Dec 2015 cancer current awareness2 by Musgrove Park Hospital Library

Clinical Librarian Service Musgrove Park Academy

Current Awareness

Cancer Issue 2 December/January 2015/2016

Bumper Christmas Issue!

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This monthly Current Awareness Bulletin is produced by the Clinical Librarian, Musgrove Park Academy, to provide Hope Directorate staff with a range of cancer/haematology related resources to support practice. It includes recently published guidelines and research articles, news and policy items.

This guide provides a selection of resources relevant to the subject area and is not intended to be a comprehensive list. For further help or guidance, please contact a member of library staff. As this is a bumper issue, with twice as many items as usual, you may wish to use the Find facility (Ctrl F) to search for items of interest. This guide has been compiled by: Terry Harrison MLGS Clinical Librarian, HOPE Directorate Musgrove Park Hospital Library Service Terence.Harrison@tst.nhs.uk

Contents Click on a section title to navigate to contents

Page Recent journal articles

New books

Cochrane Reviews

Other evidence updates

Cancer in the News

Reports, publications and resources

Training & Networking Opportunities, Conferences, Events

Literature & Evidence search services

Training and Athens

Library contact details: Library Musgrove Park Academy Musgrove Park Hospital Taunton Somerset TA1 5DA Email: Library@tst.nhs.uk Tel: 01823 34 (2433) Fax: 01823 34 (2434) Clinical Librarian email: Terence.Harrison@tst.nhs.uk

RECENT JOURNAL ARTICLES BACK TO TOP This is a list of recent journal articles on the topic of cancer (and haematology). Some articles are available in the library, or on-line via an Athens password, by following the link. If you would like an article which is not available as full text, please contact library staff: Library@tst.nhs.uk

Does the Approach of Disclosing More Detailed Information of Cancer for the Terminally Ill Patients Improve the Quality of Communication Involving Patients, Families and Medical Professionals? Purpose: Effective and faithful communication between patients and medical professionals could improve patients' quality of life and is an essential and fundamental factor in cancer treatment. The purpose of this study was to examine whether disclosing more detailed information about disease progression to terminally ill patients could improve the quality of communication. Methods: This was a before/after study of 91 consecutive terminal cancer patients. Based on the previous studies, we categorized cancer disclosure into 4 groups: A: 'non-disclosure', B: 'disclosure of cancer diagnosis', C: 'disclosure of life-threatening disease', and D: 'disclosure of poor prognosis'. We disclosed more detailed information based on the SPIKES protocol and compared the scores of 3 communication items of Support Team Assessment Schedule (Japanese version) measured between at admission and one-week after this approach. Results: A, B, C and D groups included 8, 25, 40, and 18 cases, respectively. This approach to cancer disclosure was implemented in 37.5% of group A, 60% of group B, and 40% of group C. In group B, all 3 communications were significantly improved (2.40 ± 0.51 vs 1.53 ± 0.83, 1.93 ± 0.96 vs 1.00 ± 0.38, 2.13 ± 0.64 vs 1.13 ± 0.64; p = 0.0035, 0.0062, 0.0013). In group C, all 3 communications were significantly improved (1.25 ± 0.58 vs 0.81 ± 0.66, 1.13 ± 0.34 vs 0.69 ± 0.48, 1.31±0.60 vs 0.56 ± 0.63 ; p = 0.020, 0.0082, 0.0057). Conclusions: This study revealed that disclosing more detailed information of cancer for terminally ill cancer patients contributed to improving the quality of communication, irrespective of the stage of disclosure.

Launching an Interactive Cancer Projects Map: A Collaborative Approach to Global Cancer Research and Program Development Global Oncology (GO), a nonprofit organization, and the Center for Global Health (CGH) at the National Cancer Institute (NCI) have developed a Web-based tool that facilitates planning of research, training opportunities, and community-based programs in cancer control. This tool, called the Global Cancer Project Map (GCPM; http://gcpm.globalonc.org), is an interactive Web site that enables viewers to locate cancer projects and research programs as displayed on a world map (Figure 1). GCPM currently displays more than 800 projects of more than 620 investigators working at more than 160 institutions in 88 countries (Table 1). The inaugural version of the GCPM was officially launched on March 25, 2015, at the Symposium on Global Cancer Research, sponsored by NCI, the Consortium of Universities for Global Health (CUGH), and the Dana-Farber Cancer Institute.

Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were

associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2–antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH).

Lenalidomide plus Rituximab as Initial Treatment for Mantle-Cell Lymphoma A total of 38 participants were enrolled at four centers from July 2011 through April 2014. The median age was 65 years. On the basis of the Mantle Cell Lymphoma International Prognostic Index scores, the proportions of participants with low-risk, intermediate-risk, and high-risk disease at baseline were similar (34%, 34%, and 32%, respectively). The most common grade 3 or 4 adverse events were neutropenia (in 50% of the patients), rash (in 29%), thrombocytopenia (in 13%), an inflammatory syndrome (“tumor flare”) (in 11%), anemia (in 11%), serum sickness (in 8%), and fatigue (in 8%). At the median follow-up of 30 months (through February 2015), the overall response rate among the participants who could be evaluated was 92% (95% confidence interval [CI], 78 to 98), and the complete response rate was 64% (95% CI, 46 to 79); median progression-free survival had not been reached. The 2-year progression-free survival was estimated to be 85% (95% CI, 67 to 94), and the 2-year overall survival 97% (95% CI, 79 to 99). A response to treatment was associated with improvement in quality of life.

Definitive Chemoradiotherapy vs. Surgery After Induction for Stage III Lung Cancer Stage III non–small-cell lung cancer (NSCLC) is highly variable in its presentation and is usually treated with multimodality therapy tailored to each patient. To compare surgery versus definitive concurrent chemoradiotherapy boost after induction in this setting, investigators conducted a multicenter, phase III trial (ESPATUE) involving good-performance patients (status, 0–1) with medically operable, pathologically proven stage IIIA (N2) or IIIB (N3 contralateral mediastinal nodes or T4) disease. Because the trial was closed due to slow accrual after only 246 of the planned 500 patients were enrolled, it was underpowered for the primary endpoint of overall survival (OS)

Haemophagocytic lymphohistiocytosis in adults: a multicentre case series over 7 years Haemophagocytic lymphohistiocytosis (HLH) is a syndrome of uncontrolled immune activation that has gained increasing attention over the past decade. Although classically known as a familial disorder of children caused by mutations that affect cytotoxic T-cell function, an acquired form of HLH in adults is now widely recognized. This is often seen in the setting of malignancy, infection or rheumatological disorders. We performed a retrospective review across 3 tertiary care centres and identified 68 adults with HLH. The average age was 53 years (range 18–77 years) and 43 were male (63%). Underlying disorders included malignancy in 33 patients (49%), infection in 22 (33%), autoimmune disease in 19 (28%) and idiopathic HLH in 15 (22%). Patients were treated with diseasespecific therapy and immunomodulatory agents. After a median follow-up of 32·2 months, 46 patients had died (69%). The median overall survival was 4 months (95% CI: 0·0–10·2 months). Patients with malignancy had a worse prognosis compared to those without (median survival 2·8 months versus 10·7 months, P = 0·007). HLH is a devastating disorder with a high mortality. Further research is needed to improve treatment and outcomes.

Remission and platelet responses with romiplostim in primary immune thrombocytopenia: final results from a phase 2 study In anecdotal reports, some patients with immune thrombocytopenia (ITP) maintained platelet counts 9 after discontinuing romiplostim. Here, we examined rates of platelet response (≥50 × 10 /l), remission, splenectomy and adverse events in patients with primary ITP duration ≤6 months who were treated

with romiplostim for ≤12 months. The starting dose of romiplostim was 1 μg/kg; concomitant and 9 rescue treatments were permitted to maintain platelet counts. Patients with platelet counts ≥50 × 10 /l at the end of 12 months entered a dose taper in which the romiplostim dose was decreased as long 9 as platelet counts were maintained. Remission (platelet count ≥50 × 10 /l for 24 consecutive weeks with no ITP treatments) was evaluated in patients once romiplostim was discontinued. Over the 12 months, a high response rate (>90%) was observed. Platelet response occurred quickly (median, ~2 weeks) and was observed for a cumulative median of 11 months. Remission was observed in 24 patients (32%); there were no significantly predictors of remission. Most (20/24) patients had remission start before the forced taper. No new safety signals were identified. Thus, in patients with early-stage ITP, romiplostim was well tolerated and induced rapid responses, with remission occurring in approximately one-third of patients (NCT01143038, Amgen 20080435).

Diagnosis as the First Critical Point in the Treatment Trajectory: An Exploration of Operable Lung Cancer Patients’ Lived Experiences Background: Significant advances have been made in the surgical treatment of lung cancer while patient experiences with diagnosis, treatment, and rehabilitation remain only sparsely researched. Objective: The objective of this study was to investigate how the diagnosis affects the daily lives of patients with operable lung cancer in order to identify their needs for care interventions from the point of diagnosis to hospitalization. Methods: We investigated patients’ lived experiences from a longitudinal perspective at 4 critical time points during the treatment trajectory; we present here the findings from the first time point, diagnosis. Data were collected through interviews conducted 7 to 10 days following diagnosis of lung cancer. Data from 19 patients are included, and the analysis is based on Ricoeur’s interpretation theory. The study framework is inspired by Schutz’s phenomenological sociology. Results: The findings are presented as themes that summarize and express the ways in which a diagnosis affects patients’ daily lives: the cancer diagnosis comes as a shock, it changes everyday awareness; it presents the patient with an unfamiliar body, disturbs social relationships, forces the patient to face a new life situation, and demands one-on-one supportive care. Conclusions: Diagnosis is the first critical point for patients with operable lung cancer and disrupts their daily life. Patients need psychosocial support during the period from diagnosis to surgical intervention and patient-tailored one-on-one information. Implications for Practice: This article contributes to the knowledge base of support needs of lung cancer patients. Interventions aimed at supportive care during the period between diagnosis and surgical intervention should be researched.

Predictors for Weight Loss in Head and Neck Cancer Patients Undergoing Radiotherapy: A Systematic Review Background: Head and neck cancer patients are at high risk of weight loss because of their disease process and the treatment of their disease. Recognition of predictors for weight loss may be able to give proactive or reactive nutritional treatment to patients at risk. Objective: The aim of this study is to identify the independent risk factors for head and neck cancer patients developing weight loss undergoing radiotherapy. Methods: A comprehensive literature search was performed on January 2014. Articles reporting studies of the predictors for weight loss in head and neck cancer patients undergoing radiotherapy were included. These studies were published between 1982 and 2014. Study quality was assessed using a modified quality assessment tool that was designed previously for an observational study. The effects of studies were combined with the study quality score using a best-evidence synthesis model. Results: Twenty-two observational studies involving 6159 patients were included. There was strong evidence for 3 predictors, including advanced tumor stage, a higher body mass index before treatment, and the use of concurrent chemoradiotherapy. We also identified 8 moderate evidence predictors and 30 limited evidence predictors. Conclusion: The scientific literature to date indicates that patients with advanced tumor stage, or a higher body mass index before treatment, or the use of concurrent chemotherapy are at high risk to have weight loss during radiotherapy. Implications for Practice: These data provide evidence to guide healthcare professionals in admitting patients who will have weight loss and choosing an optimal prophylactic strategy.

Palliative Cancer Patients’ Experiences of Participating in a Lifestyle Intervention Study While Receiving Chemotherapy Background: Lifestyle interventions have promise in terms of their potential health benefits and as an empowerment tool for cancer patients. Nevertheless, documentation of palliative cancer patients experiences of participating in lifestyle interventions remains poor. Objective: The objective of this study was to explore how palliative cancer patients experience participation in a feasibility study focusing on multiple lifestyle interventions (physical, nutritional, smoking cessation, and stress management) while receiving chemotherapy. Methods: This was a qualitative design with semistructured interviews of 9 palliative cancer patients 3 to 4 months after inclusion to the lifestyle intervention. Data were analyzed according to a qualitative content analysis within a hermeneutic approach. Results: Three main themes emerged: (1) adopting a healthier lifestyle, (2) taking on a more active role, and (3) boosting confidence. Participation made some participants feel guilty when they were not able to reach their own lifestyle goals. Conclusions: Participation in lifestyle interventions is valued by palliative cancer patients and may strengthen their coping abilities. However, some of the participants also expressed feelings of guilt and inadequacy. Thus, the organizational aspects of interventions need to be considered carefully to minimize the possibility of causing increased strain on the participants, who already experience the burden of coping with their disease. Implications for Practice: This study provides a unique insight into the palliative cancer patients experiences of participating in a trial focusing on multiple lifestyle interventions while receiving chemotherapy. The results may provide guidance for healthcare professionals in their efforts to help palliative cancer patients adopt a healthier lifestyle and to help patients increase their coping abilities.

Evaluation of a Community-Based Exercise Program for Breast Cancer Patients Undergoing Treatment Background: Exercise is important during treatment for breast cancer to alleviate the usual declines in physical and emotional health and overall health-related quality of life (HRQL). Objective: This study evaluated the effectiveness, safety, and enjoyment of a community exercise program for breast cancer patients who were currently undergoing or within 3 months of completing chemotherapy or radiation treatment. Methods: Breast cancer patients Engaging in Activity while Undergoing Treatment (BEAUTY) is a 12-week program of resistance, aerobic, and flexibility exercise. Participants completed pre and post fitness assessments, and questionnaires to measure HRQL, fatigue, cognitive function, and depressive symptoms. Participants had access to group exercise classes and were provided a home-based exercise program. Results: Participants (n = 80) were middle aged (mean age, 50.3 [SD, 9.0] years), and the majority were diagnosed with stage II breast cancer (53.8%). From baseline to 12 weeks, resting heart rate (mean [INCREMENT], +4.15 beats/min) and body mass index increased slightly (mean [INCREMENT], +0.47 kg/m2). No clinically significant changes in HRQL or other psychosocial questionnaires, but social well-being decreased (t77 = 3.83, P = .000) slightly, and emotional well-being improved (t77 = −2.15, P = .034). Participants attended an average of 7.5 (SD, 6.5) classes; feedback about the program was positive, and no exercise-related injuries were reported. Conclusions: The BEAUTY program was feasible and effective in managing chemotherapy and radiation treatment–related declines in physical fitness and HRQL. Implications for Practice: This study supports the need to integrate exercise programming as part of treatment plans for breast cancer patients.

A Woman’s Decision to Choose Bilateral Mastectomy Background: Rates of bilateral mastectomy as treatment for unilateral breast cancer have been rising. Quantitative analyses have resulted in assumptions about why women choose this procedure, without confirmation from the women. Objective: The objective of this study was to explore a woman’s decision making in the choice of bilateral mastectomy as a treatment for unilateral breast cancer, regardless of stage. Methods: A qualitative descriptive design was used. In-depth interviews were conducted by 2 researchers using a semistructured interview guide to elicit data, which were coded and analyzed using thematic analysis. Results: Twenty-three women were interviewed. Five themes

were identified that address specific determinants of the decision-making process: finding something, collecting evidence, perceived level of risk, identifying priorities, and making the decision. Nine women reported that their physicians recommended bilateral mastectomy. Conclusions: Women who recalled being advised of their risk of recurrence reported overestimates of that risk. The reasons women chose bilateral mastectomy were to avoid a lifetime of follow-up screenings with the subsequent fear of hearing that the breast cancer had returned and wanting to stay alive and well for their children and families. Implications for Practice: Except for women carrying genetic susceptibility to breast cancer, bilateral mastectomy is not considered the standard of care. Yet women are being offered or choosing this procedure. Nurses can be advocates for women by speaking positively about how women have the right to choose their treatment based on best evidence and personal choice. This evidence should include benefits and risks of the treatment.

A Longitudinal Study of Depressive Symptoms in Patients With Head and Neck Cancer Undergoing Radiotherapy Background: Although patients with head and neck cancer are at increased risk for depressive symptoms compared with other cancer patients, few longitudinal studies have evaluated changes in and predictors of this symptom over time. Objective: The aim of this study was to determine whether levels of depressive symptoms changed over time and whether specific demographic, clinical, symptom, or psychosocial characteristics were associated with depressive symptoms. Methods: In a longitudinal study of patients with head and neck cancer, depressive symptoms were assessed with the Center for Epidemiologic Studies–Depression scale, from the initiation of radiotherapy and for 6 months after. Hierarchical linear modeling was used to evaluate for changes in as well as for potential predictors of interindividual differences in depressive symptoms. Results: The severity of depressive symptoms increased during radiotherapy and then decreased over time. The portion of patients who reported clinically meaningful levels of depressive symptoms at each assessment ranged from 29% to 42%. Several known predictors of pretreatment severity of depressive symptoms (ie, physical symptoms, less social support, dissatisfaction with looks) were corroborated. In addition, having surgery before radiotherapy was associated with lower levels of depressive symptoms at initiation of radiotherapy. Conclusion: A moderate proportion of patients with head and neck cancer reported levels of depressive symptoms that indicated the need for clinical evaluation. Several patient characteristics were associated with depressive symptoms. Implications for Practice: Knowledge on prevalence, time course, and predictors of depressive symptoms from this study can be used to identify patients at higher risk for more severe depressive symptoms.

Cancer Patients’ Perceptions of the Barriers and Facilitators to Patient Participation in Symptom Management During an Episode of Admission Background: Symptoms by definition are subjective, and patients’ role in their assessment and management will impact on patient outcomes; thus, symptom management is an area of acute care practice where facilitation of patient participation is vital if quality outcomes are to be achieved. Objective: This study originated from a large multimethod research program exploring patient participation in symptom management in an acute oncology setting. The purpose of this article is to explore patients’ perceptions of the barriers and facilitators to participating in their symptom management during an episode of admission to an acute oncology ward and the relationships between these perceptions and patients’ preference for participation. Methods: One hundred seventyone cancer inpatients consented and completed an interview-administered questionnaire. Patients’ preference for participation was measured using the Control Preference Scale. Responses to openended survey questions were evaluated using content analysis. Results: Ten categories were identified in the analyses of patient perceptions of the barriers and facilitators to participating in care decisions relating to their symptoms. Patients, irrespective of their Control Preference, reported multiple barriers and facilitators to participating in their symptom management. Conclusions: Patients overall perceived information as the most critical component of participation. Irrespective of patients’ preference for participation, there were similarities in the barriers and facilitators to the operationalization of participation in the acute care setting reported. Implications for Practice: Understanding patient perceptions of barriers and facilitators of participating in symptom management

has provided important insights into person and system factors in the acute care sector impacting quality patient symptom outcomes.

Understanding Oestrogen Receptor Function in Breast Cancer and its Interaction with the Progesterone Receptor. New Preclinical Findings and their Clinical Implications Oestrogen antagonists have been used for decades for the treatment of patients with oestrogen receptor (ER)-positive breast cancers, to the benefit of many millions of women worldwide. However, the clinical outcomes of these women vary considerably, something that has been an important focus for research, but an unresolved issue. One key observation has been that patients with ER-positive and progesterone receptor (PR)-positive breast cancers tend to have better clinical outcomes than those with ER-positive, PR-negative tumours.

45 or 50 Gy, Which is the Optimal Radiotherapy Pelvic Dose in Locally Advanced Cervical Cancer in the Perspective of Reaching Magnetic Resonance Image-guided Adaptive Brachytherapy Planning Aims? In locally advanced cervical cancer, the dose delivered results from the sum of external beam radiotherapy and brachytherapy, and is limited by the surrounding organs at risk. The balance between both techniques influences the total dose delivered to the high-risk clinical target volume (HR-CTV). The aim of the present study was to compare the ability of reaching different planning aims after external beam radiotherapy pelvic doses of 45 Gy in 25 fractions or 50.4 Gy in 28 fractions, both considered as standard prescriptions.

Locoregional Treatment in Early Stage Breast Cancer: More Evidence and Yet More Questions? Elective comprehensive radiation therapy of the regional lymph nodes used to be a common procedure for all patients with involved axillary lymph nodes and for those with medially located tumours, irrespective of axillary nodal involvement. In the late 1980s, treatment of especially the internal mammary lymph nodes became less popular following the demonstration of increased longterm cardiac mortality associated with post-mastectomy radiation therapy and rising doubts about its contribution to the cure of breast cancer patients [1].

Neuropathic Pain Features in Patients with Bone Metastases The results of previous randomised controlled trials suggest that radiation oncologists should consider the presence of neuropathic pain when they prescribe dose fractionations for painful bone metastases. Although validated screening tools for neuropathic pain features are currently available, the prevalence of such features among patients with painful bone metastases is still poorly understood. The purpose of this study was to estimate the prevalence of neuropathic pain features among patients who received palliative radiotherapy for painful bone metastases.

Synchronous bilateral tongue cancer treated with chemoradiotherapy using superselective intraarterial infusion via bilateral superficial temporal arteries: a case report. We report a case of synchronous bilateral tongue cancer involving a 57-year-old man. The patient was referred to our hospital in 2006 and was pathologically diagnosed with bilateral tongue squamous cell carcinoma. Two catheters were superselectively inserted into the bilateral lingual arteries via the bilateral superficial temporal arteries. Radiotherapy combined with superselective intra-arterial chemotherapy using cisplatin and docetaxel was performed. The total dose of cisplatin was 258 mg/body, and that of docetaxel was 154.8 mg/body. Radiotherapy was performed at 2

Gy/fraction/day, and the total dose delivered to the primary tumor was 60 Gy/30 fractions. A complete response was achieved after treatment. There was no recurrence or cervical node metastasis during follow-up; however, the patient died of esophageal cancer 28 months after the completion of treatment.

Primary sclerosing mucoepidermoid carcinoma of the thyroid: A case report and review of the literature. Introduction: Primary sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) of the thyroid is a very rare disease. It is a recently described carcinoma of the thyroid gland associated with Hashimoto’s thyroiditis and considered to have a relatively indolent clinical course. Presentation of case: We present the clinical and histopathologic findings of a 37-year-old woman recently diagnosed with sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid. The patient, clinically euthyroid, who presented with a thyroid swelling since last 2 years along. Ultrasonography of the neck revealed a hypoechoic mass with extracapsular invasion at right thyroid gland, measuring 4. 7 cm × 1. 9 cm. Fine needle aspiration cytology suggested thyroid papillary carcinoma. Computed tomography (CT) and Ultrasonography also showed a 8mm sized heterogeneous mass at the right supraclavicular lymph node. The frozen section revealed metastatic carcinoma in right level VI, right supraclavicular lymph node. Therefore, total thyroidectomy, central neck dissection and right selective neck dissection were performed. Discussion: It is generally accepted that SMECE is a relatively indolent tumor. But it should be considered that the extended resection of SMECE with neck metastasis. Conclusion: Although SMECE is considered to be a relatively slow growing and non-aggressive tumor, occasional metastasis do occur. Physicians should be aware of extended operation, include total thyroidectomy and/or neck node dissection for metastatic lesion of neck node.

Radiotherapy induced hearing loss in head neck cancers: Screening with DPOAE. Objective:To assess the role of DPOAE in radiotherapy induced hearing loss. Study design:Prospective, observational case series in a medical college. Methods:The study enrolled 25 patients with head and neck cancer planned for radiotherapy in the dose of 2-2.25 Gy per day.All cases underwent PTA and DPOAE in a sound proof room at the time of enrolment, 6th, 12th and 20th week post-treatment. The results were analysed statistically. Results:We found significant difference at 0.5, 1, 4, 8 and 10 KHz on comparing baselinePTA to other follow up. The pair wise comparison of follow ups revealed significant difference in all frequencies except 4 and 14 KHz. DPOAE had significant difference (p < 0.05) between baseline and other follow up in all frequencies except at 5 KHz. Conclusion: OAE is simple, objective and cost effective tool that doesn’t require infrastructure and special training. Although high frequency audiometry is a preferred tool but OAE can be equally used to observe the RT induced hearing loss.

Iatrogenic Horner’s syndrome with abducent nerve paralysis after cervical schwannoma excision. Horner’s syndrome usually occurs after surgical intervention around carotid artery. A complete intracranial course of abducent nerve prevents its injury during neck surgery. We encountered an unusual complication in a 31-year-old female who underwent schwannoma excision under general anaesthesia. Patient developed Horner’s syndrome and lateral rectus palsy in immediate postoperative period. Post-operative investigations did not reveal any abnormality in abducent nerve. Patient was managed conservatively and improved. We believe that either both neural injuries occurred independently or cautery may have caused Horner’s syndrome and abducent palsy simultaneously.

Reporting of a primary sinonasal neuroendocrine small cell carcinoma in the paediatric age group.

Background- Primary Sinonasal Small Cell Carcinomas, Neuroendocrine type (SCCNET)are rare tumours. Few cases have been reported in the head and neck region of adult patients. They have a fair response to multimodality therapy; but the prognosis remains poor. Case Report- We report here a case of SCCNETin a 5 year old child. He presented with right eye swelling with diminution of vision and right sided neck swelling. Cervical lymph node biopsy revealed poorly differentiated metastatic neuroendocrine carcinoma; confirmed by immunohistochemistry. 18 FDG- PET CT scan revealed a nasopharyngeal mass extending to other paranasal sinuses and base of frontal lobe with bilateral extensive cervical lymphadenopathies. He was treated with neoadjuvant platinum based combination chemotherapy followed by radical radiotherapy. At 17 months post diagnosis he is alive but on palliative care. Conclusion- SCCNETs have an unfavorable outcome. Further improvements in our understanding of the pathology and treatment strategies are needed to combat the disease.

Multiple extramedullary plasmacytoma involving the vallecula: A case report with 3-year follow-up. Introduction: Extramedullary plasmacytoma (EMP) is a rare, malignant plasma-cell tumour that accounts for more than 0.04% of all head and neck malignancies. Multifocal EMPs involving at least two sites in the upper airway are extremely rare; to date, only 3 cases have been reported in the related English-language literature. Case report: A 63-year-old woman presented with ahusky voice and globus pharyngis for two years. Physical examination revealed two sessile laryngeal polypoid lesions and a smooth, bulging mass at the right vallecula. After excision, a left epiglottic cyst, right false vocal-fold EMP, and right vallecular EMP were confirmed. The patientwas diagnosed with stage I EMP (Durie-Salmon myeloma staging)after a battery of blood, urine, bone marrow, skeletal imaging, head and neck computed tomography, and bone scan studies. The patientrefused any post-excisional radiotherapy; however, no recurrence of the EMP or progression to multiple myeloma was detected over the subsequent 3 years. Discussion: It is difficult to associate multifocal polyps or nodules in the upper airway with EMPs because EMPs have no specific macroscopic appearance or symptom profile. The present case of multifocal EMPs at the larynx and oropharynx is novel, and this is the first case report on vallecular EMP in the related English-language literature. Moreover, this is the first case of multiple EMP that did not progress to multiple myeloma within a 3-year follow-up without adjuvant radiotherapy. Therefore, this case calls into question the need for adjuvant radiotherapy in cases of EMPs if complete excision with negative margins has been performed. However, the patient described herein was still at risk of developing multiple myeloma later in life, hence requiring lifelong follow-up.

Valproic acid suppresses growth and enhances cisplatin cytotoxicity to larynx cancer cells. Larynx cancer is the most common head and neck neoplasia in developed nations. The treatment of advanced larynx cancer include chemotherapy, often using cisplatin. The limitations of many antineoplastic drugs are their low delivery into respiratory tissues, thus the need of higher doses which results in severe side effects, and the development of drug resistance by cancer cells. Therefore the need of drugs and drug combinations that potentiates each other, increasing safety by reducing doses and act on several pathways at the same time, acting more specifically on cancer cells. Histone deacetylase inhibitors are a promising new class of anticancer agents. Among them valproic acid is a well-established drug in psychiatry with a potential use in cancer treatment. Here we study the mechanisms of action of valproic acid on larynx cancer cells. Valproic acid treatment resulted in reduced proliferation and migration, increase in apoptosis, and cell cycle arrest in larynx cancer cells tested in our study. Valproic acid treatment induced the hyperacetylation of histone 3 K18 (H3 K18ac), resulting in de novo expression of CDKN1Aand simultaneously repressing of CCND1, thus affecting cell cycle progression. Moreover, valproic acid significantly potentiates the antineoplastic activity of cisplatin on larynx cancer cells, at low doses by increasing apoptosis, cell cycle arrest and reduced migration. Overall, our results suggest that valproic acid can potentially be used as a therapeutic agent against larynx tumors, but it can also be used in combination with current treatments of choice to enhance their efficiency on cancer cells while reducing side effects.

Ezrin and podoplanin expressions are associated in invasion front of lip cancer. Introduction. Human podoplanin has a role in the invasion process of the epithelial malignant cells and its upregulation is correlated with poor prognosis in patients with head and neck cancer. The cytoplasmic tail of the podoplanin can bind to ezrin, a protein that have been associated with metastasis and lower survival rate in patients with oral cancer. The aim of this study was to evaluate the association between podoplanin and ezrin immunoexpressions by the cells of the invasive tumor front in the lip cancer. Method. 48 squamous cell carcinomas arising in the inferior lip were immunohistochemically investigated for the membranous and cytoplasmic expressions of podoplanin and ezrin in peripheral and central areas of the tumor front. The association between the membranous and cytoplasmic expression of podoplanin and ezrin by malignant cells was evaluated by chi-square test and Spearmanâ&#x20AC;&#x2122;s correlation coefficient with a significance level of 5% for both tests. Results.The results showed a strong membranous and cytoplasmic podoplanin expression by peripheral cells of the invasive tumor front, with no expression of this protein by central cells. The ezrin immunostaining was homogeneous and mainly observed in the cytoplasm of malignant cells. A statistically significant difference was found between the expression of podoplanin in peripheral and central tumor cells (p<0,001). The cytoplasmic expression of ezrin was higher than membranous (p<0.001) in squamous cell carcinoma of the lip. There was not a statistical significant correlation between the expression of membranous podoplanin and membranous or cytoplasmic ezrin by peripheral tumor cells. Conclusion.The interpretation of our results reinforce that the tumor cells in the invasive front tumor expressed strongly both podoplanin (membranous and cytoplasmic) as cytoplasmic ezrin and it suggests a participation of these proteins in the process of invasion in lip cancer.

Increased in dose to organ at risks did not correlate with the weight loss but did correlate with the lateral neck dimension reduction and volume changes for head and neck patients treated with intensity-modulated radiotherapy. Aims: The aim of this study is to investigate the weekly patient geometric and volumetric changes and the resulting dosimetric changes throughout a course of radiotherapy in head and neck cancer patients. Methods: The study population consists of 5 head and neck cancer patients treated with intensity modulate radiotherapy. Weekly cone-beam computed tomography images were recruited and the impact of the weekly patient geometric and volumetric changes to the organ at risk was studied by comparing accumulated dose from weekly CBCT-based plans with CT-based plans. Results: Significant increased in spinal cord dose were observed despite of insignificant weight lost. The increased dose was due to the reduction in lateral dimension at the neck. This study shows that if there were no changes in volume, the mean dose for the parotid gland will be lower compared to the plan mean dose. Increased in mean dose to the parotid gland did not correlate with the weight loss but did correlate more with the volume reduction. Conclusion: This study shows the impact of weight loss largely affected the dose deposited to the critical organs when there is a great change in lateral separation and volume changes. Therefore, it is worthwhile to take additional measure in lateral neck separation as a guide in making re-planning decision.

Cisplatin can be safely used in head and neck cancer patients with history of renal transplantation: A case report and literature review. The chemotherapeutic agent cisplatin is usually contraindicated in renal transplant recipients due to its well-known side effect of nephrotoxicity, but is an important (and sometimes irreplaceable) drug in the management of cancer. We report a case of cisplatin usage concurrently with radiation in unresectable head and neck cancer (SCC), along with a review of the literature, demonstrating the safety of its use. A 52-year-old lady with unresectable T4N2cMx oropharyngeal SCC was on immunosuppression with tacrolimus x 6 years following a cadaveric kidney transplant. She was treated with definitive concurrent chemoradiation with cisplatin. She received prophylactic intravenous saline (IVF) three-times-a-week. She received 6 weekly doses of 40mg/m2 cisplatin (cumulative dose 240mg/m2) I.V concurrent with radiation, with no significant change in renal function (creatinine between 0.5-0.8mg/dl). She was followed clinically for 9 months , without any evidence of

nephrotoxicity. She had a complete response to therapy, but was unfortunately diagnosed with metastatic breast cancer and died due to sepsis. Upon extensive literature review, we found 11 other reports of cisplatin use in renal transplant recipients: 5 patients with testicular cancer, 4 with bladder cancer, 1 each with T-ALL and ovarian cancer. Only two patients with testicular cancer developed renal failure, 6&7 years after chemotherapy (unlikely to be related to cisplatin). We conclude that cisplatin can be safely used in patients with renal transplant recipients with preserved renal function, with no acute or delayed nephrotoxicity.

Primary signet-ring squamous cell carcinoma of the oral cavity: The first intraoral case. Objective: Report a case of primary signet-ring squamous cell carcinoma in the floor of the mouth and highlight the importance of complete oral examination. Case report: We report the case of a 54-yearold man who complained of pain and difficulty to open the mouth. The patient presented to the outpatient clinic after he had visited 18 dentists without any definite diagnosis. Oral examination showed a mass in the submandibular gland and an ultrasound revealed an expansive lesion. Histopathological analysis showed the presence of a tumor infiltrating adjacent tissue with groups of cells exhibiting a signet-ring appearance. PAS and mucicarmine was negative. Immunohistochemical staining for CK7 and EMA was strongly positive and Ki67 staining was weakly positive. The lesion was completely submucosal and no ulceration was observed. Conclusion: This finding together suggested squamous cell carcinoma originating from the excretory duct of the submandibular gland. This case illustrates a rare malignant neoplasm and the importance of oral examination, including palpation. This study reports the first case of signet-ring intraoral submucosal squamous cell carcinoma originating from the excretory duct of the submandibular gland.

Pilomatrix carcinoma of the head and neck: Case report and literature review. Pilomatrix carcinoma is a rare cutaneous malignancy of hair matrix cells. They exhibit an aggressive and infiltrative growth pattern and, despite treatment to the local disease, there is a high propensity for recurrence. In previously reported cases, regional lymph node metastasis is always associated with distant metastatic disease on presentation, thus rendering the treatment palliative in nature. We present the unique case of a 63-year-old man with a pilomatrix carcinoma of the left parotid region. He had bilateral cervical lymph node spread but no detectable distant metastasis. The patient underwent a wide excision of the lesion with a radical parotidectomy, temporal bone resection, bilateral neck dissections, and post-operative radiation. The literature reports a poor prognosis associated with regional spread occurring with distant metastasis. The patient we report is alive at over two years post-operatively. With only one other case of a head and neck pilomatrix carcinoma ever reported in Canada, our report and review of the literature contributes to what little is known currently about the treatment of this malignancy.

Multiple primary melanomas versus single melanoma of head and neck: A comparison of genetic, diagnostic and therapeutic implications. Single primary and multiple primary melanomas of the head and neck region may be confused at first glance because of the common clinical and dermoscopic patterns. An inaccurate diagnosis may lead the clinician to a wrong diagnostic and therapeutic pathway because multiple primary melanomas occurring in familial or sporadic settings are often involved in individual cancer susceptibility. We investigated clinical, demographic, histological and survival differences between multiple primary melanomas and single melanoma occurring in head and neck region. A retrospective analysis of medical and histologic records from 217 melanomas of head and neck region was performed.Malignant neoplasms affecting MPMs patients were also reported. Mutational analysis of specific genes was performed when clinical data and family history were suggestive for familial/hereditary setting. Two hundred five out of 217 patients (94.5%) were affected by single primary melanoma (SPM) and 12 (5.5%) by multiple primary melanomas (MPMs) of the head and neck region. Individuals affected by MPMs were distinguished by a significantly higher mutation

frequency and a higher prevalence of malignant neoplasms such as renal cancer. Genetic testing revealed germline mutations affectingMITF E318K, CDKN2A genes. Our data highlight the importance of strict cancer surveillance in individuals with MPMs and the role of appropriate genetic counseling and testing in selected patients. Finally, personalized clinical and instrumental screening and follow-up strategies should be based also on mutational status. A heightened level of suspicion is required in the clinical management of mutation carriers.

Clival chordoma presenting as sphenoid sinus mass. Chordomas are midline tumors of the central nervous system, which arise from remnants of the primitive notochord while the heterotopic rests are usually situated extradurally within the bones of the axial skeleton. The tumor is locally aggressive with a high recurrence rate but rarely gives rise to metastases. We present a case of 40 year female with complaint of headache, intermittent vomiting & diminution of vision. CECT Paranasal sinus suggested the possibility of Sphenoid sinus malignancy or metastases was suggested.A functional endoscopy sinus surgery was done and the mass was excised and sent for histopathological examination. Tumor cell were pleomorphic with hyperchromatic nuclei and vacuolated cytoplasm in myxoid background. Immunohistochemically cells were reactive for Cytokeratin, Epithelial membrane antigen. Final diagnosis of Chordoma was made.The purpose of this case report is to add a rare tumor in females to the differential diagnosis of neoplasms of sphenoid sinus and to familiarize otorhinolaryngologists and head and neck surgeons with its pathologic features.

Apoptosis and cell surface GRP78 expression in benign and malignant parotid gland tumors. Background:Glucose-regulated protein 78 (GRP78) has emerged as an important regulator of tumor cell signaling and viability. Aim: We have analyzed cell surface GRP78 in benign and malignant parotid salivary tumors in correlation to apoptosis. Material and Methods: Primary cell-cultures were produced from tissue biopsies. Cell surface GRP78 stained by anti GRP78 antibody was analyzed by fluorocytometry. Apoptosis was determined by Annexin V/PI. Results: A significant decrease in the percent of cell surface GRP78 was determined in benign parotid tumor in comparison to normal tissue. Cell surface GRP78 expression in malignant tumors was significantly higher and correlated with decrease in apoptosis. Conclusions:This study is the first report describing cell surface GRP78 expression in parotid salivary tumor. The evidence of high surface GRP78expression in malignant parotid tissue in contrast to the benign tumor might add a diagnostic tool and serve as a future target for treatment of malignant parotid tumors.

Expression of excision repair cross-complementation group 1 (ERCC1), ribonucleotide reductase M1 (RRM1) and class III beta-tubulin in head and neck carcinoma and its clinical significance. Background:Additional therapeutic options based on molecular tumor profiling have been increasingly tried in head and neck cancer (HNCa). This study explored biomarker expression profiles of HNCa with the goal of developing therapeutic strategies. Materials and methods:Eighty three patients consisting of 74 cases of squamous cell carcinoma (SCC) and nine cases of undifferentiated carcinoma (UDC) were enrolled. Expression of ERCC1, TUBB3, and RRM1 which previously reported to be indicators of therapeutic responses in non-small cell lung cancer was investigated by immunohistochemistry (IHC). Human papilloma virus (HPV) status was examined by IHC for p16, in situ hybridization (ISH), and DNA chip analysis. Epstein-Barr virus (EBV) was detected by ISH. Results:HPV was detected in 27 of 74 SCC cases, most frequently in the oropharynx. EBV was detected in 11 cases including all 9 UDC cases. Expression of biomarkers was high throughout the primary location of HNCa, except for laryngeal SCC, which displayed low expression of ERCC1. High expression of ERCC1 was found in 64 of 70 cases of SCC, RRM1 in 56 of 70 cases of SCC, and TUBB3 in 37 of 71 cases of SCC. None of UDC expressed high levels of TUBB3. Also, high expression of TUBB3 was an independent predictor of better overall survival in SCC, and positivity of p16 was related to longer disease free survival and overall survival. Conclusions:Unlike lung

carcinoma, expression of ERCC1 or RRM1 did not correlate with clinical parameters or HPV status. However, p16 and TUBB3 might be useful predictive biomarkers in HNCa.

Head and neck squamous cells carcinoma, DNMT3B gene and folate pathway: A review. The head and neck cancer includes the oral cavity (40%), pharynx (25%) and larynx (15%), and is currently considered the fifth most common type in the world and is associated with a high mortality rate when diagnosed in advanced stages. The most common histological type (90% of cases) is squamous cell carcinoma. The main risk factors include the consumption of tobacco and alcohol, viral infections and deficiencies or imbalances of vitamins and micronutrients such as folate. Accumulative genetic alterations have been associated with phenotypic progression of SCCHN, resulting in the inactivation of several tumor suppressor genes and activation of oncogenes. DNA methylation is a modification that has multiple functional roles, including control of gene expression, chromatin structure stability and maintenance of genomic stability. DNA methylation is the transfer of methyl groups to the position 5 of cytosine residues located in cytosine-guanine dinucleotides (CpG) through reactions catalyzed by proteins named DNA methyltransferases (DNMTs). An abnormal methylation may play an important role in the development of several diseases, especially by acting directly on the process of tumorigenesis and / or silencing tumor suppressor genes containing CpG islands in their promoter regions. DNMT3B gene contains single nucleotide polymorphisms (SNPs) that affect gene function. Your overexpression has been associated with inactivation of tumor suppressor genes, suggesting an oncogenic role. According to the results of the studies described in the literature in HNSCC and polymorphisms in the DNTM3B gene, it is concluded that had difference in genotype frequency for the different ethnic groups in world.

Impact of EPA nutritional approach on cachexic patients with advanced hypopharyngeal cancer treated by induction chemotherapy. Background :Induction chemotherapy is often performed when treating hypopharyngeal cancer in order to preserve organs. A significant problem for treatment is that cachexia usually occurs in advanced hypopharyngeal cancer patients during the induction chemotherapy. Eicosapentaenoic acid (EPA) is reported to modulate the immune function and improve catabolism in cachexic patients with advanced cancer. Objective:To investigate the nutritional effects of induction chemotherapy on patients with hypopharyngeal cancer and to improve prognosis through the use of EPA. Material and methods: Thirty-one patients with hypopharyngeal cancer received induction chemotherapy during the period of 2011-2012. Nutritional parameters (albumin, total protein, and body weight) were evaluated before and after induction chemotherapy. Results:All patients experienced varying degrees of malnutrition. Serum albumin levels and total protein levels became significantly worse than those recorded prior to induction chemotherapy. In contrast, our data indicated that EAP significantly improved the condition of cachectic patient after induction chemotherapy. A 71-year-old man with stage IV hypopharyngeal cancer received induction chemotherapy. The response was progressive disease, and cachexia rapidly became worse. EPA enteral nutritional supplementation was adopted in order to improve his cachexia. Within 2 weeks of EPA treatment, the systemic inflammatory response was resolved, and the serum levels of albumin increased. These improvements allowed us to conduct radical surgery. There were no postoperative complications, and no recurrence has been observed. A prospective randomized trial is now being conducted to confirm the effectiveness of EPA nutritional treatment. ConclusionIn patients with hypopharyngeal cancer who experienced malnutrition after induction chemotherapy, EPA nutritional treatment significantly improved the cachexia and therefore made it possible to conduct radical treatment.

Asymptomatic renal metastasis from laryngeal primary: A common malignancy with uncommon pattern of relapse. Background: Loco-regional failure is the predominant pattern of failure in the patients of head and neck squamous cell carcinoma treated with chemo-radiotherapy. Distant metastasis is a relatively

rare phenomenon. Rare reports of head and neck malignancies with renal metastases are available in literature though none of them have carcinoma of larynx as the primary. Case report: We highlight a case of locally advanced squamous cell carcinoma of the supraglottic larynx in a 49 year old gentleman who was initially managed with induction chemotherapy followed by concurrent chemoradiation. Later the disease relapsed in the form of asymptomatic bilateral renal metastasis. He was started on targetedtherapy with tablet gefitinib. However on disease progression, treatment was changed to bio-chemotherapy with combination of injection paclitaxel, carboplatin and cetuximab.To the best of our knowledge, this is the first reported case of asymptomatic renal metastasis from a laryngeal primary. Conclusion: This case report underscores the importance of awareness of unusual pattern of relapse in carcinoma larynx. Patients of carcinoma larynx should be kept onperiodicfollowup and appropriate investigations should be done expeditiously on suspicion of recurrence.

Metformin and oral squamous cell carcinoma? Recently, more evidence has been presented for the potential anti-cancer effect of metformin, a drug used successfully to treat diabetes mellitus Therefore, the aim of this study was twofold: to compare diabetic patients with oral cancer who were treated with metformin to non-diabetic patients with oral cancer who did not receive metformin treatment, and to provide a review of the current literature in regard to oral cancer. Patients and Methods Files of all patients treated for oral cancer at the Department of Craniomaxillofacial and Oral Surgery, University Hospital Zurich between January 2007 and August 2012 were evaluated retrospectively. Age, gender distribution, and presence of metformin-treated, type 2 diabetes were taken into consideration. Results A total of 154 patients were treated (91 male and 63 female); their median age was 63.7 years (24-89 years). Six patients (3.9%) had diabetes; of those, 2 (1.3%) were treated with insulin and 4 (2.6%) with metformin. Conclusion A lower prevalence of oral cancer was found in diabetic patients being treated with metformin, but further studies need to be performed with a larger population.

Oral lipoma: Many features of a rare oral benign neoplasm. Lipomas are common benign soft tissue neoplasms composed of mature white adipocytes. They are the most common soft tissue mesenchymal neoplasms. However, they are relatively uncommon in the oral and maxillofacial regions. Their overall incidence in the oral cavity is thought to be between 1% and 4% of all benign oral lesions. Specific anatomic locations within the oral and maxillofacial region include the parotid region, buccal mucosae, lips, submandibular region, tongue, palate, floorof-mouth and vestibule. Infrequent locations of orofacial lipomas include the maxillary bones, especially the mandible. Among lipomas, different subtypes can be described: simple lipoma, lipoma with chondro-osseous metaplasia, chondroid lipoma, fibrolipoma, infiltrating lipoma, angiolipoma, myolipoma of soft tissue, angiomyolipoma, spindle cell/pleomorphic lipoma (SCL/PM), myxolipoma, angiomyxolipoma, dendritic myxofibrolipoma, sialolipoma, congenital lipoma, hibernoma and atypical lipomatous tumor (ALT). We report an unusual large-sized lipomatous tumor located on the left side of floor-of-mouth, one of the rarest sites of intraoral lipoma. The final diagnosis of the lesion was fibrolipoma. The unusual characteristics of this case report were the large-sized dimensions of the neoplasm, which were 3 cm along the main diameter, and the histological subtype which is not common among the lipomas of the floor-of-mouth and of the oral cavity in general.

Phase II Trial of curcumin in advanced head and neck cancer treatment. Introduction: In India patients often present with advanced head and neck cancer requiring aggressive treatment, which leaves them functionally disabled. In most of these cases, the palliative and supportive care is provided for overall disease management. This study investigates the therapeutic potential of oral curcumin with piperine in the palliative management of advanced squamous cell carcinoma of head and neck region. Methods: 40 patients with advanced, incurable or metastatic squamous cell carcinoma of head and neck region or those who have failed all standard treatment were included in this study. Patients received capsules of curcumin with piperine (3.6 g/day) for a

period of 8 weeks. QOL was assessed using EORTC QLQ-C30 (version 3) & QLQ-H&N35 questionnaires. Bioavailability of curcumin and its metabolites was assessed at baseline and after 1, 2 and 8 weeks of treatment. Results: There were 35 men and 5 women with a median age of 53.5 years. Stage at presentation was III in 2(5%), IIIB in 2(5%), IV in 2(5%), IVA in 14(35%), IVB in 19(47.5%) and IVC in 1(2.5%) patient respectively. 21 patients (52.5%) completed 8 weeks of treatment. Significant improvement was seen in global health status whereas other elements of physical functional scale deteriorated at the end of treatment. A significant improvement in pain, fatigue, constipation and financial difficulty scores was observed along with the scores of pain, senses problem, speech problem, less sexuality and felt ill parameters. The study therapy was well tolerated and no grade 3/4 toxicities were observed. A very low and transient level of curcumin and its metabolites was observed in the plasma of patients. Conclusions: The present study indicates the therapeutic potential of curcumin and piperine in the palliative treatment of advance head and neck cancer as a cost-effective substitute. Further studies on similar line seem warranted.

Carotid cavernous fistula: A rare complication of maxillofacial trauma. Background: Carotid cavernous fistula (CCF) is an abnormal communication between the internal carotid artery and the cavernous sinus. It is a rare complication caused by maxillofacial trauma and can lead to amaurosis. This paper describes two cases of young men with late CCF diagnosis. Case report: The first patient was 23 years old and had a basilar skull and he also had paralysis on the right side of his face. The diagnosis of CCF for this patient occurred three weeks after the onset of symptoms through an arteriography. Embolization treatment was then performed. The second patient was 21 years old and had a LeFort ll fracture on the right side of his face. He showed symptoms of CCF and was also treated by embolization. The classical clinical symptoms of chemosis, paralytic mydriasis, absence of consensus and photomotor reflex, restriction of eye mobility, proptosis, thrill and murmur were present in both cases. Conclusion:This paper emphasizes the need for early diagnosis and prompt treatment to prevent loss of visual function in patients with carotid cavernous fistula.

Susceptibility to cancer of the first-degree relatives of HNSCC patients being tobacco consumers and carrying both GSTM1-GSTT1 null genotypes. Background: The environmental and genetic factors are known to be associated with development of head and neck cancer, and the familial aggregation may act as an indicator for heritable susceptibility of HNSCC. The study assess the susceptibility of head and neck cancer in the first-degree relative of the patients, the GSTs null genotypes in First Degree Relatives (FDRs) along with HNSCC patients and controls was evaluated which can serve as a possible marker in FDRs being tobacco consumers carrying null genotypes. Materials and methods: The population based case-control family study includes 170 HNSCC patients, 300 first-degree relatives of HNSCC patients and 300 controls. The genotyping of GSTM1 and GSTT1 genes were done by multiplex PCR and calculated using logistic regression analysis. Results: GSTM1and GSTT1 null genotype was significantly associated to an increase the risk of HNSCC (OR=1.65, 95%CI=1.31-2.42 P=0.008 and OR=1.51, 95%CI=1.01-2.26, P=0.017 respectively). A greater risk was observed in individuals carrying both GSTM1 and GSTT1 null genotype (OR=2.56, 95% CI= 1.38-4.73, P=0.002). The combine effect of tobacco habits and GST null polymorphism, a high risk of HNSCC was found in tobacco-betel quid chewer and carrying both GST null genotypes (OR=9.68, P=<0.0001). It was observed that FDRs of HNSCC patients carrying GSTM1 null genotypes have higher risk of cancer compared to those of controls (OR=1.42, 95% CI=1.08-1.96, P=0.03), also risks is higher among those who carry both null genotypes (OR=1.87, 95%CI=1.09-3.201, P=0.02). Conclusion: Our study suggests thatGSTM1 and GSTT1 null genotypes and tobacco consumption increase the risk of HNSCC. Furthermore, it revealed that the first-degree relatives of HNSCC patients highly susceptible to cancer if they carry both GSTM1 and GSTT1 null genotype and as well expose to tobacco.

Reliability of SPECT-CT lymphoscintigraphy compared to PET-CT for uncommon cancer cells migration in initially N0 velum neoplasia. Background A man with a squamous cell carcinoma of the left velum was staged cT1N0M0 by PETCT. SPECT-CT lymphoscintigraphy revealed unusual retropharyngeal sentinel station. Methods and Results Preoperative SPECT-CT lymphoscintigraphy revealed 2 sentinel stations: one usual in level II left and another unusual, in left retropharyngeal level. Due to the potentially harmful surgical access, the retropharyngeal level was not removed. Level II sentinel node was removed and disease free. Six month after surgery, follow-up PET-CT showed left retropharyngeal recurrence. Conclusions This event shows that lymphoscintigraphy combined to a SPECT-CT can predict the uncommon lymphatic migration in velum neoplasia.

Oral metastasis of angiosarcoma of the bladder: A case report. Introduction: Bladder cancer is one of the most common cancers worldwide. Oral bladder cancer metastasis are unusual. Case Presentation:This study describes case of a 28 year-old male patient presenting a symptomatic mouth lesion. The lesions exhibited erythematous and ulcerative surface and the incisional biopsy was done followed by histopathological analysis. Was necessary a immunohistochemical panel (AE1/AE3, CK7, CK9, CK10, CK20, s-100, HMB-45, desmine, actin, Factor VIII, CD-34, vimentin and CD-31) to establish the definitive diagnosis of angiosarcoma. Discussion: Angiosarcoma is a rare tumor in the oral cavity, especially in cases of metastasis of a tumor found in the bladder.

Unusual peritoneal relapses in human papilloma virus related oropharyngeal squamous cell carcinoma. Background: Human papilloma virus (HPV) associated oropharynx cancer is increasing in incidence. It differs from previously described oropharyngeal cancers in terms of aetiology, pathological features and epidemiology. We describe two cases of unusual distant relapse which appears to be another characteristic of this disease. Methods: Retrospective review of relapse patterns of all cases of oropharynx cancer treated between 2009 and 2012. Results and Discussion:69 patients were treated with radical intent, of which thirteen developed a relapse. Two of these patients developed unusual peritoneal relapses after complete loco-regional response following chemoradiotherapy. The cause of these unusual relapses is not clear, though intrinsic biological propensity and tumour seeding through PEG tube placement are possible reasons. Conclusions:HPV associated oropharyngeal cancer appears to be associated with unusual patterns of relapse, including peritoneal metastases. Thus, patients presenting with abdominal pain or bowel obstruction with a previous history of HPV associated oropharyngeal cancer should be investigated for possible metastatic involvement.

Malignant peripheral nerve sheath tumour of the tongue: A rare presentation with an unusual pattern of recurrence. Malignant peripheral nerve sheath tumour (MPNST) of oral cavity is an extremely uncommon malignancy. Less than 15 cases have been reported since 1973 though none of them describes a distant metastasis. Surgical resection is the treatment modality of choice. Currently, postoperative radiotherapy has established its role in the management of MPNST. We present a rare case of MPNST of the tongue in a gentleman who presented with features of hypoglossal nerve palsy. Excisional biopsy showed a malignant spindle cell tumor in the sub-epithelial connective tissue. The tumour cells were immunopositive for S-100 and Vimentin while immunonegative for pan-cytokeratin, smooth muscle actin (SMA) and desmin. He underwent surgery followed by adjuvant chemoradiation. Later the disease recurred in the form of isolated pelvic bone metastasis. Palliative chemotherapy was offered to him. With this case report we intend to refer to such unusual presentation and pattern of recurrence in a MPNST of tongue.

The dilemma of microinvasion. Microinvasive oral squamous cell carcinoma is an early stage malignant tumor showing invasion of the epithelial cells confined to the superficial lamina propria without invasion of the deeper structures and are diagnosed mainly based on certain pre-defined histopathological criteria. Such lesions are generally a matter of debate in respect to the clinical presentation, metastatic ability, therapeutic intervention and prognosis. This short communication attempts to compile the available information regarding microinvasive oral squamous cell carcinoma and highlight the importance of efficient communication to the clinician regarding the nature of the lesion for appropriate management.

Radical management of solid ameloblastoma of the mandible: Report of a case with 5-year follow-up. Introduction:Ameloblastoma is a true neoplasm of odontogenic epithelial origin. This pathology can be classified into 4 groups: unicystic, solid or multicystic, peripheral, and malignant. Solid ameloblastomas of the mandible are the most common of them, and represent a challenging group of tumors to treat; in addition the follicular histopathological subtype has a high likelihood of recurrence. Thus, the challenges in the management of this tumor are to provide complete excision in addition to reconstruct the bony defect, in order to provide the patient with reasonable cosmetic and functional outcome. Case report:The authors report a case of a solid multilocular ameloblastoma of follicular subtype in a 39-year-old female who was successfully treated by partial resection of the mandible with immediate reconstruction using iliac crest, as donor site. Results:After 15 months, the patient was rehabilitated using titanium implant dentistry, and has been followed up for 5 years without signs or symptoms of recurrence. Conclusion:Correct surgical planning is the key for successful management of solid ameloblastoma with multilocular features, which is best treated using radical resection with immediate reconstruction, which ensures complete tumor excision, prevents recurrence, and enables fast and safe dental rehabilitation. Biomedical prototypes should be used since they provide acceptable precision and are useful for surgical planning.

Canalicular adenoma of parotid: A cytology diagnosis and review of literature. The canalicular adenoma is an uncommon, benign salivary gland tumor that most frequently occurs in upper lip and very rarely in other sites. We describe an unusual case of canalicular adenoma of parotid gland in a women aged 24 years who presented with slightly painful, firm parotid swelling since 6 years duration. Fine needle aspiration cytology of nodule revealed a benign neoplasm and cytological diagnosis of canalicular adenoma was made.

Evidence-based analysis: The rise and fall of Head and Neck Oncology I: the audit and subsequent investigations. Head and Neck Oncology, an open access journal with a closed peer-review system, achieved its first official impact factor on the 2nd of July, 2012. As a result, it achieved the prestigious status of boasting the highest impact factor of any journal in the head and neck discipline in the world. On the 4th of July, 2012 BioMed Central (the former publisher of the journal) reported serious editorial misconduct following an unannounced internal audit. On the 6th of July, 2012 BioMed Central asked all four Editors-in-chief to stand down or face serious consequences. BioMed Central also stated that they were looking for replacement Editors. On the 11th July, 2012 BioMed Central decided to initiate its first investigation, promising the Editors-in-chief a meeting to discuss the upcoming results. BioMed Central also blocked the Editors’ access to the editorial tools, preventing them from looking at the journal’s peer-review history. On the 1st August, 2012 BioMed Central emailed the Editors-in-chief a list of no less than 80 allegations of wrongdoing. The publishing-house requested a ‘satisfactory’ response within 24 hours or the journal would be closed. BioMed Central went on to cease publishing Head and Neck Oncology and emailed authors with articles under consideration for the journal and

editorial board members to confirm the same. The journal moved to another publisher with its editorial board intact, releasing its first new issue on the 9th September, 2012. On the 8th of August, 2012 BioMed Central started its second investigation against the journal but this was upgraded on the 15th of August to an article-based investigation. On 17th of October, 2012 BioMed Central made a formal complaint against the three UK-based Editors-in-chief (Colin Hopper, Waseem Jerjes and Tahwinder Upile) to University College London and cooperated with a joint investigation that was carried out by University College London and University College London Hospitals. The investigation found no case to follow up. BioMed Central’s senior staff failed to reach a definitive conclusion regarding any of the allegations against the three Editors-in-chief. From the 26th of November to the 6th of December, 2013 BioMed Central began asking Head and Neck Oncology authors to consider post-publication peer-reviews. The publisher stated that if they did not accept the reviews they would put a note, stating that the piece was ‘badly handled’, next to the authors’ articles. On the 5th of February, 2014 BioMed Central implemented that and added notes next to many of the articles indexed on PubMed and archived in PubMed Central. The notes alleged that one of the Editors, Waseem Jerjes, selfhandled 15 articles that he co-authored. It is confirmed later in this piece, however, that 3 editorial board members actually handled 9 out of the 15 articles in question. BioMed Central was asked to send a hard and electronic copy of the journal’s peer-review history to the Editors for examination. The publisher refused to do so. From their combined experience, it is the editor’s belief, that this is the first time that a publisher has behaved in such a manner against its own Editors-in-Chief and the academic community of the head and neck oncology discipline. In a series of communications, I share my experience and scientifically analyse the good and the bad in the hope that it will benefit future generations of academics. The Editors continue to provide support to the editorial board members, authors and readers of Head and Neck Oncology. In the following paragraphs, I aim to highlight the issues surrounding the journal and BioMed Central and its senior staff (Deborah Kahn, Jigisha Patel and Shreeya Nanda) regarding the internal audit and the subsequent investigations.

Volumetric variations and the effects of these differences on dosimetry during the course of volumetric modulated arc therapy for head and neck cancer. BACKGROUND:To observe the changes in the patients anatomy and the effects of these differences on dose distribution throughout the treatment in order to design an optimal adaptive plan and to find the optimal time for replanning in head and neck cancer patients who receive primary radiotherapy or chemoradiotherapy. MATERIAL AND METHODS:Fifteen head and neck cancer patients were evaluated prospectively. VMAT plan with simultaneous integrated boost or sequential tecnique was performed. The last CBCT of 3th and 5th week were fusioned deformably with planning CT. Initial plans were adapted to these CBCT images. An adaptive plan was generated during the week when normal tissues overdosed more than 5% or the target volume underdosed more than 5%. The volumetric changes and dosimetric differences in target volumes, parotid glands and spinal cord were compared between planning CT and CBCT images. Also adaptive plan doses were compared with delivered doses in terms of target volumes, parotid glands and spinal cord. RESULTS:While there was no significance at the comparison of the volumes in GTV and PTV70 between the planning CT and 3rd week CBCT, it became significant at 5th week. Primary and lymph node GTVs reduced by 44.8% and 70.9% respectively. Parotid glands and spinal cord doses increased in 3rd week as well as; it rose a significant level for the ipsilateral parotid and spinal cord in 5th week. Adaptive plan was needed in 10 patients. Adaptive plan provided a 1 Gy dose reduction in contralateral parotid glands, 1.4 Gy in ipsilateral parotid glands and 1 Gy in spinal cord. CONCLUSION:Significant changes were observed in the volume of target and parotid glands despite it not reflected much in dosimetry. A new CT scan can be recommended to evaluate for an adaptive plan in 5th week in the absence of clinically usable online correction methods.

Expression of hypoxia inducible factor-1 alpha (HIF-1&#945;) in oral squamous cell carcinoma and its correlation with neoangiogenesis and 3-year survival from the disease. Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide. OSCC falls into a larger category known as head and neck squamous cell carcinomas (HNSCCs). This collection constitutes all squamous cell carcinomas of the oral cavity, larynx, pharynx and oesophagus of which

OSCC is the most common. Cancer cells involve morphological cellular transformation, dysregulation of apoptosis, uncontrolled cellular proliferation, invasion, angiogenesis, and metastasis. Also, one of the hallmarks of cancer is the elevated uptake of glucose even under normal oxygen conditions, known as aerobic glycolysis or the “Warburg effect”. The Warburg effect is the cellular phenomenon in which the tumor cells primarily use glycolysis for energy production instead of mitochondrial oxidative phosphorylation like normal cells. These cellular responses have been shown to cause distinct transformations like the upregulation of proteins such as hypoxia-inducible factor 1-α that help the tumor survive adverse conditions in which normal cells cannot persist. HIF-1α stimulates transcriptional induction of a series of genes that participate in iron metabolism, glucose metabolism, cell proliferation / survival and angiogenesis.

Prognostic factors and survival in patients with squamous cell carcinoma lymph nodes metastases from an unknown primary to the head and neck. Purpose. To analyze the clinicopathological characteristics, treatment modalities, and potential prognostic factors of cancer of unknown primary tumor(CUP) in a consecutive group cases. Methods. This retrospective study enrolled consecutive patients who were admitted to the Sun Yat-sen University Cancer Center between 1980 and 2011. Results. The key prognostic factors influencing the survival were the lymph nodes extracapsular extension (ECE), N classification, recurrence, emergence of primary tumor and treatment modalities. Multivariate analysis revealed that N classification and recurrence were independent risk factor for patient survival. Conclusions. N classification and recurrence were independent prognostic factor that influenced the treatment outcome. Our data indicate that combined surgery and postoperative radiotherapy for CUP offers the best chance for long-term survival.

Adenomatoid odontogenic tumour: hamartoma or neoplasm? A contribution to debate. The Adenomatoid Odontogenic Tumour (AOT) is about 2-7% of all odontogenic tumours, especially affecting young female individuals. Histologically, the parenchymal cells exhibit a heterogeneous cellular patterns and organization. This study aimed at understanding the biological and cellular mechanisms in this tumour. Eight formalin fixed paraffin embedded blocks of AOT were studied by immunohistochemical staining for proteins p63 and Ki-67 using the System EnVision System™ (Dako Cytomation, Glostrup, Denmark). The analysis was performed considering the distribution of immunoreactivity, and using scores: - (0 to 5% of positive cells); +1 (6-25% positive cells) +2 (26-50% positive cells); 3 + (> 50% positive cells). All the 8 cases examined were positive for proteins p63 and Ki-67. Expression of p63 protein was intensive and involved all cell groups, whereas Ki-67 was predominantly detected in cubic cells lining the duct-like structures. The results suggest that the intense immunostaining of p63 protein reflects the low degree of differentiation of the AOT cellular components and contributes to cellular and architectural heterogeneity observed in this tumour. Besides, expression of the Ki-67 protein suggests that cell proliferation in the AOT is low, which explains the benign biological behavior of the tumour. The findings of this study indicate the AOT as a true neoplasm with low proliferative cell index.

Human papilloma virus in head and neck carcinoma: Experience from a regional cancer center in Gujarat. Aim: We investigated the etiological role of HPVs in patients with head and neck cancers and aimed to study its detection tumor tissues taken cancer patients.Methods: 100 patients with malignancies of buccal mucosa, tongue and right maxilla were included in the study. Tumor biopsy was taken for histopathology and molecular studies for by multiplex PCR. Results: Out of 100 head and neck cancers, 81 % were males and 19 % females, 69% belonged to age >50 yrs and 31 % were < 50 yrs, 58 % were from urban area. Tobacco chewing is one of the contributory factor in the genesis of oral carcinomas and we noted that 35% were non-chewers and 65 % chewers. 61% were smokers and 39 % non- smokers. HPV genome was detected in 20% of the cases. High risk HPV-16 was detected in

35% and HPV 52 in 20%. Out of the 43 biopsies from buccal mucosa 7 cases had HPV, from 20 cases of carcinoma tongue 9 cases had HPV positive(40%), one case of carcinoma thyroid had HPV positive, 3 cases of carcinoma maxilla had HPV positive. The oral cavity tumors like the buccal mucosa and tongue significantly had more HPV positive as compared to oropharynx. Other HPV types detected were HPV-33(15%), HPV-39(5%), HPV-45(10%), HPV-52(20%) and HPV58(15%).Conclusion: The SCC of Head and Neck had 20% of HPV types. Different HPV types were HPV16, 33, 39, 45,52 and 58. Though the biopsies were from carcinomas, our study did not show that there is 100% co-relation of HPV as a sole etiological agent in the genesis of the squamous cell carcinoma. Oral cancers occurred typically in > 50yrs of age and, old heavy drinkers and heavy smokers.

Bilateral dentigerous cyst in non-syndromic patient: Case report and review of literature. Introduction:The dentigerous cyst is the most common odontogenic cyst associated with full or partially erupted teeth. Their bilateral occurrence is rare and usually associated with syndromes.Case Report: The objective of this work is to report a case of bilateral dentigerous cyst in the anterior region of the maxilla in a 43 years-old woman referred to the oral and maxillofacial surgery department, Dentistry Faculty of Bauru, University of S達o Paulo with absence of the upper canine teeth. Radiographic examination showed the teeth impacted maxillary cuspids and two unilocular radiolucent independent. Incisional biopsy was performed and the diagnosis of lesions was of dentigerous cyst. The proposed treatment was surgical enucleation of the cyst and the removal of impacted teeth under general anesthesia. The patient remained symptom free follow-up period of five years.

Management of oral carcinoma in a patient with severe trimus using a novel approach. Trismus is often present in patients diagnosed with oral malignancy. Trismus is a debilitating condition and is treated adequately with release of fibrosis and interposition of vascularised tissue to provide long term improvement in mouth opening. Treatment of an oral cancer in a patient with trismus becomes challenging because of difficult access and further deterioration of mouth opening following treatment of the malignancy. Herein we describe the planning of access and management of oral carcinoma with severe trismus using nasolabial flaps.

Immunoprofile of primary gingival angiosarcoma: A case report and review of the literature. The angiosarcoma of the oral cavity is extremely rare, with only a few such cases reported in the literature. We used a case of primary gingival angiosarcoma arising in maxilla as an opportunity to review the clinicopathological and immunohistochemical profile of this tumor in the oral cavity. A 59years-old man had a fibrous mass involving the gingival and alveolar mucosa in the maxillary left molar region associated with extensive bone destruction. A biopsy was performed and the tumor was histopathologically diagnosed as angiosarcoma. Whereas that early diagnosis is crucial and that the definitive diagnosis of angiosarcoma is challenging due to the rarity of the tumour, this paper illustrates a case of gingival angiosarcoma in maxilla, highlighting their clinical and demographic features, as well as the importance of immunohistochemistry to establish the final histopathological diagnosis.

Radiation-induced high grade spindle cell sarcoma of the sternomastoid muscle: case report. Sarcomas developing as primary malignancies of the head and neck are a rare complication after radiation therapy. This kind of sarcoma has variable clinicopathological appearances and behaviour. Radiation-induced spindle cell rhabdomyosarcoma (RMS)of the sternomastoid muscle is a very rare sarcoma and has very seldom been described in the literature. Herein we report the development of a rapidly growing mass over the lateral side of the neck appearing after 7 yearsin a patient with a

history of laryngeal carcinoma who received radiotherapy. The process of diagnosis and management using combined surgery and targeted brachytherapy are discussed. The patient experienced discomfort and oozing of the wound up to 2 months after surgery; however, complete response with satisfactory adaptation and shrinkage of the pectoralis major pedicled muscle flap occurred after 1 year. The patient is currently disease free 5 years postoperatively. Radiation-induced spindle cell rhabdomyosarcoma ofthe sternomastoid muscleafter treatment for laryngeal carcinoma may occur a long time after radiation therapy and be clinically aggressive, radiographically distinctive, and require multidisciplinary management.

Prediction of occult cervical lymph node metastasis in clinically negative supraglottic squamous cell carcinoma. Objective:Supraglottic laryngeal carcinomas are often accompanied by occult cervical lymph node metastasis.The aim of this study was to explore predictive factorsof cervical lymph node metastasisin clinically negative supraglottic squamous cell carcinoma (SCCA). Methods and Materials:From January 1990 to December 2009, a series of 221 patients with clinically negative cervical nodal metastases in supraglottic laryngeal SCCAwere treated in Sun Yat-sen University Cancer Center.The overall survival (OS) rate and occult cervical lymph node metastasis free survival (OCLNM-FS) rate were calculated using a life-table method. The survival curves were constructed by the Kaplan-Meier method and compared using a log-rank test. The relative significant factors in predicting OCLNMFSwere assessed by multivariate Cox proportional hazards model. Results: The 5-year OS rate in 221 patients was 58.6%. The 5-year OS rates of the positive cervical lymph node metastasis group and negative cervical lymph node metastasis group were 63.1% and 44.1%,respectively (p=0.020). The 5-year OCLNM-FS rate in 221 patients was 76.7 %. Smoking index, histological differentiation, T stage, resection margins, and the treatment modality of surgery pluspostoperative radiotherapy for the primary site were found to be associated with OCLNM-FS by univariate analysis. By multivariate analysis, the significant predictors were found to be histological differentiation (HR, 1.507; 95% CI, 1.006 to 2.257) and a combination treatment of surgery plus postoperative radiation for the primary tumor (HR, 1.035; 95% CI, 0.892 to 3.494). Conclusion: Cervical lymph node metastasis in clinically negative supraglottic SCCA results in lower 5-year OS rates. The histological differentiation and the treatment modality of surgery plus postoperative radiotherapy for the primary tumor site were found to be independent predictors for OCLNM-FS.

Do patients with oral and oropharyngeal squamous cell carcinoma benefit from elective contralateral neck dissection? A long-term analysis. Objectives: Oral and oropharyngeal squamous cell carcinoma (SCC) puts the patient at risk for bilateral neck lymph node metastasis. For this reason, routine bilateral neck dissection is preferred by some surgeons as the treatment of choice, even in N0 necks他despite the morbidity of this procedure. Method: Utilizing data of 496 patients with SCC of the head and neck region treated at the Department of Otorhinolaryngology and Head and Neck (ORL) at the Medical University Hospital Graz from 1999 to 2009, we retrospectively evaluated the effect of bilateral neck dissection on recurrence-free and overall survival rates in patients with oral and oropharyngeal cancer. Results: Long-term survival of 152 patients with oral and oropharyngeal cancer did not show a statistical benefit of elective contralateral neck dissection in patients with a clinical negative contralateral neck. Neither loco-regional, recurrence-free survival nor overall survival rates differed. Conclusion: We could not find a statistical benefit for operating on patients with oral and oropharyngeal SCC with an elective neck dissection on the contralateral clinical negative neck side. Stomatin-like protein-2 is over-expressed during progression of clinically N0 tongue squamous cell cancer.

Stomatin-like protein 2 (SLP-2) contributes to tumorigenesis, progression and decreased overall survival in several human cancers. The present study investigated the clinical and prognostic

significance of SLP-2 in clinically N0 tongue squamous cell cancer. Immunohistochemistry was performed to examine SLP-2 protein expression in paraffin-embedded tissues from 181 patients with clinically N0 tongue squamous cell cancer (cN0 TSCC). Statistical analyses were used to evaluate the diagnostic value and the associations of SLP-2 expression with clinical parameters. Real-time PCR and western blotting analyses were employed to examine SLP-2 expression in four tongue squamous cell cancer cell lines, primary cultured normal tongue epithelial cells (TEC) and eight matched pairs of tongue squamous cell cancer samples and adjacent non-cancerous tissue samples from the same patient. SLP-2 protein level was positively correlated with clinical stage, T classification, N classification, recurrence and even vital status. Patients with higher SLP-2 expression had shorter overall survival time than patients with lower SLP-2 expression. SLP-2 mRNA and protein was upregulated in tongue squamous cell cancer cell lines and cancerous tissues compared with the expressing in TEC and adjacent non-cancerous tissue samples,respectively. Our results suggest that SLP-2 expression is associated with cN0 TSCC progression. The examination of SLP-2 protein expression is potentially valuable in prognostic evaluation of cN0 TSCC. The Deleterious nature of the invasive front and dysplasia at margin in the long term outcome from surgical treatment of squamous cell carcinoma of the head and neck.

Introduction The characteristic of the cells at the leading edge of malignancy may have a deleterious prognostic significance. Materials and methods A 10-year retrospective analysis was undertaken, data from 282 patients were reviewed and a detailed pathological review was undertaken, the data was entered upon a database which was independently validated for accuracy. Individuals recorded were followed for 5 years from the initial surgical insult. Results The TNM classification was validated in the follow-up study as a prognostic indicator. Transfusion had an adverse effect on survival and chance of recurrence. Dysplasia at margin, clearance (mm) of resection (i.e. surgical margin) and the nature of the invasive tumour front at the margin all had an adverse effect upon the likelihood of cancer recurrence. Discussion The nature of the invasive front should be considered in any prognostic discussion and when planning surgery. Transfusion triggers should be revised to avoid transfusion of blood products (which have cancer growth promoting properties). The survival rates after recurrence of disease is poor, in part due to the entrenched adaptive behaviors of the residual tumour cells which manifest several areas of resilience (i.e. radiotherapy, chemotherapy) and which may have already invaded local important structures (making them resilient to surgery ). To improve the overall survival rates, we must address the surgical margin from the onset before considering adjunctive treatments which alter local vasculature (blood and lymphatic) and tumour spread patterns. Intra-operative margin analysis is important to address regions of concern before wound healing becomes entrenched and the chance to take corrective action is missed.

One-Stage Skin Grafting of the Exposed Skull with Artificial Dermis after cancer removal: Long-term Experiences. Various surgical procedures claim to show high success rate in scalp reconstruction. However, it is still difficult to cover wide range of scalp defects accompanied with skull exposure after cancer removal. Between March 2007 and March 2010, one-stage skin grafting with artificial dermis was performed in 8 patients with scalp defect accompanied with skull exposure after malignancy resection. A burr hole was made with several millimeter gap to the skullâ&#x20AC;&#x2122;s outer table, and thus vascular diploic space was exposed. After the application of artificial dermis to the exposed vascular diploic space, the split-thickness skin graft was performed. As artificial dermis, AlloDerm was used in 5 patients, whereas Matriderm was used in 3 patients. All patients were males, and their mean age was 60.7 years old. All patients were due to post- oncologic surgery defects. The mean defect size was 247.9 cm2. In all patients, skin graft was well taken, and radiation-induced skin defects occurred in 2 of 3 patients to whom a postoperative radiotherapy was performed but those were cured by secondary intention. Follow-up period was on average 19.6 months, and all patients demonstrated stable coverage without having complications including break down of skin graft or osteomyelitis that requires re-operation. To this end, the authors make our report on the one-stage skin grafting with artificial dermis as a reliable, simple and safe technique to cover exposed skull after cancer removal.

A new tool to inform intra-operative decision making in skin cancer treatment: the non-invasive assessment of basal cell carcinoma of the skin using elastic scattering spectroscopy. Introduction: The aim of this study was to evaluate findings of elastic scattering spectroscopy (ESS) co-registered with histopathology in patients with basal cell carcinoma against normal and some common benign skin disorders. Materials & Methods: Clinically suspicious head and neck skin lesions were included. Those lesions with surrounding innocuous skin were interrogated by ESS, coregistered biopsies were taken and examined histo-pathologically; the results were then compared using a variety of statistical techniques. Results: Our analysis showed obvious and consistent spectral differences between normal and pathological skin. Discriminating elastic spectral differences were consistently identified between basal cell carcinoma (BCC) and other skin lesions of similar appearance. Conclusions: This preliminary study shows that ESS can distinguish between basal cell cancer, common benign conditions and variants of normal skin. ESS can also help determine the diagnosis between benign lesions with a high degree of accuracy suggesting ESS can add significant objectivity to dermatological diagnosis and management even of benign conditions.

Unusual metastases from papillary thyroid carcinoma. Papillary thyroid carcinoma is the most common type of well-differentiatedthyroid carcinoma. Metastases usually occur in regional lymph nodes. Here,we report a patient with unusual metastases from papillary thyroidcarcinoma.A 55-year-old woman had a history of right papillary thyroid carcinoma and underwent local excision of the right thyroid lobe in another hospital previously. The patient was found to have metastatic papillary thyroid carcinoma to the left parietooccipital lobe, bilateral lung, the left caput humeri, the left triceps brachii muscle, the right collum ossis femoris and left thumb. She eventually suffered multiple organ failure and died. Therefore, if not timely and thorough treatment, papillary thyroid carcinoma may alsometastatic to brain, lung, askeletal muscle, bone and other various sites through direct hematogenic routes.

Microscopic endo-nasal access in pituitary surgery for tumour removal: 8 year review of nasal complications. Introduction Trans-sphenoidal pituitary resection is possible via the traditional microscopic transseptal approach or the newer endoscopic trans-nasal approach. There is little in the literature to describe the nasal complications of the endo-nasal microscopic resection of pituitary lesions. We describe our experience of a single surgeon series & specifically the nasal complications from this method Method We preformed an 8-year retrospective case notes review of transnasal endoscopic resections of 70 pituitary tumours. The data was collected upon a proforma developed after consultation with the multidisciplinary team and validated by independently by random interval analysis. Results Gross tumour removal rate was achieved in 77.1% (n= 54/70) by 24 months followup. One patient was experiencing a purulent nasal discharge requiring antibiotic intervention whilst another had persistent maxillary nerve damage with paraesthesia. No patient experienced persistent epistaxis, septal perforation, anosmia, CSF leaks or meningitis. Unfortunately one patient succumbed from the consequences of internal carotid artery damage. Conclusion Nasal complication rates from this method are low. The microscope can be successfully used in an endo-nasal approach to the sella on its own. It can also be a useful adjunct to the endoscope and this skill should not be forgotten by ENT and neurosurgeons. It appears the method of approaching the sella (transnasal versus transseptal) rather than the instrument used that helps determine the rate of nasal complications.

High hypoxia-inducible factor-1&#945; expression genotype associated with Eastern Cooperative Oncology Group performance in head and neck squamous cell carcinoma.

Objective: The Eastern Cooperative Oncology Group performance status (ECOG-PS) scale evaluates the physical functioning of cancer patients, and frequently exhibits a high predictive value. The aim of this study is to assess whether C1772T and G1790A HIF-1α polymorphisms are associated with ECOG-PS in head and neck squamous cell carcinoma (HNSCC). Materials and Methods: RFLP analysis was used to investigate HIF-1α C1779T and G1790A polymorphisms in 100 HNSCC patients and 88 controls. Results: HNSCC subjects with poor ECOG-PS exhibited associations with the TT genotype and large-size tumors. Conclusions: In conclusion, our study demonstrated that the C1772T and polymorphism of the HIF-1α gene are associated with poor ECOG-PS. Our data suggests that the presence of the TT genotype in HNSCC individuals might contribute to the higher clinical aggressiveness of malignant disease. Such findings may have implications for interruptions in the disease process and modifications in treatment regiments.

Re-irradiation in Head & Neck cases using IMRT technique: a retrospective study with toxicity and survival report. Purpose: The incidence of recurrence after radiation therapy or appearance of secondary primary tumors is not minimal. The aim of this study is the evaluation of survival and toxicity in patients after IMRT re-irradiation due to relapsed head and neck carcinoma. Methods and materials: In a retrospective way, we studied 15 patients who underwent IMRT re-irradiation, from January 2007 to March 2012, due to histological proof of recurrent disease or second primary tumor in head and neck area after previous irradiation and no evidence of distal metastases. The median follow up was 45 months. The combined RTOG/EORTC criteria were employed to assess acute and late toxicity. Results: At the time of last follow up, 12 patients had no evidence of disease (80%) and three patients have died due to brain or lung metastases and mediastinum lymphadenopathy. Two patients had relapses within the irradiated area 2 years post re-irradiation. The median OS and RFS were 35 months and 45 months, respectively. A correlation was noted (spearman rho=0.52, P=0.047) between acute mucositis of re-irradiation and summation dose (previous and second course). In terms of acute toxicity, three (20%), two (13.3%) and nine patients (60%) presented grade III, II and I of acute mucositis, respectively; two (13.3%), nine (60%) and four (26.6%) presented grade III, II and I acute skin toxicity, respectively. Edema of the larynx and fungal infection of the pharynx were observed in all cases. Late radiation toxicities were observed in seven patients: paralysis of true vocal cord which needed laryngoplasty in one patient, two patients had odynofagia , one patient had dysphagia . one patient presented carotid stenosis and two patients presented long-term anorexia. Conclusion: The IMRT technique allows the re-irradiation with safety and tolerated toxicity. However, future prospective studies of these approaches with much more patients are warranted.

Management of the clinically negative neck (N0) of T2N0M0 supraglottic laryngeal carcinoma: A retrospective study. Objective: The most effective therapeutic approach for the cN0 patients with T2N0M0 supraglottic laryngeal carcinoma (SGLC) remains a subject of much debate. The purpose of this study was to answer the following question: among patients with T2N0M0 SGLC, are the survival significantly different between patients that received neck dissection and those that had another therapeutic treatment (radiotherapy, ‘wait and see’ policy)? Methods and Materials: A retrospective analysis of 101 consecutive T2N0M0 cases of squamous cell carcinoma of the supraglottic larynx, treated between 1993 and 2009, was performed. Overall survival (OS), loco-regional control (LRC),local disease-free survival (LDFS) and neck disease-free survival (NDFS) were estimated using the Kaplan-Meier method. Log-rank test was employed to identify significant prognostic factors for OS, LRC, LDFS, NDFS. Results: For treating the primary tumor, the 5-year OS, LDFS, LRCwere not significant difference between surgery group, radiotherapy group and surgery plus radiotherapy group (χ2=2.256, P=0.324; χ2=1.181, P=0.554; χ2=4.441, P=0.109).For treating the neck, the 5-year OS, NDFS, LRC of the patients with T2N0M0 supraglottic cancer were not significantly different between patients in the neck dissection treatment group, neck radiotherapy group and ‘wait and see’ policy group.(χ2=2.422, P=0.298; χ2=1.576, P=0.455; χ2=0.003, P=0.998). Conclusion: Our result suggests that neck dissection is not superior to radiotherapy or a ‘wait and see’ policy in terms of survival and control of neck disease. A ‘wait and see’ policy may be the best choice for these patients.

Surgical extent impacts the value of the established prognosticators in glioblastoma patients: a prospective translational study in Asia. Background:While multimodal treatments have survival benefits in patients with glioblastoma, tumor volume resection still remains the most effective treatment. Methods: In this prospective translational study we analyzed the clinical values of the established survival predictorsin the context of extensive tumor resection(at least near-total resection)in 234 newly diagnosed glioblastoma patients.Common survival factors such as adjuvant therapymodality, O6-methylguanine DNA methyltransferase (MGMT) and isocitrate dehydrogenase 1 (IDH1) were analyzed. Results:The more extensive resection resulted in a favorable outcome, especially the median progression-free survival (PFS) up to 11.1 months.Age at diagnosis, the initial alkylating radiochemotherapyand MGMT promoter status were correlated with survival in univariate analysis, but their independent predictive values were lost upon multivariate analysis. Multivariate analysis identified the only independent prognosticatorsfor a longer overall survival (OS) were gross-total resection (GTR)(relative risk [RR], 0.36;P=0.003) and higher KPS score (RR, 0.41; P=0.008), and GTR (RR, 0.56; P=0.050), higher KPS (RR, 0.52;P=0.028) andIDH1 mutation (RR, 0.42; P=0.011) for a favorable PFS. Interestingly, in the subgroup of patients receiving GTR, neither MGMT nor IDH1 effectively predicted OS or PFS; and also radiotherapy-alone did not significantly improve the outcome though alkylating radiochemotherapy showed a strong survival advantage. Further analysis showed an additive effect of surgical extent and molecular predictor IDH1mutation. Conclusion:Surgical extent most significantly impacts the value ofmolecular and clinical predictors, and therefore should be takeninto full account when assessing a new therapyor stratification variablein GBMs.

Prognostic significance of pre-treatment latent membrane protein 1 from nasopharyngeal swabs for stage III-IVA nasopharyngeal carcinoma. Background:Previous studies have proposed that latent membrane protein 1(LMP1) gene is related to the pathogenesis and progression of nasopharyngeal carcinoma (NPC). However, the role of pretreatment LMP1 as a prognostic factor has not been fully addressed, and most previous studies did not utilize polymerase chain reaction (PCR) detection techniques. We aimed to investigate whether the presence of pre-treatment LMP1 detected by PCR from nasopharyngeal swabs would allow prognostication and potentially treatment stratification prior to any intervention. Methods: From June 2007 to June 2008,a total of 87 patients with stage III-IVA NPC who completed radical radiation therapy were enrolled prospectively. All underwent nasopharyngeal swabs for LMP1 prior to treatment. Results: Of the 87 swab samples, LMP1 was detected in 75 (86.2%). Overall survival rates were significantly higher in patients without LMP1 expression (LMP1-) compared to those with LMP1 (LMP1+) (100% vs. 71.6%, respectively, p=0.034). In addition, clear trends of improved regional relapse-free, distant metastasis-free, and progression-free survival rates were noted in the LMP1group compared to the LMP1+ group (p=0.076, p=0.067, p=0.058 respectively). Local control between the two groups was similar (p=0.165). Conclusion:Pre-treatment LMP1 as detected by nasopharyngeal swabs using PCR is an adverse prognostic factor for Stage III-IVA NPC, and potentially can be used as a treatment stratification tool.

Treatment and prognosis of patients with recurrent laryngeal carcinoma: a retrospective study. Introduction Although recurrent laryngeal carcinoma is a common clinical problem, the data regarding its natural history and prognostic factors are limited. The aims of this study were to evaluate the treatment outcomes of patients with recurrent laryngeal carcinoma and to identify the value of several prognostic factors. Methods A retrospective analysis of 224 consecutive cases of recurrent laryngeal carcinoma, treated between 1996 and 2009, was performed. Overall survival was estimated using the Kaplanâ&#x20AC;&#x201C;Meier method. Log-rank test was employed to identify significant prognostic factors for overall survival. The Cox proportional hazards model was applied to identify covariates significantly associated with the aforementioned endpoint. Results The estimated 3-, 5- and 10-year survival rates of the entire patient sample were 56.6%, 46.4% and 39.2%, respectively. On univariate analysis, the

age, smoking index, grade, primary site, initial T stage, initial UICC stage and nodal status of the primary tumor, as well as the disease-free interval, extent of the recurrence, suitable for surgery were all powerful prognostic factors for survival. On multivariate analysis, four variables retained statistical significance: the initial T stage, nodal status, extent of the recurrence and suitable for surgery. Conclusion Our result suggests that lower initial T stage, no initial cervical lymph node metastasis, only localrecurrence and patients suitable for salvage surgeryare favorable prognostic factors for overall survival of patients with recurrent laryngeal cancer.

Anaplastic large cell anaplastic lymphoma kinase + non-Hodgkin lymphoma in a 10-year-old male discovered during dental visit: a case report. Non-Hodgkin lymphoma (NHL) is rare in children, even if they are the third most frequent tumor. Management of a NHL child is complex and coordinate presence of haematologists, surgeons, radiotherapist, neurologists, psychologists and others expert personnel is required. Our patient presented with a bulky mass, approximately 5 cm in diameter, which grew from his upper left maxilla bone, causing gum bulge, and thus left side of his face from lip to eye appeared swollen. A total body TC-PET exam revealed that the mass was growing in the mouth and in the maxillary bone, and that there were many bulky nodes both in the right and left neck. Histological H&E assessment revealed an anaplastic large-cell proliferation underlying epithelial tissue without epithelial infiltration. The patient underwent a first cycle of chemotherapy according to the â&#x20AC;&#x153;International Protocol of ALCLâ&#x20AC;?, the Maxillofacial Surgery Unit and the Dentistry Unit of the same hospital took care of his dental situation, to avoid infective foci could spread to the whole body. After 1 year and 3 months from the first cycle of chemotherapy, a bulky splenic mass was discovered. Laparoscopic biopsy revealed a relapse of the ALK+ ALCL in a splenic node. The patient is now alive in good conditions, followed-up continuously by Pediatric and Emato-oncology Operative Unit of University Hospital of Parma. Rapidity of action and a correct multidisciplinary (oncology-maxillofacial surgery- dentistry) approach has been the key to: curing the illness, diagnosing promptly its relapse, avoiding spread of infective foci from his teeth during chemotherapy cycles.

A novel platform for nucleic acid biomarker-based diagnosis of thyroid cancer. The standard of care for patients with clinically significant thyroid nodules is an ultrasound-guided fine needle aspiration biopsy with cytologic evaluation. Nearly 20% of patients are found to have indeterminate cytology, requiring surgical thyroidectomy to exclude malignancy; nucleic acid-based biomarkers to improve diagnosis are promising, but there is clearly a need for improved technology to bring these into common clinical practice. Here we demonstrate the use of a thermoplastic disposable microfluidic chip to extract nucleic acids from thyroid cancer cell lines and thyroid tissue for potential use as a rapid cancer diagnostic. The micro-solid phase extraction chip was used to extract microRNA, mRNA, and DNA from the well characterized thyroid cancer cell line BCPAP and from human thyroid tissue obtained during surgery. In our study, we successfully used the microchip to extract and detect thyroid-cancer associated nucleic acids from as few as 50-500 cells (fewer cells than in a typical one milliliter fine needle aspirate) and from human thyroid specimens. Our data suggest this microfluidic platform may serve as a technology that may improve the speed, reliability and cost of thyroid cancer diagnosis in cases of indeterminate cell aspirates.

Efficacy, cosmesis and skin toxicity in a hypofractionated irradiation schedule for cutaneous basal cell carcinoma of the head and neck area. AIM: To evaluate efficacy and acute and chronic toxicity of a hypofractionated irradiation schedule in elderly patients with basal cell carcinoma (BCC) of the skin. PATIENTS AND METHODS:Between February 2005 and November 2011, 42 retrospectively selected patients diagnosed with skin BCC of the head and neck area were treated with 3-dimensional conformal radiotherapy (3DCRT) as an adjuvant therapy. Radiotherapy schedule was 5x600cGy once weekly. Acute and late radiotherapy skin toxicity and cosmetic outcome were assessed in long-term follow-up according to EORTC/RTOG

criteria, while cosmesis was evaluated by an expert in plastic surgery. RESULTS:Patients’ median age was 78 years while median follow up was 15 months. Only two local recurrences were observed at 15 and 32 months post 3DCRT. Grade I,II and III acute skin toxicity was observed in 30/42, in 9/42 and in 2/42 patients, respectively. Late toxicity as grade I,II was observed in 14/42 and in 2/42 patients. ‘’Excellent’’ or ‘’good’’ cosmesis was achieved in 30/42 and in 12/42 patients, respectively. CONCLUSION:Our irradiation schedule achieves very high local control rate with very good cosmetic and functional results, and could be an alternative radiotherapy treatment for elderly patients with BCC of the head and neck area.

Lymph node ratio and capsule penetration as independent risk factors in head and neck squamous cell carcinoma. Introduction: Knowledge of independent prognostic factors in patients with head and neck squamous cell carcinoma (SCC) is key for appropriate treatment decisions. Given the availability of aggressive therapeutic options with known side effects and burdens for the patient, the correct choice of treatment is vital. Materials and Methods: Using a retrospective database of patients treated over a 10-year period, independent prognostic factors for disease-free survival (DFS) and overall survival (OS) were assessed. Univariate analysis was used to identify significant variables, and multivariate Cox regression analysis was used to determine independent prognostic factors. Results: Between 1 January 1999 and 31 December 2009, 291 patients with head and neck SCCs were analyzed to identify prognostic factors for DFS and OS. Although univariate analysis identified several significant factors, multivariate Cox regression analysis showed that capsule penetration and lymph node ratio were the only significant factors for DFS and OS. Conclusions: Lymph node ratio is an independent predictor of survival and should be examined in every patient undergoing neck dissection. Capsule penetration of lymph nodes was another independent prognostic factor. In cases of capsule penetration or inappropriate lymph node ratio, adjuvant therapies are necessary.

Chemotherapy plus radiotherapy makes curability a possibility in nasopharyngeal carcinoma patients with distant metastasis at diagnosis. Background: Systemic chemotherapy is the major treatment for nasopharyngeal carcinoma (NPC) patients with distant metastasis at diagnosis; Addition of radiotherapy has not been explored in these patients. Methods: We retrospectively analyzed 226 NPC patients with distant metastasis at diagnosis who receivedchemotherapy alone or chemotherapy+radiotherapy. Survival was analyzed using Kaplan–Meier analysis and the log-rank test. Results: Median follow-up was 65.5 months (range, 27– 113). Median overall survival (OS) was 16 months (95% CI 14.3–17.7) for chemotherapy group and 36 months (26.9–45.1) for chemotherapy+radiotherapy group (P<0.001). Median progression-free survival (PFS) was 7 months (4.9–9.1) for chemotherapy alone group and 28 months (18.2–37.8) for chemotherapy+radiotherapy group (P<0.001). Cox multivariate analysis indicated that chemotherapy regime (paclitaxel + cisplatin-based regimens vs. other cisplatin-based regimens) and radiotherapy were independent prognostic factors. Conclusions: Adding radiotherapy to 4-6 cycles of paclitaxelbased chemotherapy significantly improved PFS and OS in distant metastaticNPC patients. Chemotherapy+radiotherapy make curability a possibility in thesepatients.

A Novel application of a polyglycolic acid sheet in treating oral and oropharyngeal cancer. In oral and oropharyngeal cancer surgery, various techniques have been applied to improve the postoperative outcome. Recently, a polyglycolic acid (PGA) sheet has been used in surgery when treating head and neck cancer. The objective of the current study is to determine whether the use of a PGA sheet reduces postoperative complications in transoral surgery for oral and oropharyngeal cancer. We reviewed a series of 38 oral and oropharyngeal cancer patients who underwent transoral surgery. We evaluated the outcomes of PGA application and compared them to those of patients who received surgery prior to the introduction of this technique. In all patients, the postoperative clinical course was without significantcomplications. Patients with oropharyngeal cancer in whom the PGA

sheet was used showed significantly lower incidence of pain following surgery. The application of a PGA sheet in the treatment of oral and oropharyngeal cancer is a convenient and versatile method for reducing postoperative pain and complications.

Impact of acute radiation induced toxicity of glutamine administration in several hypofractionated irradiation schedules for head and neck carcinoma. Purpose: The aim of this study was to investigate the treatment efficacy, acute and late toxicity using a hypofractionated irradiation schedule combined with oral administration of glutamine (GLN) in elderly patients with advanced squamous cell carcinoma of head and neck (SCCHN). Methods and materials: In a retrospective way, we studied 31patientswith advanced SCCHNtreated with hypofractionated radiotherapy and administration of GLN. The irradiation schedules consisted of three hypofractionated schedules. The one was consisted of 21 irradiation fractions (56.7 Gy) within 29days, by using intensive modulated radiation therapy technique or 3D conformal radiotherapy. The second and the third schedule were performed with 3D conformal techniques by 49.5 Gy in 18 daily fractions and 59.8 Gy in 26 daily fractions, respectively. All patients received 30gr powdered GLN daily, as soon as oral mucositis was presented.. The median follow-up was 18 months (range: 9-24). The severity of skin toxicity and oral mucositis was graded according to the RTOG/EORTC criteria. Results:Overall complete response was seen in 12 patients (38.7%), while 5 patients (16.1%) had partial response, 7 patients (22.6%) had stable disease and 7 patients (22.6%) had progressive disease. The median relapse free survival was 14 months. Three patients (9.7%) experienced grade 3 acute skin toxicity. Twenty one (67.7%) and seven (22.6%) patients had grade II and grade I acute skin toxicity, respectively. A significant decrease was noted in the incidence of toxicity after the administration of GL (P<0.01, chi2 test). The mean score of dysphagia related pain and oral mucositis regressed significantly (P<0.01, Wilcoxon test) at the last week of irradiation after the GLN administration. Conclusion: In elderly patients suffered from SCCHN with comorbitities and unfit for daily irradiation and chemotherapy, it is possible an alternative schedule of hypofractionation when combined with the administration of GLN.

High HIF-1&#945; expression genotypes increase odds ratio of oral cancer. Objective: the aim of this study is to assess whether C1772T and G1790A HIF-1α polymorphisms are associated with odds ratio of OSCC development. Materials and Methods:restriction fragment length polymorphism (RFLP) analysis was used to investigate HIF-1α C1779T and G1790A polymorphisms in 48 patients with epithelial dysplasia (ED) and 40 patients with oral squamous cell carcinoma (OSCC). Additionally, 88 elderly individuals without HNSCC were enrolled as a control group. Results: the frequency of the TT, GA, and AA genotypes was higher in patients with ED and OSCC when compared with controls. However, CT genotype was associated with moderate epithelial dysplasia in ED patients, while TT genotype was more frequent in OSCC patients. Conclusions: In conclusion, our study demonstrated that the T and A alleles of C1772T and G1790A polymorphisms of the HIF-1α gene increased the risk of ED and OSCC. C1772T and G1790A polymorphisms of the HIF-1α gene had differing patterns of allelic imbalance in the precancerous lesions and subsequent carcinoma, suggesting a complex genetic pattern of progression from dysplasia to carcinoma. These findings suggest an additional role for HIF-1α in OSCC development. Further studies are necessary to elucidate the HIF-1α pathway in carcinogenesis, which would facilitate the development of novel therapeutic strategies for the prevention and treatment of OSCC and other solid tumors

Identification of high-risk human papillomaviruse (HPV-16 & 18) infection by multiplex PCR (MPXPCR) and its expression in oral sub mucous fibrosis and oral squamous cell carcinoma. A human papilloma virus (HPV) is well established as heterogeneous virus family and important in human carcinogenesis. It not only causes the vast majority of cervical cancers, but also plays an important role in anogenital as well as oral cancers. Aim of the present study was to detect the HPV 16 and 18 by type specific PCR and multiplex-PCR and also asses their expression by

immunohistochemistry (IHC). We analyzed the paraffin embedded tissue sections of 208 and 222 OSMF and OSCC patients respectively. Out of 208 OSMF, 25.96% individuals showed positivity for HR-HPV 16 URR infection and 1.92% for HR-HPV18. In 222 OSCC cases, 32.43% were positive for HR-HPV 16 URR infection and 12% for HPV 18 E6. 1.44% of OSMF samples were positive for coinfection with both HPV 16 URR and 18 E6 infections in late stages of the disease and 3.6% samples were positive for HPV 16 URR and 18 infections co-infection with OSCC cases. IHC analysis showed 12.2% extensive positive expression of HPV 16 URR in case of OSMF. While in case of OSCC, 19.7% cases showed extensive positive expression. In case of higher grade in malignant lesions, immunostaining showed significant (p<0.021) association of HPV 16 URR in OSCC cases. This study concluded that multiplex PCR (MPX-PCR) could be helpful for quick screening of HR-HPVs and it is highly convenient, simple and cost-effective tool for large scale multi-institutional study for developing countries. Surgical outcome of Carotid body tumor resection after percutaneous embolisation with ethylene-vinyl alcohol copolymer (Onyx®). Introduction: Carotid body tumors are highly vascularized tumors that can only be treated curatively by complete surgical resection. Preoperative embolization is widely used to reduce intraoperative bleeding and minimize surgical complications. Objective: To assess the surgical outcome of carotid body tumor resection after percutaneous embolisation using Onyxâ. Methods: Retrospective analyzation of 5 consecutive patients with carotid body tumors from 08/2008 until 12/2011 after embolization via percutaneos intratumoral injection using Onyx and comparison to the literature. Results: In 4 of 5 patients, complete devascularization was achieved. No complications occurred during embolization. All carotid body tumors were resected completely. Duration of surgery varied between 35-289 minutes with an average of 148 minutes. Mean estimated intraoperative blood loss was 327 mL ranging from 40-1400 mL. We experienced 1 Horner’s syndrome, 1 temporary hypoglossal nerve paresis and a permanent paresis of the recurrent laryngeal nerve. Conclusion: Preoperative embolization reduces intraoperative blood loss, improves operative field visualisation and consecutively diminishes damage to nerval and vascular structures. Percutaneous embolization via direct intratumoral puncture appears to achieve a higher degree of devascularization by affecting arterial vessels, capillary bed and venous drainage. Existing data suggest a decrease in intraoperative blood loss and fluoroscopy times over transarterial embolization.

ARID1A is a tumor suppressor and inhibits glioma cell proliferation via the PI3K pathway. ARID1A plays an important role in malignant tumorigenesis, but its role in gliomas remains unclear. This study aims to identify a possible biomarker that could be used in the diagnosis and tumor grade assessment of gliomas. Additionally, the biological role of ARID1A was further characterized in glioma cells. Data was collected from sporadic gliomas specimens (n = 55) and normal brain tissues (n = 5), and ARID1A expression was examined by quantitative RT PCR and western blot. We verified the differential expression of ARID1A and evaluated the associations of ARID1A expression with the pathologic characteristics of gliomas. An ARID1A overexpression plasmid was constructed and transfected into the human glioblastoma cell line U87, and cell proliferation and apoptosis were examined. Our results showed that the ARID1A mRNA in gliomas was significantly down regulated compared to that in normal brain tissues. As the pathological grade (World Health Organization (WHO) classification 2007) increased, the expression of ARID1A is decreased. Overexpression of ARID1A was able to inhibit cell proliferation and arrest cell cycle progression in the G1/S phase, as well as induce cell apoptosis in glioma cells. Furthermore, ARID1A overexpression was accompanied by suppression of glioma cell proliferation via the PI3K pathway and decreased expression of pAKT and pS6K. Therefore, ARID1A may be a useful target for the diagnosis and therapy of gliomas.

Integrin &#945;v&#946;6 as a novel marker for diagnosis and metastatic potential of thyroid carcinoma.

Although most patients with thyroid carcinoma havegood response to surgery and radioiodine, diagnostic difficulties can lead to the development of more aggressive tumors characterized by lymphatic and distant metastasis. Thus, it is urgent to identify new molecular markers to improve diagnostic accuracy and to predict the metastatic potential of thyroid carcinoma.We examined the expression of integrin αvβ6 in thyroid tissue specimens by immunohistochemistry and evaluated the relationship between αvβ6 expression and clinicopathological features of 150 thyroid carcinoma patients.Integrin αvβ6 expression was consistently negative in normal thyroid tissue, and occasional/weak in thyroid adenoma. In contrast, thyroid carcinoma, metastatic lymph nodes, thyroid nodular goiter, and thyroiditis tissues showed a positive αvβ6 expression. Overall, αvβ6 expression distinguished thyroid carcinoma from non-malignant tissues witha sensitivity of 78.9% and specificity of 62%. We also observed significant association of αvβ6 expression with age and lymph node status.No significant difference. In conclusion, the detection of αvβ6 expression may help to improve diagnostic accuracy and predict metastatic potential for thyroid carcinomas.

The effect of intensity-modulated radiotherapy versus conventional radiotherapy on quality of life in patients with nasopharyngeal cancer: a cross-sectional study. Purpose: Previous reports suggested thatdosimetric superiority of Intensity modulated radiotherapy (IMRT)over conventional radiotherapy(CRT) could translate into improved quality of life (QoL) for patients with nasopharyngeal carcinoma(NPC). However, such advantage has not been confirmed using NPC-specific questionnaire with long-term follow-up. The purpose of this cross-sectional study was to compare the changing tendency of QoL between patients received IMRT and CRT with different follow-up time using a NPC-specific QoL instrument, and further validate the advantage of IMRT in QoL of NPC patients. Methods: We developed a modified NPC-specific QoL questionnaire (NPCQLQ) which contains 35 items based on EORTC QLQ-30in combination with NPC-specific side effects. One hundred and forty-two patients with localized NPC who were successfully treated defenitely without recurrence at the time of this analysis were enrolled and completed the questionnaire. Seventy-five patients were treated with IMRT and 67 received CRT. The median follow-up time was 25 months (range 12-42 months). Patients were divided into three sub-groups according totheir differentfollow-up time: 12-18, 19-28 and 29-42 monthsafter treatment, respectively.QoL of NPC patients was compared between different radiation techniques at three different follow-up intervals using Two Independent Samples Tests. K Independent Samples Tests was used to compared the changing tendency of IMRT vs. CRT with the prolongation of follow-up time. Results: At 12-18 months after treatment, all QoL scores of patients were comparable in both groups. At 19-28 months, a statistically significant improvement of QoL in symptom scales in the IMRT group was observed when compared to that of the CRT group(78.48±9.30vs. 69.66±12.03, p=0.008). At 29-42 months, QoL scores of physical functioning scales, global health status and symptom scaleswere significantly superior in the IMRT group (90.72±9.87, 83.16±13.65and 66.67±23.57,respectively) than those in the CRT group (50.00±31.47, 78.46±11.79 and 67.85±13.86, respectively). QoL scores in all the six scales of patients showed no significant change with prolonged follow-up time within the IMRT group. However, patients received CRT demonstrated a trend toward a declining QoL in physical functioning scales, global health status and symptom scales with longer follow up, but only the change of global health status reached a statistically significence (p=0.026). Conclusions: IMRT substantially improved QoL in NPC patients when compared to conventional radiotherapy, and the superiority become significant with prolonged follow-up time.

Antioxidants — On the Wrong Side of the Tracks? Antioxidants, available in many over-the-counter forms (vitamins C, E), are commonly regarded as safe and possibly cancer-protective. However, regulation of reactive oxygen species in cancers is quite complex, and though cells have evolved multiple mechanisms to control potentially mutagenic and damaging reactive oxygen species (ROS), increasing evidence suggests that cancers tune ROS levels to a sweet spot that avoids catastrophic toxicity while preserving generation of new mutations and inhibiting immune control. Two recent studies in mouse models directly addressed how antioxidants might affect melanoma progression. Le Gal and colleagues showed that antioxidants

increased melanoma invasiveness and metastasis. Both N-acetylcysteine (NAC) and Trolox (a vitamin E analogue) affected RHOA kinase pathways that regulate invasiveness and migration. NAC administration in a Braf/Pten mouse model of melanoma doubled the number of lymph node metastases. Piskounova and colleagues made similar observations but took things further, determining that melanoma cells experience oxidative stress in circulation. They showed that melanomas passaged through subcutaneous tissue had a substantially different redox status than did melanomas moving through the circulation or implanted in the spleen. In their assays, NAC also increased the metastatic efficiency of melanoma cells by 10-fold. Having detected greater levels of reduced glutathione in efficiently metastatic cells, the authors reasoned that NADPH-generating enzymes allow these cells to withstand oxidative stress. Since folate metabolism is critical for this process, they tested whether methotrexate would suppress metastases, which it did.

Breast Cancer Vaccines as Therapy: Another Chapter The promise of cancer vaccines to prevent or treat breast cancer has been tantalizing for decades, but to date the promise has not translated into an approved therapy. Although cancer vaccines have demonstrated an ability to produce an immune response, with few exceptions, improvements in clinical outcomes have been harder to demonstrate. Now, in a collaborative effort among the National Cancer Institute, Therion Biologics Institute, and academic investigators, a phase II randomized trial comparing docetaxel alone or in combination with the PANVAC vaccine has been conducted in patients with metastatic breast cancer. PANVAC (CEA-MUC-1-TRICOM) is a viral-vector cancer vaccine consisting of a priming dose with recombinant vaccinia vector and subsequent doses with recombinant fowlpox vector. Each vector encodes for the transgene for CEA and MUC-1 as well as three co-stimulatory molecules (B7.1, ICAM-1, and LFA-3). Participating patients received prior chemotherapy treatment for metastatic disease (70% had <3 regimens), but none had received docetaxel. Patients received weekly docetaxel (3 of 4 weeks) with or without PANVAC. The priming dose of PANVAC was given 3 weeks prior to the first cycle of docetaxel, and the booster dose was given on day 1 of each docetaxel dose. A total of 48 patients were randomized on the study over a 6 year period. Progression-free survival (PFS; the primary outcome) was nonsignificantly longer with combination docetaxel and PANVAC than with docetaxel alone (7.9 and 3.9 months, respectively; P=0.09). Patients receiving the combination experienced more edema likely due to a longer duration of therapy with docetaxel as well as to injection-site reactions.

Moreâ&#x20AC;Ś Dose and Fractionation in Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer: Lessons Learned and Where Do We Go Next? After target volume definition, irradiation dose and fractionation are the major outcome-determining factors of radiation therapy. Randomized trials asking the question of the irradiation dose with the optimal therapeutic ratio have been performed in many cancer sites: doses differed by 8 to 10 Gy (11%-16%) in primary radiation therapy for prostate cancer (1-4), 14 Gy (23%) in definitive radiochemotherapy for stage III non-small cell lung cancer (NSCLC) (5), 14.4 Gy (29%) in definitive radiochemotherapy for esophageal cancer (6), and 10 Gy (33%) in Hodgkin lymphoma (7). Tumor Response After Stereotactic Body Radiation Therapy to Nonspine Bone Metastases: An Evaluation of Response Criteria To evaluate the applicability of the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and University of Texas MD Anderson (MDA) Cancer Center criteria in the setting of stereotactic body radiation therapy (SBRT) to nonspine bone metastases. Radiation Therapy Intensification for Solid Tumors: A Systematic Review of Randomized Trials

To systematically review the outcomes of randomized trials testing radiation therapy (RT) intensification, including both dose escalation and/or the use of altered fractionation, as a strategy to improve disease control for a number of malignancies. Stormy “Fourcast” for Brachytherapy Cure with no side effects: radiation medicine's “holy grail.” It is not possible in 100% of patients, of course. Sometimes the trade-off is lifelong difficulty with swallowing or urinating, decreased enjoyment with intimacy, and other toxicities that decrease quality of life. Our job in radiation oncology is to maximize the therapeutic ratio and get as close as possible. I am a brachytherapist at heart, truly believing that delivering a high dose to the core while sparing surrounding tissues renders lessprecise modalities indefensible. How Important Is a Reproducible Breath Hold for Deep Inspiration Breath Hold Breast Radiation Therapy? Deep inspiration breath hold (DIBH) for left-sided breast cancer has been shown to reduce heart dose. Surface imaging helps to ensure accurate breast positioning, but it does not guarantee a reproducible breath hold (BH) at DIBH treatments. We examine the effects of variable BH positions for DIBH treatments. Is Pilocarpine Effective in Preventing Radiation-Induced Xerostomia? A Systematic Review and MetaAnalysis Pilocarpine has been used in the treatment of xerostomia, however it is still uncertain whether it has a preventive effect on radiation-induced xerostomia. Our systematic review and meta-analysis demonstrated that concomitant administration of pilocarpine during radiation could increase unstimulated salivary flow rate, and reduce clinician-rated xerostomia grade. It may also relieve patients’ xerostomia at 6 months, and possibly at 12 months. But it had no effects on stimulated salivary flow rate. Effect of dosimetric outliers on the performance of a commercial knowledge-based planning solution Using a commercial knowledge based planning solution, we investigated the effect of dosimetric outliers on resulting plan quality by adding 5-40 dosimetric outliers to a 70-plan model for head and neck cancer. Model cleaning or adding 5/10 outliers marginally improved salivary gland/swallowing muscle sparing, whilst adding >20 showed a modest deterioration in resulting plan quality. These results demonstrate the robustness of consistently planned knowledge-based models to moderate proportions of dosimetric outliers. Boron Neutron Capture Therapy in the Treatment of Recurrent Laryngeal Cancer To investigate the safety and efficacy of boron neutron capture therapy (BNCT) as a larynx-preserving treatment option for patients with recurrent laryngeal cancer. Cost-effectiveness analysis of chemoradiotherapy versus transoral robotic surgery for human papillomavirus-associated, clinical N2 oropharyngeal cancer We performed a cost-effectiveness analysis comparing primary CRT with TORS followed by riskadapted adjuvant RT or CRT (for positive margins or extracapsular extension) for HPV-associated oropharyngeal cancer. We found that under most assumptions, primary CRT was the cost-effective strategy and typically dominated initial surgery. However, when we assumed that primary TORS hypothetically improved relative locoregional control outcomes by 30-50% while keeping the long-term NED utilities the same, it became the cost-effective strategy. Patterns of local-regional management following neoadjuvant chemotherapy in breast cancer: Results from ACOSOG Z1071 (Alliance) Local-regional management following neoadjuvant chemotherapy in ACOSOG 1071 were reviewed. All patients had node positive breast cancer treated with neoadjuvant chemotherapy, sentinel node and completion axillary dissection. Review of the records revealed wide variability in practice,

particularly regarding administration of radiation therapy, often conflicting with practice recommendations and guidelines. The study emphasizes the need for education, clinical practice statements and trials to address these issues and reduce variability in practice. A Phase II Trial of Concurrent Chemotherapy and Proton Therapy for Stage 3 Non-Small Cell Lung Cancer: Results and Reflections following Early Closure of a Single-Institution Study This phase II study evaluated outcomes of concurrent high dose proton therapy with chemotherapy for stage III non-small cell lung cancer. Although the study closed early, due to competing multiinstitutional trials, the favorable outcomes support the limited clinical data for the use of proton therapy with concurrent chemotherapy in this patient population. Additionally, we identify a cohort of unfavorable risk patients being treated with proton therapy, but are ineligible for current clinical trials. Predictors of Locoregional Failure and the Impact on Overall Survival in Patients with Resected Exocrine Pancreas Cancer The role of radiotherapy as adjuvant treatment for resectable pancreas cancer is controversial. The present study showed reduced rates of local relapse in patients receiving chemoradiotherapy vs chemotherapy alone. Local relapse was an independent predictor of worse overall survival compared with patients who had no relapse. Exploratory Study of 4D Versus 3D Robust Optimization in Intensity-Modulated Proton Therapy for Lung Cancer To mitigate uncertainties and interplay effects in optimizing intensity-modulated proton therapy for lung cancers, we used 4D robust optimization that generated plans on 4D-CTs with the clinical target volume of individual phases receiving non-uniform doses to achieve a uniform cumulative dose. Compared to 3D robust optimization, 4D robust optimization provided more robust target dose distribution to uncertainties and led to better target coverage, comparable dose homogeneity, and normal tissue protection with interplay effects considered. Closing the Cancer Divide through Ubuntu: Information and Communication Technology powered models for global radiation oncology There is growing consensus that Information and Communication Technologies (ICTs) have tremendous potential to catalyze global health collaborations. Advanced ICTs can be employed to leverage the recent major upsurge in Global Health interest into greater space-time flexible collaborative action against cancer and for enhancing greater effectiveness of existing global health initiatives. The recent call for greater action in closing the cancer divide through collaborations, including that in the Red Journal, inspired the 2015 Global Health Catalyst cancer summit, which brought together a unique combination of global oncology leaders, Diaspora leaders, ICT and palliative care experts, industry, nonprofits, and policy makers. RECQ1 A159C polymorphism is associated with overall survival of patients with resected pancreatic cancer: a replication study in NRG Oncology RTOG 9704 RECQ1 A159C polymorphism has previously been associated with significantly reduced survival in resectable pancreatic cancer patients who were treated with preoperative chemoradiation. To confirm this association, this genotype was evaluated in resected pancreatic cancer patients who were treated with postoperative chemoradiation. The variant C allele was significantly associated with reduced survival and increased risk of death, which suggests a promising prognostic or predictive value for patients with resectable pancreatic cancer who are treated with chemoradiation. Patterns of failure after radical cystectomy for pT3-4 bladder cancer: Implications for adjuvant radiation therapy 334 patients with pT3-4 bladder cancer underwent radical cystectomy and pelvic lymph node dissection, with or without adjuvant chemotherapy. Local-regional failures (LF) were identified on follow-up imaging, and a recurrence map was generated. On multivariable analysis, pT and pN stage were associated with a higher risk for LF. pT4 or N1 patients had a >30% risk of LF at 2 years. 34% of patients with LF had local-regional only disease at the time of recurrence.

Pathological response, when increased by longer interval, is a marker but not the cause of good prognosis in rectal cancer : 17-year follow-up of the Lyon R90-01 randomized trial The ***** R90-01 randomized trial investigated whether the interval between preoperative radiation therapy and surgery influenced rectal cancer outcome. This study after a follow-up of 17 years provided good evidence on three points: Radiotherapy-induced sterilization could serve as a marker of good prognosis; the rate of local relapse after five years was very low, and radiotherapy-induced cancers are very unusual. The interval duration (the treatment being the same) although it is modifying the sterilization rate has no impact on the survival. Resistance exercise and inflammation in breast cancer patients undergoing adjuvant radiotherapy: Mediation analysis from a randomized controlled intervention trial Breast cancer patients receiving whole-breast irradiation may suffer from fatigue, pain, or depression. Exercise interventions have shown benefits regarding these symptoms. As mechanisms inflammatory pathways have been hypothesized. This randomized controlled trial showed significantly increased pro-inflammatory interleukin-6 (IL-6) during radiotherapy in breast cancer patients. This effect was counteracted by resistance exercise. IL-1 receptor antagonist (Il-1ra) was not affected. IL-6 and the IL-6/IL-1ra ratio partially mediated the beneficial effect of exercise on physical fatigue and pain.