Is Dental Specialty Referral Associated With Earlier Presentation of Oral Cavity Squamous Cell Carcinoma?

BACKGROUND: Oral cavity squamous cell carcinoma (OSCC) may mimic other more common odontogenic processes such as infection, trauma, and benign pathology. Delays in diagnosis and treatment are known to result in poorer survival outcomes. PURPOSE: The study purpose was to measure the association between referral type and OSCC stage at time of presentation. STUDY DESIGN, SETTING, SAMPLE: This was a retrospective cohort study composed of newly diagnosed OSCC patients treated with surgical resection from 2014 to 2023 at Roswell Park Comprehensive Cancer Center. Patients who presented with self-referrals or had surgical treatment outside of Roswell Park Comprehensive Cancer Center were excluded. PREDICTOR VARIABLE: The primary predictor was referral source (dental vs medical specialty). MAIN OUTCOME VARIABLE: The primary outcome was pathological T stage (pT stage). The secondary outcome was overall survival (OS). COVARIATES: Covariates included demographic data and cancer-related variables (symptomatology, subsite, and risk factors). ANALYSES: A multivariate logistical regression model for pT stage was constructed using all significant covariates as well as preoperative patient and tumor characteristics. For OS, Kaplan-Meier survival curves were constructed and compared with the log-rank test. A P < .05 was considered statistically significant. RESULTS: A total of 215 subjects were included in the study sample. The majority were referred by a dental provider (n = 132, 62.3%). Dental referrals presented with significantly earlier T stage disease (RRpT3/T4 0.65, P < .01) and had lower rates of cervical nodal positivity (RRpN1-N3 0.62, P = .01). Dental referral independently increased the odds of early pT stage presentation (odds ratio 5.10, P < .01) after controlling for age, sex, oral pain symptoms, social history (smoking and drinking), head neck cancer history, and tumor subsite. Dental referrals had significantly improved OS (P = .03) and were also associated with lower rates of oral pain symptoms (RRoral pain 0.80, P = .02), lymphovascular invasion (RRLVI 0.50; P = .04), and perineural invasion (RRPNI 0.63, P = .04). CONCLUSIONS AND RELEVANCE: Among subjects with similar risk factors, those referred from dental providers were found to have earlier stage disease. Unfortunately, over half of dental referrals still presented with pain symptoms and more than a third presented with locally advanced disease. Dental providers appear to be positioned to detect earlier OSCC; however, there is room for improvement.

Effect of Doxepin Mouthwash or Diphenhydramine-Lidocaine-Antacid Mouthwash vs Placebo on Radiotherapy-Related Oral Mucositis Pain: The Alliance A221304 Randomized Clinical Trial.

Importance: Oral mucositis causes substantial morbidity during head and neck radiotherapy. In a randomized study, doxepin mouthwash was shown to reduce oral mucositis-related pain. A common mouthwash comprising diphenhydramine-lidocaine-antacid is also widely used. Objective: To evaluate the effect of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash for the treatment of oral mucositis-related pain. Design, Setting, and Participants: A phase 3 randomized trial was conducted from November 1, 2014, to May 16, 2016, at 30 US institutions and included 275 patients who underwent definitive head and neck radiotherapy, had an oral mucositis pain score of 4 points or greater (scale, 0-10), and were followed up for a maximum of 28 days. Interventions: Ninety-two patients were randomized to doxepin mouthwash (25 mg/5 mL water); 91 patients to diphenhydramine-lidocaine-antacid; and 92 patients to placebo. Main Outcome and Measures: The primary end point was total oral mucositis pain reduction (defined by the area under the curve and adjusted for baseline pain score) during the 4 hours after a single dose of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash compared with a single dose of placebo. The minimal clinically important difference was a 3.5-point change. The secondary end points included drowsiness, unpleasant taste, and stinging or burning. All scales ranged from 0 (best) to 10 (worst). Results: Among the 275 patients randomized (median age, 61 years; 58 [21%] women), 227 (83%) completed treatment per protocol. Mucositis pain during the first 4 hours decreased by 11.6 points in the doxepin mouthwash group, by 11.7 points in the diphenhydramine-lidocaine-antacid mouthwash group, and by 8.7 points in the placebo group. The between-group difference was 2.9 points (95% CI, 0.2-6.0; P = .02) for doxepin mouthwash vs placebo and 3.0 points (95% CI, 0.1-5.9; P = .004) for diphenhydramine-lidocaine-antacid mouthwash vs placebo. More drowsiness was reported with doxepin mouthwash vs placebo (by 1.5 points [95% CI, 0-4.0]; P = .03), unpleasant taste (by 1.5 points [95% CI, 0-3.0]; P = .002), and stinging or burning (by 4.0 points [95% CI, 2.5-5.0]; P < .001). Maximum grade 3 adverse events for the doxepin mouthwash occurred in 3 patients (4%); diphenhydramine-lidocaine-antacid mouthwash, 3 (4%); and placebo, 2 (2%). Fatigue was reported by 5 patients (6%) in the doxepin mouthwash group and no patients in the diphenhydramine-lidocaine-antacid mouthwash group. Conclusions and Relevance: Among patients undergoing head and neck radiotherapy, the use of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash vs placebo significantly reduced oral mucositis pain during the first 4 hours after administration; however, the effect size was less than the minimal clinically important difference. Further research is needed to assess longer-term efficacy and safety for both mouthwashes. Trial Registration: ClinicalTrials.gov Identifier: NCT02229539.

A pilot study of the effects of mild systemic heating on human head and neck tumour xenografts: Analysis of tumour perfusion, interstitial fluid pressure, hypoxia and efficacy of radiation therapy.

PURPOSE: The tumour microenvironment is frequently hypoxic, poorly perfused, and exhibits abnormally high interstitial fluid pressure. These factors can significantly reduce efficacy of chemo and radiation therapies. The present study aims to determine whether mild systemic heating alters these parameters and improves response to radiation in human head and neck tumour xenografts in SCID mice. MATERIALS AND METHODS: SCID mice were injected with FaDu cells (a human head and neck carcinoma cell line), or implanted with a resected patient head and neck squamous cell carcinoma grown as a xenograft, followed by mild systemic heating. Body temperature during heating was maintained at 39.5 ± 0.5 °C for 4 h. Interstitial fluid pressure (IFP), hypoxia and relative tumour perfusion in the tumours were measured at 2 and 24 h post-heating. Tumour vessel perfusion was measured 24 h post-heating, coinciding with the first dose of fractionated radiotherapy. RESULTS: Heating tumour-bearing mice resulted in significant decrease in intratumoural IFP, increased the number of perfused tumour blood vessels as well as relative tumour perfusion in both tumour models. Intratumoural hypoxia was also reduced in tumours of mice that received heat treatment. Mice bearing FaDu tumours heated 24 h prior to five daily radiation treatments exhibited significantly enhanced tumour response compared to tumours in control mice. CONCLUSIONS: Mild systemic heating can significantly alter the tumour microenvironment of human head and neck tumour xenograft models, decreasing IFP and hypoxia while increasing microvascular perfusion. Collectively, these effects could be responsible for the improved response to radiotherapy.

Microplastics pollution in the Asian water tower: Source, environmental distribution and proposed mitigation strategy.

Microplastics generated from fragmentation of leftover plastics and industrial waste has reached in the remotely located Asian water tower (AWT) region, the 3rd pole of earth and origin site of several freshwater rivers. The accumulation of microplastics in AWT ecosystem has potential to alter the climatic condition contributing in global warming and disturbing the biodiversity structural dynamics. The present paper provides a comprehensive critical discussion over quantitative assessment of microplastics in different ecosystems (i.e. river, lakes, sediment and snow or glacier) of AWT. The hydrodynamic fate and transport of microplastics and their ecological impact on hydromorphology and biodiversity of AWT has been exemplified. Furthermore, key challenges, perspectives and research directions are identified to mitigate microplastics associated problems. During survey, the coloured polyethylene and polyurethane fibers are the predominant microplastics found in most areas of AWT. These bio-accumulated MPs alter the rhizospheric community structure and deteriorate nitrogen fixation process in plants. Significance in climate change, MPs pollution is enhancing the emissions of greenhouse gases (NH3 by ∼34% and CH4 by ∼9%), contributing in global warming. Considering the seriousness of MPs pollution, this review study can enlighten the pathways to investigate the effect of MPs and to develop monitoring tools and sustainable remediation technologies with feasible regulatory strategies maintaining the natural significance of AWT region.

Lower lip cysticercosis: An unusual case report.

Cysticercosis is a disease that occurs when humans are infected with Taenia solium larvae. The parasitic illness cysticercosis, which is common in impoverished nations, hardly ever affects the mouth. Oral cysticercosis is rare that might be challenging to diagnose clinically. This rare case report documents an oral cysticercosis case in a 38-year-old male patient who had an asymptomatic lesion in the buccal mucosa of his lower lip. A T. solium larva was identified on histopathological examination in a cystic cavity after an excisional biopsy.

Plasmablastic lymphoma of the sphenoid bone in an immunocompetent patient: A diagnostic challenge.

ABSTRACT: Plasmablastic lymphoma is a rare type of highly aggressive B-cell non-Hodgkin lymphoma that usually occurs in immunocompromised patients and involves chiefly extra-nodal sites such as the oral cavity, jaw, gastrointestinal tract, soft tissue, bone, and skin. People above the age of 50 years are more commonly affected, with male predominance having a survival rate of 8 to 15 months. Here, we describe the case of a 48-year-old man who had an isolated plasmablastic lymphoma of the right sphenoid bone without any immunodeficiency. Plasmablastic lymphoma in immunocompetent patients at rare sites is a diagnostic challenge for both clinicians and pathologists because of vague clinical and histomorphology findings. This rare case report reemphasizes the utility of complete assimilation of clinical, histopathological, and immunohistochemical findings in such rare cases.

Severe Oral Mucositis After Intensity-Modulated Radiation Therapy for Head and Neck Cancer.

Importance: Oral mucositis (OM) is a common and debilitating adverse effect observed in patients with head and neck cancer (HNC) receiving radiation therapy (RT). Previous studies examining associations between OM and clinical outcomes were performed in the era of 3-dimensional conformal RT planning with low rates of concurrent chemotherapy, and thus may not reflect current practice. Objective: To prospectively assess patient-reported OM and identify its associations with clinical outcomes and quality of life. Design, Setting, and Participants: This cohort study performed at a single institution included 702 consecutive patients who underwent definitive or adjuvant intensity-modulated RT (IMRT) for primary HNC from February 9, 2015, to May 27, 2022. Data were analyzed from November 28, 2022, to August 18, 2023. Main Outcomes and Measures: Severity of OM was assessed based on highest reported mouth and throat soreness (MTS) score during radiotherapy according to the Oral Mucositis Weekly Questionnaire-Head and Neck Cancer survey, which was administered weekly during IMRT. Linear mixed models were used to compare mean MTS scores grouped by disease site and chemotherapy regimen. Fisher exact tests and 1-way analysis of variance tests were performed to identify associations between severity of OM and clinical outcomes. Results: Among 576 eligible patients, the median age was 62.5 (IQR, 56.3-69.1) years, and 451 patients (78.3%) were men. In terms of race and ethnicity, 6 patients (1.0%) were American Indian or Alaska Native; 2 (0.3%), Asian; 31 (5.4%), Black; 8 (1.4%), Hispanic or Latino; 509 (88.4%), White; and 28 (4.9%), unknown. The most common treatment site was oropharynx (268 [46.5%]), and most patients received concurrent chemotherapy (464 [80.6%]). By the end of treatment, 360 patients (62.5%) developed severe OM and 568 (98.6%) developed some degree of OM. Linear mixed models found no significant differences in OM between HNC disease sites. Groups with greater highest severity of OM reported had higher rates of measured outcomes (listed respectively by MTS score 0, 1, 2, 3, and 4): feeding tube placement (0%, 3.6% [2 of 56], 6.6% [10 of 152], 14.7% [40 of 272], and 21.6% [19 of 88]; P = .001), hospitalization (12.5% [1 of 8], 10.7% [6 of 56], 15.1% [23 of 152], 23.9% [65 of 272], and 28.4% [25 of 88]; P = .02), opiate use (0%, 19.6% [11 of 56], 42.8%[65 of 152], 61.4% [167 of 272], and 64.8% [57 of 88]; P < .001) and experienced greater weight loss (median, -0.7 [IQR, -1.7 to -0.4] kg; median, 3.9 [IQR, 1.1 to 6.1] kg; median, 5.0 [IQR, 2.2 to 7.7] kg; median, 4.7 [IQR, 2.1 to 7.7] kg; and median, 7.7 [IQR, 2.8 to 10.6] kg; P < .001). Conclusions and Relevance: In this cohort study of patients with HNC, 62.5% developed severe OM. Higher severity of OM was associated with feeding tube placement, hospitalization, opiate use, and weight loss. Improvements in OM prevention and management are needed.

Valorisation of fruit peel bioactive into green synthesized silver nanoparticles to modify cellulose wrapper for shelf-life extension of packaged bread.

Fruit peels are rich source of bioactive compounds such as polyphenols, flavonoids, and antioxidants but are often discarded as waste due to limited pharmaceutical and nutraceutical applications. This study aimed to valorise pomegranate and citrus fruit peel into green synthesised silver nanoparticles (AgNPs) in order to modify cellulose-based wrapping material for prospective food packaging applications and propose an alternate and sustainable approach to replace polyethene based food packaging material. Four different concentrations of AgNO3 (0.5 mM, 1 mM, 2 mM, and 3 mM) were used for green synthesis of AgNPs from fruit peel bioactive, which were characterised followed by phytochemical analysis. Ultraviolet-Visible spectroscopy showed surface plasmon resonance at 420 nm, XRD analysis showed 2θ peak at 27.8°, 32.16°, 38.5°, 44.31°, 46.09°, 54.76°, 57.47°, 64.61° and 77.50° corresponding to (210), (122), (111), (200), (231), (142), (241), (220) and (311) plane of face centred cubic crystal structure of AgNPs. Fourier-transform infrared spectroscopy analysis of AgNPs green synthesised from pomegranate and kinnow peel extract showed a major peak at 3277, 1640 and 1250-1020 1/cm while a small peak at 2786 1/cm was observed in case of pomegranate peel extract which was negligible in AgNPs synthesized from kinnow peel extract. Particle sizes of AgNPs showed no statistically significant variance with p > 0.10 and thus, 2 mM was chosen for further experimentation and modification of cellulose based packaging material as it showed smallest average particle size. Zeta potential was observed to be nearly neutral with a partial negative strength due to presence of various phenolic compounds such as presence of gallic acid which was confirmed by ultrahigh performance liquid chromatography-photodiode array(UHPLC-PDA) detector. Thermal stability analysis of green synthesised AgNPs qualified the sterilisation conditions up to 100 °C. AgNPs green synthesized from both the peel extracts had higher polyphenolic content, antioxidant and radical scavenging activity as compared to peel extracts without treatment (p < 0.05). The cellulose based food grade packaging material was enrobed by green synthesised AgNPs. The characterisation of modified cellulose wrappers showed no significant difference in thickness of modified cellulose wrappers as compared with untreated cellulose wrapper (p > 0.42) while weight and grammage increased significantly in modified cellulose wrapper (p < 0.05). The colour values on CIE scale (L*, a* and b*) showed statistically significant increase in yellow and green colour (p < 0.05) for modified cellulose wrappers as compared to control wrapper. The oxygen permeability coefficient, water vapour permeability coefficient, water absorption capacity and water behaviour characteristics (water content, swelling degree and solubility) showed significant decrease (p < 0.05) for modified cellulose wrapper as compared to control wrapper. A uniform distribution and density of green synthesised AgNPs across cellulose wrapper matrix was observed through scanning electron microscopy (SEM) images with no significant aggregation, confirming successful enrobing and stable immobilisation of nanoparticles from cellulose matrix. A seven-day storage study of bread wrapped in modified and control cellulose wrappers showed delayed occurrence of microbial, yeast and mould count in bread packaged in modified cellulose wrappers and thus, resulting in shelf life extension of bread. The results are encouraging for the potential applications of modified cellulose wrappers to replace polyethene based food packaging.

Ru(II)-Catalyzed Regioselective Annulation of 2-Hydroxystyrenes with Allenyl Acetates via Vinylic C-H Activation.

Herein, we disclose an unprecedented and robust Ru(II)-catalyzed non-oxidative [5+1] annulation of 2-hydroxystyrenes with allenyl acetates to access biologically relevant chromene skeletons. The heteroatom on allene plays a pivotal role in controlling the regioselectivity of migratory insertion, and the reaction proceeds through a Ru-σ-allyl pathway, which has been elusive so far in C-H activation reactions with allenes. The protocol is sustainable in nature as it proceeds at room temperature and avoids the use of any toxic metal oxidants. In addition, the synthetic utility of the protocol was also demonstrated by late stage functionalization and modular synthesis of various natural product conjugates.

Two- Versus Four-Times Weekly Acupuncture-Like Transcutaneous Electrical Nerve Stimulation for Treatment of Radiation-Induced Xerostomia: A Pilot Study.

Background: Xerostomia occurs in the majority of patients undergoing chemoradiation therapy for head and neck cancer (HNC). Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) treatment has been studied as an encouraging modality to improve salivary function and related symptoms. The purpose of this study was to compare ALTENS treatment by using a four-times weekly schedule for 6 weeks versus a twice-weekly schedule for 12 weeks with a validated xerostomia scale at 15 months from the start of ALTENS treatment. Materials and Methods: This single-center randomized study was conducted in 30 patients treated with radiotherapy with or without chemotherapy for HNC between 2014 and 2017, who had at least grade 1 or 2 symptomatic dry mouth (xerostomia) according to CTEP NCI Common Terminology Criteria for Adverse Events (CTCAE version 4.0). These patients were randomly assigned to receive ALTENS four-times weekly for 6 weeks or two-times weekly for 12 weeks. The University of Michigan 15-item Xerostomia-related Quality of Life Scale (XeQoLS) was administered at 6, 9, 15, and 21 months from the start of ALTENS treatment. A random-effects generalized linear model was used to model the overall XeQoLS score at the 15-month endpoint; adjusted for a random time effect, a fixed treatment arm, and interaction of time and treatment. Comparison between arms was based on a 0.05 nominal significance level. Results: XeQoLS decreased for all patients (although not statistically for each arm) from a mean of 22 and 21 at baseline (in the four times per week and twice weekly arms) to 12 in both arms at 15 months, with no difference between arms (p = 0.68). There were no attributable grade 1-3 adverse events. Arms were balanced for age, gender, race, and baseline xerostomia. Conclusions: This study demonstrates that both ALTENS regimens are safe, well tolerated, and appear to be equally effective. We now routinely make ALTENS units available for home use.

Managing the Oral Health of Cancer Patients During the COVID-19 Pandemic: Perspective of a Dental Clinic in a Cancer Center.

The practice of dentistry has been dramatically altered by the coronavirus disease 2019 (COVID-19) pandemic. Given the close person-to-person contact involved in delivering dental care and treatment procedures that produce aerosols, dental healthcare professionals including dentists, dental assistants and dental hygienists are at high risk of exposure. As a dental clinic in a comprehensive cancer center, we have continued to safely provide medically necessary and urgent/emergent dental care to ensure that patients can adhere to their planned cancer treatment. This was accomplished through timely adaptation of clinical workflows and implementation of practice modification measures in compliance with state, national and federal guidelines to ensure that risk of transmission remained low and the health of both immunocompromised cancer patients and clinical staff remained protected. In this narrative review, we share our experience and measures that were implemented in our clinic to ensure that the oral health needs of cancer patients were met in a timely manner and in a safe environment. Given that the pandemic is still on-going, the impact of our modified oral healthcare delivery model in cancer patients warrants continued monitoring and assessment.

Daily Time of Radiation Treatment Is Associated with Subsequent Oral Mucositis Severity during Radiotherapy in Head and Neck Cancer Patients.

BACKGROUND: Limited treatment options are available for oral mucositis, a common, debilitating complication of cancer therapy. We examined the association between daily delivery time of radiotherapy and the severity of oral mucositis in patients with head and neck cancer. METHODS: We used electronic medical records of 190 patients with head and neck squamous cell carcinoma who completed radiotherapy, with or without concurrent chemotherapy, at Roswell Park Comprehensive Cancer Center (Buffalo, NY) between 2015 and 2017. Throughout a 7-week treatment course, patient mouth and throat soreness (MTS) was self-reported weekly using a validated oral mucositis questionnaire, with responses 0 (no) to 4 (extreme). Average treatment times from day 1 until the day before each mucositis survey were categorized into seven groups. Multivariable-adjusted marginal average scores (LSmeans) were estimated for the repeated- and maximum-MTS, using a linear-mixed model and generalized-linear model, respectively. RESULTS: Radiation treatment time was significantly associated with oral mucositis severity using both repeated-MTS (n = 1,156; P = 0.02) and maximum-MTS (n = 190; P = 0.04), with consistent patterns. The severity was lowest for patients treated during 8:30 to <9:30 am (LSmeans for maximum-MTS = 2.24; SE = 0.15), increased at later treatment times and peaked at early afternoon (11:30 am to <3:00 pm, LSmeans = 2.66-2.71; SEs = 0.16/0.17), and then decreased substantially after 3 pm. CONCLUSIONS: We report a significant association between radiation treatment time and oral mucositis severity in patients with head and neck cancer. IMPACT: Although additional studies are needed, these data suggest a potential simple treatment time solution to limit severity of oral mucositis during radiotherapy without increasing cost.

Long-term outcomes of interventions for radiation-induced xerostomia: A review.

Xerostomia, or dry mouth, is a significant problem affecting quality of life in patients treated with radiation therapy for head and neck cancer. Strategies for reduction of xerostomia burden vary widely, with options including: sialagogue medications, saliva substitutes, acupuncture, vitamins, hyperbaric oxygen, submandibular gland transfer, and acupuncture or associated treatments. In this review, we sought to evaluate long-term outcomes of patients treated with various interventions for radiation-induced xerostomia. A literature search was performed using the terms "xerostomia" and "radiation" or "radiotherapy"; all prospective clinical trials were evaluated, and only studies that reported 1 year follow up were included. The search results yielded 2193 studies, 1977 of which were in English. Of those, 304 were clinical trials or clinical studies. After abstract review, 23 trials were included in the review evaluating the following treatment modalities: pilocarpine (three); cevimeline (one); amifostine (eleven); submandibular gland transfer (five); acupuncture like transcutaneous electrical nerve stimulation (ALTENS) (one); hyperbaric oxygen (one); and acupuncture (one). Pilocarpine, cevimeline, and amifostine have been shown in some studies to improve xerostomia outcomes, at the cost of toxicity. ALTENS has similar efficacy with fewer side effects. Submandibular gland transfer is effective but requires an elective surgery, and thus may not always be appropriate or practical. The use of intensity-modulated radiation therapy, in addition to dose de-escalation in select patients, may result in fewer patients with late xerostomia, reducing the need for additional interventions.

Routine surveillance scanning in HNSCC: Lung screening CT scans have value but head and neck scans do not.

OBJECTIVES: To examine the utility of computed tomography (CT) imaging during routine surveillance for the detection of recurrent head and neck squamous cell carcinoma (HNSCC). MATERIALS/METHODS: Clinical characteristics of HNSCC patients treated between 2008 and 2017 with radiation therapy or concurrent chemoradiation were abstracted from medical records. In patients who achieved a complete response to treatment by positron emission tomography scan, surveillance CT scans were conducted to the maxillofacial area, neck, and chest every 3 months in year 1, every 6 months in year 2, and every 12 months in years 3 and beyond. RESULTS: Within the entire cohort (n = 534), complete response was achieved in 446 patients (83.5%); of these, 84 (15.7%) patients had a recurrence. Among the 84 patients with disease recurrence, 25 (30%) patients remained alive, of which 15 (18%) underwent successful salvage treatment and became free of disease. Lung screening CT scans detected failure in 8 of these successfully salvaged patients. Among the 8 patients successfully salvaged for locoregional recurrence, 3 failures were asymptomatic at onset and detected by laryngoscope or dental exam. The remaining 5 failures were symptomatic and detected upon work up prompted by symptoms. Maxillofacial and neck surveillance CT imaging failed to detect any successfully salvaged patients. CONCLUSIONS: Routine surveillance for HNSCC patients with lung CT imaging had value but routine head and neck CT scans failed to identify any successfully salvaged patients. Given this finding, routine CT imaging surveillance in HNSCC patients should be restricted to annual lung screening with low-dose chest CT.

Mitigation of Radiation-Induced Epithelial Damage by the TLR5 Agonist Entolimod in a Mouse Model of Fractionated Head and Neck Irradiation.

Radiation treatment of head and neck cancer frequently causes severe collateral damage to normal tissues including mouth mucosa, salivary glands and skin. This toxicity limits the radiation dose that can be delivered and affects the patient's quality of life. Previous studies in mice and nonhuman primates showed that entolimod, a toll-like receptor 5 (TLR5) agonist derived from bacterial flagellin, effectively reduced radiation damage to hematopoietic and gastrointestinal tissues in both total-body and local irradiation scenarios, with no protection of tumors. Here, using a mouse model, we analyzed the efficacy of entolimod administered before or after irradiation in reducing damage to normal tissues. Animals received local fractionated radiation to the head and neck area, thus modeling radiotherapy of head and neck cancer. Tissue damage was evaluated through histomorphological examination of samples collected at different time points up to four weeks, mice were exposed locally to five daily fractions of 5, 6 or 7 Gy. A semiquantitative scoring system was used to assess the severity of observed pathomorphological changes. In this model, radiation damage was most severe in the lips, tongue and skin, moderate in the upper esophagus and minor in salivary glands. The kinetics of injury appearance and recovery of normal morphology varied among tissues, with maximal damage to the tongue, esophagus and salivary glands developing at earlier times (days 8-11 postirradiation) relative to that of lip and skin mucosa (days 11-15 postirradiation). While both tested regimens of entolimod significantly reduced the extent of radiation damage and accelerated restoration of normal structure in all tissues analyzed, administration of entolimod 1 h after each irradiation was more effective than treatment 30 min before irradiation. These results support the potential clinical use of entolimod as an adjuvant for improving the therapeutic index of head and neck cancer radiotherapy by reducing the radiation toxicity in normal tissues.

Evaluation of cytomegalovirus reactivation and tolerability in seropositive umbilical cord transplant patients after implementation of an intensive prevention strategy.

OBJECTIVE/BACKGROUND: Cytomegalovirus (CMV) causes significant morbidity and mortality in CMV seropositive patients undergoing umbilical cord blood transplants (UCBT). Our study aimed to describe the incidence of CMV reactivation and burden of disease, as well as the tolerability of an intensive prevention strategy as compared to historical prevention. METHODS: This was a retrospective chart review of 33 CMV seropositive patients that underwent UCBT. The intensive prevention strategy in UCBT consisted of ganciclovir 5mg/kg/d intravenously or valganciclovir 900mg by mouth daily initiated at the beginning of the conditioning regimen until Day -2. Then from Day -1 to Day +100, patients received valacyclovir 2g by mouth three times daily, and from Day +101 to Day +365, acyclovir 800mg by mouth twice daily. Historical standard prevention was acyclovir 800mg by mouth twice daily initiated at the beginning of the conditioning regimen until Day +365. RESULTS: Thirty-three patients were included from 2008 to 2014. There were no differences in the adverse effects experienced between the two regimens (p=.4). CMV reactivation occurred significantly later with intensive prevention (p=.003). The median CMV viral titer at reactivation was lower in the intensive versus the historic prevention (1,800copies/mL and 2,700copies/mL, respectively), but was not significantly different. CMV disease occurred significantly less often in the intensive group (p=.039). CONCLUSION: The results from this study indicate that the intensive prevention strategy was well tolerated, significantly delayed CMV reactivation, and patients had less CMV disease.

Recurrent case of central giant cell granuloma with multiple soft tissue involvement.

Central giant cell granuloma is a fairly common lesion in the jaws aetiology of which is still completely unknown but thought to be of a reactive process to some unknown stimuli. It usually arises either peripherally in periodontal ligament, mucoperiosteum, or centrally in the bone. The histological hallmark for both peripheral and central giant cell granuloma (CGCG) is the presence of distinctive multinucleated giant cells (MGCs) in a prominent fibrous stroma. Central giant cell granuloma is an uncommon benign proliferative lesion that almost exclusively occurs within the jaw. Eventually, it may become aggressive leading to the expansion and perforation of cortex resulting into mobility and displacement of teeth with root resorption. The present case focuses on the dilemma and perplexity in diagnosing aggressive CGCGs, due to its close proximity with respect to pathology, behavior and prognosis from giant cell tumors (GCT). Central giant cell granuloma persuaded extensive destruction to the hard and soft tissues with high rate of recurrence encourage us the need of exploring the possibilities of giant cell tumors having a definitive presence in the jaws.

Autologous platelet rich plasma after third molar surgery: a comparative study.

PURPOSE: This study is an attempt to evaluate the use of autologous platelet rich plasma (PRP) to promote wound healing and osseous regeneration in human third molar extraction sockets. MATERIALS AND METHOD: PRP was prepared after two centrifugation and the gelling agent used was freshly prepared 10% calcium chloride.PRP gel was placed in one of the extracted sockets of bilateral impacted mandibular third molars. IOPA Xrays were used to evaluate the wound dehiscence, probing depth, bone density & alveolar bone level after 1st, 2nd and 7th day and 3rd & 6th month respectively. RESULTS: On evaluation, it was found that PRP grafted sockets showed dehiscence in 8% cases. The decrease in alveolar bone level was highly significant in PRP grafted sockets in 3rd and 6th month post operatively. There was significant difference between pre-operative density of adjacent bone and bone formed in extraction sockets at 3rd and 6th month in PRP grafted sockets. There was significant reduction in probing depth from initial period to 3 and 6 months in both the groups, but PRP grafted sockets showed greater decrease in probing depth. CONCLUSION: PRP is an inexpensive and widely available modality to minimize postoperative complication and enhance both hard and soft tissue healing potentials. This autologous product eliminates concern about immunogenic reaction and disease transmission. Its beneficial outcomes in dental clinic, including decrease in bleeding and rapid wound healing hold promise for further procedures.PRP is thus a new application in tissue engineering and developing area for clinician and researchers.