck patients who require large reconstructions usually present poor clinical and healing conditions. An early experience using this flap for late-stage head and neck tumour treatment is reported. Forty-seven supraclavicular artery flaps were used to treat head and neck oncologic defects after cutaneous, intraoral and pharyngeal tumour resections. Dissection time, complications, donor and reconstructed area outcomes were assessed. The mean time for harvesting the flaps was 50 min by the senior author. All donor sites were closed primarily. Three cases of laryngopharyngectomy reconstruction developed a small controlled (salivary) leak that was resolved with conservative measures. Small or no strictures were detected on radiologic swallowing examinations and all patients regained normal swallowing function. Five patients developed donor site dehiscence. These wounds were treated with regular dressing until healing was complete. There were four distal flap necroses in this series. These necroses were debrided and closed primarily. The supraclavicular flap is pliable for head and neck oncologic reconstruction in late-stage patients. High-risk patients and modified radical neck dissection are not contraindications for its use. The absence of the need to isolate the pedicle offers quick and reliable harvesting. The arc of rotation on the base of the neck provides adequate length for pharyngeal, oral lining and to reconstruct the middle and superior third of the face. (C) 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

The impact of atmospheric particulate matter on cancer incidence and mortality in the city of São Paulo, Brazil

This study aimed to verify the impact of inhalable particulate matter (PM10) on cancer incidence and mortality in the city of São Paulo, Brazil. Statistical techniques were used to investigate the relationship between PM10 on cancer incidence and mortality in selected districts. For some types of cancer (skin, lung, thyroid, larynx, and bladder) and some periods, the correlation coefficients ranged from 0.60 to 0.80 for incidence. Lung cancer mortality showed more correlations during the overall period. Spatial analysis showed that districts distant from the city center showed higher than expected relative risk, depending on the type of cancer. According to the study, urban PM10 can contribute to increased incidence of some cancers and may also contribute to increased cancer mortality. The results highlight the need to adopt measures to reduce atmospheric PM10 levels and the importance of their continuous monitoring.

Reorganization of secondary and tertiary health care levels: impact on the outcomes of oral cancer screening in the São Paulo State, Brazil

This study presents the strategies for prevention and early detection of oral cancer by means of screening in the elderly population of São Paulo, the richest and the most populous state of Brazil. This research was a retrospective longitudinal study based on the analysis of secondary data. The variables - number of participating cities, coverage of screening, and number of suspicious and confirmed cases of oral cancer - were divided into two periods: 2001-2004 and 2005-2008. Data were analyzed statistically by the chi-square test at 5% significance level. The implementation of a nationwide public oral health policy in 2004 and the reorganization of the secondary and tertiary health care were evaluated as mediator factors able to interfere in the achieved outcomes. From 2001 to 2008, 2,229,273 oral examinations were performed. There was an addition of 205 participating cities by the end of the studied period (p<0.0001). The coverage of oral cancer screening increased from 4.1% to 16% (p<0.0001). There was a decrease in the number of suspicious lesions (from 9% in 2005 to 5% in 2008) (p<0.0001) and in the rate of confirmed oral cancer cases per 100,000 examinations (from 20.89 in 2001 to 10.40 in 2008) (p<0.0001). After 8 years of screening, there was a decrease in the number of suspicious lesions and confirmed cases of oral cancer in the population. The reorganization of secondary and tertiary health care levels of oral care seems to have contributed to modify these numbers, having a positive impact on the outcomes of oral cancer screening in the São Paulo State.

Extensive extranodal metastases of basal-like breast cancer with predominant myoepithelial spindle cell differentiation

A differentiation towards myoepithelial cells has been demonstrated in several types of lesions in the breast. These include multifocal myoepitheliomatosis, the rare mixed tumor or pleomorphic adenoma, adenoid cystic carcinoma, adenomyoepithelioma and myoepithelial carcinoma (malignant myoepithelioma). Myoepithelial carcinoma is the only lesion purely composed of myoepithelial cells. All these tumors are benign and/or of low-grade malignancy, with the exception of malignant myoepithelioma. In contrast to the statement of the current World Health Organization (WHO), recent studies have reported that regional and distant metastases may occur in about 50% of pure myoepithelial carcinomas. The presented case of a breast carcinoma with dominant myoepithelial/spindle cell differentiation in a 58-year-old woman is an excellent example to document the highly aggressive biological behavior of this tumor phenotype. Despite an extensive chemotherapy and radiotherapy, the tumor was rapidly progressive, forming a finally exulcerating local tumor relapse and widespread metastases to the myocardium, lungs, liver, kidneys and skin. Similarities in morphology and biological behavior compared to patients with "triple-negative" (hormone receptor and Her2) monophasic sarcomatoid carcinomas and pure spindle cell sarcomas are discussed.

Education of tobacco use prevention and cessation for dental professionals--a paradigm shift

The use of tobacco continues to be a substantial risk factor in the development and progression of oral cancer, periodontitis, implant failure and poor wound healing. Dental and dental hygiene education providers have made great advances towards the incorporation of tobacco education into their curricula in recent years. Unfortunately, however, both medical and dental education research has consistently reported schools providing only basic knowledge-based curricula that rarely incorporate more effective, behaviourally-based components affecting long-term change. The limited training of oral healthcare students, at least in part, is reflected in practising dental professionals continuing to report offering incomplete tobacco interventions. In order to prepare the next generation of oral healthcare providers, this paper proposes a paradigm shift in how tobacco use prevention and cessation (TUPAC) may be incorporated into existing curricula. It is suggested that schools should carefully consider: to what level of competency should TUPAC be trained in dental and dental hygiene schools; the importance of establishing rapport through good communication skills; the core knowledge level for TUPAC; suggested instructional and assessment strategies; the importance of continuing professional education for the enhancement of TUPAC.

Consensus Report: 2nd European Workshop on Tobacco Use Prevention and Cessation for Oral Health Professionals

Tobacco use has been identified as a major risk factor for oral disorders such as cancer and periodontal disease. Tobacco use cessation (TUC) is associated with the potential for reversal of precancer, enhanced outcomes following periodontal treatment, and better periodontal status compared to patients who continue to smoke. Consequently, helping tobacco users to quit has become a part of both the responsibility of oral health professionals and the general practice of dentistry. TUC should consist of behavioural support, and if accompanied by pharmacotherapy, is more likely to be successful. It is widely accepted that appropriate compensation of TUC counselling would give oral health professionals greater incentives to provide these measures. Therefore, TUC-related compensation should be made accessible to all dental professionals and be in appropriate relation to other therapeutic interventions. International and national associations for oral health professionals are urged to act as advocates to promote population, community and individual initiatives in support of tobacco use prevention and cessation (TUPAC) counselling, including integration in undergraduate and graduate dental curricula. In order to facilitate the adoption of TUPAC strategies by oral health professionals, we propose a level of care model which includes 1) basic care: brief interventions for all patients in the dental practice to identify tobacco users, assess readiness to quit, and request permission to re-address at a subsequent visit, 2) intermediate care: interventions consisting of (brief) motivational interviewing sessions to build on readiness to quit, enlist resources to support change, and to include cessation medications, and 3) advanced care: intensive interventions to develop a detailed quit plan including the use of suitable pharmacotherapy. To ensure that the delivery of effective TUC becomes part of standard care, continuing education courses and updates should be implemented and offered to all oral health professionals on a regular basis.

Body mass index, hormone replacement therapy, and endometrial cancer risk: a meta-analysis

Background: Body mass index (BMI) is a risk factor for endometrial cancer. We quantified the risk and investigated whether the association differed by use of hormone replacement therapy (HRT), menopausal status, and histologic type. Methods: We searched MEDLINE and EMBASE (1966 to December 2009) to identify prospective studies of BMI and incident endometrial cancer. We did random-effects meta-analyses, meta-regressions, and generalized least square regressions for trend estimations assuming linear, and piecewise linear, relationships. Results: Twenty-four studies (17,710 cases) were analyzed; 9 studies contributed to analyses by HRT, menopausal status, or histologic type, all published since 2003. In the linear model, the overall risk ratio (RR) per 5 kg/m2 increase in BMI was 1.60 (95% CI, 1.52–1.68), P < 0.0001. In the piecewise model, RRs compared with a normal BMI were 1.22 (1.19–1.24), 2.09 (1.94–2.26), 4.36 (3.75–5.10), and 9.11 (7.26–11.51) for BMIs of 27, 32, 37, and 42 kg/m2, respectively. The association was stronger in never HRT users than in ever users: RRs were 1.90 (1.57–2.31) and 1.18 (95% CI, 1.06–1.31) with P for interaction ¼ 0.003. In the piecewise model, the RR in never users was 20.70 (8.28–51.84) at BMI 42 kg/m2, compared with never users at normal BMI. The association was not affected by menopausal status (P ¼ 0.34) or histologic type (P ¼ 0.26). Conclusions: HRT use modifies the BMI-endometrial cancer risk association. Impact: These findings support the hypothesis that hyperestrogenia is an important mechanism underlying the BMI-endometrial cancer association, whilst the presence of residual risk in HRT users points to the role of additional systems. Cancer Epidemiol Biomarkers Prev; 19(12); 3119–30.

Impact of CD39 and purinergic signalling on the growth and metastasis of colorectal cancer

Despite improvements in prevention and management of colorectal cancer (CRC), uncontrolled tumor growth with metastatic spread to distant organs remains an important clinical concern. Genetic deletion of CD39, the dominant vascular and immune cell ectonucleotidase, has been shown to delay tumor growth and blunt angiogenesis in mouse models of melanoma, lung and colonic malignancy. Here, we tested the influence of CD39 on CRC tumor progression and metastasis by investigating orthotopic transplanted and metastatic cancer models in wild-type BALB/c, human CD39 transgenic and CD39 deficient mice. We also investigated CD39 and P2 receptor expression patterns in human CRC biopsies. Murine CD39 was expressed by endothelium, stromal and mononuclear cells infiltrating the experimental MC-26 tumors. In the primary CRC model, volumes of tumors in the subserosa of the colon and/or rectum did not differ amongst the treatment groups at day 10, albeit these tumors rarely metastasized to the liver. In the dissemination model, MC-26 cell line-derived hepatic metastases grew significantly faster in CD39 over-expressing transgenics, when compared to CD39 deficient mice. Murine P2Y2 was significantly elevated at both mRNA and protein levels, within the larger liver metastases obtained from CD39 transgenic mice where changes in P2X7 levels were also noted. In clinical samples, lower levels of CD39 mRNA in malignant CRC tissues appeared associated with longer duration of survival and could be linked to less invasive tumors. The modulatory effects of CD39 on tumor dissemination and differential levels of CD39, P2Y2 and P2X7 expression in tumors suggest involvement of purinergic signalling in these processes. Our studies also suggest potential roles for purinergic-based therapies in clinical CRC.

Survivin in skin pathologies

Survivin is a member of the inhibitor of apoptosis (IAP) protein family acting at the intersection between proliferation and cell survival. This protein exhibits low or undetectable expression in most adult tissues but is increased in the majority of cancers. Suggested to be one of the most cancer-specific proteins identified to date, survivin acts as a signalling node in tumour maintenance and, after first promising results, is now attracting increasing attention as a target in anti-cancer therapy. In the skin, survivin has been implicated in a number of pathological conditions such as psoriasis and tumours of melanocytic and epithelial origin. Its expression can correlate with tumour severity, metastasis and decreased patient survival and has been inversely correlated with the sensitivity to cytotoxic agents used in anti-cancer therapy. Survivin may also be of importance for normal epidermal homeostasis possibly supporting self-renewal of epidermal stem cells. In this review, the authors summarize and discuss current data of survivin in skin biology and provide a comprehensive compilation of survivin expression in skin pathologies with focus on future therapeutical use.

[Bone metastasis in prostate cancer]

Bone metastasis and skeletal complications have a devastating impact on the quality of life and are a major cause of morbidity in prostate cancer patients. In addition to established bone-targeted therapies, new drugs such as endothelin A receptor antagonists, MET and VEGFR-2 antagonists or radiopharmaceuticals are in the focus of development. The standard care in prostate cancer patients with bone metastases to prevent skeletal-related events (SRE) are bisphosphonates. Denosumab, a human monoclonal antibody against RANKL, appeared to be superior to zoledronic acid for prevention of SRE and has been shown to prolong bone metastases-free survival. In contrast to zoledronic acid, denosumab clearance is not dependent on kidney function and can be administered subcutaneously. Similar rates of toxicity were observed for both substances; however, long-term data for denosumab are limited.

Cyclin D1 in non-small cell lung cancer: a key driver of malignant transformation

PURPOSE: To review the evidence implicating the deregulation of cyclin D1 in the pathogenesis of non-small cell lung cancer (NSCLC), and to discuss the opportunities for targeted clinical intervention. METHODS: Data published until June 2006 are summarized, and previously unpublished results from our own research are included. RESULTS: In normal cells, cyclin D1 complexes with and activates cyclin-dependent kinases (CDK) and acts as a transcriptional regulator. The protein is frequently overexpressed in a wide range of cancers, sometimes coincident with CCND1 (cyclin D1) gene amplification (5-20% of tumours). A low level of somatic mutations have been seen in certain tumours. CCND1 is amplified in NSCLC and cyclin D1 is frequently overexpressed in tumours and pre-invasive bronchial lesions, generally from one parental allele. Mutation analyses revealed a frequent CCND1 gene polymorphism (A870G) that modulates alternative splicing and allows expression of an alternative cyclin D1 transcript (transcript cyclin D1b). The encoded cyclin D1b protein lacks a specific phosphorylation site required for nuclear export. Genotype has been correlated with the risk and/or severity of disease or drug response across a range of malignancies, including lung cancer. Together, these findings suggest a strong pathological role for cyclin D1 deregulation in bronchial neoplasia. CONCLUSION: Current data indicate that cyclin D1 overexpression is not a consequence of, but rather a pivotal element in the process of malignant transformation in the lung and other tissues. This understanding may open new avenues for lung cancer diagnosis, treatment and prevention.

Prevention of postmenopausal bone loss with long-cycle hormone replacement therapy

OBJECTIVE: Postmenopausal bone loss and osteoporotic fractures can be prevented by hormone replacement therapy (HRT). However, opposed HRT may increase the risk of breast cancer above that associated with estrogen alone and in non-hysterectomized women estrogen substitution alone increases the risk of uterine cancer, which triggered renewed interest in long-cycle HRT regimens (estrogen replacement therapy with progesterone-free intervals up to 6 months). The effects on bone of such long-cycle HRT regimens are unknown. The objective of the present study was to compare the effects on bone and the endometrium of long-cycle HRT and conventional HRT. METHODS: Seventy-three healthy non-hysterectomized postmenopausal women were randomized to either conventional HRT (estradiol (E2) 2 mg/d during 12 days, E2 2 mg/d plus 1 mg/d of norethisterone acetate (NETA) during 10 days, E2 1 mg/d for 6 days) or long-cycle HRT treatment (two cycles with E2 2 mg/d during 28 days, followed by one cycle of conventional HRT and repeated every 3 months). Primary endpoint was the change in bone mineral density (BMD) at the lumbar spine (LS) over 24 months. RESULTS: BMD at LS increased significantly versus baseline in both treatment groups (conventional HRT +3.8 +/- 0.6%, long-cycle HRT +3.3 +/- 0.5%, p < 0.0001 for both) with no significant difference between treatment groups over 24 months. Similar significant BMD increases versus baseline were observed at the femoral neck, while biochemical markers of bone turnover (osteocalcin and deoxypyridinoline) were significantly decreased over 24 months. There were no endometrial or breast related adverse events reported. CONCLUSION: Long-cycle HRT may be a valid alternative to conventional HRT with regard to protection against postmenopausal bone loss.

Treatment of superior vena cava (SVC) syndrome and inferior vena cava (IVC) thrombosis in a patient with colorectal cancer: combination of SVC stenting and IVC filter placement to palliate symptoms and pave the way for port implantation

Thrombosis of the inferior vena cava is a life-threatening complication in cancer patients leading to pulmonary embolism. These patients can also be affected by superior vena cava syndrome causing dyspnea followed by trunk or extremity swelling. We report the case of a 61-year-old female suffering from an extended colorectal tumor who became affected by both of the mentioned complications. Due to thrombus formation within the right vena jugularis interna, thrombosis of the inferior vena cava, and superior vena cava syndrome, a combined interventional procedure via a left jugular access with stenting of the superior vena cava and filter placement into the inferior vena cava was performed As a consequence, relief of the patient's symptoms, prevention of pulmonary embolism, and paving of the way for further venous chemotherapy were achieved.

Estrogen receptor modulators and down regulators: optimal use in postmenopausal women with breast cancer

Endocrine treatments have been used in breast cancer since 1896, when Beatson reported on the results of oophorectomy for advanced breast cancer. In the second half of the last century, different endocrine-based compounds were developed and, in this review, the role of the selective estrogen receptor modulators (SERMs) and selective estrogen receptor down regulators (SERDs) in the postmenopausal setting are discussed. Tamoxifen is the most investigated and most widely used representative of these agents, and has been introduced in the advanced disease, in the neoadjuvant and adjuvant setting, and for the prevention of the disease. Its role has been challenged in recent years by the introduction of third-generation aromatase inhibitors that have proven higher activities than tamoxifen with different toxicity patterns. Several other SERMs have been investigated, but none have been clearly superior to tamoxifen. SERDs act as pure estrogen antagonists and should compare favourably to tamoxifen. For the time being, they have been used in the treatment of advanced breast cancers and their role in other settings still needs investigation. The increased use of aromatase inhibitors as first-line endocrine therapy has resulted in new discussions regarding the role that tamoxifen and other SERMs or SERDs may play in breast cancer. The sequencing of endocrine therapies in hormone-sensitive breast cancer remains a very important research issue.

Adding cetuximab to capecitabine plus oxaliplatin (XELOX) in first-line treatment of metastatic colorectal cancer: a randomized phase II trial of the Swiss Group for Clinical Cancer Research SAKK

BACKGROUND: To determine the activity and tolerability of adding cetuximab to the oxaliplatin and capecitabine (XELOX) combination in first-line treatment of metastatic colorectal cancer (MCC). PATIENTS AND METHODS: In a multicenter two-arm phase II trial, patients were randomized to receive oxaliplatin 130 mg/m(2) on day 1 and capecitabine 1000 mg/m(2) twice daily on days 1-14 every 3 weeks alone or in combination with standard dose cetuximab. Treatment was limited to a maximum of six cycles. RESULTS: Seventy-four patients with good performance status entered the trial. Objective partial response rates after external review and radiological confirmation were 14% and 41% in the XELOX and in the XELOX + Cetuximab arm, respectively. Stable disease has been observed in 62% and 35% of the patients, with 76% disease control in both arms. Cetuximab led to skin rash in 65% of the patients. The median overall survival was 16.5 months for arm A and 20.5 months for arm B. The median time to progression was 5.8 months for arm A and 7.2 months for arm B. CONCLUSION: Differences in response rates between the treatment arms indicate that cetuximab may improve outcome with XELOX. The correct place of the cetuximab, oxaliplatin and fluoropyrimidine combinations in first-line treatment of MCC has to be assessed in phase III trials.