Management of the oral sequelae of cancer therapy.

Oral cancer and the oral sequelae of treatment for oral and other malignancies can significantly affect a patient's oral and systemic health, as well as have a profound impact on quality of life. Compromised oral health prior to, during, and following cancer therapy can affect treatment outcomes. Increasingly, dental professionals in the community are being called upon to provide care for these individuals. Radiation therapy is routinely used for tumors of the head and neck, delivering a concentrated radiation dose to the tumor, but also to the immediately surrounding tissue. Oral complications are related to the site radiated and the total radiation dose. Cancer chemotherapy is provided as a primary treatment for some cancers and as an adjunctive modality for other cancers. The goal is to eradicate the rapidly growing cells of the tumor, but chemotherapy is often toxic to other cells that rapidly divide normally including the oral mucosa. The use of combined chemotherapy and radiation is now considered standard for most locally advanced tumors of the head and neck. The toxicities of this combined therapy are essentially the same as with radiation alone, but develop more rapidly and are typically more severe when they reach maximum level. The most common oral sequelae of cancer treatment are: xerostomia, the sensation of a dry mouth as a result of damage to the salivary glands and/or medication; mucositis, the inflammation and ulceration of the oral mucosa; and infection as a result of the loss of mucosal integrity. Management of oral health during cancer therapy includes identifying at-risk patients, patient education, appropriate pretreatment interventions, and timely management of complications. Appropriate preventive and therapeutic measures will help minimize the risk of oral and associated systemic complications, improve treatment outcomes, and improve the patient's quality of life.

The prevalence of oral mucosal lesions in adults from the Turin area.

AIM: To assess the prevalence of oral mucosal lesions (OML) and evaluate its association with tobacco and alcohol consumption and the wearing of removable dentures in an adult population from the Turin area, Italy. MATERIALS AND METHODS: A retrospective study, based on an invitational self-selected screening, was performed on 4098 subjects. It included clinical examination plus biopsies when necessary. Patient history included age, sex, denture wearing and risk habits. Internationally accepted criteria were adopted to classify the OMLs. RESULTS: Males were observed to have more OMLs (557/2040; 27.3%vs 471/2058; 22.89%). Overall OML prevalence was linked to risk habits and age. Tobacco was linked to leukoplakia, melanin pigmentation, smoker's palate, frictional lesions and papilloma. It was negatively related to recurrent aphthous stomatitis and oral lichen planus. Alcohol was linked to leukoplakia, frictional lesions and median rhomboid glossitis. The tobacco-alcohol association was linked to frictional lesions, leukoplakia, melanin pigmentation and smoker's palate. Denture wearers had an overall higher prevalence of OMLs, in particular candidiasis, traumatic and frictional lesions. CONCLUSIONS: The prevalence of OMLs in Turin seems to be comparable to those in other European studies and emphasize that risk habits and denture wearing have some relationship with the presence of OMLs.

Oral ulcers in children under chemotherapy: clinical characteristics and their relation with Herpes Simplex Virus type 1 and Candida albicans.

OBJECTIVE: The objective of this study was to determine the clinical characteristics of oral ulcers in pediatric oncology patients undergoing chemotherapy and their relation with the presence of Herpes Simplex Virus (HSV) type 1 and Candida albicans. STUDY DESIGN: The sample consisted of 20 ulcerative lesions from 15 children treated with chemotherapy in the Pediatric Service of the Regional Hospital of Concepción, Chile. Two calibrated clinicians performed clinical diagnosis of the ulcers and registered general data from the patients (age, general diagnosis, absolute neutrophil count, and number of days after chemotherapy) and clinical characteristic of the ulcers: number, size, location, presence or absence of pain and inflammatory halo, edge characteristics, and exudate type. Additional to clinical diagnosis, culture for Candida albicans (C) and polymerase chain reaction (PCR) for Herpes Simplex Virus type 1 was performed. RESULTS: Ten ulcers occurred in patients with acute lymphoblastic leukemia, five in patients with acute myeloblastic leukemia and five in patients with other neoplastic diseases. Eight ulcers were HSV (+) / C (-), 6 HSV (-) / C (-), 4 HSV (+) / C (+) and 2 HSV (-) / C (+). Preferential location was the hard palate. Most lesions were multiple, painful, with inflammatory halo, irregular edges and fibrinous exudate. The average size was 6,5 millimeters, and the mean number of days after chemotherapy was 7.5 days. CONCLUSIONS: Oral ulcers in children with oncological diseases did not present a specific clinical pattern. They were strongly associated with HSV.

Phase II trial of recombinant leukocyte A interferon in patients with advanced chronic lymphocytic leukemia.

Recombinant leukocyte A interferon is a highly purified single molecular species of alpha-interferon prepared by recombinant DNA methods. In 1982, a phase II trial to evaluate the efficacy of recombinant leukocyte A interferon for patients with previously treated chronic lymphocytic leukemia was begun, and 19 patients were entered in this study. Patients received one of two dose schedules depending on their pretreatment platelet counts. Those with platelet counts greater than 100,000/mm3 received 50 X 10(6) units/m2 intramuscularly three times weekly, with dose reductions to 25 X 10(6) units/m2 and 5 X 10(6) units/m2 for unacceptable toxicity. Those with platelet counts less than 100,000/mm3 received 5 X 10(6) units/m2 intramuscularly three times weekly. Toxicity was dose-dependent and included fever, chills, fatigue, anorexia, myalgias, headache, leukopenia, and thrombocytopenia. Response was evaluable in all but one of the patients entered in this study. Two of the 12 patients treated with 50 X 10(6) units/m2 had a partial response, three had no response, and seven had progressive disease. Of the six patients starting at 5 X 10(6) units/m2 in whom response was evaluable, two had no response and four had progressive disease. Five patients with progressive disease (three at 50 X 10(6) units/m2 and two at 5 X 10(6) units/m2) had an acceleration of disease while receiving recombinant leukocyte A interferon. It is concluded that the dose and schedule of recombinant leukocyte A interferon therapy tested in this study are not effective in previously treated patients with advanced chronic lymphocytic leukemia.

Review article: oral ulceration--aetiopathogenesis, clinical diagnosis and management in the gastrointestinal clinic.

Oral ulceration is a common complaint of patients attending out-patient clinics. The aim of this review is to provide the gastroenterologist with a differential diagnosis of oral ulceration, and a practical guide for the management of recurrent aphthous stomatitis, including topical and systemic therapy. The association of recurrent aphthous stomatitis with Behçet's disease and other systemic disorders, including coeliac disease, is discussed. Recent evidence concerning the immunopathogenesis of Behçet's disease is reviewed, including renewed interest in the role of Streptococcus sanguis and possible infectious triggering of an inappropriate immunoinflammatory response, resulting in tissue damage. The efficacy and limitations of conventional treatment for this mutisystem disorder are outlined together with the potential role of novel biological agents, such as anti-tumour necrosis factor-alpha therapy. Oral ulceration, as a manifestation of inflammatory bowel disease and a complication of drug therapy, is described. Guidance is given concerning indications for referral of patients with oral ulceration to an oral physician/surgeon for further investigations, including biopsy if appropriate.

Acyclovir-resistant herpes simplex virus infections in a bone marrow transplant population.

Over a 3-month period, four patients who had received unrelated donor (UD) bone marrow transplants (BMT) presented with severe mucocutaneous herpes simplex virus (HSV) infection while receiving acyclovir (ACV) prophylaxis. Sensitivity testing of the isolates revealed three to be acyclovir-resistant and in one patient the infection was also characterised by a marked failure to respond to foscarnet (phosphonoformic acid). The emergence of ACV-resistant HSV infections in themselves is a new and challenging problem, and yet a far greater problem will become evident if these infections develop resistance to non thymidine kinase dependent therapy.

Successful foscarnet therapy for mucocutaneous infection with herpes simplex virus in a recipient after unrelated bone marrow transplantation.

A 36-year-old Japanese man who received an unrelated bone marrow transplant (BMT) developed severe mucocutaneous infection with herpes simplex virus (HSV) type 1 during oral acyclovir prophylaxis. The lesions progressed despite treatment with intravenous acyclovir and vidarabine. The HSV isolates were sensitive acyclovir, vidarabine and foscarnet in vitro, but peripheral CD3- or CD19-positive cells were barely detectable even 4 months after transplant. A 12-day course of treatment with foscarnet led to a rapid improvement. Foscarnet therapy should be considered for all severe HSV infections following BMT, regardless of whether or not the HSV isolates are sensitive to acyclovir.

Herpes simplex virus, Candida albicans and mouth ulcers in neutropenic patients with non-haematological malignancy.

Mouth ulcers are a frequent cause of morbidity in patients rendered neutropenic as a result of chemotherapy. We report here a series of 28 such patients from whom swabs were taken for viral isolation and mycological culture. In 13 patients, herpes simplex virus (type I) was isolated and in 17 patients Candida albicans was cultured. Both organisms were isolated in 9 patients. Our results suggest that both a viral and fungal element may be important in the aetiology of oral ulceration and that antiviral and antifungal agents may each have a role in the prophylaxis and treatment of such patients.

Periodontal disease and periodontal management in patients with cancer.

Periodontal infection may exacerbate during cancer therapy and may result in oral pain and infection, and systemic infection, which may cause morbidity and can lead to mortality in neutropenic cancer patients. Periodontal disease in head and neck cancer patients treated with radiation therapy may lead to acute and chronic complications. The literature was reviewed by a search of Medline of the National Library of Medicine. The search was conducted to identify publications assessing periodontal disease in cancer patients. In addition, a review of papers referenced in the retrieved papers was conducted to identify additional publications for review. Periodontal disease should be assessed and managed prior to medical treatment of cancer for those with oropharyngeal cancer, and for patients in whom neutropenia may develop during treatment. Pretreatment assessment and management, and maintenance of oral hygiene have been shown to be effective in preventing oral and systemic complications during treatment. A complete oral and periodontal examination is appropriate for all patients planned to receive head and neck radiation therapy and those to be treated with medical protocols that are anticipated to result in neutropenia. Oral and periodontal care must continue following cancer therapy, and requires that the health care provider have an understanding of the malignant disease, oral manifestations of the disease, medical management of the disease, and of the oral complications that may develop.

Effect of smokeless tobacco on the replication of herpes simplex virus in vitro and on production of viral lesions in hamster cheek pouch.

Previous experiments have shown that combination of herpes simplex virus (HSV) infection and simulated snuff-dipping in hamster buccal pouches enhances the development of micro-invasive squamous cell carcinoma in cheek pouch epithelium. The effect has now been determined of water-extractable components of snuff (snuff-extract) on the growth and the cell-lysing activity of HSV. Various dilutions of snuff-extract in tissue culture medium significantly inhibited the growth of HSV in Vero cell monolayers by inhibiting the viral DNA replication. Moreover, HSV was inactivated and its cell-lysing activity lost when it was incubated with snuff-extract in cell-free condition. Snuff also had a similar anti-herpetic effect in vivo; HSV infection of pouch tissues followed by simulated snuff-dipping resulted in significant inhibition of viral growth. Thus snuff interferes with the DNA synthesis and cytolytic activity of HSV in vitro and in vivo, and this in turn, may increase its oncogenic capacity.

Oral cavity complications of bone marrow transplantation.

Bone marrow transplantation, once regarded as experimental, has evolved into a standard treatment for a variety of malignancies. Considerable advances have been made in histocompatibility typing, pretransplantation chemotherapy, and posttransplantation immunosuppressive therapy as well as prophylaxis and treatment of infections. Oral complications develop in almost all patients, and their early recognition may result in the institution of prompt treatment and prolonged survival. Mucositis, often severe and extremely painful, develops in more than three quarters of bone marrow transplant recipients, and its prevention, unfortunately, remains unsatisfactory. Herpes simplex virus and Candida albicans account for most oral infections, although their incidence has been dramatically reduced by the institution of prophylactic agents. Graft versus host disease continues to be a significant complication of marrow transplantation, and the detection of commonly occurring oral changes may support its diagnosis.

Neonatal herpes simplex virus infections. Presentation and management.

Neonatal herpes simplex virus (HSV) infections are recognized to be severe because of their association with significant morbidity and mortality. Through ongoing studies performed by the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group, the presentation, natural history, outcome and value of antiviral chemotherapy have been considered. Infants developing neonatal HSV infections can be classified according to the extent of disease, disseminated or localized. Localized infection can be subdivided into either central nervous system (CNS) disease, occurring in 35% of infected infants, or skin, eye and mouth (SEM) disease, in 41% of infants. Disseminated disease accounts for 24% of neonatal HSV infection. Therapeutic outcome depends upon disease classification. Administration of either 15 or 30 mg/kg/day of vidarabine resulted in significantly decreased mortality for infants with life-threatening disseminated and CNS disease as compared to placebo recipients. Approximately one-third of children developed normally following disseminated disease or CNS infection. When disease was localized to the SEM, no death occurred, and 88% of treated infants developed normally. While these data indicate that therapy is effective for management of infants with neonatal HSV infection, improvements are necessary. Hopefully, a study in progress will demonstrate improved outcome with acyclovir treatment.

The role of an immunoperoxidase technique in the diagnosis of oral herpes simplex virus infection in patients with leukemia.

Laboratory techniques are often used to confirm a clinical diagnosis of oral herpes simplex virus (HSV) infection in patients with leukemia. In the present study, an immunoperoxidase technique (IPT) was used to examine smears taken from the oral mucosa of 44 patients with leukemia at Vancouver General Hospital. It was found that the IPT was as sensitive and specific as viral culture in confirming the presence of HSV. The IPT was found to be more predictive of symptomatic oral HSV disease than viral culture because it did not give positive results if there was only viral shedding in the absence of clinical disease. As the IPT is rapid and inexpensive as well as being specific, sensitive, and predictive, it has a definite role in the laboratory confirmation of oral HSV lesions in leukemics.

Oral manifestations in patients with aplastic anemia.

OBJECTIVE: The aim of the present study was to characterize the prevalence and risks of oral complications in aplastic anemia (AA). STUDY DESIGN: Approximately 79 patients with AA (age, 37 +/- 17 years) and 66 control patients with schizophrenia (age, 33 +/- 12 years) were examined. Records were reviewed for demographic, clinical, and radiographic information. Prior medical therapy, laboratory values, disease duration, and medical treatment response were noted for patients with AA. Odds ratios (OR) and 95% CI were calculated for oral manifestations in cases and in control subjects. Univariate analysis identified important variables for logistic regression. RESULTS: Patients with AA presented more frequently with oral petechiae (OR = 49; 95% CI, 2.9-825), gingival hyperplasia (OR = 27; 95% CI, 1.6-463.5), spontaneous gingival bleeding (OR = 27; 95% CI, 1.6-463.5), and herpetic lesions (OR = 27; 95% CI, 1.6-463.5). Prior cyclosporine use was associated with gingival hyperplasia (P =.0001). No other predictors for oral manifestations or treatment outcomes were found. CONCLUSIONS: Oral soft tissue changes and infections were more common in patients with AA. Prior cyclosporine use was predictive of the presence of gingival hyperplasia.

Oral recurrent human herpes virus infection and bone marrow transplantation survival.

OBJECTIVE: This study was conducted to compare the survival rates of bone marrow transplantation (BMT) patients who were affected with the survival rates of those who were not affected by oral recrudescent human herpes virus-1 infection (HHV-1) after transplantation. STUDY DESIGN: Fifty-two consecutive patients who underwent BMT were included in the study. The time of death after BMT was displayed, by means of the Kaplan-Meier method, for the following parameters: age and gender of the patient, donor gender, primary disease, stem cells, conditioning regimen, platelet number after day 100, acute and chronic graft-versus-host disease, oral recurrent HHV-1 infection post-BMT, oral lichenoid lesions of graft-versus-host disease, graft-versus-host disease at the salivary glands, parenteral nutrition, and oral mucositis. The data were initially analyzed by means of the log-rank test and then included in the Cox proportional hazards model. RESULTS: The multivariate analysis demonstrated a significance of 5% for only the platelet numbers and oral recurrent HHV-1 infection. CONCLUSION: The present study provides evidence that platelet numbers below 100,000 cells/mm(3) after day 100 and oral recurrent HHV-1 infection are independent negative prognostic variables in BMT patients' 24-month survival rates.

Herpesviridae-associated persistent mucocutaneous ulcers in acquired immunodeficiency syndrome. A clinicopathologic study.

Persistent mucocutaneous ulcers in AIDS represent a variety of disease entities. The purpose of this study was to characterize clinicopathologic features of persistent oral ulcers associated with cytomegalovirus and herpes simplex virus in AIDS. Forty-seven persons infected with HIV with persistent ulcers (mean, 2.4 ulcers/person) were included in this study. A biopsy specimen from a representative ulcer was taken from each patient. Hematoxylin-eosin, periodic acid-Schiff, cytomegalovirus, and herpes simplex virus immunocytochemical stains were performed on tissue sections. The most common sites of involvement were the buccal/labial mucosa (27%), tongue (25%), and gingiva (18%). Mean ulcer size was 1.8 cm with a mean duration of 5.6 weeks. The ulcerogenic viral agents were cytomegalovirus alone in 53% of cases, cytomegalovirus and herpes simplex virus coinfection in 28% of cases, and herpes simplex virus alone in 19% of cases. Treatment response to ganciclovir with or without topical steroids resulted in lesion resolution in the cytomegalovirus and cytomegalovirus/herpes simplex virus groups; however, recurrence/resistance was relatively high (23%). Herpes simplex virus/cytomegalovirus ulcers responded to oral acyclovir in combination with systemic ganciclovir. Increasing the oral acyclovir dosage resulted in resolution of herpes simplex virus-only ulcers in all but one case. Cytomegalovirus and herpes simplex virus are associated with persistent mucocutaneous ulcers in AIDS. These lesions responded to systemic antiviral therapy but are difficult to differentiate from other ulcerogenic diseases such as aphthous major, necrotizing stomatitis, and ulcerations not otherwise specified without biopsy and histopathologic examination.

Relationships of personality traits and stress to gingival status or soft-tissue oral pathology: an exploratory study.

OBJECTIVES: The purpose of this study was to examine the relationships of personality traits and stress with gingival inflammation and with soft-tissue oral pathology. METHODS: Personality traits of psychoticism (P), extroversion and introversion (E), and neuroticism (N) were measured with Eysenck's personality questionnaire (EPQ). Stress was measured with a modified organizational and individual assessment survey (OIAS) developed by Hendrix. Military recruits from Ft. Leonard Wood, Missouri, were examined for soft-tissue oral pathology and gingival status at weeks one (n = 241) and six (n = 61) of basic combat training (BCT). The EPQ and OIAS were administered to 217 recruits during week six of BCT. A discriminant analysis was used to determine correlations among study variables. RESULTS: Significant correlations (P < .05) were found between personality traits and various measures of tolerance of stress. Little variance was found between groups originally presenting with or without disease. Only physical stress (P < .005) was shown to affect soft-tissue pathology, while gingival inflammation correlated significantly to E scores (P < .02), tolerance to change (P < .02), and anxiety (P < .05). CONCLUSIONS: Data support a possible relationship among certain personality traits, stress variables, and gingival inflammation or soft-tissue pathology in recruits with extreme personality characteristics or perception of high physical stress levels in basic combat training.