Efficacy of Pulsed Electromagnetic Field Therapy for Pain Management After Impacted Mandibular Third Molar Surgery. A Randomized Clinical Trial.

BACKGROUND: Postoperative pain and swelling associated with the removal of the third molar (M3) adversely affect the patient's quality of life. PURPOSE: The study aims to measure pain reduction and analgesic use in patients treated with pulsed electromagnetic field (PEMF) therapy following M3 removal and compares it to patients who did not receive PEMF. STUDY DESIGN, SETTING, SAMPLE: The single-center study was designed as a randomized, prospective, controlled, double-blinded trial on a sample of patients with impacted mandibular M3 ascertained by x-ray orthopantomography and computed tomography. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLES: The predictor variable is postoperative pain management. It was assigned randomly to each subject who received either PEMF or standard therapy. MAIN OUTCOME VARIABLES: The pain was quantified using a 100 mm visual analog scale and the number of analgesics taken. Each subject kept a daily clinical diary for 7 days, recording the amount of pain using the visual analog scale and the number of analgesic tablets taken. COVARIATES: The study covariates were age, sex, tobacco use, and Pell and Gregory's classification of M3s. ANALYSES: Student's t test was used, placing the statistical significance for P value < .05. The primary planned analysis was a 2-group, continuity-corrected, χ2 test of equality of proportions. RESULTS: The study sample included 90 patients, 47 men and 43 women, with an average age of 32.43 ± 8.80 years. PEMF was statistically associated with improved pain reduction (2.08 vs 5.04 with a P value = .0002) and consumption of fewer analgesics than the control group (2.6 vs 5.8 with a P value = .0062). CONCLUSIONS AND RELEVANCE: The study's results attest to the effectiveness of PEMF therapy in pain control after M3 surgery.

Incidence and Predictors of Infections and All-Cause Death in Patients with Cardiac Implantable Electronic Devices: The Italian Nationwide RI-AIAC Registry.

BACKGROUND: The incidence of infections associated with cardiac implantable electronic devices (CIEDs) and patient outcomes are not fully known. AIM: To provide a contemporary assessment of the risk of CIEDs infection and associated clinical outcomes. METHODS: In Italy, 18 centres enrolled all consecutive patients undergoing a CIED procedure and entered a 12-months follow-up. CIED infections, as well as a composite clinical event of infection or all-cause death were recorded. RESULTS: A total of 2675 patients (64.3% male, age 78 (70-84)) were enrolled. During follow up 28 (1.1%) CIED infections and 132 (5%) deaths, with 152 (5.7%) composite clinical events were observed. At a multivariate analysis, the type of procedure (revision/upgrading/reimplantation) (OR: 4.08, 95% CI: 1.38-12.08) and diabetes (OR: 2.22, 95% CI: 1.02-4.84) were found as main clinical factors associated to CIED infection. Both the PADIT score and the RI-AIAC Infection score were significantly associated with CIED infections, with the RI-AIAC infection score showing the strongest association (OR: 2.38, 95% CI: 1.60-3.55 for each point), with a c-index = 0.64 (0.52-0.75), p = 0.015. Regarding the occurrence of composite clinical events, the Kolek score, the Shariff score and the RI-AIAC Event score all predicted the outcome, with an AUC for the RI-AIAC Event score equal to 0.67 (0.63-0.71) p < 0.001. CONCLUSIONS: In this Italian nationwide cohort of patients, while the incidence of CIED infections was substantially low, the rate of the composite clinical outcome of infection or all-cause death was quite high and associated with several clinical factors depicting a more impaired clinical status.

Maxillofacial surgical oncology during Covid-19 phase-1 and phase-2 of Italian lockdown. Single centre experience.

AIM: The aim of this retrospective study is to analyse the impact of Covid-19 on oncological surgical activity of Oral and Maxillofacial Surgery Unit of Magna Graecia University of Catanzaro, Italia. MATERIALS OF THE STUDY: This single-centre study includes patients treated for head and neck cancer (HNC) during lockdown months of March, April, May 2020 (Phase-1) and October, November and December 2020 (Phase-2); the data were compared with the same months for the previous two-year period (2018-2019). RESULTS: 35 oncological surgeries were performed at our Maxillofacial Surgery Unit in 2020. Applying both analysis of t-Student and ANOVA emerged an increase in activity for 2020. DISCUSSION: The epidemic of the 2019 novel coronavirus infection, declared a global pandemic by WHO on March 2020, has interfered with ordinary medical practice, in particular, with head and neck surgical oncology. Data for all three years (2018-19-20) were normalized for the number of beds available (in 2020, half compared to 2018-19) and were compared. CONCLUSIONS: The study demonstrates how it is possible, following strict guidelines and standard surgical protocols, to address the growing demand for surgery on cancer patients and to contain the spread of Covid-19 infection. KEY WORDS: Head and neck cancer, Oral oncology, Covid-19 infection, Maxillofacial surgery, Prevention and control, Telemedicine.

Mortality after cardioverter-defibrillator replacement: Results of the DECODE survival score index.

BACKGROUND: Device replacement is the ideal time to reassess health care goals regarding continuing implantable cardioverter-defibrillator (ICD) therapy. Only few data are available on the decision making at this time. OBJECTIVES: The goals of this study were to identify factors associated with poor prognosis at the time of ICD replacement and to develop a prognostic index able to stratify those patients at risk of dying early. METHODS: DEtect long-term COmplications after implantable cardioverter-DEfibrillator replacement (DECODE) was a prospective, single-arm, multicenter cohort study aimed at estimating long-term complications in a large population of patients who underwent ICD/cardiac resynchronization therapy - defibrillator replacement. Potential predictors of death were investigated, and all these factors were gathered into a survival score index (SUSCI). RESULTS: We included 983 consecutive patients (median age 71 years (63-78)); 750 (76%) were men, 537 (55%) had ischemic cardiomyopathy; 460 (47%) were implanted with cardiac resynchronization therapy - defibrillator. During a median follow-up period of 761 days (interquartile range 628-904 days), 114 patients (12%) died. In multivariate Cox regression analysis, New York Heart Association class III/IV, ischemic cardiomyopathy, body mass index < 26 kg/m2, insulin administration, age ≥ 75 years, history of atrial fibrillation, and hospitalization within 30 days before ICD replacement remained associated with death. The survival score index showed a good discriminatory power with a hazard ratio of 2.6 (95% confidence interval 2.2-3.1; P < .0001). The risk of death increased according to the severity of the risk profile ranging from 0% (low risk) to 47% (high risk). CONCLUSION: A simple score that includes a limited set of variables appears to be predictive of total mortality in an unselected real-world population undergoing ICD replacement. Evaluation of the patient's profile may assist in predicting vulnerability and should prompt individualized options, especially for high-risk patients.

Colorectal cancer metastatic to the breast: A case report.

BACKGROUND: Breast metastases from colorectal cancer (CRC) are very uncommon. There is no unanimous consensus regarding the best treatment for this rare condition, and management is, especially in elderly patients, limited to diagnosis and palliative care. Capecitabine, an oral fluoropyrimidine derivative, might be helpful in controlling the disease and may be a treatment option for patients unable to receive more aggressive chemotherapy. CASE SUMMARY: We report a case of synchronous massive breast metastasis from CRC in an 85 year old patient who came to the hospital presenting a huge mass originating from the axillary extension of the right breast. A whole body computed tomography also showed a mass in the right colon. The patient underwent a simple right mastectomy along with right hemicolectomy. The resected breast showed massive metastasis from CRC with intense and homogeneous nuclear CDX2 staining, while the colon specimen revealed poorly differentiated adenocarcinoma stage pT4a pN0 pM1 (breast) (Tumor Node Metastasis 2017). Three months later she developed a subcutaneous mass at the site of the previous mastectomy. An ultrasound guided biopsy was carried out again and revealed a metastasis from CRC. The patient then started treatment with capecitabine plus bevacizumab, obtaining stable disease (RECIST criteria) and a clinical benefit after 3 mo of therapy. CONCLUSION: In our experience, capecitabine and bevacizumab may be a useful treatment option for breast metastases from primary CRC in elderly patients.

Telemedicine in Oral and Maxillo-Facial Surgery: An Effective Alternative in Post COVID-19 Pandemic.

The aim of this work was to demonstrate the advantages of using telemedicine (TM) in the management of the outpatients with maxillofacial surgical pathologies during the COVID-19 pandemic. The study was conducted at the MaxilloFacial Surgery Unit of "Magna Graecia" University of Catanzaro, on two different groups of patients: a group of follow-up patients (A1: patients in oncological follow-up after surgical treatment performed before the COVID-19 pandemic; A2: suffering from chronic lesions such as precancerous lesions), and a group B of patients with first urgent visits (B1: patients with suspected oncological pathology; B2: patients with suspected urgent disease such as medication-related osteonecrosis of the jaws (MRONJ), odontogenic abscesses, temporomandibular joint (TMJ) dislocation, etc.). Participation in the study required possession of a smartphone with Internet access, e-mail and the use of a messaging service (WhatsApp or Telegram) to send photos and messages; completion by the patient of a COVID-19 screening questionnaire; submission of a satisfaction questionnaire by the doctors and patients. A total of 90 patients were included in this study. A high percentage of satisfaction emerged from the analysis of the satisfaction questionnaires of both patients and doctors.TM thus represents an excellent opportunity to improve accessibility to oncological and non-management activities, reducing the risk of Covid-19 dissemination and should be promoted and implemented in the post-pandemic era.

Jaw bones regeneration using mesenchymal stem cells. A single-center experience.

PURPOSE: Mesenchymal stem cells (MSC), which are multipotent stromal cells, are considered to be a promising resource in tissue engineering and tissue regeneration. MSCs have been used to generate new maxillary bone with clinically successful results. The aim of this study was to determine the role of MSC in bone regeneration procedures in patients with benign maxillary lesions. METHODS: A study was conducted on five patients treated for maxillary bone defects resulting from biopsy of benign lesions at the University Hospital of Magna Græcia, Catanzaro, Italy from January 2015 to October 2016. MSC from autologous bone marrow were used for bone regeneration. The bone mineral density was compared, using the Hounsfield scale, before and after treatment. Follow-up was monthly for six months, and the patients underwent a computed tomography scan of the maxilla at 6 months. RESULTS: Five patients, who underwent biopsy of osteolytic odontogenic benign tumors, were included in the study. There were no intraoperative or postoperative complications. The mean volume of the newly formed bone was 2.44cm3 (range 2,0-3,1) and the mean bone density was 1137 Hounsfield Units (range 898-1355). CONCLUSIONS: Bone regeneration with MSC from autologous bone marrow appears to be a valid treatment option for maxillary bone defects. KEY WORDS: Bone regeneration, Mesenchymal stem cells, BM-MSC, Upper jaw, Mandible.

Niraparib in ovarian cancer: results to date and clinical potential.

Ovarian cancer is the first cause of death from gynaecological malignancy. Germline mutation in BRCA1 and 2, two genes involved in the mechanisms of reparation of DNA damage, are showed to be related with the incidence of breast and ovarian cancer, both sporadic and familiar. PARP is a family of enzymes involved in the base excision repair (BER) system. The introduction of inhibitors of PARP in patients with BRCA-mutated ovarian cancer is correlated with the concept of synthetic lethality. Among the PARP inhibitors introduced in clinical practice, niraparib showed interesting results in a phase III trial in the setting of maintenance treatment in ovarian cancer, after platinum-based chemotherapy. Interestingly, was niraparib showed to be efficacious not only in BRCA-mutated patients, but also in patients with other alterations of the homologous recombination (HR) system and in patients with unknown alterations. These results position niraparib as the first PARP-inhibitor with clinically and statistically significant results also in patients with no alterations in BRCA 1/2 and other genes involved in the DNA repair system. Even if the results are potentially practice-changing, the action of niraparib must be further studied and deepened.

Update on Poly-ADP-ribose polymerase inhibition for ovarian cancer treatment.

BACKGROUND: Despite standard treatment for epithelial ovarian cancer (EOC), that involves cytoreductive surgery followed by platinum-based chemotherapy, and initial high response rates to these, up to 80 % of patients experience relapses with a median progression-free survival of 12-18 months. There remains an urgent need for novel targeted therapies to improve clinical outcomes in ovarian cancer. Of the many targeted therapies currently under evaluation, the most promising strategies developed thus far are antiangiogenic agents and Poly(ADP-ribose) polymerase (PARP) inhibitors. Particularly, PARP inhibitors are active in cells that have impaired repair of DNA by the homologous recombination (HR) pathway. Cells with mutated breast related cancer antigens (BRCA) function have HR deficiency, which is also present in a significant proportion of non-BRCA-mutated ovarian cancer ("BRCAness" ovarian cancer). The prevalence of germline BRCA mutations in EOC has historically been estimated to be around 10-15 %. However, recent reports suggest that this may be a gross underestimate, especially in women with high-grade serous ovarian cancer (HGSOC). The emergence of the DNA repair pathway as a rational target in various cancers led to the development of the PARP inhibitors. The concept of tumor-selective synthetic lethality heralded the beginning of an eventful decade, culminating in the approval by regulatory authorities both in Europe as a maintenance therapy and in the United States treatment for advanced recurrent disease of the first oral PARP inhibitor, olaparib, for the treatment of BRCA-mutated ovarian cancer patients. Other PARP inhibitors are clearly effective in this disease and, within the next years, the results of ongoing randomized trials will clarify their respective roles. CONCLUSION: This review will discuss the different PARP inhibitors in development and the potential use of this class of agents in the future. Moreover, combination strategies involving PARP inhibitors are likely to receive increasing attention. The utility of PARP inhibitors combined with cytotoxic chemotherapy is of doubtful value, because of enhanced toxicity of this combination; while, more promising strategies include the combination with antiangiogenic agents, or with inhibitors of the P13K/AKT pathway and new generation of immunotherapy.

Targeting angiogenesis in endometrial cancer - new agents for tailored treatments.

INTRODUCTION: Endometrial carcinoma represents the most frequent gynecologic tumor in developed countries. The majority of women presents with low-grade tumors but a significant subset of women experience recurrence and do not survive their disease. Patients with stage III/ IV or recurrent endometrial cancer have a poor prognosis. Identification of active and tolerable new targeted agents versus specific molecular targets is a priority objective. Angiogenesis is a complex process that plays a crucial role in the development of many types of cancer and in particular endometrial cancer. AREAS COVERED: In this review, the authors highlight the main angiogenetic molecular pathways and the anti-angiogenic agents in Phase II clinical trials for endometrial cancer treatment. The authors focus on reports from recent years on angiogenesis inhibitors used in endometrial cancer, including anti- vascular endothelial growth factor (VEGF) monoclonal antibodies (bevacizumab and aflibercept), mammalian target of rapamycin inhibitors (mTORi) (everolimus, temsirolimus and ridaforolimus), PI3 K inhibitors (BKM120), tyrosine kinase inhibitors (brivanib, sunitinib, dovitinib and nintedanib) and thalidomide. EXPERT OPINION: These anti-angiogenic drugs, while used either alone or in combination with chemotherapy, have presented mixed results in treating endometrial cancer patients. Challenges for the future include the identification of new pathways, early identification and overcoming resistance and the use of these molecules in combination with old and new chemotherapeutic and targeted agents.

Old Tyrosine Kinase Inhibitors and Newcomers in Gastrointestinal Cancer Treatment.

Gastrointestinal cancer treatment is based more on molecular biology that has provided increasing knowledge about cancer pathogenesis on which targeted therapy is being developed. Precisely, targeted therapy is defined as a "type of treatment that uses drugs, such as monoclonal antibodies or tyrosine kinase inhibitors, to identify and attack specific cancer cells". Nowadays, the United States Food and Drug Administration has approved many targeted therapies for gastrointestinal cancer treatment, as many are in various phases of development as well. In a previous review we discussed the main monoclonal antibodies used and studied in gastrointestinal cancer. In addition to monoclonal antibodies, tyrosine kinase inhibitors represent another class of targeted therapy and following the approval of imatinib for gastrointestinal stromal tumours, other tyrosine kinase inhibitors have been approved for gastrointestinal cancers treatment such as sunitinib, regoragenib, sorafenib and erlotinib. Moving forward, the purpose of this review is to focus on the efficacy data of main tyrosine kinase inhibitors commonly used in the personalized treatment of each gastrointestinal tumour and to provide a comprehensive overview about experimental targeted therapies ongoing in this setting.

Triple-negative breast cancer: new perspectives for targeted therapies.

Breast cancer is a heterogeneous disease, encompassing a large number of entities showing different morphological features and having clinical behaviors. It has became apparent that this diversity may be justified by distinct patterns of genetic, epigenetic, and transcriptomic aberrations. The identification of gene-expression microarray-based characteristics has led to the identification of at least five breast cancer subgroups: luminal A, luminal B, normal breast-like, human epidermal growth factor receptor 2, and basal-like. Triple-negative breast cancer is a complex disease diagnosed by immunohistochemistry, and it is characterized by malignant cells not expressing estrogen receptors or progesterone receptors at all, and human epidermal growth factor receptor 2. Along with this knowledge, recent data show that triple-negative breast cancer has specific molecular features that could be possible targets for new biological targeted drugs. The aim of this article is to explore the use of new drugs in this particular setting, which is still associated with poor prognosis and high risk of distant recurrence and death.

Triple-negative breast cancer: investigating potential molecular therapeutic target.

INTRODUCTION: Triple-negative breast cancer (TNBC) makes up about 10 - 20% of all breast cancers and the lack of hormone receptors and human epidermal growth factor receptor-2/Neu expression is responsible for poor prognosis, no targeted therapies and trouble in the clinical management. Tumor heterogeneity, also within the same tumor, is a major cause for this difficulty. Based on the introduction of new biological drugs against different kinds of tumor, many efforts have been made for classification of genetic alterations present in TNBC, leading to the identification of several oncogenes and tumor suppressor genes involved in breast cancer carcinogenesis. AREAS COVERED: In this review we investigated the molecular alteration present in TNBC which could lead to the creation of new targeted therapies in the future, with the aim to counteract this disease in the most effective way. EXPERT OPINION: In this context some hormone receptors like G-protein-coupled receptor 30 and androgen receptors may be a fascinating area to investigate; also, angiogenesis, represented not only by the classical VEGF/VEGFR relationship, but also by other molecules, like semaphorins, fibroblast growth factor and heparin-binding-EGF-like, is a mechanism in which new developments are expected. In this perspective, one technique that may show promise is the gene therapy; in particular the gene transfer could correct abnormal genetic function in cancer cells.

Angiogenesis and antiangiogenic agents in cervical cancer.

Standard treatment of cervical cancer (CC) consists of surgery in the early stages and of chemoradiation in locally advanced disease. Metastatic CC has a poor prognosis and is usually treated with palliative platinum-based chemotherapy. Current chemotherapeutic regimens are associated with significant adverse effects and only limited activity, making identification of active and tolerable novel targeted agents a high priority. Angiogenesis is a complex process that plays a crucial role in the development of many types of cancer. The dominant role of angiogenesis in CC seems to be directly related to human papillomavirus-related inhibition of p53 and stabilization of hypoxia-inducible factor-1α. Both of these mechanisms are able to increase expression of vascular endothelial growth factor (VEGF). Activation of VEGF promotes endothelial cell proliferation and migration, favoring formation of new blood vessels and increasing permeability of existing blood vessels. Since bevacizumab, a recombinant humanized monoclonal antibody binding to all isoforms of VEGF, has been demonstrated to significantly improve survival in gynecologic cancer, some recent clinical research has explored the possibility of using novel therapies directed toward inhibition of angiogenesis in CC too. Here we review the main results from studies concerning the use of antiangiogenic drugs that are being investigated for the treatment of CC.

Pleomorphic adenoma of the parotid: extracapsular dissection compared with superficial parotidectomy--a 10-year retrospective cohort study.

The purpose of this study was to investigate the complication rates and effectiveness of extracapsular dissection compared with superficial parotidectomy for pleomorphic adenomas of the parotid gland from 2002 to 2012. The authors carried out a retrospective cohort study of 198 patients with pleomorphic adenomas of the parotid gland. Extracapsular dissection (ED) or superficial parotidectomy (SP) was performed. The recurrence rate and complications of the two surgical techniques were measured with a univariate analysis of each variable using the appropriate statistical analysis (chi-squared test or t-test). A total of 198 patients were enrolled between January 2003 and December 2012. The study included 97 females (48.99%) and 101 males (51.01%) whose mean age was 50.97 years (range 14-75). The type of surgery performed was ED in 153 patients (77.27%, 80 males and 73 females) and SP in 45 patients (22.73%, 21 males and 24 females). The mean follow-up time was 61.02 +/- 4.9 months for the patients treated with ED and 66.4 +/- 4.5 months for the patients treated with SP. Transient facial nerve injury and facial paralysis were significantly more frequent after SP than after ED (P = 0.001 and P = 0.065, resp.). No significant differences in capsular rupture, recurrence, and salivary fistula were observed after SP or ED: 2.2% versus 3.9%, 2.2% versus 3.3%, and 2.2% versus 0.65%, respectively. Extracapsular dissection may be considered the treatment of choice for pleomorphic adenomas located in the superficial portion of the parotid gland because this technique showed similar effectiveness and fewer side effects than superficial parotidectomy.

Antiarrhythmic strategies in patients with atrial fibrillation managed by cardiologists and internists: Antithrombotic Agents in Atrial Fibrillation (ATA-AF) survey.

AIMS: To provide insights on the antiarrhythmic management of atrial fibrillation among patients enrolled in the Antithrombotic Agents in Atrial Fibrillation (ATA-AF) study, and to assess the adherence of the Italian cardiologists and internists to guidelines recommendations. METHODS AND RESULTS: The ATA-AF study is a multicenter, observational study with prospective data collection on the management and treatment of patients with atrial fibrillation. From March to July 2010, 6910 patients with atrial fibrillation were recruited in 164 Italian Cardiology (Card) and 196 Internal Medicine (IMed) centers. Permanent atrial fibrillation was diagnosed in 50.8%, persistent atrial fibrillation in 24.4%, paroxysmal in 15.5%, and first-detected atrial fibrillation in 9.3% of the patients. Rhythm control (rhyC) strategy was pursued in 27.5% (39.6% Card vs. 12.9% IMed; P < 0.0001) and rate control (raC) in 51.4% (43.7% Card vs. 60.7% IMed; P < 0.0001); in 21.1% the antiarrhythmic strategy was not defined. Patients assigned to rhyC were younger and with less comorbidities than those assigned to raC. Adjusted multivariable analysis showed that atrial fibrillation type, setting of management, age and site of patient discharge were the most important independent predictors of rhyC assignment. The severity of atrial fibrillation-related symptoms was not associated with rhyC assignment. At discharge, beta-blockers, amiodarone and class 1c antiarrhythmic drugs were the drugs mainly used in the Card centers; and beta-blockers, digitalis, amiodarone and diltiazem/verapamil were used in the IMed centers. Amiodarone was overused in both Card and IMed centers. CONCLUSION: In the present study, rhyC was the strategy mainly pursued by cardiologists and raC by internists; treatment strategy assignment and antiarrhythmic therapy often do not agree with the guideline recommendations.

Correlation between fertility drugs use and malignant melanoma incidence: the state of the art.

The relationship between fertility, reproductive hormones, and risk of malignant melanoma has acquired much interest in recent years. Melanocytes are hormonally responsive cells, and some in vitro studies demonstrated that estrogen hormones stimulate the growth of melanocytes. Moreover, estrogen receptors have been identified in melanoma cells, as well as in melanocytic nevi and in normal skin. Some evidences suggest a possible link between fertility treatments and the increased risk of malignant melanoma. This article addresses this association through a scrupulous search of the literature published thus far. The aim of this review is to determine the incidence of malignant melanoma in women treated with fertility drugs and to examine if the exposure to fertility treatments really increases the risk of malignant melanoma. In particular, our analysis focused on the different types of drugs and different treatment schedules used. Finally, this study provides additional insights regarding the long-term relationships between fertility drugs and the risk of malignant melanoma.

An unusual case of spleen metastasis from carcinoma ex pleomorphic adenoma of the parotid gland.

Carcinoma ex pleomorphic adenoma is a rare tumor arising from the salivary glands that spreads through direct extension, through the lymphatic vessels, and, rarely, hematogenously. When distant metastases have been found, they have been reported mainly in the lung. We present an unusual case of carcinoma ex pleomorphic adenoma of the parotid gland with splenic metastases. The patient presented with a primary carcinoma ex pleomorphic adenoma of the parotid gland and he underwent a total parotidectomy with laterocervical lymphadenectomy ipsilateral and adjuvant radiation therapy to the right parotid area. One year later, the patient showed an ipsilateral supraclavicular lymph node recurrence, treated with surgery and radiation therapy. Two more years later, the patient developed lung and splenic lesions, detected through CT and PET. He underwent splenectomy and pathologic assessment of the specimen showed metastatic carcinoma ex pleomorphic adenoma. To our knowledge, there is no reported case of a carcinoma ex pleomorphic adenoma metastasizing to the spleen. Patients treated for carcinoma ex pleomorphic adenoma should be investigated for distant metastases with a long-term follow-up examination for local and distant metastases and new splenic lesions in these patients should be investigated.

Beyond bevacizumab: investigating new angiogenesis inhibitors in ovarian cancer.

INTRODUCTION: Ovarian cancer is the most lethal gynecological cancer, mainly because of the advanced stage of the disease at diagnosis, with recent research investigating novel targets and agents into the clinical practice, with the aim to improve prognosis and quality of life. Angiogenesis is a significant target for ovarian cancer therapy. AREAS COVERED: Areas covered in this review include the most common molecular pathways of angiogenesis, which have provided novel targets for tailored therapy in ovarian cancer patients. These therapeutic strategies comprise monoclonal antibodies and tyrosine kinase inhibitors. These drugs have as molecular targets such as vascular endothelial growth factor (VEGF), VEGF receptor, platelet-derived growth factor, fibroblast growth factor, angiopoietin and Ephrin type-A receptor 2. EXPERT OPINION: The expansion in understanding the molecular biology that characterizes cancer cells has led to the rapid development of new agents to target important pathways, but the heterogeneity of ovarian cancer biology indicates that there is no predominant defect. This review attempts to discuss progress till date in tackling a more general target applicable to ovarian cancer angiogenesis.

Identification of prognosis-related proteins in gingival squamous cell carcinoma by twodimensional gel electrophoresis and mass spectrometry-based proteomics.

OBJECTIVES: The aim of this study was to identify differentially expressed proteins in oral squamous carcinoma cells that could be potential prognosis-related cancer biomarkers. MATERIALS AND METHODS: We compared protein expression patterns from gingival squamous cellc carcinoma (GSCC) tissues and adjacent non-cancerous matched tissues by proteomic analysis using two-dimensional gel electrophoresis coupled to mass spectrometry (2D-PAGE/MS). RESULTS: Seventeen protein spots were found to be over-expressed and eight were under-expressed in cancerous tissue compared to the normal counterpart. Of these, annexin A2 and ezrin were validated by Western blot. We also demonstrated by immunohistochemistry that POSTN is highly expressed in the neoplastic tissues examined. Among the differentially expressed proteins, we focused our attention on Chloride intracellular channel 1 (CLIC1). CONCLUSION: The 2D-PAGE/MS-based proteomics appears an efficient approach in detecting and identifying differentially expressed proteins that might function as potential biomarkers and/or molecular targets for early cancer diagnosis and prognosis and that might contribute to a innovative therapeutic strategies in GSCC. However, further validation and functional studies are needed to confirm and to support these promising, still preliminary data. KEY WORDS: Cancer biomarkers, Oral squamous cell carcinoma, Proteomics.