Aspirin and other non-steroidal anti-inflammatory drug prescriptions and survival after the diagnosis of head and neck and oesophageal cancer

Peer reviewed

AN INVESTIGATION ON ROUTINE FOLLOW-UP CARE FOR HEAD AND NECK CANCER

BACKGROUND: Follow-up care aims to provide surveillance with early detection of recurring cancers and to address treatment complications and other health issues in survivorship. It is assumed that follow-up care fulfills these aims, however little evidence supports routine surveillance detecting curable disease early enough to improve survival. Cancer survivors are a diverse patient population, suggesting that a single follow-up regimen may not meet all patients’ follow-up needs. Little is known about what effective follow-up care should include for head and neck cancer patients in a Canadian setting. Identification of subgroups of patients with specific needs and current practices would allow for hypotheses to be generated for enhancing follow-up care. OBJECTIVES: 1a) To describe the follow-up needs and preferences of head and neck cancer patients, 1b) to identify which patient characteristics predict needs and preferences, 1c) to evaluate how needs and preferences change over time, 2a) to describe follow-up care practices by physician visits and imaging tests, and 2b) to identify factors associated to the delivered follow-up care. METHODS: 1) 175 patients who completed treatment between 2012 and 2013 in Kingston and London, Ontario were recruited to participate in a prospective survey study on patients’ needs and preferences in follow-up care. Bivariate and multivariate analyses were employed to describe patient survey responses and to identify patient characteristics that predicted needs and preferences. 2) A retrospective cohort study of 3975 patients on routine follow-up from 2007 to 2015 was carried out using data linkages across registry and administrative databases to describe follow-up practices in Ontario by visits and tests. Multivariate regression analyses assessed factors related to follow-up care. RESULTS: 1) Patients’ needs and preferences were wide-ranging with several characteristics predicting needs and preferences (ORECOG=2.69 and ORAnxiety=1.13). Needs and preferences declined as patients transitioned into their second year of follow-up (p<0.05). 2) Wide variation in practices was found, with marked differences compared to existing consensus guidelines. Multiple factors were associated with follow-up practices (RRTumor site=0.73 and RRLHIN=1.47). CONCLUSIONS: Patient characteristics can be used to personalize care and guidelines are not informing practice. Future research should evaluate individualized approaches to follow-up care.

The Role of Perceived Social Support, Resilience, and Depression on Communicative Participation in Head and Neck Cancer Survivors

Thesis (Master's)--University of Washington, 2016-08

CAREGIVING FOR A FAMILY MEMBER WITH HEAD AND NECK CANCER

Objective: To know the perception of informal caregivers regarding the care for a family member with head and neck cancer. Methods: Qualitative study conducted between March and May 2014 in the radiotherapy outpatient center of the Centro de Alta Complexidade em Oncologia – CACON (Oncology High Complexity Center) of the Hospital Universitário de Brasília – HUB (University Hospital of Brasília) using semi-structured interviews with nine caregivers about the experience of caring for family members. Data underwent Content Analysis and four units of meaning were identified: “Representation of cancer in the Family”, “The care as debt, individual reward or reconstruction of family ties”, “Repercussions of cancer on the caregiver’s personal life” and “Social support and network used by caregivers”. Results: Feelings of sadness and surprise at the moment of diagnosis were attributed to cancer, as well as the idea of punishment. The care was seen as personal satisfaction, accomplishment and opportunity for family rapprochement. Work overload and change in routine were altered functions. Religiosity, exchange of experience in the waiting room and institutional support appeared as coping strategies. Conclusion: The experience of caring for family members with head and neck cancer directly interferes in the lives of caregivers. Pointing out the institutional embracement as a strategy within the social network reinforces the importance of integrating the caregivers as a significant part of the health care plan developed by the health team.

Olfactomedin-4 is a candidate biomarker of solid gastric, colorectal, pancreatic, head and neck, and prostate cancers

International audience

Dermoscopic, histopathologic and molecular characterization of head and neck melanoma

Almost 18-35% of cutaneous melanomas are located in the head and neck region (2-5% of them in the scalp) and according to multiple epidemiological studies they are supposed to have a worse prognosis with respect to those of other body areas. The aim of this phD project is to perform a global evaluation of head/neck region cutaneous melanomas with a distinct analysis of histological, dermoscopic and molecular features of the selected cases. The diffuse distribution of folliculotropism (≥3 HF/specimen), the presence of atypical melanocytes into the isthmus, and the perifollicular involvement were associated with melanoma recurrence. The dermoscopic parameter grey circles in lentigo maligna was correlated to the depth of folliculotropism, with a higher probability of an isthmic or bulge follicular extension of neoplastic melanocytes. The detection of grey circles, light/dark brown pseudonetwork and light brown structureless areas in lentigo maligna melanoma was associated with the distribution of folliculotropism (focal/diffuse). MiR-146a-5p expression was shown to be significantly greater in melanomas with a mitotic rate ≥1/mm2 as well as in ulcerated lesions compared to those without ulceration. No difference emerged evaluating regression when considering all melanomas subtypes, but an higher expression was noticed in the lentigo maligna melanoma group. Moreover, miR-146a-5p expression was lower in head/neck region cutaneous melanomas with Breslow thickness ≥0.8 mm. These results give further insights for the management of cutaneous melanomas with specific adverse prognostic elements. As the majority of head/neck region cutaneous melanomas are wild type of BRAF and NRAS mutations and not suitable for targeted therapies, the discovery of new molecular targets may provide relevant opportunities for their treatment.

Bright-field multiplex immunohistochemistry for tumor. Microenvironment evaluation in mucosal melanoma of the head and neck region: technical aspects, results, and correlation with clinicopathologic features and molecular landscape

Mucosal melanoma of the head and neck region (MM-H&N) is a rare disease, characterized by a poor prognosis and limited therapeutic strategies, especially regarding targeted therapy (lower rate of targetable mutations compared to cutaneous melanoma) and immunotherapy (lack of diagnostic tools able to predict the response). Meanwhile, bright-field multiplex immunohistochemistry (BF-mIHC) is emerging as a promising tool for characterizing tumor microenvironment (TME) and predicting response to immunotherapy in several tumors, including melanoma. This PhD project aims to develop a BF-mIHC protocol to evaluate the TME in MM-H&N, analyze the correlation between immune markers/immune profiles and MM-H&N features (clinicopathologic and molecular), and find new biomarkers useful for prognostic-therapeutic stratification of these patients. Specific aims are: (I) describe the clinicopathological features of MM-H&N; (II) analyze the molecular status of MM-H&N and correlate it with the clinicopathological features; (III) analyze the molecular status of multiple specimens from the same patient to verify whether molecular heterogeneity of MM-H&N could affect the results with relevant prognostic-therapeutic implications; (IV) develop a BF-mIHC protocol to study TME in MM-H&N; (V) analyze the correlation between immune markers/immune profiles and MM-H&N features (clinicopathologic and molecular) to test whether BF-mIHC could be a promising tool for prognostic-therapeutic characterization of these patients.

Prognostic significance of NDRG1 expression in oral and oropharyngeal squamous cell carcinoma

Human N-myc downstream-regulated gene 1 (NDRG1) is a metastasis suppressor gene with several potential functions, including cell differentiation, cell cycle regulation and response to hormones, nickel and stress. The purpose of this study was to investigate the immunoexpression of NDRG1 in oral and oropharyngeal squamous cell carcinomas searching for its role in the clinical course of these tumors. We investigated immunohistochemical expression of NDRG1 protein in 412 tissue microarray cores of tumor samples from 103 patients with oral and oropharyngeal squamous cell carcinomas and in 110 paraffin-embedded surgical margin sections. The results showed NDRG1 up-regulation in 101/103 (98.1 %) tumor samples, but no expression in any normal tissue sample. Western blot assays confirmed the immunohistochemical findings, suggesting that lower levels of NDRG1 are associated with a high mortality rate. NDRG1 overexpression was related to long-term specific survival (HR = 0.38; p = 0.009), whereas the presence of lymph-node metastasis showed the opposite association with survival (HR = 2.45; p = 0.013). Our findings reinforce the idea that NDRG1 plays a metastasis suppressor role in oral and oropharyngeal squamous cell carcinomas and may be a useful marker for these tumors.

[Bullet and shrapnel injuries in the face and neck regions. Current aspects of wound ballistics]

A basic understanding of the ballistic behaviour of projectiles or fragments after entering the human body is essential for the head and neck surgeon in the military environment in order to anticipate the diagnostic and therapeutic consequences of this type of injury. Although a large number of factors influence the missile in flight and after penetration of the body, the most important factor is the amount of energy transmitted to the tissue. Long guns (rifles or shotguns) have a much higher muzzle energy compared to handguns, explaining why the remote effects beyond the bullet track play a major role. While most full metal jacket bullets release their energy after 12-20 cm (depending on the calibre), soft point bullets release their energy immediately after entry into the human body. This results in a major difference in extremity wounds, but not so much in injuries with long bullet paths (e.g. diagonal shots). Shrapnel wounds are usually produced with similarly high kinetic energy to those caused by hand- and long guns. However, fragments tend to dissipate the entire amount of energy within the body, which increases the degree of tissue disruption. Of all relevant injuries in the head and neck region, soft tissue injuries make up the largest proportion (60%), while injuries to the face are seen three times more often than injuries to the neck. Concomitant intracranial or spinal injury is seen in 30% of cases. Due to high levels of wound contamination, the infection rate is approximately 15%, often associated with a complicated and/or multiresistant spectrum of germs.

Detecção do rearranjo da prpoteína BCL2/JH em carcinomas epidermóides de boca e faringe

The BCL2 protein found in the internal mothocondrial membrana regulates the apoptosis preventing the programmed cell death. The translocation (14:18), detected in 70 to 85% of the follicular lymphoma, lead the super expression of BCL2 protein, by juxtaposition of BCL2 gene to the JH segment of the immunoglobulins' heavy chain gene. However, the found of the BCL2 expression in head and neck carcinoma are contradictious. OBJECTIVE: To investigate the presence of the translocation (14:18) of the BCL2 gene in head and neck carcinoma. METHOD: Sixteen DNA samplers were examinated being 13 of squamous cells carcinoma (SCC) and 3 of epidermoid (CE), y means of chain reaction of the polymerase (PCR). RESULTS: The BCL2/JH rearrangement in 2 (15%) of the CCE 13 cases and in none of the 3 cases of CE. The average of the frequency of molecules with rearrangement was 46,44x107. Was not observed association between the rearrangement presence and the exhibition to tobacco and alcohol (p=0, 6545). CONCLUSION: Different from the results found in follicular lymphoma, the presence of the translocation (14; 18) in head and neck carcinomas is not common and, when it occurs, it can be an occasional mutation not associated to exhibition to the tobacco and alcohol.

Research Smad2 and Smad6 as predictors of overall survival in oral squamous cell carcinoma patients

Background: To test if the expression of Smad1-8 mRNAs were predictive of survival in patients with oral squamous cell carcinoma (SCC). Patients and Methods: We analyzed, prospectively, the expression of Smad1-8, by means of Ribonuclease Protection Assay in 48 primary, operable, oral SCC. In addition, 21 larynx, 10 oropharynx and 4 hypopharynx SCC and 65 matched adjacent mucosa, available for study, were also included. For survival analysis, patients were categorized as positive or negative for each Smad, according to median mRNA expression. We also performed real-time quantitative PCR (QRTPCR) to asses the pattern of TGF beta 1, TGF beta 2, TGF beta 3 in oral SCC. Results: Our results showed that Smad2 and Smad6 mRNA expression were both associated with survival in Oral SCC patients. Cox Multivariate analysis revealed that Smad6 positivity and Smad2 negativity were both predictive of good prognosis for oral SCC patients, independent of lymph nodal status (P = 0.003 and P = 0.029, respectively). In addition, simultaneously Smad2(-) and Smad6(+) oral SCC group of patients did not reach median overall survival (mOS) whereas the mOS of Smad2(+)/Smad6(-) subgroup was 11.6 months (P = 0.004, univariate analysis). Regarding to TGF beta isoforms, we found that Smad2 mRNA and TGF beta 1 mRNA were inversely correlated (p = 0.05, R = -0.33), and that seven of the eight TGF beta 1(+) patients were Smad2(-). In larynx SCC, Smad7(-) patients did not reach mOS whereas mOS of Smad7(+) patients were only 7.0 months (P = 0.04). No other correlations were found among Smad expression, clinico-pathological characteristics and survival in oral, larynx, hypopharynx, oropharynx or the entire head and neck SCC population. Conclusion: Smad6 together with Smad2 may be prognostic factors, independent of nodal status in oral SCC after curative resection. The underlying mechanism which involves aberrant TGF beta signaling should be better clarified in the future.

Cross talk Initiated by Endothelial Cells Enhances Migration and Inhibits Anoikis of Squamous Cell Carcinoma Cells through STAT3/Akt/ERK Signaling

It is well known that cancer cells secrete angiogenic factors to recruit and sustain tumor vascular networks. However, little is known about the effect of endothelial cell-secreted factors on the phenotype and behavior of tumor cells. The hypothesis underlying this study is that endothelial cells initiate signaling pathways that enhance tumor cell survival and migration. Here, we observed that soluble mediators from primary human dermal microvascular endothelial cells induce phosphorylation of signal transducer and activator of transcription 3 (STAT3), Akt, and extracellular signal-regulated kinase (ERK) in a panel of head and neck squamous cell carcinoma (HNSCC) cells (OSCC-3, UM-SCC-1, UM-SCC-17B, UM-SCC-74A). Gene expression analysis demonstrated that interleukin-6 (IL-6), interleukin-8 (CXCL8), and epidermal growth factor (EGF) are upregulated in endothelial cells cocultured with HNSCC. Blockade of endothelial cell-derived IL-6, CXCL8, or EGF by gene silencing or neutralizing antibodies inhibited phosphorylation of STAT3, Akt, and ERK in tumor cells, respectively. Notably, activation of STAT3, Akt, and ERK by endothelial cells enhanced migration and inhibited anoikis of tumor cells. We have previously demonstrated that Bcl-2 is upregulated in tumor microvessels in patients with HNSCC. Here, we observed that Bcl-2 signaling induces expression of IL-6, CXCL8, and EGF, providing a mechanism for the upregulation of these cytokines in tumor-associated endothelial cells. This study expands the contribution of endothelial cells to the pathobiology of tumor cells. It unveils a new mechanism in which endothelial cells function as initiators of molecular crosstalks that enhance survival and migration of tumor cells.

Relationship between the appearance of tongue carcinoma on intraoral ultrasonography and neck metastasis

To evaluate the usefulness of intraoral ultrasonography (IOUS) as a tool for predicting neck metastasis. Squamous cell carcinoma (SCC) of the tongue is aggressive and has a great propensity to metastasize to cervical lymph nodes. SCC of the oral cavity has a worse prognosis when associated with metastatic cervical nodes. Therefore, the metastatic potential of tongue carcinoma should be graded preoperatively to help determine the requirement for neck dissection. Nineteen patients (11 men, 8 women) between 36 and 79 years of age (mean age 60) with T1 to T4a TNM-stage tongue carcinomas were evaluated preoperatively with IOUS. Clinical and pathological TNM classifications were performed. The average tumor thicknesses measured using histological sections were significantly (p < 0.01) lower than those with IOUS (1.3 vs. 1.6 cm, respectively). A significant correlation was observed between the tumor thickness measured using ultrasonography and that measured using histological sections (pathology). Based on this greater accuracy, the cutoff point of tumor thickness based on IOUS evaluation for predicting neck metastasis was determined to be 1.8 cm. Some factors may influence neck metastasis. A knowledge of these would help to avoid unnecessary surgical intervention for N0 patients. The results of this study indicates that there is a significant correlation between neck metastasis and tumor thickness. Intraoral ultrasonography is useful tool for identifying tongue tumors and measuring their thickness, with the thickness measured by IOUS showing a very good correlation with histological measurements. Moreover, IOUS provides prognostic information prior to surgical treatment since tumor thickness can predict the chance of recognizing metastatic cervical nodes.

Predictors of higher number of stages in Mohs micrographic surgery for the treatment of squamous cell carcinoma of the head

BACKGROUND - Squamous cell carcinomas of the skin of the bead are better treated with Mobs micrographic surgery which has the lowest recurrence rates and allows spare normal tissue. There are some characteristics of squamous cell carcinoma that can be related to a higher number of surgical stages. OBJECTIVE - To study characteristic of head squamous cell carcinoma that predicts a higher number of Mohs surgical stages. METHODS - A retrospective analysis of 51 squamous cell carcinomas of the bead treated with Mobs surgery was performed to determine risk factors for a higher number of surgical stages. The characteristics analyzed were clinical limits, morphology, recurrence, histological differentiation and size and compared to the number of surgical stages. The analysis was performed by Fisher`s exact test and multivariate logistic regression. RESULTS - The recurrent squamous cell carcinomas showed a tendency for a higher number of stages (p=0,081). The Odds Ratio for a higher number of Mobs stages was three for inaccurate limits; although not statistically significant, it corroborates clinical and previous publication. CONCLUSION - Clinical characteristics of squamous cell carcinoma as recurrence and inaccurate limits would not predict, but could indicate tendency of a higher number of Mobs micrographic surgery stages.

HIGH EXPRESSION OF CANCER TESTIS ANTIGENS MAGE-A, MAGE-C1/CT7, MAGE-C2/CT10, NY-ESO-1, AND GAGE IN ADVANCED SQUAMOUS CELL CARCINOMA OF THE LARYNX

Background. Despite diagnostic and therapeutic advances in head and neck cancer, the 5-year survival of patients with laryngeal cancer has not improved in the last 30 years. Several recent studies indicate that specific targets for immunotherapeutic approaches can be useful in the control of cancer. There is considerable interest in the expression of cancer testis antigens in human cancers since they may serve as the basis for an immunologic approach to therapy. Methods. We evaluated by immunohistochemical analysis the expression of cancer testis antigens MAGE-A4 (57B), MAGE-C1 (CT7-33), MAGE-A1 (MA454), MAGE-A3 (M3H67), MAGE-C2 (CT10.5), NY-ESO-1 (E978), and GAGE (GAGE) in squamous cell carcinoma (SCC) of the larynx. Results. A total of 63 cases (57 men and 6 women) of laryngeal SCC were available for this study. The findings were correlated with the clinical course and laboratory data. Expression of at least 1 cancer testis antigen was detected in 42 of 63 of the laryngeal SCCs (67%). In 34 of 42 of the positive cases (81%) there was simultaneous expression of >= 2 cancer testis antigens. There was significant correlation between antigen expression and advanced tumor stage (stage III/IV) in cases with reactivity to only 1 antibody (p = .01) as well as in the cases with reactivity to >= 2 primary antibodies (>= 2 mAbs, p = .04). There was no association between survival and expression of any of the analyzed antigens. Conclusions. We find a high incidence of cancer testis antigen expression in SCCs of the larynx, which was correlated with advanced clinical stage. Our data indicate that cancer testis antigens could be valuable vaccine targets in laryngeal tumors, especially in those with a worse prognosis. (C) 2010 Wiley Periodicals, Inc. Head Neck 33: 702-707, 2011