Overexpression of p53 protein in squamous cell carcinomas of head and neck without apparent gene mutations.

Structural alterations of p53 and overexpression of the p53 protein are found in a large proportion of human cancers. In this study, we examined the frequency of p53 mutations and p53 overexpression in squamous cell carcinomas (SQCC) of head and neck. Expression of p53 was detected by immunochemistry (IHC) with monoclonal antibodies defining three distinct epitopes: PAb421 (species cross-reactive epitope on normal and mutated p53), PAb1801 (epitope on normal and mutated human p53), and PAb240 (conformational epitope of mutated p53 and denatured normal p53). Genetic alterations of p53 were identified by single-strand conformational polymorphism (SSCP) analysis and DNA sequencing in selected cases. IHC assays revealed nuclear p53 immunostaining in 53% of cases (32 of 60) with PAb1801, 38% (23 of 60) with PAb421, and 32% (19 of 60) with PAb240. Cases positive with PAb421 or PAb240 were also positive with PAb1801, whereas PAb421 and PAb240 identified overlapping but distinct tumor subsets. Areas of carcinoma in situ present in the tumor specimens showed nuclear p53 immunostaining in 11 of 26 cases. SSCP analysis for exons 5-9, the most common sites of p53 abnormalities, revealed mutations in 26% (15 of 58) of the evaluable cases. Comparison of the SSCP results with the IHC results for PAb1801 identified 11 cases that were positive by both methods, 4 cases with p53 mutations that were negative by IHC, 20 cases positive by IHC but without detectable p53 mutations, and 23 cases negative by both methods. IHC with PAb240, which is thought to be specific for mutated p53, was positive in 9 cases with demonstrable p53 mutations and in 9 cases with no detectable mutations. DNA sequence analysis of nine tumors identified point mutations, nonsense mutations, and frame-shift mutations. In conclusion, our study shows that p53 overexpression in SQCC of head and neck as detected by IHC is a frequent finding, and that overexpression is associated with common types of p53 mutations in some cases. However, IHC identifies p53 overexpression in some tumors with apparently normal SSCP patterns and, conversely, tumors with nonsense or frameshift mutations may not express any p53 detectable by IHC.

Controlled mold geometry for surgical deficit treatment planning.

The relatively precise placement of brachytherapy sources afforded by stereotactic frames for brain implants is not generally achievable for other sites, which lack the fixed geometry of the cranium and its contents. An exception is a source-containing rigid mold that delivers brachytherapy when inserted securely in a surgical defect. A technique has been developed in which an acrylic mold of the region to be treated is suspended in a demountable aluminum box, which is then filled to a suitable level with dental stone to form a casting that supports the mold and that can be removed intact. First, the box is aligned on a mill table and a ball mill is used to drill three parallel holes in the acrylic mold, with precisely known locations and depths and as widely separated as possible. The spherical air cavities that result from plugging these holes with ball-milled acrylic rods become reference markers in subsequent computed tomography (CT) scans. After optimum CT-coordinate locations have been planned for 125I seeds in catheters, they are transformed to mill coordinates using a matrix developed from the known marker coordinates in the two systems. Catheter holes are then drilled with the mold in the reassembled casting and box. The method has been used to treat both recurrent maxillary cancer and recurrent orbital rhabdomyosarcoma.

Osseointegrated implants and functional prosthetic rehabilitation in microvascular fibula free flap reconstructed mandibles.

The mandibulectomy deformity can be alleviated by immediate mandibular reconstruction using the microvascular fibula free flap. Before the advent of microvascular reconstruction, conventional and maxillofacial prosthetic rehabilitation offered limited success after surgery due to the failure to reestablish the bony foundation and soft tissues (tongue, floor of mouth, vestibule) anatomically and physiologically. With proper multidisciplinary pretreatment planning and postoperative treatment, osseointegrated implants can be strategically placed in patients with these reconstructed mandibles to restore occlusal and masticatory function. The records of seven patients who underwent reconstructive surgery and osseointegrated implants were reviewed, with an emphasis on the variety of prosthetic designs and principles used to maximize long-term efficiency and preservation of tissues.

Sequelae and complications related to dental extractions in patients with hematologic malignancies and the impact on medical outcome.

OBJECTIVE: The purpose of this retrospective study was to evaluate sequelae and complications after dental extractions and to analyze their impact on medical treatment in patients with myelodysplastic syndrome, acute and chronic leukemia, and multiple myeloma during a 3-year period. STUDY DESIGN: The study population included 388 patients with hematologic malignancies. All medical and dental charts were reviewed in a retrospective fashion to identify patients who received dental extractions. Preexisting dental disease and intervention (extraction) were evaluated, and parameters such as days of hospitalization and survival rate were compared with those of the remainder population who did not receive dental extractions. RESULTS: Of the 388 patients, 69 underwent dental extractions and 9 had sequelae and complications after the intervention. The resulting complication rate of 13% was reported. Although some patients did experience delay of chemotherapy or bone marrow transplant (BMT), or both, no significant difference was found in the number of days in the hospital for BMT and the survival rate for the patients with sequelae and complications (n = 9) and for the remainder population (n = 319) ( >.05). CONCLUSION: Dental extraction intervention provided in the prechemotherapy and pre-BMT time frame did not have a negative bearing on medical outcome.

Clinical manifestations of head and neck irradiation.

Treatment of squamous cell carcinoma of the oral cavity, salivary gland tumors, and Hodgkin's disease may include radiation therapy to the head and neck region. This therapy has treatment-related sequelae to the oral cavity and can contribute to increased rates of dental caries in these patients. To prevent radiation-induced caries, patients are instructed to use a high-potency fluoride application in addition to their standard dentifrice during radiation therapy and the postradiation phases of their treatment. Traditionally, patients are prescribed a 5,000-ppm fluoride (F) gel that is applied using mouthguards. However, due to oral postoperative conditions, many patients are not complaint with this treatment. In many cases, the availability of a fluoride product that is easier to use could result in successful patient compliance.

Aesthetic improvement of the forehead utilizing methylmethacrylate onlay implants.

Forehead augmentation occasionally is necessary for obtaining a desirable upper facial contour. The final contour must be sexually appropriate and must project beyond the cornea of the eyes an amount that makes the contour aesthetically pleasing. Methylmethacrylate onlay implants, preformed or sculpted at the time of surgery, lend themselves to obtaining a desirable contour which can be modified easily at surgery, which is completed in a one-stage procedure, has few complications, and yields an aesthetically pleasing result. The methods for fabricating and implanting the onlay prosthesis in a single step and the results of such procedures, which have been performed over a 12-year period without complications, are presented.

Osseointegrated implants in microvascular fibula free flap reconstructed mandibles.

In the past, prosthodontic rehabilitation of patients who underwent segmental mandibular resection relied on removable prostheses, which were less than ideal. The advent of the microvascular free flap has provided improved appearance and function through reconstruction of the skeletal integrity of the mandible. In select patients osseointegrated implants strategically placed in the reconstructed mandible can be used to restore masticatory function. Patient selection criteria and techniques are discussed.

Quality of life of maxillectomy patients using an obturator prosthesis.

BACKGROUND: The psychosocial adaptation of patients who had undergone a resection of the maxilla for cancer of the maxillary antrum and/or hard palate with the placement of an obturator prosthesis to restore speech and eating function was studied. METHODS: Forty-seven patients were interviewed who had a maxillectomy with an obturator prosthesis at Memorial Sloan-Kettering Cancer Center, an average of 5.2 years (SD = 2.4 years) ago, 94% of whom had some of their soft palate resected. Interviews were conducted by telephone by a trained research interviewer, using a series of questionnaires to assess their satisfaction with the functioning of their obturator, and the psychological, vocational, family, social, and sexual adjustment. Measures included the Obturator Functioning Scale (OFS). Psychosocial Adjustment to Illness Scale (PAIS), Mental Health Inventory (MHI), Impact of Event Scale, and Family Functioning Scale. RESULTS: Using multiple regression and discriminant function analyses, satisfactory functioning of the obturator prosthesis, as measured by the OFS, was found to be (1) the most highly significant predictor of adjustment, as measured by the PAIS (p < .0001) and the MHI Global Psychological Distress Subscale (MHI-GPD) (p < .001), and (2) significantly related to their perception of the negative socioeconomic impact of cancer upon their lives. The most significant predictor of better obturator functioning were the extent of resection of their soft palate (one third or less, p < .001), and hard palate (one fourth or less, p < .01). Specific aspects of obturator functioning that most significantly correlated with better adjustment (PAIS, MHI-GPD) were: less difficulty in pronouncing words (r = .40 and r = .51, respectively, p < .01), chewing and swallowing food (r = .27-.46, p < .05), and less change in their voice quality after surgery (r = .52 and r = .56, respectively, p < .001). CONCLUSIONS: These findings suggest that a well-functioning obturator significantly contributes to improving the quality of life of maxillectomy patients.