Ellen M. Van Cann

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.

Nonvascularized Bone Grafts for Segmental Reconstruction of the Mandible—A Reappraisal

PURPOSE To evaluate the success rate and complications of segmental mandibular reconstructions with autogenous nonvascularized iliac crest bone grafts, and to refine treatment strategies. PATIENTS AND METHODS Seventy-four patients with segmental mandibular defects were included. Malignant lesion, immediate reconstruction, smoking habit, radiotherapy, site of the defect, surgical approach, and method of graft fixation were analyzed as factors of influence on success. Success was defined as maintenance of bone continuity and stability, and absence of infection 1 year after reconstruction upon clinical and radiographic examination. Complications were divided into recipient and donor-site complications and classified as minor or major. The reconstruction was considered functionally complete if prosthetic rehabilitation was accomplished or if there was a sufficient remaining dentition for mastication. RESULTS In 56 (76%) patients, the initial reconstruction was successful. Multivariate analyses showed that symphyseal involvement (SI) and intraoral approach (IA) were significantly associated with failure (P(SI) = .022, P(IA) = .038) and major recipient-site complications (P(SI) = .022, P(IA) = .038). Thirty-two (43%) patients showed complications in the first postoperative year: 27 recipient-site complications and 6 donor-site complications. Nineteen (70%) recipient-site complications were classified as major. The reconstruction was functionally complete in 48 (86%) of the 56 patients with a successful initial reconstruction. CONCLUSIONS Nonvascularized iliac crest bone grafts for segmental reconstruction of the mandible is the method of choice on the condition that the defect is truly lateral and only an extraoral approach is used. In these cases, microvascular tissue transfer is not necessary.

Free Vascularized Flaps for Reconstruction of the Mandible: Complications, Success, and Dental Rehabilitation

PURPOSE To evaluate complications and success of mandibular reconstruction with free fibula flaps, iliac crest flaps, and forearm flaps with reconstruction plates and to evaluate dental rehabilitation after these reconstructions. PATIENTS AND METHODS Eighty-three patients with segmental mandibular defects were included. Correlation analyses were used to determine the relationship between reconstruction type and clinical parameters with recipient-site complications and success. The dental rehabilitation was evaluated in successfully reconstructed survivors. RESULTS Multivariate analyses showed significant correlations between flap type and success (P < .0001). Of the patients, 51 (61%) were alive 2 years after the reconstruction. Mandibular reconstruction with a free forearm flap and reconstruction plate was associated with higher complication rates at the recipient site and higher failure rates compared with reconstruction with free vascularized bone flaps. Of the 32 successfully reconstructed survivors, 14 (44%) had a complete dental rehabilitation, of which 10 had dental implants and 4 did not. Only 6 (29%) of the edentulous survivors ultimately had an implant-supported prosthesis. CONCLUSIONS Reconstruction of the mandible with a free vascularized bone flap is superior to reconstruction with a free forearm flap with a reconstruction plate. Complete dental rehabilitation was reached in fewer than half of the surviving patients.

Cannabinoid receptor-2 immunoreactivity is associated with survival in squamous cell carcinoma of the head and neck

The prediction of progression of individual tumours, prognosis, and survival in squamous cell carcinoma (SCC) of the head and neck is difficult. Cannabinoid-1 (CB1) and cannabinoid-2 (CB2) receptor expression is related to survival in several types of cancer, and the aim of this study was to find out whether the expression of CB1 and CB2 receptors is associated with survival in primary SCC of the head and neck. We made immunohistochemical analyses of the cannabinoid receptors on tissue arrays from 240 patients with the disease. Receptor immunoreactivity was classified as none, weak, moderate, or strong staining. Overall survival and disease-specific survival were plotted using Kaplan-Meier survival curves. A multivariate Cox proportional hazard model was created with all the relevant clinical and pathological features. Strong immunoreactivity of the CB2 receptor was significantly associated with reduced disease-specific survival (p=0.007). Cox-proportional hazard ratio (HR) showed that CB2 receptor immunoreactivity contributed to the prediction of survival (HR 3.6, 95% CI 1.5-8.7, p=0.004). Depth of invasion (HR 2.2, 95% CI 1.2-4.2, p=0.01) and vascular invasion (HR 2.5, 95% CI 1.4-4.5, p=0.001) were also associated with survival.

Retrobulbar hematoma associated with selective serotonin reuptake inhibitor: A case report

OBJECTIVE The aim was to raise awareness among surgeons performing orbital surgery of the risk of hemorrhage associated with selective serotonin reuptake inhibitors. STUDY DESIGN This is an observational case report. RESULTS An 80-year-old woman who used paroxetine developed a retrobulbar hematoma with impaired vision immediately after surgery for an orbital blowout fracture. CONCLUSION Surgeons should be aware of the increased risk of hemorrhage among patients on selective serotonin reuptake inhibitors who require orbital surgery.

Poor prognosis in human papillomavirus-positive oropharyngeal squamous cell carcinomas that overexpress hypoxia inducible factor-1α.

Hypoxia induces stabilization of the transcription factor HIF‐1alpha (HIF‐1α), associated with (chemo‐)radiotherapy resistance in oropharyngeal squamous cell carcinoma (SCC). We investigated the effect of HIF‐1α expression on survival in relation to human papillomavirus (HPV) status in oropharyngeal SCC.

Intraoral ultrasonography to measure tumor thickness of oral cancer : A systematic review and meta-analysis

Early oral cancer is preferably treated by surgery. Its complete removal is essential for locoregional control and disease-free survival. Inadequate resection margins require adjuvant therapy such as re-resection or (chemo)radiation, that causes extra morbidity and oral discomfort. Intraoral ultrasonography (US) is reported to be of value in determining tumor thickness. Intraoperative visualization of the tumor may facilitate the resection and ensure adequate surgical margins. Furthermore, accurate prediction of tumor thickness could help determine the treatment strategy of the clinically node-negative neck, as thickness and depth of invasion are predictors of cervical metastasis as well as prognosticators of survival. The 8th edition of the American Joint Committee on Cancer staging system for oral squamous cell carcinoma has included depth of invasion as parameter for cT-stage. The aim of this review is to analyze the accuracy of intraoral US in determining tumor thickness in oral cancer. A systematic search was conducted, and the quality of the included papers was assessed using the QUADAS-2 tool for diagnostic accuracy studies. Subsequently, a meta-analysis was performed on the available individual participant data of 240 patients. Most of the twelve included studies focused on T1-2 tongue cancer (n = 129). Meta-analysis showed a high correlation in tumor thickness within this subgroup as measured by intraoral US and histopathology (r = 0.82, p < .001), with minor overestimation of 0.5 mm on US. It is concluded that intraoral US is very accurate in determining tumor thickness in early oral tongue cancer.

Cell-free nucleic acids in body fluids as biomarkers for the prediction and early detection of recurrent head and neck cancer: A systematic review of the literature

Liquid biopsy is a minimally invasive detection method for molecular biomarkers in body fluids which may serve as a novel tool in management of head and neck cancer. The purpose of this systematic review is to outline the current status of liquid biopsy in head and neck squamous cell carcinoma (HNSCC) patients by systematically identifying and qualifying all published studies on the diagnostic or prognostic value of cell-free nucleic acids detection for posttreatment disease monitoring and/or disease outcome. A search was performed in PubMed, EMBASE, and Cochrane Library. Thirty articles met the inclusion criteria for further analysis. Study and patient characteristics, molecular analysis method and treatment or prognostic outcomes were extracted. Seventeen studies investigated circulating miRNAs in blood. Of these studies, 16 found statistically significant results for a total of 24 different candidate miRNAs for prognostication or treatment monitoring. The remaining studies investigated circulating tumor DNA by targeting somatic mutations, allelic imbalances, hypermethylation, or HPV-DNA. Of these studies, 2 found a statistically significant association between nucleic acid levels (tumor DNA targeted by allelic imbalances and HPV-DNA) in blood and/or saliva and prognostic outcome. One study found significantly different pre- and posttreatment levels of mitochondrial DNA in serum. Despite large differences among these studies in both design and results, individual results are promising and provide ground for more large-scale studies with standardized serial assessment of patient samples in the future.

Use of the 2‐μm continuous wave thulium laser for the resection of oral squamous cell carcinomas does not impair pathological assessment

Current resection modalities for oral squamous cell carcinomas (OSCC) vary from cold steel over CO2 laser to monopolar electro‐surgery (MO). We compared thulium laser (TL) as a new modality with MO with regards to pathological assessment.

Early and late complications in the reconstructed mandible with free fibula flaps

Evaluation of mandibular reconstructions with free fibula flaps. Identification of factors associated with major recipient site complications, that is, necessitating surgical intervention under general anaesthesia.