Dental Caries Postradiotherapy in Head and Neck Cancer.

BACKGROUND: Treatment for head and neck cancer (HNC) such as radiotherapy (RT) can lead to numerous acute and chronic head and neck sequelae, including dental caries. The goal of the present study was to measure 2-y changes in dental caries after radiotherapy in patients with HNC and test risk factors for caries increment. METHODS: Cancer and dental disease characteristics, demographics, and oral health practices were documented before and 6, 12, 18, and 24 mo after the start of RT for 572 adult patients with HNC. Patients were eligible if they were age 18 y or older, diagnosed with HNC, and planned to receive RT for treatment of HNC. Caries prevalence was measured as decayed, missing, and filled surfaces (DMFS). The association between change in DMFS and risk factors was evaluated using linear mixed models. RESULTS: On average, DMFS increased from baseline to each follow-up visit: 6 mo, +1.11; 12 mo, +2.47; 18 mo, +3.43; and 24 mo, +4.29 (P < 0.0001). The increase in DMFS during follow-up was significantly smaller for the following patient characteristics: compliant with daily fluoride use (P = 0.0004) and daily oral hygiene (brushing twice daily and flossing daily; P = 0.015), dental insurance (P = 0.004), and greater than high school education (P = 0.001). DMFS change was not significantly associated with average or maximum RT dose to the parotids (P > 0.6) or salivary flow (P > 0.1). In the subset of patients who had salivary hypofunction at baseline (n = 164), lower salivary flow at follow-up visits was associated with increased DMFS. CONCLUSION: Increased caries is a complication soon after RT in HNC. Fluoride, oral hygiene, dental insurance, and education level had the strongest association with caries increment after radiotherapy to the head and neck region. Thus, intensive oral hygiene measures, including fluoride and greater accessibility of dental care, may contribute to reducing the caries burden after RT in HNC. KNOWLEDGE TRANSFER STATEMENT: The results of this study can be used by clinicians when deciding how to minimize oral complications related to cancer therapy for patients with head and neck cancer. Identification of modifiable factors (e.g., oral hygiene and prescription fluoride compliance) associated with increased caries risk can minimize radiation caries burden.

Oral Mucosal Injury Caused by Targeted Cancer Therapies.

Targeted cancer therapies have fundamentally transformed the treatment of many types of cancers over the past decade, including breast, colorectal, lung, and pancreatic cancers, as well as lymphoma, leukemia, and multiple myeloma. The unique mechanisms of action of these agents have resulted in many patients experiencing enhanced tumor response together with a reduced adverse event profile as well. Toxicities do continue to occur, however, and in selected cases can be clinically challenging to manage. Of particular importance in the context of this monograph is that the pathobiology for oral mucosal lesions caused by targeted cancer therapies has only been preliminarily investigated. There is distinct need for novel basic, translational, and clinical research strategies to enhance design of preventive and therapeutic approaches for patients at risk for development of these lesions. The research modeling can be conceptually enhanced by extrapolating "lessons learned" from selected oral mucosal conditions in patients without cancer as well. This approach may permit determination of the extent to which pathobiology and clinical management are either similar to or uniquely distinct from oral mucosal lesions caused by targeted cancer therapies. Modeling associated with oral mucosal disease in non-oncology patients is thus presented in this context as well. This article addresses this emerging paradigm, with emphasis on current mechanistic modeling and clinical treatment. This approach is in turn designed to foster delineation of new research strategies, with the goal of enhancing cancer patient treatment in the future.

The pathogenesis of mucositis: updated perspectives and emerging targets.

Mucositis research and treatment are a rapidly evolving field providing constant new avenues of research and potential therapies. The MASCC/ISOO Mucositis Study Group regularly assesses available literature relating to pathogenesis, mechanisms, and novel therapeutic approaches and distils this to summary perspectives and recommendations. Reviewers assessed 164 articles published between January 2011 and June 2016 to identify progress made since the last review and highlight new targets for further investigation. Findings were organized into sections including established and emerging mediators of toxicity, potential insights from technological advances in mucositis research, and perspective. Research momentum is accelerating for mucositis pathogenesis, and with this has come utilization of new models and interventions that target specific mechanisms of injury. Technological advances have the potential to revolutionize the field of mucositis research, although focused effort is needed to move rationally targeted interventions to the clinical setting.

Oral complications at 6 months after radiation therapy for head and neck cancer.

OBJECTIVE: To examine oral complications 6 months after modern radiation therapy (RT) for head and neck cancer (HNC). METHODS: Prospective multicenter cohort study of patients with HNC receiving intensity-modulated radiation therapy or more advanced RT. Stimulated whole salivary flow, maximal mouth opening, oral mucositis, oral pain, oral health-related quality of life (OH-QOL), and oral hygiene practices were measured in 372 subjects pre-RT and 216 subjects at 6 months from the start of RT. RESULTS: Mean stimulated whole salivary flow declined from 1.09 to 0.47 ml/min at 6 months (p < .0001). Mean maximal mouth opening reduced from 45.58 to 42.53 mm at 6 months (p < .0001). 8.1% of subjects had some oral mucositis at 6 months, including 3.8% with oral ulceration. Mean overall pain score was unchanged. OH-QOL was reduced at 6 months, with changes related to dry mouth, sticky saliva, swallowing solid foods, and sense of taste (p ≤ .0001). At 6 months, there was greater frequency of using dental floss and greater proportion using supplemental fluoride (p < .0001). CONCLUSIONS: Despite advances in RT techniques, patients with HNC experience oral complications 6 months after RT, with resulting negative impacts on oral function and quality of life.

Oral mucosal injury in oncology patients: perspectives on maturation of a field.

In the past decade, there have been important strategic advances relative to pathobiological modeling as well as clinical management for oral mucositis caused by cancer therapies. Prior to the 1990s, research in this field was conducted by a relatively small number of basic and clinical investigators. Increasing interest among researchers and clinicians over the past twenty years has produced a synergistic outcome characterized by a number of key dynamics, including novel discovery models for pathobiology, increased experience in designing and conducting clinical trials, and creation of international collaborations among cancer care professionals who in turn have modeled clinical care paradigms based on state-of-the-science evidence. This maturation of the science and its clinical translation has positioned investigators and oncology providers to further accelerate both the foundational research and the clinical modeling for patient management in the years ahead. The stage is now set to further capitalize upon optimizing the interactions across this interface, with the goal of strategically enhancing management of patients with cancer at risk for this toxicity while reducing the cost of cancer care.

Methodology for the MASCC/ISOO Mucositis Clinical Practice Guidelines Update.

Members of the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) recently completed the process of updating the MASCC/ISOO Clinical Practice Guidelines for the prevention and treatment of mucositis. These guidelines, originally published in 2004, and last updated in 2007, provide clinicians with objective, evidence-based recommendations for the management of mucositis secondary to cancer therapy. This brief paper describes the methodology used to conduct the most recent systematic review in 2011, and develop new guidelines, providing the basis for the update. The overriding aims of the process were to assess evidence of effectiveness of interventions for the prevention and treatment of mucositis and to produce clinical practice guidelines for the management of mucositis using best available evidence.

Exposed farcture of the Medial Malleolus: the role of the reconstructive ladder

This is the first reported case of an adipofascial posterior tibial artery perforator flap in Trinidad and Tobago. The concept of the reconstruction ladder is discussed in order to illustrate the selection of this flap as the most appropriate reconstructive option. The case report describes the use of an adipofascial posterior tibial artery perforator flap to reconstruct a wound with an exposed fracture of the medial malleolus at its base.

Urban legends: recurrent aphthous stomatitis.

Recurrent aphthous stomatitis (RAS) is the most common idiopathic intraoral ulcerative disease in the USA. Aphthae typically occur in apparently healthy individuals, although an association with certain systemic diseases has been reported. Despite the unclear etiopathogenesis, new drug trials are continuously conducted in an attempt to reduce pain and dysfunction. We investigated four controversial topics: (1) Is complex aphthosis a mild form of Behçet's disease (BD)? (2) Is periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome a distinct medical entity? (3) Is RAS associated with other systemic diseases [e.g., celiac disease (CD) and B12 deficiency]? (4) Are there any new RAS treatments? Results from extensive literature searches, including a systematic review of RAS trials, suggested the following: (1) Complex aphthosis is not a mild form of BD in North America or Western Europe; (2) Diagnostic criteria for PFAPA have low specificity and the characteristics of the oral ulcers warrant further studies; (3) Oral ulcers may be associated with CD; however, these ulcers may not be RAS; RAS is rarely associated with B12 deficiency; nevertheless, B12 treatment may be beneficial, via mechanisms that warrant further study; (4) Thirty-three controlled trials published in the past 6 years reported some effectiveness, although potential for bias was high.

Verapamil as an Adjunct to Local Anaesthetic for Brachial Plexus Blocks.

BACKGROUND: Calcium channel blockers potentiate the effects of local anaesthetics. We examined the effect of adding verapamil to local anaesthetic solution on anaesthetic duration in patients undergoing surgery under brachial plexus block. METHODS: This study was a prospective, randomized, controlled, double blind study. Sixty patients undergoing elective upper limb surgery were divided into two groups of 30 each. Group A received 40 ml of 1% lignocaine with 0.25% bupivacaine, while Group B patients had 2.5 mg verapamil added. RESULT: Onset of sensory blockade time was marginally faster in Group B (23.2 ± 3.94 minutes) as compared to Group A (23.9 ± 4.13 minutes). However this difference was statistically not significant. The increase in duration of sensory blockade in Group B (185 ± 46.52 minutes) as compared to Group A (157 ± 44.28 minutes) was statistically significant (p= 0.011). Increase in duration of motor blockade in Group B (161 ± 46.14 minutes) as compared to Group A (149 ± 42,76 minutes) was statistically not significant (p = 0.15). Similarly prolongation of analgesic duration in Group B (318 ± 69.54minutes) as compared to Group A (302 ± 0.69 minutes) was statistically not significant (p=0.18). CONCLUSION: We conclude that adding verapamil to brachial plexus block can prolong sensory anaesthesia without any effect on analgesic duration.

Ibuprofen and hydrogel-released ibuprofen in the reduction of inflammation-induced migration in melanoma cells.

BACKGROUND: There is growing evidence that inflammation may exacerbate cancer metastasis and several clinical studies show that taking nonsteroidal anti-inflammatory drugs appears to reduce metastases. OBJECTIVES: The aims of this study were: (i) to examine the effects of ibuprofen on the major proinflammatory cytokine tumour necrosis factor (TNF)-alpha induction of migration of C8161 and HBL human melanoma cells; (ii) to develop ibuprofen-releasing hydrogels (Pluronics F127) for future topical use in reducing metastatic spread of primary melanoma; and (iii) to examine whether the actions of ibuprofen might be explained by induction of apoptosis. METHODS: Melanoma cells were exposed to 300 U mL(-1) TNF-alpha for a 24-h period prior to making a scratch wound to which ibuprofen or ibuprofen-loaded hydrogels were then added. The effects of relevant concentrations of ibuprofen on cell viability and apoptosis were examined. RESULTS: Ibuprofen at 10(-3) mol L(-1) significantly reduced TNF-alpha-stimulated migration of both cell types to that of nonstimulated cells (P < 0.001). TNF-alpha-unstimulated cell migration was not significantly affected. Cells responded similarly to SS and SR forms of ibuprofen. Cells treated with ibuprofen sodium salt-loaded hydrogels showed a significant reduction in migration when compared with unloaded hydrogels. Ibuprofen induced apoptosis in HBL cells but had no effect on C8161 melanoma cells apoptosis at concentrations that reduced migration. CONCLUSIONS: These results demonstrate that TNF-alpha upregulated malignant melanoma migration in vitro and that this could be reduced by ibuprofen both in solution and delivered from a hydrogel. These effects of ibuprofen cannot be attributed simply to induction of apoptosis.

Ventilatory management and weaning in a patient with central hypoventilation caused by a brainstem cavernoma.

We describe a patient with a brainstem cavernoma who was dependent on hypoxic respiratory drive initially. After excision of the lesion, the patient developed severe hypoventilation unresponsive to both hypoxia and hypercapnia. Weaning from mechanical ventilation could be achieved through central respiratory stimulation by acetazolamide. Problems associated with respiratory management of central hypoventilation due to a brainstem lesion are described.

Melanoma cell migration is upregulated by tumour necrosis factor-alpha and suppressed by alpha-melanocyte-stimulating hormone.

We reported recently that the inflammatory cytokine tumour necrosis factor alpha (TNF-alpha) can upregulate integrin expression, cell attachment and invasion of cells through fibronectin in a human melanoma cell line (HBL). Furthermore, the actions of TNF-alpha were suppressed by the addition of an anti-inflammatory peptide alpha-melanocyte-stimulating hormone (alpha-MSH). In the current study, we extend this work investigating to what extent TNF-alpha might stimulate melanoma invasion by promoting cell migration and whether alpha-MSH is also inhibitory. Two human melanoma cell lines were examined in vitro (HBL and C8161) using a scratch migration assay. Analysis using either time-lapse video microscopy or imaging software analysis of migrating 'fronts' of cells revealed that C8161 cells migrated more rapidly than HBL cells. However, when cells were stimulated with TNF-alpha both cell types responded with a significant increase in migration distance over a 16-26 h incubation time. alpha-Melanocyte-stimulating hormone had an inhibitory effect on TNF-alpha-stimulated migration for HBL cells, completely blocking migration at 10(-9) M. In contrast, C8161 cells did not respond to alpha-MSH (as these cells have a loss-of-function melanocortin-1 receptor). However, stable transfection of C8161 cells with the wild-type melanocortin-1 receptor produced cells whose migration was significantly inhibited by alpha-MSH. In addition, the use of a neutralising antibody to the beta(1)-integrin subunit significantly reduced migration in both cell types. This data therefore supports an inflammatory environment promoting melanoma cell migration, and in addition shows that alpha-MSH can inhibit inflammatory stimulated migration. The data also support a fundamental role of the beta(1)-integrin receptor in melanoma cell migration.

Dental management considerations for the patient with diabetes mellitus.

BACKGROUND: The prevalence of diabetes mellitus, or DM, in the United States is increasing steadily. The increasing longevity of the American population and more effective diagnostic protocols mean that the dental practitioner will be treating an increasing number of patients with the disease. METHODS: The authors present relevant information about DM, including a recently revised nomenclature system, pathophysiology, complications, new diagnostic criteria, medical and dental management considerations, and associated oral conditions. CONCLUSIONS: There are many important medical and dental management issues that dentists should consider when treating patients with DM. CLINICAL IMPLICATIONS: The information presented in this report should help general dentists deliver optimum treatment to patients with DM.

Fibrin induces IL-8 expression from human oral squamous cell carcinoma cells.

In recent studies, we have demonstrated that fibrin is present in association with tumor cells in oral squamous cell carcinoma (OSCC) in vivo. We hypothesized that this fibrin can directly induce the expression of known angiogenic factors from oral tumor cells. Since IL-8 is known to be the major inducer of angiogenesis caused by these cells, we examined the ability of fibrin to stimulate IL-8 expression from OSCC cells in vitro. A physiologically relevant concentration of fibrin was found to cause a dose and time-dependent stimulation of IL-8 expression from oral and pharyngeal tumor cells but not from a non-tumorigenic oral cell line. Fibrinogen, thrombin and collagen were all unable to induce significant IL-8 expression, establishing the specificity of fibrin in causing this response. Gel filtration chromatography confirmed the molecular identity of the IL-8 antigen detected in the ELISA system used. These results suggest that fibrin may promote angiogenesis in oral tumors in vivo by directly upregulating the expression of IL-8 from tumor cells.

Gastrointestinal surgical workload in the DGH and the upper gastrointestinal surgeon.

Workload implications of upper gastrointestinal (UGI) subspecialisation within the district general hospital (DGH) have been assessed by prospective data collection over a 12-month period in a DGH with six general surgeons serving a population of 320,000. The single UGI surgeon (UGIS) performed all ten oesophageal resections, ten of 11 gastric resections for malignancy and all eight pancreatic operations. He also performed 91 of the 182 cholecystectomies, 164 of the 250 endoscopic retrograde cholangiopancreatograms (ERCP) and all endoscopic procedures for the palliation of unresected oesophageal tumours. The UGIS was responsible for the management of all patients with severe pancreatitis, yet he also performed 51 colorectal resections over the 12-month period. Successful management of severely ill patients with upper GI disease requires consultant supervision on a day-to-day basis. If such UGI disease is to be managed in the DGH, two surgeons with UGI experience will be required if high quality care and reasonable working conditions are to be achieved. Such UGIS will continue to perform some colorectal surgery.