NCI monographs : a publication of the National Cancer Institute最新文献

Salivary gland dysfunction is a common side effect of cancer therapies. Salivary secretions are reduced rapidly after starting head and neck radiotherapy. Salivary gland dysfunction has also been linked to bone marrow transplantation and to cytotoxic chemotherapy. Salivary gland stimulation during radiation has been suggested as a means of reducing radiation damage. Results of an ongoing study investigating the effects of pilocarpine on radiation-induced salivary gland dysfunction suggest that parotid function was preserved, but not submandibular/sublingual function. Also, patients receiving pilocarpine had less frequent oral complaints. Further research is necessary to develop means of preventing or alleviating the salivary side effects of cancer therapies.

It is important to understand the pathogenesis of acute oral infections in patients with chemotherapy-induced myelosuppression in order to develop strategies to prevent such complications. Four distinct oral sites that can either be acutely infected or contribute to acute systemic infection are the oral mucosa, dental pulp and periapical tissues, periodontium, and salivary glands. Many cytotoxic drugs can be directly stomatotoxic to replicating oral mucosa. Once mucosal integrity is affected, secondary acute infection can occur. Even without clinical ulceration, deleterious shifts in the oral microbial population can develop. Gram-negative bacilli have been identified as frequent colonizers of myelosuppressed patients, although coagulase-negative staphylococci are being recovered with increasing frequency. Strategies to prevent oral mucosal infection include reducing trauma and preventing proliferation of organisms. Dental pulpal infection is most commonly caused by extensive dental caries. Most pulpal infection is of bacterial origin and can progress to involve the periapical tissues of the involved tooth if not treated. Specific endodontic interventions will usually stabilize or eliminate the source of the infection until the patient's hematologic status returns to normal and definitive pulpal therapy can be provided. In part because acute pulpal complications in the myelosuppressed cancer patient are relatively infrequent, research on the causative organisms and the appropriate therapy of acute, systemic infection of pulpal origin has been limited. Many adults have chronic, asymptomatic periodontal disease. In its advanced stages, extensive ulceration may be present that is not clinically observable. In patients with reduced host defenses, exacerbation of preexistent periodontal disease can have systemic sequelae and is associated with elevated levels of periodontopathic organisms or pathogens typically associated with systemic infection in myelosuppressed cancer patients. Mechanical and chemical antimicrobial techniques are available to reduce prevalence and improve patient comfort and oral hygiene. Dental extractions may be indicated to eliminate the nidus of infection of either pulpal or periodontal origin in patients who are scheduled to receive myelosuppressive chemotherapy. Data indicate that such procedures may be performed without undue risk. Unlike patients who undergo bone marrow transplantation or radiotherapy, patients who receive chemotherapy do not commonly experience subjective salivary gland dysfunction. Occasionally, a transient xerostomia may occur; this condition is frequently attributed to the patient's oral habits, such as breathing through the mouth. The dessicating effect of breathing through the mouth can contribute to oral mucosal injury during function as well as provide a setting for acute infection of commensal origin. More research is needed on the effects of chemotherapy on salivary host defenses.

Data are presented to indicate the value of hyperbaric oxygen in all stages of treatment of patients with irradiation complications following head and neck surgery. Hyperbaric oxygen stimulates angiogenesis, with increased neovascularization and optimization of cellular levels of oxygen for osteoblast and fibroblast proliferation, collagen formation, and support of ingrowing blood vessels. The hypoxic, acellular matrix in the postirradiated field is changed to a hypercellular, hyperoxic/normoxic situation. Oxygen is used as an adjunct to appropriate surgery. By using the two modalities together, the salvage rate for osteoradionecrosis and its complications of orocutaneous fistula, pathological fractures, and severe bone losses can be increased dramatically. It may also be used prophylactically in patients with periodontal disease or teeth requiring extraction in a previously irradiated area. Finally, the use of oxygen helps support tissue flaps and grafts placed into previously irradiated areas. Economically, there is considerable cost savings in the use of hyperbaric oxygen therapy with appropriate surgery. From the patient's point of view, pain relief is achieved, function is returned, and prognosis improves in a relatively short time.

Oral ulcerations are frequently observed in cancer patients receiving chemotherapy or radiation therapy. Herpes simplex virus is the most common viral pathogen association with lesions. Reactivation of latent virus is responsible for the vast majority of culture-positive infections. The natural history of this virus has been well studied in selected patient populations. These infections may cause local complications and, if untreated, may not heal for weeks. Reactivation of the virus may occur predictably in patients after bone marrow transplantation or acute leukemia. Recognition that herpes simplex virus is present in oral lesions is of importance because of the availability of safe, effective antiviral therapy. Prospective, randomized, double-blind clinical trials have demonstrated that acyclovir is the most effective agent to treat or prevent herpes simplex virus infections in immunocompromised patients.

Xerostomia is a common complication of radiation therapy to the head and neck. In such cases, the symptom is often permanent and leads to difficulty in mastication, wearing dentures, deglutition, and speaking. Other side effects include candidiasis and caries. Therapy is for the most part symptomatic and empirical. However, the use of sialogogues shows promise. Effective salivary substitutes and sialogogues that have minimal side effects need to be developed.

Oral complications from cancer chemotherapy are well documented for the hematologic malignancies but are less well defined for cancers of the head and neck. This prospective study examined 82 patients with stage III or IV disease to determine the incidence and severity of oral sequelae following a total of 141 cycles of neoadjuvant chemotherapy. Taste alteration (37%) was the most frequent problem, followed by mucositis (30%) and ulceration (22%). Xerostomia, increased salivary flow, loss of appetite, weight loss, dysphagia, bleeding, and infection were also encountered. We conclude that oral problems are common following chemotherapy for head and neck tumors and that more aggressive investigational protocols will result in a much higher incidence and severity of problems. Prevention of these sequelae by conventional as well as investigational means is important to keep them from becoming dose-limiting problems.

The role of mucositis in infectious complications in the patient with cancer is poorly understood. Consequently, neither the presence nor the severity of mucositis is routinely considered in the selection of specific antibacterial agents for the initial empirical therapy of the febrile cancer patient. In a study of children receiving remission induction chemotherapy for acute nonlymphocytic leukemia, the number of febrile days correlated more closely with the degree of mucositis than with the number of days of neutropenia. Oral mucositis appears to predispose cancer patients to systemic infections with alpha-hemolytic streptococci, Capnocytophaga, and Candida species. Overall, studies of single-drug versus combination therapy for the initial empirical therapy of febrile, neutropenic cancer patients indicate that monotherapy approaches the efficacy of combination therapy, although combination therapy may be preferred for certain cohorts of cancer patients. A concern that is closely related to the issue of combination therapy versus monotherapy is the need for vancomycin in the initial empirical regimen. Vancomycin appears to be the consensus drug of choice for patients with known gram-positive bacterial infections pending antibiotic susceptibility testing; however, there is disagreement as to whether the increased activity of vancomycin against gram-positive bacteria outweighs its expense and potential toxicity for inclusion in the initial empirical regimen. There is an explicit need for continued support of basic and clinical research to address these concerns.

No part of the body reflects the complications of cancer chemotherapy as visibly and as vividly as the mouth. The infectious, hemorrhagic, cytotoxic, nutritional, and neurologic signs of drug toxicity are reflected in the mouth by changes in the color, character, comfort, and continuity of the mucosa. The stomatologic complications of radiotherapy for oral cancer are physical and physiological in nature, transient or lasting in duration, and reversible or irreversible in type. Some linger as permanent mementos long after the cancer has been destroyed. They stem from radiation injury to the salivary glands, oral mucosa, oral musculature, alveolar bone, and developing teeth. They are expressed clinically by xerostomia, trismus, radiation dermatitis, nutritional stomatitis, and dentofacial malformation. In both cancer chemotherapy and cancer radiotherapy, the oral complications vary in pattern, duration, intensity, and number, with not every patient developing every complication.

Radiation therapy (RT) and chemotherapy have increased long-term survival with certain cancers. The use of dental investigation and treatment of chronic or delayed oral complications is developing. Altered dental root development, enamel opacities, hypocalcifications, periodontal problems, and a higher caries rate are seen in children treated with chemotherapy. The psychosocial implications of long-term survival on routine dental care are important. Prevention and treatment of long-term oral complications of radiation therapy are changing. Osteoradionecrosis remains complicated and devastating. Strategies that avoid post-RT extractions include caries prevention, oral hygiene measures, meticulous restorative dentistry, overdentures, and improved posts for endodontically treated teeth. Guidelines for post-RT extractions vary greatly. Pediatric patients who receive head and neck irradiation may have total arrest of tooth and jaw development within the portal. The dentist must be able to diagnose and treat the variety of alterations already identified and should engage in scholarly research to answer the questions that remain.