The irradiated human mandible: A quantitative study on bone vascularity.

OBJECTIVES: Hypovascularisation is thought to play an important role in the pathogenesis of osteoradionecrosis. The objective of this study was to assess the microvascular system in the irradiated mandibular bone marrow. MATERIALS AND METHODS: Mandibular bone biopsies were taken from 20 irradiated patients and 24 controls. Blood vessels were visualized using CD34 antibody stain to detect endothelial cells. The vascular density (VD) and vascular area fraction (VAF) were measured. Mean vessel lumen area, perimeter and diameter of the vessels were calculated for each vessel. A distinction was made between large and small vessels (cut-off point <400 µm2). RESULTS: Vascular density and vascular area fraction were lower in the irradiated group. The mean vascular perimeter and mean vascular diameter were higher in samples with a local radiation dose of ≥50 Gy, whereas the percentage of small vessels was lower. Larger vessel perimeter is associated with higher radiation dose. A longer interval between biopsy and radiotherapy is associated with a larger mean vessel perimeter and a lower percentage of small vessels. CONCLUSIONS: Radiation dosages higher than 50 Gy mainly affect the smaller vessels. With increased time after irradiation, the share of smaller vessels in the mandibular bone marrow seems to decrease. In search of the exact mechanisms of irradiation damage and osteoradionecrosis of the mandible, the role of the microvascular system in the mandibular bone marrow should be further explored.

Salvage surgery in post-chemoradiation laryngeal and hypopharyngeal carcinoma: outcome and review.

Our objective was to evaluate recurrence patterns of hypopharyngeal and laryngeal carcinoma after chemoradiation and options for salvage surgery, with special emphasis on elderly patients. In a retrospective study all patients who underwent chemoradiation for hypopharyngeal and laryngeal carcinoma in a tertiary care academic center from 1990 through 2010 were evaluated. Primary outcome measures were the survival and complication rates of patients undergoing salvage surgery, especially in elderly patients. Secondary outcome measures were the predictors for salvage surgery for patients with locoregional recurrence after failed chemoradiotherapy. A review of the literature was performed. Of the 136 included patients, 60 patients had recurrent locoregional disease, of whom 22 underwent salvage surgery. Fifteen patients underwent a total laryngectomy with neck dissection(s) and 7 neck dissection without primary tumour surgery. Independent predictors for salvage surgery within the group of 60 patients with recurrent disease, were age under the median of 59 years (p = 0.036) and larynx vs. hypopharynx (p = 0.002) in multivariate analyses. The complication rate was 68% (14% major and 54% minor), with fistulas in 23% of the patients. Significantly more wound related complications occurred in patients with current excessive alcohol use (p = 0.04). Five-year disease free control rate of 35%, overall survival rate of 27% and disease specific survival rate of 35% were found. For the 38 patients who were not suitable for salvage surgery, median survival was 12 months. Patients in whom the tumour was controlled had a 5-year overall survival of 70%. In patients selected for salvage surgery age was not predictive for complications and survival. In conclusion, at two years follow-up after chemoradiation 40% of the patients were diagnosed with recurrent locoregional disease. One third underwent salvage surgery with 35% 5-year disease specific survival and 14% major complications. Older patients selected for salvage surgery had a similar complication rate and survival as younger patients.

Critical weight loss is a major prognostic indicator for disease-specific survival in patients with head and neck cancer receiving radiotherapy.

BACKGROUND: Pre-treatment weight loss (WL) is a prognostic indicator for overall survival (OS) in head and neck cancer (HNC) patients. This study investigates the association between WL before or during radiotherapy and disease-specific survival (DSS) in HNC patients. METHODS: In 1340 newly diagnosed HNC patients, weight change was collected before and during (adjuvant) radiotherapy with curative intent. Critical WL during radiotherapy was defined as >5% WL during radiotherapy or >7.5% WL until week 12. Differences in 5-year OS and DSS between WL groups were analysed by Cox's regression with adjustments for important socio-demographic and tumour-related confounders. RESULTS: Before radiotherapy, 70% of patients had no WL, 16% had ≤5% WL, 9% had >5-10% WL, and 5% had >10% WL. Five-year OS and DSS rates for these groups were 71%, 59%, 47%, and 42% (P<0.001), and 86%, 86%, 81%, and 71%, respectively (P<0.001). After adjustment for potential confounders, >10% WL before radiotherapy remained significantly associated with a worse OS (HR 1.7; 95% CI 1.2-2.5; P=0.002) and DSS (HR 2.1; 95% CI 1.2-3.5; P=0.007).The 5-year OS and DSS rates for patients with critical WL during radiotherapy were 62% and 82%, compared with 70% and 89% for patients without critical WL (P=0.01; P=0.001). After adjustment, critical WL during radiotherapy remained significantly associated with a worse DSS (HR 1.7; 95% CI 1.2-2.4; P=0.004). CONCLUSION: Weight loss both before and during radiotherapy are important prognostic indicators for 5-year DSS in HNC patients. Randomised studies into the prognostic effect of nutritional intervention are needed.

[Osteoradionecrosis of the jaw, presumably caused by a removable partial denture]. / Osteoradionecrose van de mandibula, vermoedelijk veroorzaakt door een frameprothese.

An 81-years-old man developed a severe osteoradionecrosis of the mandible following surgery and radiotherapy in the head and neck area as a result of a carcinoma at the front ofthe floor of the mouth. Presumably, the osteoradionecrosis had been developed by an injury of the oral mucosa due to a removable partial denture. There are no uniform guidelines for the treatment of osteoradionecrosis of the jaw bones. Treatment modalities vary from removal of sequesters, sometimes long-term use of antibiotics, treatment with hyperbaric oxygen and wide surgical resection with or without reconstruction of the jaw.

Subset of patients with verrucous carcinoma of the oral cavity who benefit from treatment with methotrexate.

Oral verrucous carcinoma (OVC) is a low-grade variant of squamous cell carcinoma (SCC) with a distinctive morphology and specific pattern of behaviour that is often diagnosed in elderly patients. Resection is the treatment of choice, with radiotherapy as a reasonable alternative. In this retrospective case review we present our experience and outcomes in a group of 12 patients with various stages of OVC who had not been treated conventionally because of the extent of their lesions and their poor general condition. All patients were given chemotherapy with methotrexate, which was given by various routes and in different doses during the period 1972-2010. In 11 patients treatment with methotrexate alone was beneficial. One patient failed to respond. Methotrexate used alone as chemotherapy may minimise morbidity and improve quality of life, particularly among elderly patients.

Salvage laryngectomy: oncological and functional outcome.

The purpose of the research was to evaluate postoperative complications, functional outcome and survival after salvage laryngectomy. Second, to evaluate the management of the neck in combination with a laryngectomy in this group of patients. A retrospective analysis of all patients who underwent total laryngectomy for residual or recurrent squamous cell laryngeal carcinoma after (chemo)radiotherapy between November 1990 and June 2007 was performed. Of the 120 patients that were included, the complication rate was 56% (33% major and 23% minor). In univariate analyses, T-stage (p=0.05), bilateral neck dissection (p=0.09) and ASA score (p=0.08) showed a trend for postoperative major complications. Lymph node metastases were found in 26% of the neck dissection specimens, with a trend towards more regional disease at higher initial N-stage (p=0.06) and T-stage (p=0.08). Five-year disease specific survival was 58%. In univariate analyses pre-operative chemoradiation (vs. radiation) (p=0.0001), N3 neck (p=0.001) and positive surgical margins (p=0.02) were significant predictors for a worse disease specific survival, but only positive surgical margins (p<0.001) maintained significance in multivariate analysis. Eighty-seven percent of the patients were able to produce speech using a voice prosthesis, and 84% of the patients were able to have a 'normal' or 'soft' diet. There was an almost significant increase in mean body mass index (BMI) 6-12 months postoperative (p=0.057). Laryngectomy after radiotherapy offers good survival, with a substantial risk of complications and good functional outcome.