Zygomatic bone metastasis from hepatocellular carcinoma and the therapeutic efficacy of apatinib: A case report and literature review.

RATIONALE: Hepatocellular carcinoma (HCC) metastases to the zygomatic bone are extremely uncommon, and the treatment of target drugs against such case is unknown. PATIENT CONCERNS: A 48-year-old male patient was admitted to our hospital under suspicion of an advanced liver tumor due to an increase in levels of alpha-fetoprotein (AFP) after radiofrequency ablation for independent nodule in his liver 1 month before. He had a hepatitis B virus (HBV) history for 20 years without treatment. DIAGNOSIS AND INTERVENTIONS: A diagnosis of primary HCC was made based on pathological examination following right hepatectomy. Seven months after the surgery, a mass in S8 was identified and treated by ARF. Twenty days later, a right zygomatic mass was observed and the incisional biopsy revealed metastasis from HCC. Due to side effects of chemotherapy, the metastatic zygomatic mass was treated with radioactive seed implantation. Despite these interventions, there was steady increase in AFP values as well as increase in size of the zygomatic mass. Hence, the patient was started on apatinib with a dose of 500 mg/day from 1 to 28 days per cycle for a duration of 10 months. OUTCOMES: The AFP values were significantly decreased but the size of the zygomatic mass continued to increase indicating progression of disease. But the progression-free survival was more than 10 months. The patient exhibited adverse reactions which were controllable by symptomatic treatments. As of last follow-up, the patient is unwell with pain in the face, blurred vision in the right eye, dyscrasia, and exhibited difficulty in opening his mouth. LESSONS: HCC metastases to the zygomatic bone are very aggressive with a very low incidence and immunohistochemistry is useful diagnostic indicators. Still now, there is no optimal treatment strategy for these patients. Apatinib may be a promising drug in the treatment of HCC metastases to the zygomatic bone.

Osteoradionecrosis of the Zygoma.

Osteoradionecrosis occurs in 4.74% to 37.5% of patients following radiation therapy for head and neck cancer. Osteoradionecrosis mostly happens in the mandible but seldom occurs in other maxillofacial bones. Here, the authors reported a rare case of zygomatic osteoradionecrosis which occurred after maxillectomy and then radiotherapy because of maxillary myoepithelial carcinoma. After resection of zygoma sequestrum, the defect was repaired with forehead flap and healed uneventfully.

Radiation-induced craniofacial bone growth inhibition: acute and long-term effects on bone histopathology with and without cytoprotection.

BACKGROUND: The authors previously established an animal model of radiation-induced craniofacial bone growth inhibition and demonstrated the effectiveness of cytoprotection in preserving growth using amifostine, but the mechanism is unclear. The objective of this study was to investigate the acute and long-term histopathologic effects of single-dose orthovoltage irradiation on craniofacial bone with and without cytoprotection. METHODS: Sixty infant New Zealand White rabbits (7-week-old) were randomized into three groups (n = 20 per group): group 1, 0-Gy, sham irradiation; group 2, 35-Gy single-dose orthovoltage irradiation; and group 3, cytoprotection with amifostine before irradiation. Orbitozygomatic complex bone was harvested from animals 12 hours after irradiation and at skeletal maturity (21 weeks of age). Histologic parameters measured included native bone cell (osteoblast, osteoclast, and osteocyte) populations, periosteal proliferation indices (MIB-1 stains), bone turnover rates [triple fluorochromes: tetracycline administered at 7 weeks of age (before irradiation), alizarin complexone at 12 weeks, and calcein at 16 weeks of age], and endosteal space fibrosis levels. RESULTS: Orthovoltage irradiation significantly (p < 0.05) reduced osteoblast and osteoclast counts 12 hours after irradiation (age, 7 weeks) with or without pretreatment with amifostine but had no effect on osteocyte populations. Long-term analysis at age 21 weeks demonstrated significantly (p < 0.05) increased osteoblast counts, reduced endosteal space fibrosis, reduced periosteal proliferation indices, and improved bone turnover (fluorochrome stains) in amifostine-treated animals. CONCLUSION: This study suggests that amifostine cytoprotection is mediated through a combination of reduced cellular injury with enhanced promotion of cellular bone rebuilding potential.

Distraction osteogenesis of radiation-induced orbitozygomatic hypoplasia.

In the last decade, the application of distraction osteogenesis to the craniofacial skeleton has grown to include not only deformities of the mandible, but of the midface, palate, dentoalveolar region, and calvarium. A major advantage of distraction osteogenesis lies in the simultaneous soft tissue histogenesis that accompanies the bony distraction process, allowing for potentially lower relapse rates and improved cosmesis. Although this may seem appropriately suited to irradiation-induced deformities of both hard and soft tissues, there is little in the literature as to the efficacy of this technique in patients who have received radiotherapy. To introduce an effective application of this technology, and highlight some advantages and disadvantages of its application in the irradiated craniofacial skeleton, we present a case of distraction osteogenesis of the orbitozygomatic complex in a patient with radiation induced orbitozygomatic hypoplasia.

Radiation-induced craniofacial bone growth inhibition: in vitro cytoprotection in the rabbit orbitozygomatic complex periosteum-derived cell culture.

BACKGROUND: Radiotherapy for the management of head and neck cancer in pediatric patients results in severe inhibition of craniofacial bone growth. Previously, the infant rabbit orbitozygomatic complex was established as an experimental model. Amifostine, a cytoprotective agent, was found effective in preventing radiation-induced bone growth inhibition. This study was designed to investigate the effects radiation on osteogenic cells from infant rabbit orbitozygomatic complex periostea and to assess the effects of cytoprotection in vitro. METHODS: Infant New Zealand White rabbits (n = 18) were randomized into three groups and received radiation (0, 10, or 15 Gy) to both orbitozygomatic complexes. Cell cultures were developed from orbitozygomatic complex periostea, and cell numbers, proliferation, alkaline phosphatase, and collagen type I expression and mineralization were assessed. Subsequently, rabbits (n = 18) were randomized into three groups to receive either radiation at the effective dose, pretreatment with amifostine (300 mg/kg, intravenously, 20 minutes before irradiation) with the effective radiation dose, or no treatment. Cell cultures were developed and tested for proliferation and alkaline phosphatase expression. RESULTS: Irradiation resulted in a significant inhibition of cell numbers (p < 0.001) and proliferation (p < 0.01) at the 15-Gy dose and no statistically significant changes in alkaline phosphatase activity. Collagen type I expression and mineralization were also significantly reduced at the 15-Gy dose. Pretreatment with amifostine significantly (p < 0.05) enhanced the number of surviving cells. CONCLUSIONS: Amifostine is capable of protecting orbitozygomatic complex periosteum-derived osteogenic cells from the deleterious effects of radiation. This study provides the basis for understanding the cellular mechanisms of radiation-induced craniofacial bone growth inhibition and cytoprotection by amifostine.

An in vitro model of radiation-induced craniofacial bone growth inhibition.

Radiation-induced craniofacial bone growth inhibition is a consequence of therapeutic radiation in the survivors of pediatric head and neck cancer. Previously, the infant rabbit orbitozygomatic complex (OZC) was established as a reliable animal model. The purpose of this study was to develop a cell culture model from the rabbit OZC to study the effects of radiation in the craniofacial skeleton. Infant (7-week-old) New Zealand white rabbits were used in this study. Periostea from both OZC were harvested in sterile conditions, introduced into cell culture by way of sequential digestion, and subcultured at confluence. Cultures were analyzed for cellular proliferation (methylthiazoletetrazolium assay), alkaline phosphatase activity, collagen type I expression, and mineralization. Electron microscopy was performed to reveal the in vitro ultrastructure. Subsequently, rabbits were irradiated with sham or 15 Gy radiation, and cell cultures were developed and analyzed for cell numbers. Cell cultures, grown from OZC periostea, expressed osteoblast-like phenotype, with high alkaline phosphatase activity, collagen type 1 expression, and mineralization in an osteogenic environment. Electron microscopy confirmed the characteristic ultrastructural features of osteogenesis in vitro. Finally, significantly (P < 0.01) fewer cells were obtained from animals treated with 15 Gy radiation compared with those from control animals.A primary cell culture with osteoblast-like cellular phenotype was developed from infant rabbit OZC periosteum. This cell culture system responded to in vivo administered radiation by a significant decrease in cell numbers. This in vitro model will be subsequently used to study the cellular mechanisms of radiation and radioprotection in craniofacial osteoblast-like cells.

Ruptured pseudoaneurysm of the internal maxillary artery complicating CT-guided fine-needle aspiration in an irradiated, surgical bed.

BACKGROUND: CT-guided fine-needle aspiration (FNA) is a safe procedure, but major complications can occur rarely. Pseudoaneurysm rupture in the head and neck region following CT-guided FNA is an emergency that can result in life-threatening hemorrhage. This case emphasizes the salient risk factors for pseudoaneurysm formation and rupture in the head and neck region following CT-guided FNA. METHODS: A patient was seen with oral and facial hemorrhage as a result of a ruptured pseudoaneurysm 11 weeks following CT-guided FNA in a previously irradiated surgical bed. RESULTS: The patient was treated with coil embolization in and around the pseudoaneurysm and discharged without any further complications. CONCLUSIONS: Although CT-guided FNA is a safe and effective procedure, some patients may be at increased risk for rare but major complications. Caution should be used in proceeding with CT-guided FNA in an irradiated surgical bed of the head and neck.

Radiation-induced craniofacial bone growth inhibition: efficacy of cytoprotection following a fractionated dose regimen.

BACKGROUND: Severe craniofacial growth disturbances are noted in 66 to 100 percent of children with head and neck cancers who received radiotherapy during their growing years. The authors have previously demonstrated the prevention of radiation-induced craniofacial bone growth inhibition following single-dose orthovoltage radiation to the orbitozygomatic complex in an infant rabbit model through the administration of the cytoprotective agent amifostine (WR-2721) before radiation treatment. The purpose of this study was to investigate the efficacy of cytoprotection using a fractionated dose regimen that better approximates the clinical application of radiation therapy. METHODS: Thirty 7-week-old male New Zealand rabbits were randomized into three groups (n = 10), each receiving six fractions of orthovoltage radiation to the right orbitozygomatic complex: group C, sham irradiation control; group F35, total dose of 35 Gy; and group F35A, total dose of 35 Gy with administration of amifostine 200 mg/kg intravenously 20 minutes before each fraction. Bone growth was evaluated up to skeletal maturity (age 21 weeks) with serial radiographs and computed tomography scans for cephalometric analysis, bone volume, and bone density measurements. RESULTS: Fractionated radiation resulted in significant (p < 0.05) bone growth inhibition compared with sham radiation in 16 of 21 cephalometric parameters measured and significantly (p < 0.05) reduced bone volume of the rabbit orbitozygomatic complex. Pretreatment with amifostine before each radiation fraction prevented growth deformities in four cephalometric parameters and significantly (p < 0.05) attenuated these effects in another seven parameters compared with radiated animals. Bone volumes were also significantly (p < 0.05) improved in F35A animals compared with F35 animals. CONCLUSIONS: This study establishes that fractionation of orthovoltage radiation does not prevent the development of growth disturbances of the rabbit craniofacial skeleton and also demonstrates that preirradiation administration of amifostine is highly effective in the prevention and attenuation of radiation-induced craniofacial bone growth inhibition.

Efficacy of radioprotection in the prevention of radiation-induced craniofacial bone growth inhibition.

It has been reported that radiotherapy-induced craniofacial deformities can occur in 66 to 100 percent of survivors of childhood head and neck cancers. Recent interest in the effectiveness of radioprotectors in the protection of normal tissue against radiation injury led us to investigate a possible role of radioprotection in the prevention of radiation-induced craniofacial bone growth inhibition. Therefore, the objective of this study was to use the radioprotective agent amifostine (Ethyol, WR-2721) as a probe to determine the effectiveness of radioprotection in the prevention of radiation-induced craniofacial bone growth inhibition after single-dose orthovoltage radiation to the infant rabbit orbital-zygomatic complex. Seven-week-old male New Zealand white rabbits were randomized into three groups (n = 10 each): group 1, 0 Gy (sham radiation); group 2, 35-Gy single-dose orthovoltage radiation; and group 3, 35-Gy single-dose orthovoltage radiation and amifostine (300 mg/kg intravenously, given 20 minutes before radiation). Serial radiographs and computed tomographic scans were obtained for cephalometric analysis, bone volume, and bone density measurements until skeletal maturity at 21 weeks. Significant (p < 0.05) reductions in orbital-zygomatic complex linear bone growth, bone volume, and bone density were observed after 35-Gy radiation compared with nonirradiated controls. No significant differences were noted between groups in cephalometric analysis of the nontreated (nonirradiated) left orbital-zygomatic complex, indicating no crossover effect from the radiation beam. However, pretreatment with amifostine, 20 minutes before 35-Gy radiation, resulted in significant (p < 0.05) preservation of linear bone growth, bone volume, and bone mineral density in the rabbit orbital-zygomatic complex compared with controls. This study demonstrated for the first time the effectiveness of a radioprotector in the prevention of radiation-induced craniofacial bone growth inhibition, and it paves the way for investigation into the pathogenic mechanism and prevention of radiotherapy-induced craniofacial deformities.

Radiation-induced craniofacial bone growth inhibition: development of an animal model.

Craniofacial deformities caused by therapeutic radiation-induced bone growth inhibition can occur in up to 100% of survivors of childhood head and neck cancers. The mechanism of radiation-induced craniofacial bone growth inhibition is poorly understood. The objective of this study is to establish a model of radiation-induced craniofacial bone growth inhibition to study the pathophysiology of radiation on growing membranous bone. Seven-week-old male New Zealand white rabbits were randomized into 4 groups (n = 10/group) and received a single dose of orthovoltage radiation (0, 15, 25, or 35 Gy) to the right orbital-zygomatic complex. Serial radiographs and computed tomography scans were performed for cephalometric analysis, bone volume, and bone density measurements until skeletal maturity at 21 weeks. Statistically significant ( P < 0.05) reductions in orbital-zygomatic complex linear bone growth, bone volume, and bone density were found after radiation with 25 or 35 Gy compared with nonirradiated control animals. A significant ( P < 0.05) decrease in orbital-zygomatic complex volume was noted after 15-Gy radiation but there were no significant effects on linear bone growth as assessed by cephalometric analysis at this dose. This study establishes the rabbit orbital-zygomatic complex as a suitable model for the study of radiation-induced craniofacial bone growth inhibition and will permit investigation into the underlying cellular and molecular basis of this injury.

Correction of the contracted eye socket and orbitozygomatic hypoplasia using postauricular skin flap and temporal fascial flap.

The authors corrected a contracted eye socket and orbitozygomatic hypoplasia simultaneously, secondary to previous surgery and radiotherapy. A one-stage surgical reconstruction was undertaken using both a postauricular skin flap and a temporal fascial flap, which were rotated for eye socket reconstruction and bone graft coverage. Hydroxyapatite was inserted as an onlay bone graft substitute to enlarge the orbitozygomatic region. The authors' experience with 12 patients resulted in contours that were satisfying and encouraging. f1

Osteomyelitis occurring in the zygomatic bone.

Osteomyelitis of bones in the middle third of the face is rare, especially in westernized populations. The actiology is usually due to odontogenic sources or infected fracture sites. An unusual case of osteomyelitis of the zygomatic bone resulting from the use of radiotherapy in the management of recurrent basal cell carcinoma is presented. This illustrates a late complication of therapy for a cancer which commonly occurs in the head and neck region and is rapidly increasing in incidence in the UK.