Interplay between membrane lipid peroxidation, transglutaminase activity, and cyclooxygenase 2 expression in the tissue adjoining to breast cancer.

Breast cancer, a leading cause of cancer related deaths worldwide, is one of the most common neoplasms in women. The increased generation of reactive oxygen species (ROS) in breast lesion is critically involved in the mutagenic processes that drive to breast carcinoma initiation and progression. To date, the molecular events occurring in the tissue adjoin the cancer lesion have not been elucidated. Here, we investigated the role of excess ROS generation during human breast carcinogenesis by evaluating oxidative stress biomarkers, tissue transglutaminase (t-TGase) activity, and expression levels of ubiquitin and cyclooxygenase-2 (COX-2) in the normal tissue adjoin to fibroadenoma (nFA), atypical ductal hyperplasia (nADH), and invasive ductal carcinoma (nIDC) from 45 breast cancer patients. We found that lipid peroxidation and nitric oxide production significantly increased in nIDC respect to nFA and nADH (P < 0.005) whereas the 4-hydroxy-2-nonenal (HNE) protein-adducts increased only in nADH (P < 0.005). The increased lipid damage observed in nIDC correlates with estrogen receptor exposure in IDC (R(2) = 0.89). Moreover, nIDC and invasive ductal carcinoma (IDC) showed a 10-fold higher t-TGase activity compared to nFA and nADH. Contrary, COX-2 expression levels significantly decreased nIDC and IDC respect to the nFA and nADH (P < 0.001). The analysis of the free ubiquitin expression revealed equal levels in nADH and nIDC samples whereas high molecular weight-ubiquitin conjugate increased about fivefold only in nIDC (P < 0.01 vs. nADH). These novel findings reveal an interplay between membrane lipid peroxidation, t-TGase activity, and COX-2 expression levels in the tissue adjoining to neoplastic lesion during breast cancer progression.

Electrochemotherapy of cutaneous metastastes from breast cancer in elderly patients: a preliminary report.

BACKGROUND: The management of cutaneous metastases often represents a challenge because they may be widespread and may recur after radiotherapy or chemotherapy; breast cancer accounts for 51% of the total cases of cutaneous metastases. When surgical excision of chest wall recurrences is not possible and other local treatments such as radiotherapy or radiotherapy with hyperthermia fail, topical chemotherapy and electrochemotherapy (ECT) might be taken into account.ECT is a new local treatment of solid tumors which can be defined as the local potentiation, by means of permeabilizing electric pulses, of the antitumor activity of a non permeating anticancer drug with high intrinsic cytotoxicity. METHODS: This prospective observational study took place throughout March 2010 to October 2011. Twelve consecutive elderly patients (1 man and 11 women, median age of 76 years) with regional or distant skin or subcutaneous metastases from breast cancer, with or without visceral disease, were included in the study. Patient enrollment was carried out according to the ESOPE criteria. Bleomycin administration was followed by the application of brief electric pulses to each tumor nodule within 8 min after intravenous infusion of the drug. Electric currents were delivered by means of a 2-3 cm long needle electrode according to lesion size. All treatments were performed using the CliniporatorTM device. RESULTS: We observed Complete Response(CR) in 75.3% (107 metastases), Partial Response(PR) in 17% (24 metastases), no change in 7.7% (11 metastases) . No serious ECT-related adverse events were reported; adverse events consisted of pain in the treated area one to two days after treatment (1 patient, 8.3%) and ulceration of treated area (1 patient, 8.3%). CONCLUSION: ECT could be suggested as a primary local therapy in patients not suitable for surgical removal of the primary tumor, and clinicians should not hesitate to use it even in the elderly.

The sentinel lymph node: a suitable technique in breast cancer treatment?

AIM: The sentinel lymph node biopsy (SLNB) was firstly introduced by Giuliano and co. in 1994 for the treatment of breast cancer; in comparison to the axillary lymph node dissection (ALND), the sentinel lymph node biopsy has shown both a lower morbidity and acceptable distance results. We want to show that this technique is reliable and should be used routinely in selected cases. MATERIALS OF STUDY: The study on the sentinel lymph node has been carried out, prior informed consent, in 128 patients aged between 27 and 80 years and suffering from non-multicentric infiltrating breast carcinoma, with a diameter not greater than 3 cm, clinically negative axillary, and hospitalized from January 1998 to September 2005 at the Department of Gerontology, Geriatrics and Metabolic Diseases of the Second University of the Study of Naples. For the recruitment of patients subjected to the sentinel lymph node research study, we have respected the inclusion criteria. RESULTS: Histological examination of the tumor revealed 95 cases of ductal carcinoma, 16 cases of mucinus carcinoma, 13 of lobular carcinoma and 4 of medullary carcinoma. The sentinel lymph node was detected through lymphoscintigraphy in 96.9% of the cases (124 patients), whereas it was not possible to identify it in 4 patients (3.1% of the cases), 2 of which had previously been subject to excision biopsy. DISCUSSION: The SLNB is characterized by an identification rate of SLN > 90% with a false negative rate less than 5%. In our study we have found an SLN identification rate of 96.9% with false-negative rates of 3.9%. Our data show that in only 6,3% of the patients (4 non- identified and 4 false-negative cases) it was necessary to perform ALND because the SLN resulted positive; however no metastasis were observed in level III lymph nodes. CONCLUSIONS: Since its inception, the sentinel lymph node technique has gained an increasingly important role in the conservative treatment of the breast carcinoma due to the short duration of the surgery, the decrease of post-operative pain, the risk of lymphedema onset and hospital confinement, the high predictive power and the diagnostic accuracy. We strongly believe that the sentinel lymph node technique is reliable and should be used routinely in selected cases.

Congenital adrenal hyperplasia and Leydig cell tumor of testis. Case report and review of literature.

Adrenogenital Syndrome, more properly defined as Congenital Adrenal Hyperplasia (CAH), is related to the enzyme 21-beta-hydroxylase deficiency, with impaired glucocorticoids and aldosterone syntheses and increased ACTH synthesis. This report describes a case of a monorchid patient suffering from Adrenogenital Syndrome and Leydig cell tumor of his testis. A right orchidectomy with implantation of testis prosthesis was performed, after informing the patient on the consequences of his castration and obtaining his consent. Histology showed a testis measuring 4 x 3 x 2.5 cm with a 6 cm long spermatic cord; there was a yellowish, well-defined nodule measuring 3.5 x 1.5 cm, surrounded by normal parenchyma. This nodule had morphologic and immunohistochemical characteristics of a Leydig cell tumor, even found in the spermatic cord; those cells showed positivity to inibine, MART-1 and vimentine.

[Excisional biopsy with wire localisation of non-palpable breast lesions: indications and limitations]. / Biopsia escissionale con repere metallico delle lesioni non palpabili della mammella: indicazioni e limiti.

Preoperative localisation of non-palpable breast lesions is necessary for excisional biopsies. This can be achieved with methods such as anchor wire, charcoal marking, or radio-guided localisation. The aim of the present study was to evaluate retrospectively our experience with the wire localisation technique. One hundred and eighty-two patients with non-palpable breast lesions (diameter: 0.4-1.5 cm) were operated on under local anaesthesia. Intraoperative X-rays were performed in all cases. No serious perioperative complications occurred. Three patients (2 with postoperative haematomas and 1 with wound infection) underwent conservative therapy. The lesions were benign in 67/182 patients (37%), ductal and/or lobular invasive cancer in 42 (23%), carcinoma in situ in 23 patients (12.5%) and ADH-ALH in 50 patients (27.5%). Our experience confirms that wire localisation biopsies constitute an excellent method for the excision of non-palpable breast lesions. This technique is characterised by high reliability (100% total excisions) and assures a prognostic evaluation of high-risk lesions such as ductal an/or lobular atypical hyperplasia.

Angiosarcoma of the breast: a new therapeutic approach?

INTRODUCTION: Angiosarcomas are highly malignant endothelial cell tumors with poor prognosis. These can be due to breast cancer itself or to subsequent therapeutic modalities. No evidence-based guidelines exist concerning the ideal treatment of angiosarcomas. PRESENTATION OF THE CASE: We report the case of a 76-year-old woman who developed an exuberant and aggressive post radiation angiosarcoma of the breast and discuss different aspects of therapy for this disease. A total left mastectomy was performed, followed by a right mastectomy. The lesions into the chest wall, and multiple abdominal skin nodules were treated with local Electrochemotherapy (ECT) with intravenous bleomicin. DISCUSSION: No evidence-based guidelines exist concerning the ideal treatment of angiosarcomas. Electrochemotherapy (ECT) is an efficient palliative treatment of cutaneous and subcutaneous tumor nodules. It consists of the combination of a cytotoxic drug and electroporation, using appropriate electrical parameters; destabilization of the membrane is reversible, ensuring a high survival of permeabilized cells and the delivery of non-permeant molecules inside the cell. CONCLUSION: Due to the rarity of the disease, prospective studies concerning adjuvant or neoadjuvant therapy are limited and no evidence-based guidelines exist. The response to chemotherapy seems to be poor. Treatment with ECT in addition to systemic chemotherapy achieves a complete response in all the lesions and improving patient body image perception.

The effects of low-thrombin fibrin sealant on wound serous drainage, seroma formation and length of postoperative stay in patients undergoing axillary node dissection for breast cancer. A randomized controlled trial.

BACKGROUND: Breast cancer surgery with axillary lymphadenectomy may be associated with prolonged stay of the drain in the axilla due to high wound output, which may require further treatments and prolong the length of stay, impairing quality of life. No definitive data are available concerning how to prevent this complication. Our aim was to assess the efficacy of a new low-thrombin fibrin glue in reducing the serous output from the axillary surgical wound in patients undergoing axillary node dissection for breast cancer, and its long-term effects on lymphedema. METHODS: Sixty patients undergoing surgery between September 2012 and June 2013 were enrolled. Thirty patients received Artiss®(Baxter, UK) fibrin glue plus drainage, and 30 drainage alone. A multivariate analysis was performed to identify predictors of seroma, and subgroup analyses were performed. Lymphedema was assessed 12 months after surgery. RESULTS: Patients who received fibrin glue had reduced serum output collected in the drain after surgery (94.3 ± 22.4 vs 176 ± 24.6 ml p < 0.001) and shorter length of postoperative hospital stay (p = 0.001). Incidence of seroma at 4-week follow-up did not differ between groups. At multivariate analysis, BMI ≥ 30 kg/m(2) was the only independent predictor of seroma formation (OR = 2.7, 95%CI 1.4-5.3; p = 0.002). Overweight patients receiving Artiss® had fewer seroma at 4-week follow-up compared with control overweight patients (0% vs 55.6%, p = 0.03). No differences were observed in lymphedema between groups (6.7% vs 10%, p > 0.99). CONCLUSIONS: Low-thrombin fibrin glue reduced the amount of fluid produced in the axilla after breast surgery. Overweight patients may be the ideal candidates for this treatment. Such sealant did not increase the rates of lymphedema.

Preventive NPWT over closed incisions in general surgery: does age matter?

Surgical site events (SSE), including surgical wound complications and surgical site infections, are a major concern in patients undergoing general surgery operations. These increase the costs of care, and can lead to prolonged hospital stay and need for further treatments, ultimately resulting in poor quality of life. Negative pressure wound therapy (NPWT) has been recently reported as a preventive strategy to avoid SSE, but little is known on the topic, and particularly in geriatric population. Our primary aim was to assess the efficacy of NPWT by means of a pocket device (PICO, Smith & Nephew, London, UK) in preventing SSE compared with conventional dressings in patients undergoing surgery with primary wound closure for breast and for colorectal diseases in our Unit. Our secondary aims were to assess the efficacy and safety of PICO in elderly patients, and to seek for differences between breast and abdominal results. All consecutive patients undergoing breast and colorectal surgery in our Unit between September 2012 and May 2014 were prospectively enrolled in this open label controlled study. Breast patients receiving NPWT were assigned to group B1, those receiving conventional dressings were assigned to group B2. Colorectal patients were assigned to group C1 (NPWT) and C2 (conventional dressings) in similar fashion. Each group included 25 patients, and at least 10 (40%) patients aged over 65 years to allow sub-analyses. NPWT significantly reduced SSE in both breast and colorectal patients compared with controls. No significant differences were observed according to age. Similar benefits were observed in breast and colorectal patients. Our results suggest that PICO is an effective tool to prevent SSE in patients undergoing general surgery, irrespective of age. Its use is recommended in frail, elderly patients at risk of SSE.

Sutureless fixation with fibrin glue of lightweight mesh in open inguinal hernia repair: effect on postoperative pain: a double-blind, randomized trial versus standard heavyweight mesh.

BACKGROUND: Open inguinal hernia repair is associated with a low incidence of complications that can be influenced by the type of mesh and its method of fixation. Our aim was to investigate the frequency and severity of postoperative pain and other complications when lightweight, large-pore meshes, compared with heavyweight, small-pore meshes, are fixed with human fibrin glue (HFG) during open inguinal hernia repair. METHODS: A cohort of 80 patients undergoing open inguinal repair were enrolled. Forty patients received a lightweight and large porous mesh and 40 a standard heavyweight mesh with small pores. In all patients, HFG was used for mesh fixation. RESULTS: Patients who received lightweight, large-pore mesh reported less pain than those in the control group both postoperatively (2.8 ± 1.1 vs. 4.9 ± 1.1; P = .0003) and at 1-month follow-up (1.7 ± 1.0 vs. 3.1 ± 1.0; P = .0038), and took fewer analgesics. There was no difference in days off work/activity. No differences were observed concerning postoperative complications. After 6 months there was no difference in groin pain between groups. CONCLUSION: Patients who underwent open inguinal hernia repair with lightweight, large-pore mesh fixed with HFG experienced less pain throughout the first month after operation compared with those receiving standard mesh.