Extracellular matrix educates an immunoregulatory tumor macrophage phenotype found in ovarian cancer metastasis.

Recent studies have shown that the tumor extracellular matrix (ECM) associates with immunosuppression, and that targeting the ECM can improve immune infiltration and responsiveness to immunotherapy. A question that remains unresolved is whether the ECM directly educates the immune phenotypes seen in tumors. Here, we identify a tumor-associated macrophage (TAM) population associated with poor prognosis, interruption of the cancer immunity cycle, and tumor ECM composition. To investigate whether the ECM was capable of generating this TAM phenotype, we developed a decellularized tissue model that retains the native ECM architecture and composition. Macrophages cultured on decellularized ovarian metastasis shared transcriptional profiles with the TAMs found in human tissue. ECM-educated macrophages have a tissue-remodeling and immunoregulatory phenotype, inducing altered T cell marker expression and proliferation. We conclude that the tumor ECM directly educates this macrophage population found in cancer tissues. Therefore, current and emerging cancer therapies that target the tumor ECM may be tailored to improve macrophage phenotype and their downstream regulation of immunity.

Restorative Rehabilitation of the Cleft Affected Occlusion - A Service Evaluation.

Cleft Lip and/or Palate (CLP) is the most common cranio-facial abnormality thought to be caused by a combination of genetic and environmental factors causing challenges with feeding, dental development and speech. Cleft affected individuals often present a unique set of challenges with regards to their oro-facial and dental development and require multidisciplinary care. This article aims to describe the role of the restorative dentist in the multidisciplinary management of cleft affected individuals and outlines the various clinical presentations and restorative challenges. This article describes the various treatment modalities provided for cleft affected individuals under the National Health Service (NHS) at Liverpool University Dental Hospital (LUDH) and ranges from minimally invasive techniques to conventional fixed and removable prosthodontics.

Accidental Ingestion of an Implant Screwdriver: A Case Report and Literature Review.

Head and neck oncology patients are high risk for ingestion or aspiration of dental instruments during treatment, due to altered anatomy and sensation. This article describes a case report of accidental ingestion of an implant screwdriver during the prosthetic phase of oral rehabilitation of a 79 year old oncology patient. The management protocol is described which included referral to the medical Accident and Emergency department, where the object was safely removed from the stomach via endoscopy. A review of similar cases of ingestion/inhalation in the literature suggests implant screwdrivers should be retrieved as safe passage through the gastrointestinal system is not assured. Awareness of the medical history and risk factors should alert clinicians to be extra cautious, and preventative strategies should be implemented at all times. Preventative measures include ligation of instruments with floss/suture material, treatment in a more vertical position, and use of rubber dam where possible.

The zygomatic implant perforated (ZIP) flap: a new technique for combined surgical reconstruction and rapid fixed dental rehabilitation following low-level maxillectomy.

This aim of this report is to describe the development and evolution of a new surgical technique for the immediate surgical reconstruction and rapid post-operative prosthodontic rehabilitation with a fixed dental prosthesis following low-level maxillectomy for malignant disease.The technique involves the use of a zygomatic oncology implant perforated micro-vascular soft tissue flap (ZIP flap) for the primary management of maxillary malignancy with surgical closure of the resultant maxillary defect and the installation of osseointegrated support for a zygomatic implant-supported maxillary fixed dental prosthesis.The use of this technique facilitates extremely rapid oral and dental rehabilitation within a few weeks of resective surgery, providing rapid return to function and restoring appearance following low-level maxillary resection, even in cases where radiotherapy is required as an adjuvant treatment post-operatively. The ZIP flap technique has been adopted as a standard procedure in the unit for the management of low-level maxillary malignancy, and this report provides a detailed step-by-step approach to treatment and discusses modifications developed over the treatment of an initial cohort of patients.

Restorative dentistry and oral rehabilitation: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK and provides recommendations on the pre-treatment oral and dental assessment, during and after treatment and oral rehabilitation. Restorative dentists are core members of the multidisciplinary team treating head and neck cancer patients, involved from the treatment planning phase through to long-term rehabilitation. Recommendations • Preventative oral care must be delivered to patients whose cancer treatment will affect the oral cavity, jaws, salivary glands and oral accessibility. (G) • Close working and communication between the surgeons, oncologists and restorative dental specialists is important in ensuring optimal oral health outcomes. (G) • Intensity-modulated radiotherapy has been shown to reduce long-term xerostomia and should be offered to all appropriate patients. (R) • If patients are deemed at risk of trismus they should be warned and its progressive and potentially irreversible nature explained. (G) • Where it is known that adjuvant radiotherapy will be given, extractions should take place at primary surgery to maximise the time for healing and minimise the number of surgical events for patients. (G) • Osseointegrated implants should be considered for all patients having resection for head and neck cancer. (G).

Elective dental extractions and osseointegrated implant replacement to facilitate transoral endoscopic ENT surgical procedures.

BACKGROUND: Transoral endoscopic ENT surgical procedures are a mainstay of treatment for a variety of conditions and are often preferable to open surgery where possible. Cases of micrognathia, prominent incisor teeth or trismus may create difficulties in gaining sufficient access to undertake such procedures. Extraction of the anterior maxillary teeth can help overcome these problems in appropriate cases, with subsequent prosthetic tooth replacement supported by dental implants. To date, this approach has not been reported in the literature. CASE REPORTS: This paper reports on two cases which illustrate this approach; the first case involved pharyngeal pouch management where previous open surgery had failed, and the second case involved glottic carcinoma management where oral access was compromising resection. CONCLUSION: This technique is recommended to facilitate effective transoral surgical procedures as a low-morbidity alternative to either open surgery or non-surgical therapies.

Characteristics and referral of head and neck cancer patients who report chewing and dental issues on the Patient Concerns Inventory.

BACKGROUND: Patients experience considerable dental-related difficulties following head and neck cancer (HNC) treatment including problems with chewing, dry mouth, oral hygiene, appearance and self-esteem. These can go unrecognised in busy follow-up clinics. The Patient Concerns Inventory (PCI) is specifically for HNC patients, enabling them to select topics they wish to discuss and members of the multi-professional team they want to see. AIM: The study aimed to identify the clinical characteristics of patients raising dental concerns on the PCI and to explore the outcome of onward referral. Assessments included the PCI and the University of Washington Quality of Life Questionnaire (UW-QOL) version 4, with clinic details collated from hospital and cancer databases. METHOD: PCI data were obtained from 317 HNC patients between 2007 and 2011. Their mean age was 63 years and 60% were male. Most had oral squamous cell carcinoma and underwent surgery. The median (IQR) time from treatment to first PCI was 13 (4-42) months. RESULTS: Three comparison groups were identified: patients with significant chewing problems, patients without significant chewing problems who wanted to discuss dental-related concerns and patients without significant chewing problems who did not want to discuss such concerns. Fifty-two percent reported either a significant chewing problem on the UW-QOL or a wish to discuss dental-related concerns. A quarter specifically asked to talk to a dental professional. Clinical characteristics significantly associated with dental issues were stage, primary treatment and free flap reconstruction. Clinic letters were copied to only 10% of general dental practitioners (GDPs). CONCLUSION: Better communication with GDPs is essential.

Do head and neck cancer survivors attend a high street dentist on a regular basis?

Head and neck cancer (HNC) patients face complex oral health issues following treatment. The aims of this study were to determine the proportion of HNC patients attending their dentist regularly and investigate clinicodemographic characteristics associated with attendance. Two surveys asked about patient attendance patterns and dentition. Pre-treatment orthopantomographs were evaluated for those treated between 2007-2009. The response rate was 66% (444/672). 69% (305/444) saw a high street dentist regularly. 28% of edentulous patients attended regularly compared with 84% with natural teeth, p < 0.001. Associations at p < 0.001 with regular attendance were the leaving of formal education (> 16 years) and earlier clinical staging. HNC patients should be encouraged to see a dentist regularly for routine dental care and cancer surveillance in partnership with the cancer service.

Systematic review of primary osseointegrated dental implants in head and neck oncology.

The aim of this paper is to provide a systematic review of articles concerning primary osseointegrated dental implants in the head and neck oncology setting. We searched MEDLINE (1950 to March 2009) and Embase (1980 to March 2009) using the terms head and neck, oral, maxillofacial, craniofacial, jaws, mandible, maxilla, zygoma, dental implants, osseointegrated implants, implants, tumour, cancer, oncology, immediate, simultaneous, and primary. Two authors independently reviewed the abstracts, and all those written in the English language that referred to the placement of primary dental implants in patients with cancer of the head neck were included. Articles that referred to craniofacial or extraoral implants were excluded. Of 892 abstracts 83 were eligible for further consideration; the full articles were evaluated, and 41 that complied fully with the inclusion criteria are presented as a tabulated summary. There are three case reports, 13 reviews, and 25 clinical studies. Eight of the clinical studies refer solely to the insertion of dental implants at the time of primary oncological resection, and only two were of a prospective design. We have concisely summarised publications concerning primary dental implants, and our findings will help to inform head and neck cancer teams, particularly oncological surgeons, restorative dentists, and maxillofacial prosthodontists of the evidence base surrounding this approach to oral rehabilitation.

A new clinical training scheme for overseas dentists under Tier 5.

Since the introduction of the Points Based Immigration System to the UK the opportunities for overseas trained dentists to train in the UK have been limited. This paper describes a new opportunity which has resulted from the Tier 5 Medical Training Initiative.

360 degrees peri-implant, keratinised, soft-tissue grafting with stereolithographic-aided dressing plate.

Surgical procedures to improve the quality of peri-implant soft tissue are a routine part of dental implant practice, especially in the edentulous patient with a significant lack of attached keratinised tissue. The use of a dressing plate at the recipient site can be beneficial in supporting free, keratinised, soft-tissue grafts during the early healing phase, especially if grafting is undertaken around all aspects of the implant and not just to the facial section. This paper outlines the use of a dressing plate, constructed on a stereolithographic model, for use at second-stage implant surgery to allow for 360 degrees peri-implant, keratinised, soft-tissue grafting.

Isolation and characterization of microsatellite loci in the long-fingered bat Miniopterus fuliginosus.

We isolated and characterized 10 microsatellite loci in the long-fingered bat Miniopterus fuliginosus. These loci were tested on 48 individuals from Anhui Province of China, and all loci were highly polymorphic. The mean number of observed alleles per locus was 13.6 (range from six to 27). Observed and expected heterozygosity values ranged from 0.364 to 0.957, and from 0.676 to 0.951, respectively. After Bonferroni correction, four loci deviated significantly from Hardy-Weinberg equilibrium. No pairs of loci were in linkage disequilibrium. These polymorphic markers will be used to examine population structure and genetic diversity in this species.

Isolation and characterization of microsatellite loci in the western long-fingered bat, Miniopterus magnater.

We isolated and characterized 10 microsatellite loci in the western long-fingered bat, Miniopterus magnater. These loci were tested on 48 individuals from Anhui Province of China, and all loci were highly polymorphic. The mean number of observed alleles per locus was 13.6 (range from six to 27). Observed and expected heterozygosity values ranged from 0.364 to 0.957, and from 0.676 to 0.951, respectively. After Bonferroni correction, four loci deviated significantly from Hardy-Weinberg equilibrium. No pairs of loci were in linkage disequilibrium. These polymorphic markers will be used to examine population structure and genetic diversity in this species.

Factors associated with restricted mouth opening and its relationship to health-related quality of life in patients attending a Maxillofacial Oncology clinic.

Trismus can be a problematic consequence of treatment for oral and oropharyngeal cancer. The aim of this study was to investigate the relationship between trismus, subjective function and health-related quality of life, in order to postulate a clinically relevant cut-off that might be useful as an indicator of patients who might benefit from intervention. One hundred consecutive patients attending the Maxillofacial Oncology clinic at the University Hospital Aintree were assessed during a period of four months. Mouth opening was recorded in millimetres. Subjective outcomes were evaluated using UW-QOL questionnaire for chewing, saliva, mood, anxiety and overall quality of life. The median age of patients was 63 (IQR 56-69) years. The median time since treatment was 16 (IQR 6-34) months. The median mouth opening (32 mm; range 6-53, IQR 24-40) was associated strongly with clinical T stage (Tis/T1-2 35 mm, T3-4 24 mm), radiotherapy (no 38 mm, yes 27 mm) and type of primary surgery (primary closure 38 mm, soft-tissue flaps 30 mm, composite flaps 24 mm). The amount of mouth opening and of the single question (about how much less mouth opening since treatment) was significantly associated with patients perception of chewing deficit, less than full diet and less than good overall quality of life. This study supports a 35 mm cut-off for trismus. There is merit including the two elements together (opening in mm and the single item question on mouth opening since treatment) as outcome parameters.

The further development and validation of the Liverpool Oral Rehabilitation Questionnaire: a cross-sectional survey of patients attending for oral rehabilitation and general dental practice.

BACKGROUND: Since the first version of the Liverpool Oral Rehabilitation Questionnaire (LORQ) was first published in 2004, the questionnaire has been modified to include more detail on chewing and appearance, and also details of denture, dental and implant status. AIM: The aim of this study is to report the ongoing development and validation of the LORQ version3. METHODS: A postal survey of the LORQv3 and OHIP-14 questionnaires was performed in April 2004 of 164 patients who had attended the oral rehabilitation clinic from February 2000. In addition The LORQv3 was administered to 349 patients attending six General Dental Practices, based in Liverpool, attending for routine care. RESULTS: Patients attending GDP scored appreciably better on most items in the LORQv3. The questionnaire discriminated between cancer and non-cancer oral rehabilitation patients in items such as swallowing, chewing, trismus, drooling and food clearance. There was no significant difference between rehabilitation groups for any of the seven OHIP-14 domains. The LORQv3 demonstrated good criterion validity when compared to the OHIP-14 with social items in the LORQv3 correlating well with items of the OHIP-14. Conversely various LORQv3 items did not have strong correlates within the OHIP-14 thus endorsing the additional items in the LORQv3.

Local and systemic total antioxidant capacity in periodontitis and health.

BACKGROUND: The involvement of reactive oxygen species (ROS) in periodontal pathology is unclear but will be modulated by in vivo antioxidant defence systems. The aim of this cross-sectional study was to determine both local (saliva and gingival crevicular fluid (GCF) and peripheral (plasma and serum) antioxidant capacity in periodontal health and disease. MATERIALS AND METHODS: Twenty non-smoking volunteers with chronic periodontitis were sampled together with twenty age- and sex-matched, non-smoking controls. After overnight fasting, saliva (whole unstimulated and stimulated) and blood were collected. Total antioxidant capacity (TAOC) was determined using a previously reported enhanced chemiluminescence method. RESULTS: GCF antioxidant concentration was significantly lower (p<0.001) in periodontitis subjects compared to healthy controls. Although mean levels of peripheral and salivary TAOC were also lower in periodontitis the difference was only significant for plasma (p<0.05). Healthy subjects' GCF antioxidant concentration was significantly greater than paired serum or plasma (p<0.001). Data stratified for gender did not alter the findings and a male bias was revealed in all clinical samples except GCF. CONCLUSIONS: These findings suggest that the antioxidant capacity of GCF is both qualitatively and quantitatively distinct from that of saliva, plasma and serum. Whether changes in the GCF compartment in periodontitis reflect predisposition to or the results of ROS-mediated damage remains unclear. Reduced plasma total antioxidant defence could result from low-grade systemic inflammation induced by the host response to periodontal bacteria, or may be an innate feature of periodontitis patients.

The provision of dental implants in the National Health Service Hospital dental services--a national questionnaire.

OBJECTIVE: To assess the activity of consultants in restorative dentistry in the United Kingdom in the provision of osseointegrated dental implants within the National Health Service Hospital service and to evaluate their attitudes concerning the relevant medical and oral factors considered in patient selection for implant treatment. DESIGN/SETTING: Anonymous postal questionnaire in the United Kingdom. SUBJECTS: Consultants in restorative dentistry. RESULTS: Out of the sample of 145, 109 consultants (75%) completed the questionnaire in 1999. 54 of the 109 consultants (49.5%) are involved in the provision of osseointegrated implant treatment, treating an average of 29 cases/year (range 2-150). However, over one third of the respondents treated 10 or less cases/year. 89% worked with oral surgeons as an implant team. 68% used Branemark (Nobel Biocare) implants as their main system. The majority of consultants felt that smoking, psychoses and previous irradiation were the most important medical factors that contra-indicated implant retained restorations whilst untreated periodontitis, poor oral hygiene and uncontrolled caries were the most important oral contra-indications. Many centres were experiencing significant problems with the funding of implant treatment with one centre receiving no funding. The implications for patient care and specialist training are discussed. CONCLUSIONS: There is a marked variation in the number of patients treated with endosseous dental implants within the United Kingdom National Health Service hospitals. Many consultants treat 10 or fewer patients each year. In the main, there is agreement about the factors that contra-indicate implant treatment; these are in line with national guidelines.

Drug-induced gingival overgrowth: a case with auto-correction of incisor drifting.

Drug-induced gingival overgrowth is an iatrogenic clinical condition, which affects a proportion of patients medicated for conditions such as hypertension, epilepsy and the prevention of organ transplant rejection. Clinical manifestation can vary in severity from minor problems to complete coverage of the standing teeth. Drifting of teeth can also occur, producing further aesthetic and functional problems for the patient. This report documents a case of a renal transplant patient in whom drifting of the upper incisor teeth spontaneously resolved following surgical reduction of the overgrown gingivae. Clinical issues relating to the management of gingival overgrowth are also discussed.

Correlates of total plasma homocysteine: folic acid, copper, and cervical dysplasia.

We examined correlates of total plasma homocysteine (tHcy) in 294 subjects with cervical intraepithelial neoplasia and 170 control subjects. Associations of tHcy with risk factors for cervical intraepithelial neoplasia and 24-h intakes and biochemical indices of nutrients were examined. Plasma and red blood cell folate and plasma B(12) were strong inverse correlates of tHcy (r = -0.35, -0. 31, and -0.27, respectively). Plasma copper and severity of dysplasia were positively correlated with tHcy (r = 0.14 and 0.21, respectively). A stepwise regression model that included red blood cell folate, plasma copper, grade of dysplasia, ethnicity, intake of polyunsaturated fatty acids, plasma vitamin B(12), intake of fat, and oral contraceptive use explained 29% of the variation in tHcy. Two hundred thirty-five subjects with cervical intraepithelial neoplasia were randomized to receive folic acid (10 mg/d) or placebo for 6 mo. After 2, 4, and 6 mo, mean tHcy in the folate-supplemented group (7.2 +/- 1.8, 7.0 +/- 1.9, and 7.0 +/- 2.3 micromol/L, respectively) was significantly lower than baseline and the placebo group at 2, 4, and 6 mo (8.9 +/- 3.1, 8.4 +/- 3.0, and 8.9 +/- 3.1 micromol/L, respectively). Supplementation lowered tHcy even in subjects in the highest quintile of baseline folate. Folate, vitamin B(12), copper, and severity of dysplasia are associated with tHcy. Folate supplementation significantly lowers tHcy even in folate-replete subjects.

Effect of total plasma homocysteine on cervical dysplasia risk.

We investigated whether total plasma homocysteine (tHcy) is associated with risk for cervical intraepithelial neoplasia (CIN). tHcy was evaluated, along with numerous risk factors for CIN and biochemical indexes of nutrients, in a previously reported study population of 294 subjects with CIN and 170 female controls without CIN. tHcy was significantly higher in cases than in controls (9.1 vs. 8.3 mumol/l, p = 0.002). Human papillomavirus type 16 infection [odds ratio (OR) = 6.7], oral contraceptive use (OR = 6.0), parity (OR = 2.2), and cigarette smoking (OR = 1.9) were significantly associated with CIN after adjustment for each other and for age, number of sexual partners, and plasma tHcy, folate, iron, and zinc. Human papillomavirus type 16 positivity increased risk for CIN more when tHcy was > 9.12 mumol/l (OR = 4.7) than when it was < or = 9.12 mumol/l (OR = 3.0). Cigarette use increased risk for CIN when tHcy was > 9.12 mumol/l (OR = 3.9), but not when tHcy was < or = 9.12 mumol/l (OR = 1.5). Parity increased risk for CIN more when tHcy was > 9.12 mumol/l (OR = 4.0) than when tHcy was < or = 9.12 mumol/l (OR = 2.0). These results suggest that elevated plasma tHcy is a risk factor for cervical dysplasia and that it enhances the effects of other risk factors. It is unknown whether tHcy is serving as a marker of folate deficiency or is acting through other mechanisms.