Reduction mammoplasty and mastopexy in the previously irradiated breast - a systematic review and meta-analysis.

Breast cancer is the most common cancer diagnosed in women, and early stages are treated with lumpectomy and irradiation. Irradiation, however, leads to reduced vascularization and fibrosis, which may influence the cosmetic outcome unfavourably and increase complications after subsequent surgery on irradiated breasts. Patients with significant asymmetry after treatment may desire corrective reduction mammoplasty or mastopexy, but this may be associated with increased complication rates. This systematic review and meta-analysis aimed to investigate postoperative complication rates after bilateral reduction mammoplasty or mastopexy in women who had undergone unilateral lumpectomy and irradiation. PubMed, Medline, EMBASE and Cochrane databases were searched for eligible studies. After screening titles and abstracts, 14 full text studies were reviewed, and 7 of these were included in the analysis. The meta-analysis showed a significantly higher complication rate in the irradiated breast compared to the non-irradiated breast, rate ratio 4.82 (95% CI: 1.58, 14.70), p = 0.006. The complication rate was 54% in the irradiated breast (58/107) compared to 8% (9/107) in the non-irradiated breast (p = 0.034). This study suggests that reduction mammoplasty or mastopexy in the previously irradiated breast is associated with a significantly increased risk of complications. Careful patient selection and information are paramount in the treatment of this patient group.

Extramammary Paget's Disease and Melanoma: 2 Cases of Double Cancers.

Extramammary Paget's disease (EMPD) is a rare intraepidermal neoplastic disease. There is a well-known relationship between EMPD and underlying malignancy. However, only a few cases of EMPD and cutaneous melanoma have been reported previously. In this case report we present 2 cases of such double cancers: one as a collision tumor, the other at separate sites. We discuss the pathogenesis, treatment, and importance of a thorough clinical and radiological examination and review the literature.

Sarcomatoid Tumor following Radium Treatment.

Haemangiomas are benign skin lesions that usually regress spontaneously, but radiotherapy has previously been used to assist the regression and healing of the lesions. Radium and X-rays were used as a treatment for benign skin lesions such as haemangioma until the carcinogenic effect of ionising radiation in humans was described. We report a patient diagnosed with a sarcomatoid carcinoma. Her past history was of particular interest since she had received radium treatment for a haemangioma at the same location more than 70 years before.

Case Report: Breast Seroma Mimicking Breast Implants.

Introduction Breast seroma may be caused by a variety of factors including lymphatic disruption, continuous inflammation and foreign bodies such as breast implants. In cases of breast implants associated seroma the diagnosis of Anaplastic Large Cell Lymphoma (ALCL) should be investigated. Presentation of Case A 45-year-old Caucasian woman was referred with bilateral swelling of the breasts causing tension and pain. MRI showed accumulations compatible with bilateral silicone implants. Ultrasound-guided aspiration showed no malignancy or silicone. The patient had a history of both soy- and silicone implants. Three years prior her breast implants was removed due to capsule formation. To treat the pain and rule out potential malignancy we performed capsulectomy of only the right breast, on the wish of the patient. We found brown fluid, no breast implants and histology of fluid and tissue showed no malignancy. DISCUSSION: Breast seroma usually develops weeks after surgery such as mastectomy or axillary lymph node dissection. This patient developed a seroma through months and years after her last surgery. In cases of late seroma malignancy should be ruled out. Diagnostic statements should not solely be based on radiology, but in conjunction with clinical findings. CONCLUSION: We performed capsulectomy on a patient with breast seroma mimicking breast implants. We excluded the diagnosis of breast implant-associated ALCL. Radiology has limitations and should be considered in conjunction with the patient's statement and the clinical findings.

HLA class Ia and Ib molecules and FOXP3+ TILs in relation to the prognosis of malignant melanoma patients.

HLA class Ia (HLA-ABC) and HLA class Ib (HLA-E, -F and -G) molecules and FOXP3+ tumor-infiltrating lymphocytes (TILs) are often reported as relevant factors of tumor immune regulation. We investigated their expression as prognostic factors in 200 patients with primary cutaneous melanoma (PCM). In our cohort, patients with tumors showing upregulation of HLA-ABC molecules had significantly thicker tumors (32% vs 7%, P<0.001), frequent ulceration (20% vs 6%, P=0.007) and frequent nodular melanomas (20% vs 4%, P=0.001). Additionally, high expression of HLA-G in the tumor was a sign of bad prognosis for the patients, being associated with thick tumors (30% vs 12%, P=0.017), ulceration (24% vs 5%, P<0.001) and positive sentinel node (13% vs 6%, P=0.015). HLA-E, HLA-F and FOXP3+ TILs were not indicative of the prognosis in PCM. High HLA-ABC and HLA-G were associated with tumor aggressiveness and could be relevant predictive markers for effective immunotherapy of melanoma tumors.

Myosin-1E interacts with FAK proline-rich region 1 to induce fibronectin-type matrix.

Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase involved in development and human disease, including cancer. It is currently thought that the four-point one, ezrin, radixin, moesin (FERM)-kinase domain linker, which contains autophosphorylation site tyrosine (Y) 397, is not required for in vivo FAK function until late midgestation. Here, we directly tested this hypothesis by generating mice with FAK Y397-to-phenylalanine (F) mutations in the germline. We found that Y397F embryos exhibited reduced mesodermal fibronectin (FN) and osteopontin expression and died during mesoderm development akin to FAK kinase-dead mice. We identified myosin-1E (MYO1E), an actin-dependent molecular motor, to interact directly with the FAK FERM-kinase linker and induce FAK kinase activity and Y397 phosphorylation. Active FAK in turn accumulated in the nucleus where it led to the expression of osteopontin and other FN-type matrix in both mouse embryonic fibroblasts and human melanoma. Our data support a model in which FAK Y397 autophosphorylation is required for FAK function in vivo and is positively regulated by MYO1E.

Lip carcinoma: clinical presentation, surgical treatment, and outcome: a series of 108 cases from Denmark.

OBJECTIVE: Lip carcinomas are among the most common malignant tumours of the head and neck region but reports on the course and outcome of this disease are mainly based on Mediterranean, South American, and Oceanian populations. The aim of the study was to describe the treatment and outcome of patients with lip carcinoma at a Danish department of plastic surgery. METHOD: We conducted a single institution retrospective cohort study including patients with primary cancer of the lips including squamous cell (SCC), basal cell (BCC), and basosquamous carcinomas (BSC) in a 5-year period. RESULTS: We included 108 consecutive patients. Median age was 72 years (range 28 -98) and 58% were male. Seventy patients (65%) were diagnosed with SCC, 36 (33%) BCC, and 2 (2%) BSC. The majority of lesions were stage T1 (84%) and T2 (11%). An unexpected total of 35 (32%) patients experienced wound healing problems; whereof 19 (54%) classified as mild (not demanding treatment), 10 (29%) as moderate (non-functional surgical corrections or medical treatment of infection needed) and 6 (17%) experienced severe dehiscence (requiring surgical intervention for functional improvement). Total defect size ≥20 mm and full thickness excision was directly correlated to the risk of early postoperative complications (p-value: 0.03 and 0.04). Three patients (2/36 with BCC; 6% and 1/70 with SCC; 1%) developed local recurrence and five patients with SCC (5/70; 7%) developed regional lymph node metastases. One patient (1%) died from metastatic SCC. CONCLUSION: This study confirms that lip carcinoma is associated with a risk of recurrence and mortality. However, the risk of wound complications is notable compared to other series.

The Pathophysiological Impact of HLA Class Ia and HLA-G Expression and Regulatory T Cells in Malignant Melanoma: A Review.

Malignant melanoma, a very common type of cancer, is a rapidly growing cancer of the skin with an increase in incidence among the Caucasian population. The disease is seen through all age groups and is very common in the younger age groups. Several studies have examined the risk factors and pathophysiological mechanisms of malignant melanoma, which have enlightened our understanding of the development of the disease, but we have still to fully understand the complex immunological interactions. The examination of the interaction between the human leucocyte antigen (HLA) system and prognostic outcome has shown interesting results, and a correlation between the down- or upregulation of these antigens and prognosis has been seen through many different types of cancer. In malignant melanoma, HLA class Ia has been seen to influence the effects of pharmaceutical drug treatment as well as the overall prognosis, and the HLA class Ib and regulatory T cells have been correlated with tumor progression. Although there is still no standardized immunological treatment worldwide, the interaction between the human leucocyte antigen (HLA) system and tumor progression seems to be a promising focus in the way of optimizing the treatment of malignant melanoma.

Therapeutic Options of Chondrodermatitis Nodularis Helicis.

Chondrodermatitis Nodularis Helicis is a benign inflammatory process affecting the skin and cartilage of the ear. It typically presents as a painful nodule surrounded by an area of erythema and often prevents the patient from sleeping on the affected side. Many treatments have been described in the literature, but the condition is prone to recurrence. A literature search was performed in order to identify the best possible treatment. Fifty-eight articles were included, describing and investigating nonsurgical as well as surgical treatment modalities. Large prospective, controlled, and randomised long-term studies are lacking, but based on the available literature, we recommend starting with a conservative approach using decompression devices. Simple surgical procedures should only be used if conservative measures fail.

Changing presentation of cutaneous malignant melanoma.

INTRODUCTION: The incidence of cutaneous malignant melanoma is rapidly increasing in Denmark like in other Northern and Western European countries. Our objective was to investigate the characteristics of current patients suffering from cutaneous malignant melanoma. METHODS: We evaluated patient and tumour characteristics in a cross-sectional study based on data from the Danish Melanoma Register. We included all patients diagnosed with cutaneous malignant melanoma in Healthcare Region Zealand in 2012 and 2013. RESULTS: We identified 520 patients with invasive cutaneous malignant melanoma. More females than males suffered from cutaneous malignant melanoma. Furthermore, females were younger than males, and the anatomical distribution of malignant melanoma varied between the genders. Outcome of sentinel lymph node biopsy was associated with tumour thickness. CONCLUSIONS: When comparing findings in our study with earlier Danish studies, we see a trend towards an increase in age at diagnosis. Furthermore, tumour thickness is decreasing and the topical distribution of cutaneous malignant melanoma in females changes towards a male pattern. FUNDING: none. TRIAL REGISTRATION: The study has been approved by the Danish National Data Protection Agency.

Tumor Cell Adhesion As a Risk Factor for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma.

PURPOSE: Less than 20% of patients with melanoma who undergo sentinel lymph node (SLN) biopsy based on American Society of Clinical Oncology/Society of Surgical Oncology recommendations are SLN positive. We present a multi-institutional study to discover new molecular risk factors associated with SLN positivity in thin and intermediate-thickness melanoma. PATIENTS AND METHODS: Gene clusters with functional roles in melanoma metastasis were discovered by next-generation sequencing and validated by quantitative polymerase chain reaction using a discovery set of 73 benign nevi, 76 primary cutaneous melanoma, and 11 in-transit melanoma metastases. We then used polymerase chain reaction to quantify gene expression in a model development cohort of 360 consecutive thin and intermediate-thickness melanomas and a validation cohort of 146 melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. Logic and logistic regression analyses were used to develop a model for the likelihood of SLN metastasis from molecular, clinical, and histologic variables. RESULTS: ITGB3, LAMB1, PLAT, and TP53 expression were associated with SLN metastasis. The predictive ability of a model that included these molecular variables in combination with clinicopathologic variables (patient age, Breslow depth, and tumor ulceration) was significantly greater than a model that only considered clinicopathologic variables and also performed well in the validation cohort (area under the curve, 0.93; 95% CI, 0.87 to 0.97; false-positive and false-negative rates of 22% and 0%, respectively, using a 10% cutoff for predicted SLN metastasis risk). CONCLUSION: The addition of cell adhesion-linked gene expression variables to clinicopathologic variables improves the identification of patients with SLN metastases within 90 days of melanoma diagnosis.

Melanocytic tumour with unknown malignant potential--a Danish study of 67 patients.

The aim of our single clinical centre study was to evaluate the risk of local metastases, lymph node metastases and distant metastases in patients diagnosed with melanocytic tumour with unknown malignant potential (MELTUMP). Furthermore, we evaluated several histologic tumour characteristics as potential predictive factors. From 1 January 1999 to 30 June 2011, a total of 67 consecutive patients were diagnosed with MELTUMP in our hospital. In this study, all the pathology slides were reviewed by the same independent expert dermatopathologist. All data were retrieved from patient charts. Four patients (6%) had regional nodal dissemination at the time of the diagnosis. Furthermore, one patient (1%) developed regional spread during follow-up and another patient (1%) died from distant metastases 1 year after diagnosis. We found no predictive factors with regard to histologic tumour characteristics. Our study confirms the low malignant potential of MELTUMP. We found a low risk of nodal metastasis and mortality from distant metastasis during follow-up. We recommend that all patients diagnosed with MELTUMP should be treated according to the guidelines for invasive melanoma.

Lymphoepithelioma-like Carcinoma of the Skin: A Case with Perineural Invasion.

SUMMARY: Lymphoepithelioma-like carcinoma of the skin is a rare, low malignant cutaneous neoplasm. We report a case of an elderly woman with lymphoepithelioma-like carcinoma of the skin in the forehead. The tumor was mistaken first as actinic keratosis and later as metastatic squamous cell carcinoma. A histological reassessment showed lymphoepithelioma-like carcinoma of the skin with perineural invasion, which is rare and considered more aggressive. The patient therefore received adjuvant radiotherapy after the recommended wide excision. Lymphoepithelioma-like carcinoma of the skin is a variant of squamous cell carcinoma, and histologically, it resembles the more aggressive lymphoepithelioma of the nasopharynx. The later is Epstein-Barr positive, whereas lymphoepithelioma-like carcinoma normally is not. Lymphoepithelioma-like carcinoma is an important diagnosis to know and the disease is discussed.

Dermatofibrosarcoma protuberans: clinical series, national Danish incidence data and suggested guidelines.

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma that frequently recurs locally, but rarely metastasizes. The purpose of this work is to present a clinical series of DFSP patients and national Danish incidence data in the period 2000-2012. Furthermore, the aim is to present guidelines on the management based on a review of the literature. Medical records of 26 consecutively treated patients at the Department of Plastic Surgery in Health Care Region Zealand were reviewed and histological specimens were reassessed. To investigate national Danish incidence in the period 2000-2012, data were extracted from the national pathology registry. Finally, a literature search was performed in Pubmed and Cochrane, and 23 major publications were reviewed. Studies on Mohs Micrographic surgery were excluded. All patients were treated with wide local excision (WLE) with a median margin of 2.8 cem and a median follow-up time of 36 months. We found a local recurrence rate of 4%. Our national incidence data were based on 374 patients. The overall incidence was 0.53 per 100,000 persons. The prevalence of DFSP in the age group 20-50 years was significantly higher than the group below 20 years (p < 0.0001). Surgery is the treatment of choice for primary DFSP, local recurrences, and metastases. If clear margins cannot be obtained by WLE or surgery is not an option because of unacceptable functional or cosmetic outcome, adjuvant radiotherapy or imatinib can be considered. Chemotherapy can be a final option if other treatments fail.

Patients highly value routine follow-up of skin cancer and cutaneous melanoma.

INTRODUCTION: Skin cancer follow-up is a substantial burden to outpatient clinics. Few studies have investigated patients' views on skin cancer follow-up and cutaneous melanoma. The objective was to investigate patients' perceived benefits and the impact of follow-up. MATERIAL AND METHODS: This study included an open sample of patients attending routine follow-up at the outpatient Departments of Plastic Surgery and Dermatology, Roskilde Hospital. A total of 218 follow-up patients diagnosed with cutaneous malignant melanoma (MM), non-melanoma skin cancer (NMSC) or actinic keratosis (AK) completed a structured interview. RESULTS: A total of 97% patients found follow-up useful. Continuity and consistency were important. One third of patients felt some degree of pre follow-up anxiety. The number of anxious MM patients was significantly greater than that of NMSC patients. No significant difference was found between the number of anxious MM and AK patients. Female gender, cohabitation and age younger than 50 years were associated with increased levels of anxiety. No relation was found between the number of anxious patients or the level of anxiety and the duration of the follow-up period. CONCLUSION: The majority of patients who attended found that the follow-up had been useful. Certain demographic characteristics were associated with higher levels of anxiety and may be addressed by supportive efforts targeting these groups.

Increased morbidity in patients undergoing abdominoplasty after laparoscopic gastric bypass.

INTRODUCTION: 30-40% of the adult population in Denmark are overweight and 10-13% are obese. The number of bariatric operations reached 3,000 in 2009, and it is expected that a third or more of the patients need corrective plastic surgery. MATERIAL AND METHODS: Medical charts of all patients who had abdominoplasty performed during a 2.5-year period. We included 72 patients of whom 21 had lost weight after bariatric surgery and 51 patients had lost weight through diet and exercise or had not been overweight. RESULTS: The overall complication rate was 21% (43% of the post-bariatric patients and 12% of the non-post-bariatric patients, p < 0.01). When adjusted for the maximum body mass index (BMI) and BMI at the time of abdominoplasty, post-bariatric patients still had a higher complication rate than non post-bariatric patients (OR = 4.8; 95% CI: 0.92-25.04). Post-bariatric patients had a significantly higher maximum weight, weight at the time of abdominoplasty and had lost more BMI units. CONCLUSION: Our data show that post-bariatric patients who have an abdominoplasty performed suffer a high complication rate which appears to be higher than that of patients who do not have bariatric surgery. We have also shown a tendency towards increased costs of abdominoplasty in post-bariatric patients due to a slightly longer operating time and more postoperative office visits.

Recurrence of cutaneous malignant melanoma after more than 20 years.

Late recurrence 10 years or more after treatment for localised cutaneous malignant melanoma is unusual. We present three cases with recurrences of cutaneous melanoma after 20 years or more. Two patients presented with a nodal recurrence and one patient with systemic disease. According to published reports, risk factors for late recurrence cannot be defined. Prognosis depends on the site of recurrence with short survival after distant metastases and longer survival after local and regional recurrence. Long-term follow up is advocated.

Rising incidence of Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare, aggressive, skin cancer of obscure histogenesis, the incidence of which is rising. There is no consensus on the optimal treatment. Our aim was to evaluate the staging, investigation, treatment, and follow-up of MCC in eastern Denmark, and to investigate the incidence. We suggest guidelines for treatment. First we reviewed the medical records of 51 patients diagnosed with MCC from 1995 until 2006 in eastern Denmark. The nation-wide incidence of MCC was extracted from the Danish Cancer Registry for the calculations for the period 1986-2003. We reviwed published papers about MCC based on a MEDLINE search. Fourteen of the 51 patients developed recurrence, and 37 (73%) died during the study period. Mean follow-up was 13 months (range 1-122). A total of 153 patients were identified in the Danish Cancer Registry, and showed that incidence rates had increased 5.4 fold over the 18 year period from 1986 until 2003. Rates were highest in people over the age of 65. Recommended treatment with curative intent includes excision of the primary tumour with wide margins, excision of the sentinel node, computed tomogram (CT) or positron emission tomography (PET) of the thorax and abdomen, and adjuvant radiotherapy to the surgical bed. In the case of advanced disease, systemic palliative chemotherapy remains a possibility. There is a need for prospective multicentre evaluation of staging investigations and treatment of MCC.