R. Koole

An expression profile for diagnosis of lymph node metastases from primary head and neck squamous cell carcinomas

Metastasis is the process by which cancers spread to distinct sites in the body. It is the principal cause of death in individuals suffering from cancer. For some types of cancer, early detection of metastasis at lymph nodes close to the site of the primary tumor is pivotal for appropriate treatment. Because it can be difficult to detect lymph node metastases reliably, many individuals currently receive inappropriate treatment. We show here that DNA microarray gene-expression profiling can detect lymph node metastases for primary head and neck squamous cell carcinomas that arise in the oral cavity and oropharynx. The predictor, established with an 82-tumor training set, outperforms current clinical diagnosis when independently validated. The 102 predictor genes offer unique insights into the processes underlying metastasis. The results show that the metastatic state can be deciphered from the primary tumor gene-expression pattern and that treatment can be substantially improved.

Treatment of central giant cell granuloma of the jaw with calcitonin

Giant cell granuloma of the jaw is a benign lesion that may cause local destruction of bone and displacement of teeth. The common therapy is curettage or resection, which may be associated with loss of teeth and, in younger patients, loss of dental germs. An alternative treatment has recently been introduced, in which patients receive a daily dose of calcitonin. Four patients who have been treated with calcitonin in various concentrations for at least 1 year are reported. In all patients, complete remission of the giant cell granuloma was observed, without signs of recurrence. The working mechanism of calcitonin is discussed, as are length of treatment and optimal dose.

Treatment failure and margin status in head and neck cancer. A critical view on the potential value of molecular pathology

Molecular pathology may demonstrate tumour cells not detected by histology. The idea has emerged that these cells influence the prognosis negatively and that their detection will lead to more appropriate treatment and improved patient survival. We theorized that tumour cells at surgical margins overlooked by the pathologist should demonstrate their clinical significance by causing recurrences at the primary site in the patients reported to have tumour-free margins by histology. To assess this assumption, we investigated the prognostic influence of the histologically determined status of the surgical margins. The material that formed the basis of this study consisted of 394 patients that underwent resection for their primary tumour during the years 1990-1995. In 207 patients, initial treatment was complete as assessed by conventional histopathological examination of the surgical specimen. In 187 patients, initial treatment was incomplete, defined as tumour in or close to the margin, or mild, moderate or severe dysplasia or in situ cancer at the margin. Causes for treatment failure were recorded for both groups separately. In the group with tumour-free margins, 16.9% had a second primary head and neck cancer, 8.2% had a second tumour in the lung, 10.6% had recurrent disease in the neck, 2.9% had distant metastasis, and 3.9% had local recurrence at the same site as the primary cancer. For the group without tumour-free margins, these figures were the following: second primary in the head and neck area: 17.1%, second primary in the lung: 7.0%, recurrent disease in the neck: 11.8%, distant metastasis: 8.0% and local recurrence at the primary site: 21.9%. Local recurrences were rare in patients in which the pathologist reported the resection to be complete. Although there may be tumour cells in surgical margins that evade histological detection, their clinical impact appears to be almost negligible.

Osteosarcoma of the jaw bones. Long-term follow-up of 48 cases

To evaluate the incidence and treatment results of osteosarcoma of the jaw (OSJ) in the Netherlands, data from 48 patients with a histologically proven diagnosis of osteogenic sarcoma of the maxilla or mandible were retrospectively analysed. Patient files, covering the period from 1964 to 1992, were obtained from all university hospitals in the Netherlands and the Netherlands Cancer Institute. The incidence of OSJ in the Netherlands is estimated to be at least 0.14 per 1,000,000. The overall 10-year survival was 59%. Distant metastasis occurred in 21% and local recurrences in 31% of the cases. Survival was significantly better in case of radical surgery and small tumours. Long-term survival after treatment of OSJ was good if complete surgical excision was achieved. Radiotherapy should only be considered to prevent local recurrence if surgery is not complete. The possible benefit of current chemotherapy in preventing metastatic disease is still questionable. Since other malignant neoplasms associated with OSJ occurred in 17% of the cases, lifelong follow up is mandatory for the detection of these second primary malignancies.

Reconstruction of the alveolar cleft: can growth factor-aided tissue engineering replace autologous bone grafting? A literature review and systematic review of results obtained with bone morphogenetic protein-2

The alveolar cleft in patients with clefts of lip, alveolus and palate (CLAP) is usually reconstructed with an autologous bone graft. Harvesting of autologous bone grafts is associated with more or less donor site morbidity. Donor site morbidity could be eliminated if bone is fabricated by growth factor-aided tissue engineering. The objective of this review was to provide an oversight on the current state of the art in growth factor-aided tissue engineering with regard to reconstruction of the alveolar cleft in CLAP. Medline, Embase and Central databases were searched for articles on bone morphogenetic protein 2 (BMP-2), bone morphogenetic protein 7, transforming growth factor beta, platelet-derived growth factor, insulin-like growth factor, fibroblast growth factor, vascular endothelial growth factor and platelet-rich plasma for the reconstruction of the alveolar cleft in CLAP. Two-hundred ninety-one unique search results were found. Three articles met our selection criteria. These three selected articles compared BMP-2-aided bone tissue engineering with iliac crest bone grafting by clinical and radiographic examinations. Bone quantity appeared comparable between the two methods in patients treated during the stage of mixed dentition, whereas bone quantity appeared superior in the BMP-2 group in skeletally mature patients. Favourable results with BMP-2-aided bone tissue engineering have been reported for the reconstruction of the alveolar cleft in CLAP. More studies are necessary to assess the quality of bone. Advantages are shortening of the operation time, absence of donor site morbidity, shorter hospital stay and reduction of overall cost.

Assessment of mandibular invasion of squamous cell carcinoma by various modes of imaging: constructing a diagnostic algorithm

The aim of this study was to determine the optimal combination of preoperative examination methods to predict mandibular invasion by squamous cell carcinoma of the oral cavity. Data were gathered prospectively but evaluated retrospectively. The preoperative results of clinical examination, conventional radiography, bone single photon emission computed tomography (SPECT), computed tomography and magnetic resonance imaging were compared to the histological results of resection specimens from 67 patients with tumours, adjacent or fixed to the mandible, histologically confirmed as squamous cell carcinoma. The examination methods with acceptable sensitivity and specificity were selected and diagnostic algorithms were constructed using all possible combinations. The preferred diagnostic algorithm was found to be either computed tomography or magnetic resonance imaging, followed by a bone SPECT in cases where the first scan is negative. A negative bone SPECT rules out mandibular invasion (100% sensitivity). This algorithm accurately predicted mandibular invasion in 85% of the patients, without yielding false negative results. In this study group, application of such an algorithm would have resulted in a reduction of the number of unnecessary mandibular resections by 50%. The suggested, preferred, diagnostic algorithm shortens the preoperative screening process, avoiding unnecessary costs, as well as considerably reducing the number of unnecessary mandibular resections.

Leiomyosarcomas of the oral cavity. Report of four cases and review of the literature

Leiomyosarcomas (LMS) make up 7% of all soft tissue sarcomas. In the oral cavity, the LMS is rare due to the paucity of smooth muscle in that region. Four cases of intraoral LMS are reported, plus 34 cases found in the literature reviewed. There were 24 males and 14 females. The age range at presentation was 10 months to 88 years with no predilection for any particular age group. The commonest presenting symptom was a mass. The intraoral LMS occurred most commonly in the jaws (59% of cases). The mass was painful in 61% of cases. Follow-up of the case reports was assessed. Recurrence occurred in 36% of cases. Distant metastases occurred in 39% of cases, most commonly to the lungs. Cervical nodal metastasis was reported in 15% of cases. The 5-year survival rate determined on cases with adequate follow-up (n = 13) was 23% free of disease, 8% alive with disease and 69% who died of disease. In comparison with stage I and stage II tongue squamous cell carcinomas, the intraoral LMS is very aggressive. It is best treated surgically, early and aggressively.

Osteochondroma of the mandibular condyle: A case report

Osteochondroma of the mandibular condyle is extremely rare and may cause signs and symptoms like those seen in patients with temporomandibular joint dysfunction. Differentiation between osteochondroma and condylar hyperplasia is not possible on histologic grounds alone, but the radiographic and intraoperative findings together are usually sufficient to establish a definite diagnosis.

Ectomesenchymal mandibular symphysis bone graft: an improvement in alveolar cleft grafting?

Bone grafting the alveolar cleft in cleft lip and palate (CLP) patients is widely accepted. A traditional graft is the iliac crest. Other bone graft donor sites are briefly discussed. The ratio for an ectomesenchymal bone graft in alveolar cleft repair is explained. Aspects of the embryology, bone graft physiology, and reports on mandibular symphysis bone grafting are discussed.

The transmandibular implant: A 13-year survey of its use

During the period from August 1976 until July 1989 the transmandibular implant was introduced in a total of 31 oral and maxillofacial surgery departments in the Netherlands and 1,466 patients were treated. This study includes 1,356 treated patients from 28 departments. The treatment course of 1,201 patients (89.6%) was uneventful. Of the 157 complications, 58 related to the anatomic contour of the mandible, 49 to the surgery, 25 to the prosthetic reconstruction, 8 to the psychosocial attitude of the patient, 8 to the use of medication, 5 to trauma, and 4 to the presence of a skin graft. Treatment of the complications included removal of the implant in 44 patients; in 106 patients the complication was treated satisfactorily. In the remaining 7 patients, hypesthesia was present. The reasons for the removal of the 44 implants were infection (11), operative error (5), premature loading of the implant (3), insufficient width of the mandible after a visor osteotomy (1), loss of osseointegration caused by the prosthesis (14), psychological problems (4), trauma (3), drug-related gingival hyperplasia (2), and inexplicable pain (1). The present survey shows a consistent success rate of 96.8%.