Effect of human beta-defensin-3 on head and neck cancer cell migration using micro-fabricated cell islands
Abstract
Background
To examine the effect of the natural antimicrobial peptide human β-defensin-3 (hBD-3), on the migration of a head and neck cancer cell line in vitro using microfabrication and soft-lithographic techniques.
Methods
TR146 cancer cells were seeded in Petri dishes with microfabricated wells for cell migration assays. Total 54 cell islands were used of various shape and size and experimental media type. Cell migration assays were analyzed in six group media: Dulbecco’s modified medium (DMEM); DMEM with vascular endothelial growth factor (VEGF); Conditioned media of human embryonic kidney cells (HEK 239) expressing hBD-3 via transfected cloned pcDNA3 as CM/hBD-3; CM/hBD-3 + VEGF; conditioned medium from non-transfected HEK 239 (not expressing hBD-3) as control (CM); and the last group was CM + VEGF. Cell islands were circular or square and varied in size (0.25 mm2, 0.125 mm2, and 0.0625 mm2). Cell islands were imaged at t = 0 h, 3 h, 6 h, and 24 h.
Results
The results show cancer cell islands that originally were smaller had higher migration indices. There was no difference of MIs between circular and square cell islands. MIs at the end point were significantly different among the groups except between CM and CM-hBD-3+ VEGF.
Conclusions
VEGF enhanced cancer cell migration. The combination of DMEM and VEGF showed a synergistic effect on this phenomenon of cancer cell migration. Conditioned medium with hBD-3 suppressed cancer cell migration. hBD-3 suppressed VEGF enhancement of TR146 cancer cell migration.
Feasibility of recruitment to an oral dysplasia trial in the United Kingdom
Abstract
Background
Oral epithelial dysplasia (OED) has a malignant potential. Therapeutic options for OED remain both limited and without good evidence. Despite surgery being the most common method of treating OED, recurrence and potentially significant morbidity remain problematic. Consequently, there has been much interest in non-surgical treatments for OED. Cyclo-oxygenase (COX) up-regulation is known to occur in the dysplasia-carcinoma sequence and evidence now exists that COX-2 is a prognostic marker of malignant transformation in OED. COX-inhibitors are therefore considered a potential therapeutic strategy for treating this condition. We aimed to provide both proof of principal evidence supporting the effect of topical COX inhibition, and determine the feasibility of recruitment to an OED chemoprevention trial in the UK.
Methods
Recruitment of 40 patients with oral leukoplakia to 4 study arms was planned. The total daily dose of Aspirin would increase in each group and be used in the period between initial diagnostic and follow-up biopsies.
Results
During the 15-month recruitment period, 15/50 screened patients were eligible for recruitment, and 13 (87%) consented. Only 1 had OED diagnosed on biopsy. 16 patients were intolerant of, or already taking Aspirin and 16 patients required no biopsy. Initial recruitment was slow, as detection relied on clinicians identifying potentially eligible patients. Pre-screening new patient letters and directly contacting patients listed for biopsies improved screening of potentially eligible patients. However, as the incidence of OED was so low, it had little impact on trial recruitment. The trial was terminated, as recruitment was unlikely to be achieved in a single centre.
Conclusion
This feasibility trial has demonstrated the low incidence of OED in the UK and the difficulties in conducting a study because of this. With an incidence of around 1.5/100,000/year and a high proportion of those patients already taking or intolerant of Aspirin, a large multi-centred trial would be required to fulfil the recruitment for this study. The ability of topical non-steroidal anti-inflammatory drugs to modify COX and prostaglandin expression remains an important but unanswered question. Collaboration with centres in other parts of the world with higher incidences of the disease may be required to ensure adequate recruitment.
ISRCTN
31503555.
Spinal metastasis in thyroid cancer
Abstract
Background
Thyroid carcinoma generally responds well to treatment and spinal metastasis is an uncommon feature. Many studies have looked at the management of spinal metastasis and proposed treatments, plans and algorithms. These range from well-established methods to potentially novel alternatives including bisphosphonates and vascular endothelial growth factor (VEGF) therapy, amongst others.
The purposes of this systematic review of the literature are twofold. Firstly we sought to analyse the proposed management options in the literature. Then, secondly, we endeavoured to make recommendations that might improve the prognosis of patients with spinal metastasis from thyroid carcinomas.
Methods
We conducted an extensive electronic literature review regarding the management of spinal metastasis of thyroid cancer.
Results
We found that there is a tangible lack of studies specifically analysing the management of spinal metastasis in thyroid cancer. Our results show that there are palliative and curative options in the management of spinal metastasis, in the forms of radioiodine ablation, surgery, selective embolisation, bisphosphonates and more recently the VEGF receptor targets.
Conclusions
The management of spinal metastasis from thyroid cancer should be multi-disciplinary. There is an absence; it seems, of a definitive protocol for treatment. Research shows increased survival with 131I avidity and complete bone metastasis resection. Early detection and treatment therefore are crucial. Studies suggest in those patients below the age of 45 years that treatment should be aggressive, and aim for cure. In those patients in whom curative treatment is not an option, palliative treatments are available.
p16 overexpression in malignant and premalignant lesions of the oral and esophageal mucosa following allogeneic hematopoietic stem cell transplantation
Abstract
Objectives
Secondary malignancy in the oral mucosa is recognized as one of the most serious complications in patients who received allogenic hematopoietic stem cell transplantation (HSCT). However, potential risk factors associated with carcinogenesis after HSCT that have been reported remain elusive. We experienced a rare case of secondary malignancies of the oral and esophageal mucosa and analyzed the expression of tumor suppressor gene product p16.
Case report
A 35-year-old male had malignant lesions of the oral and esophageal mucosa two years after HSCT. Partial maxillectomy and endoscopic submucosal dissection were performed. Immunohistochemical analyses revealed that the tumor cells of malignant and premalignant lesions of the oral cavity and esophagus but not keratosis were positive for p16.
Conclusions
Pathological examinations with p16 immunohistochemistry may contribute to an early diagnosis of secondary malignancy after HSCT.
Analysis of the compatibility of dental implant systems in fibula free flap reconstruction
Abstract
As a result of major ablative surgery, head and neck oncology patients can be left with significant defects in the orofacial region. The resultant defect raises the need for advanced reconstruction techniques. The reconstruction in this region is aimed at restoring function and facial contour. The use of vascularised free flaps has revolutionised the reconstruction in the head and neck. Advances in reconstruction techniques have resulted in continuous improvement of oral rehabilitation. For example, endosteal implants are being used to restore the masticatory function by the way of prosthetic replacement of the dentition. Implant rehabilitation usually leads to improved facial appearance, function, restoration of speech and mastication. Suitable dental implant placement’s site requires satisfactory width, height and quality of bone. Reconstruction of hard tissue defects therefore will need to be tailored to meet the needs for implant placement.
The aim of this feasibility study was to assess the compatibility of five standard commercially available dental implant systems (Biomet 3i, Nobel Biocare, Astra tech, Straumann and Ankylos) for placement into vascularised fibula graft during the reconstruction of oromandibular region.
Radiographs (2D) of the lower extremities from 142 patients in the archives of the Department of Radiology in University College London Hospitals (UCLH) were analysed in this study. These radiographs were from 61 females and 81 males. Additionally, 60 unsexed dry fibular bones, 30 right sided, acquired from the collection of the Department of Anatomy, University College London (UCL) were also measured to account for the 3D factor.
In the right fibula (dry bone), 90% of the samples measured had a width of 13.1 mm. While in the left fibula (dry bone), 90% of the samples measured had a width of 13.3 mm. Fibulas measured on radiographs had a width of 14.3 mm in 90% of the samples. The length ranges of the dental implants used in this study were: 7-13 mm (Biomet 3i), 10-13 mm (Nobel biocare), 8-13 mm (Astra Tech), 8-12 mm (Straumann ) and 8-11 mm (Ankylos).
This study reached a conclusion that the width of fibula is sufficient for placement of most frequently used dental implants for oral rehabilitation after mandibular reconstructive procedures.
Spinal metastasis in head and neck cancer
Abstract
Background
The incidence of head and neck cancer is relatively low in developed countries and highest in South East Asia. Notwithstanding advances in surgery and radiotherapy over the past several decades, the 5-year survival rate for head and neck cancer has stagnated and remains at 50–55%. This is due, in large part, to both regional and distant disease spread, including spinal metastasis. Spinal metastasis from head and neck cancer is rare, has a poor prognosis and can significantly impede end-stage quality of life; normally only palliative care is given.
This study aims to conduct a systematic review of the evidence available on management of spinal metastasis from head and neck cancer and to use such evidence to draw up guiding principles in the management of the distant spread.
Methods
Systematic review of the electronic literature was conducted regarding the management of spinal metastasis of head and neck malignancies.
Results
Due to the exceptional rarity of head and neck cancers metastasizing to the spine, there is a paucity of good randomized controlled trials into the management of spinal metastasis. This review produced only 12 case studies/reports and 2 small retrospective cohort studies that lacked appropriate controls.
Conclusion
Management should aim to improve end-stage quality of life and maintain neurological function. This review has found that radiotherapy +/− medical adjuvant is considered the principle treatment of spinal metastasis of head and neck cancers.
There is an absence of a definitive treatment protocol for head and neck cancer spinal metastasis. Our failure to find and cite high-quality scientific evidence only serves to stress the need for good quality research in this area.
Granulocyte colony-stimulating factor-producing squamous cell carcinoma of the lower gingiva: a case report
Abstract
The present study summarizes our experience in treating a patient with a suspected granulocyte colony-stimulating factor (G-CSF)-producing squamous cell carcinoma (SCC) of the lower gingiva, which is a rather rare entity.
A 56-year-old woman underwent surgical excision of palate leukoplakia in 1996. In 2009, however, a leukoplakic superficial tumor was detected in the lower left gingiva, for which the patient underwent gingivectomy. This was subsequently diagnosed as SCC. The patient also underwent superselective arterial injection chemotherapy combined with radiotherapy, after local recurrence was observed. The patient was subsequently found to have bone metastasis. After chemotherapy combined with radiotherapy, the patient underwent segmental resection of the lower left jaw, left supraomohyoid neck dissection, and lower jaw reconstruction using titanium plates. Resection of the left femoral tumor and left total knee replacement were also performed. Computed tomography scan performed 1 month after the surgeries revealed multiple lung, liver, spine, and subcutaneous metastases. The patient also exhibited a sudden increase in her white blood cell (WBC) count and a fever that could not be alleviated, despite treatment with antibacterial drugs. A G-CSF-producing tumor was therefore suspected. Serum G-CSF level was high at 250 pg/ml.
The patient’s WBC count increased to 32 × 103/ml and her general condition suddenly deteriorated, and she died as a result of multiple organ failure. A final diagnosis of G-CSF-producing SCC of the lower gingiva was made based on the patient’s clinical course.
Positron emission tomography in the detection of occult primary head and neck carcinoma: a retrospective study
Abstract
Background
The management of cervical lymph node metastases from an unknown primary tumor remains a controversial subject. Recently, Positron Emission Tomography (PET) has proved useful in the detection of these tumors, even after an unsuccessful conventional diagnostic workup. This study was performed to assess the role of PET in the detection of occult primary head and neck carcinomas.
Methods
A retrospective analysis of a four year period at a tertiary referral oncology hospital was conducted.
Results
Of the 49 patients with cervical metastases of carcinoma from an unknown primary, PET detected a primary in 9 patients and gave 5 false positive and 4 false negative results. Detection rate, sensitivity, specificity and accuracy were of 18.4%, 69.2%, 86.1% and 81.6%, respectively. PET was also of substantial benefit in detecting distant metastatic disease and, thus, altered therapeutic strategies in a significant amount of patients.
Conclusions
Therefore, PET is a valuable tool in the management of patients with occult primary head and neck carcinoma, not only because it provides additional information as to the location of primary tumors, but also due to the fact that it can detect unexpected distant metastases.
Enhanced patient reported outcome measurement suitable for head and neck cancer follow-up clinics
Abstract
Background
The ‘Worse-Stable-Better’ (W-S-B) question was introduced to capture patient-perceived change in University of Washington Quality of Life (UW-QOL) domains.
Methods
202 head and neck cancer patients in remission prospectively completed UW-QOL and Patients Concerns Inventory (PCI). For each UW-QOL domain, patients indicated whether over the last month things had worsened (W), remained stable (S) or were better (B).
Results
202 patients at 448 attendances selected 1752 PCI items they wanted to discuss in consultation, and 58% (1024/1752) of these were not covered by the UW-QOL. UW-QOL algorithms highlighted another 440 significant problems that the patient did not want to discuss (i.e. the corresponding items on the PCI were not selected).
After making allowance for UW-QOL algorithms to identify ‘significant problems’ and PCI selection of corresponding issues for discussion there remained clear residual and notable variation in W-S-B responses, in particular to identify patients with significant problems that were getting worse, and patients without significant problems that wanted to discuss issues that were getting worse. Changes in mean UW-QOL scores were notably lower for those getting worse on the W-S-B question, typically by 10 or more units a magnitude that suggests clinically important changes in score.
Conclusions
The W-S-B question adds little questionnaire burden and could help to better identify patients who might benefit from intervention. The results of this study suggest that the UW-QOL with the W-S-B modification should be used together with the PCI to allow optimal identification of issues for patient-clinician discussion during routine outpatient clinics.
A patient with primary Burkitt’s lymphoma of the postnasal space: case report
Abstract
Introduction
Burkitt’s lymphoma is a highly aggressive lymphoma. The endemic form is present with Epstein – Barr virus. The most common sites are the mandible, facial bones, kidneys, gastrointestinal tract, ovaries, breast and extra-nodal sites. We present the first reported case of a primary Burkitt’s lymphoma of the postnasal space occurring in an elderly Caucasian male.
Case presentation
A 72-year-old Caucasian male farmer presented with a 6-week history of a productive cough and a painless left sided cervical swelling. Examination of the neck revealed a 5 cm by 5 cm hard mass in the left anterior triangle. A CT scan of the head and neck showed a soft tissue swelling in the postnasal space. Histology of the postnasal space mass showed squamous mucosa infiltrated by a high grade lymphoma.
Immunohistochemical staining and in situ hybridisation confirmed the tumour to be Epstein – Barr virus Ribonucleic acid negative suggesting this was a rare sporadic form of the tumour presenting in a location that is atypical for the clinical subtype and age of the patient.
Conclusion
This is the first reported case of sporadic Burkitt’s lymphoma of the postnasal space of an elderly Caucasian male in the absence of Epstein – Barr virus or human immunodeficiency virus infection and further serves to illustrate the diversity of histological subtypes of malignancies that may develop at this concealed site.
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