Oliver Ristow

Treatment perspectives for medication-related osteonecrosis of the jaw (MRONJ)

The medication-related osteonecrosis of the jaw (MRONJ) is believed to be a therapy-resistant entity. Although the application of the recommended conservative and surgical treatment regimens have returned variable success rates, the increased awareness and experience with MRONJ suggests that surgical therapy can halt the progression of the disease, thereby allowing a histology-based diagnosis of the osteonecrosis. Surgical treatment protocols can achieve success rates of over 90% and novel techniques such as the visualization of bone fluorescence can assist in the intra-operative delineation of the osteonecrosis and standardize the procedure.

Tooth extraction in patients receiving oral or intravenous bisphosphonate administration: A trigger for BRONJ development?

INTRODUCTIONnScientific debate outlines tooth extraction as a potential trigger for the onset of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Therefore, the aim of this study was to investigate the outcome of tooth extractions in patients receiving bisphosphonate therapy.nnnPATIENTS AND METHODSnA retrospective cohort study was performed on patients with a history of oral or intravenous bisphosphonate administration and tooth extraction between 2007 and 2013 in a single university hospital oral and maxillofacial surgical unit. In all patients, extractions were performed according to the guidelines of the German Society of Oral and Maxillofacial Surgery. The outcome variable was the onset of typical BRONJ signs during postoperative follow-up.nnnRESULTSnIn 72 subjects (53 female, 19 male; mean age 67.5 years) receiving oral (n = 27) and/or intravenous (n = 45) bisphosphonates due to malignant tumor (n = 43) or osteoporosis (n = 29), 216 tooth extractions were performed. The mean duration of intake was 36.2 months. In 67 out of 72 patients (93.1%) and 209 out of the 216 extraction sites the postoperative course was uneventful and the wounds healed without complications. Three of the 72 patients (4.2%) developed osteonecrosis of the jaw in four of the 216 extraction sites (1.9%). Duration and route of administration, oral hygiene and steroid intake were identified as potential risk factors for the development of BRONJ.nnnCONCLUSIONnTooth extraction in patients receiving bisphosphonates can be performed in a safe and predictable way, even in high-risk patients, when performed according to established guidelines. It is not tooth extractions themselves, but rather prevailing infectious conditions that may be a key risk factor for the development of BRONJ.

Fluorescence-guided surgery for the treatment of medication-related osteonecrosis of the jaw: A prospective cohort study

INTRODUCTIONnThe delineation of the necrotic bone is a crucial step in the surgical treatment of medication-related osteonecrosis of the jaw (MRONJ). Several different approaches have been described including the innovative technique of fluorescence-guided surgery. However, until now there is a lack of data regarding the outcome. Therefore, the aim of the present study is to investigate the long-term success rates of fluorescence-guided surgery in the treatment of MRONJ.nnnPATIENTS AND METHODSn54 Patients were prospectively assigned for surgical treatment of medication-related osteonecrosis of the jaw using fluorescence-guided surgery. Patients received doxycycline 100xa0mg twice a day for at least seven days preoperatively. Surgical treatment of MRONJ included complete removal of necrotic bone, which was monitored using the visual enhanced lesion scope (Velscope), followed by smoothening sharp bony edges and meticulous wound closure. Procedure success was assessed as postoperative maintenance of full mucosal coverage without pain, infection or bone exposure during regular follow-up.nnnRESULTSnThe study included a total of 54 patients (32 female and 22 male, mean age 71.4xa0±xa09.2 years). In the last follow-up an intact mucosa and absence of exposed bone, pain or signs of infection was identified in 47 of 54 patients (87%) and 56 of 65 lesions (86.2%) after first surgery using fluorescence-guidance. In 4 patients with 6 lesions a second fluorescence-guided surgery was necessary to achieve complete mucosal closure. Respectively, including the case with second surgical attempt 51 of 54 patients (94.4%) and 62 of 65 lesions (95.4%) showed complete mucosal healing.nnnCONCLUSIONnThe study shows that fluorescence-guided surgery is a safe and successful treatment option which can be considered for all stages of MRONJ. The technique seems also promising for MRONJ cases under denosumab.

Comments on “Diagnosis and Management of Osteonecrosis of the Jaw: A Systematic Review and International Consensus”

This work provides a systematic review of the literature from January 2003 to April 2014 pertaining to the incidence, pathophysiology, diagnosis, and treatment of osteonecrosis of the jaw (ONJ), and offers recommendations for its management based on multidisciplinary international consensus. ONJ is associated with oncology-dose parenteral antiresorptive therapy of bisphosphonates (BP) and denosumab (Dmab). The incidence of ONJ is greatest in the oncology patient population (1% to 15%), where high doses of thesemedications are used at frequent intervals. In the osteoporosis patient population, the incidence of ONJ is estimated at 0.001% to 0.01%, marginally higher than the incidence in the general population (<0.001%). New insights into the pathophysiology of ONJ include antiresorptive effects of BPs and Dmab, effects of BPs on gamma delta T-cells and onmonocyte and macrophage function, as well as the role of local bacterial infection, inflammation, and necrosis. Advances in imaging include the use of cone beam computerized tomography assessing cortical and cancellous architecture with lower radiation exposure, magnetic resonance imaging, bone scanning, and positron emission tomography, although plain films often suffice. Other risk factors for ONJ include glucocorticoid use, maxillary or mandibular bone surgery, poor oral hygiene, chronic inflammation, diabetes mellitus, illfitting dentures, as well as other drugs, including antiangiogenic agents. Prevention strategies for ONJ include elimination or stabilization of oral disease prior to initiation of antiresorptive agents, as well as maintenance of good oral hygiene. In those patients at high risk for the development of ONJ, including cancer patients receiving high-dose BP or Dmab therapy, consideration should be given to withholding antiresorptive therapy following extensive oral surgery until the surgical site heals with mature mucosal coverage. Management of ONJ is based on the stage of the disease, size of the lesions, and the presence of contributing drug therapy and comorbidity. Conservative therapy includes topical antibiotic oral rinses and systemic antibiotic therapy. Localized surgical debridement is indicated in advanced nonresponsive disease and has been successful. Early data have suggested enhanced osseous wound healingwith teriparatide in thosewithout contraindications for its use. Experimental therapy includes bonemarrow stem cell intralesional transplantation, low-level laser therapy, local platelet-derived growth factor application, hyperbaric oxygen, and tissue grafting.

Comparison of auto-fluorescence and tetracycline fluorescence for guided bone surgery of medication-related osteonecrosis of the jaw: a randomized controlled feasibility study

Recent studies have indicated that bone shows auto-fluorescence under an appropriate fluorescence lamp. The aim of this preliminary study was to compare the success rates of the established tetracycline fluorescence-guided bone surgery with auto-fluorescence-guided bone surgery in the treatment of medication-related osteonecrosis of the jaw (MRONJ). Forty patients suffering from MRONJ were referred for surgical treatment and were divided randomly into two groups: auto-fluorescence (n=20) or tetracycline fluorescence (n=20) guided bone surgery. The primary endpoint was treatment success, defined as the absence of exposed bone at 8 weeks after surgery. Secondary outcomes assessed were mucosal integrity, signs of infection, pain, and loss of sensitivity; these were evaluated descriptively at 10 days, 8 weeks, 6 months, and 1 year after surgery. At 8 weeks postoperative, 18/20 patients (90%) in the auto-fluorescence group and 17/20 patients (85%) in the tetracycline fluorescence group showed mucosal integrity (P>0.05). At the last follow-up, 94% in the auto-fluorescence group and 89% in the tetracycline fluorescence group presented complete mucosal coverage with no exposed bone, infection, or pain (P>0.05). There was no significant difference between the two techniques for any of the secondary outcomes (P>0.05). The results of this preliminary study show that auto-fluorescence-guided bone surgery has comparable success rates to the established tetracycline fluorescence-guided bone surgery.

In vitro study on proliferation kinetics of oral mucosal keratinocytes

OBJECTIVEnThe limited availability of autogenous oral mucosa in oral and maxillofacial surgery for intraoral grafting after trauma or tumor resection can be balanced by the use of tissue-engineered oral mucosa. However, the use of tissue engineering in autologous grafts is still subject to further research. The aim of this study was to evaluate conditions that lead to a rapid proliferation of vital and highly proliferative oral keratinocytes, which can be used in tissue engineering and consequently help improve surgical management of intraoral mucosal defects.nnnMATERIAL AND METHODSnHuman oral keratinocytes were obtained from oral mucosal specimens and cultivated. According to their affinity to β1-integrin, epidermal stem cell populations were isolated by using collagen type IV and laminin-coated dishes. Cell proliferation and cell viability were measured by using the CASY cell counter, WST-1 assays, and real-time cell analysis (xCELLigence).nnnRESULTSnMeasurements on cell proliferation (CASY cell counter) and cell viability (WST-1 assay) showed the characteristic proliferation stages of inxa0vitro-cultivated cells. No statistically significant differences could be monitored (P > .05). Real-time cell analysis, as a more direct and precise technique, revealed a steeper growth curve of adherent cells and therefore generally higher proliferation kinetics compared with cells derived from the supernate.nnnCONCLUSIONnData from real-time cell analysis showed an increased proliferation of adherent cells compared with those derived from the supernate. These results demonstrate the increase of the proliferation capacity by cultivation of keratinocytes derived by adhesion to extracellular matrix proteins.

Current concepts in salvage procedures for failing microvascular flaps: is there a superior technique? Insights from a systematic review of the literature

Microvascular free tissue transfer is a routine procedure with high predictability and a low complication rate. However, compromised flap perfusion remains a challenge and there is no consensus regarding the appropriate flap salvage protocol. The purpose of this study was to identify techniques with implications for flap salvage procedures and to assess their efficacy. A systematic review of studies published in the literature between 1990 and 2015, with predefined inclusion and exclusion criteria, was performed. The data obtained were pooled and analyzed. A total of 39 studies qualified for data extraction. The overall level of evidence was low and the total number of reported cases was limited (330 flaps). Five studies involved control groups and supplied comparative data. Surgical anastomotic revision and thrombectomy are inevitable in every flap salvage protocol. Four techniques or combinations of these with positive effects on flap salvage success rates were identified: thrombectomy with a Fogarty catheter (six studies, 68 flaps), intraoperative use of thrombolytic drugs (16 studies, 184 flaps), placement of an arteriovenous fistula (five case reports, five flaps), and the postoperative application of medicinal leeches (11 studies, 73 flaps). Currently available data exploring flap salvage procedures are limited. None of the techniques presented yielded superior salvage outcomes.

Combination of Sturge-Weber Syndrome and Trigonocephaly.

AbstractRegarded singly, both Sturge-Weber syndrome and trigonocephaly are rare congenital disorders. The cardinal features of Sturge-Weber syndrome are facial cutaneous capillary malformation (port-wine stain), leptomeningeal angiomatosis, and glaucoma. Premature closure of the metopic suture results in trigonocephaly. However, to the best of our knowledge, the diagnosis of a combination of both Sturge-Weber syndrome and trigonocephaly has not as yet been reported. This brief clinical study thus presents a patient with the unusual findings of a Sturge-Weber syndrome and simultaneous trigonocephaly induced by premature metopic synostosis. Thus, the rare combination of a port-wine stain involving the first division of the trigeminal nerve with the diagnosis of a craniosynostosis justifies the indication of a prophylactic magnetic resonance imaging acquisition before craniofacial surgeries, in order to prevent seizures and stroke-like episodes triggered by the surgical intervention.

Short- and long-term changes of the pharyngeal airway after surgical mandibular advancement in Class II patients—a three-dimensional retrospective study

PURPOSEnTo evaluate the short- and long-term impact of mandibular-only advancement on pharyngeal airway space (PAS) changes by using cone-beam computed tomography (CBCT) and a new segmentation software. Furthermore, to determine whether a correlation exists between forward movement and PAS gain.nnnMATERIALS AND METHODSnA retrospective evaluation of a homogeneous cohort of Class II patients who hadxa0undergone mandibular-only advancement was performed. Pre- (T0), post- (T1), and 1-year post-operative (T2) CBCT scans were obtained in each case, and the changes in PAS parameters (volume and smallest cross-sectional area) were compared with new segmentation software. Mandibular advancement was measured and correlated with PAS parameters.nnnRESULTSnA significant postoperative gain in all airway parameters compared with baseline was shown for T1 (pxa0=xa00.02), with an additional increase for T2 (pxa0<xa00.001). No significant linear association between the movement of the measurement points and any other PAS parameters could be discerned (pxa0>xa00.05).nnnCONCLUSIONnOur findings indicate that bilateral mandibular-only advancement surgery results in a significant widening of the PAS in Class II patients. Long-term adaption of the PAS also occurs after surgery implying an additional gain of PAS over time. Sicat Air® software seems to be a sufficient and promising tool for PAS evaluation.

Free Vastus Intermedius Muscle Flap: A Successful Alternative for Complex Reconstruction of the Neurocranium in Preoperated Patients

Abstract The reconstruction of large cranial and scalp defects is a surgical and esthetic challenge. Single autologous tissue transfer can be insufficient due to the defect size and the anatomic complexity of the recipient site. Alloplastic patient-specific preformed implants can be used to recover hard tissue defects of the neurocranium. Nevertheless, for long-term success adequate soft tissue support is required. In this brief clinical study, the authors describe calvarian reconstruction in a 33-year-old patient with wound healing disorder after an initial resection of ependymoma. The patient suffered from osteonecrosis and wound breakdown in the fronto-parietal region. An alloplastic polymethylmethacrylate implant for hard tissue support was manufactured based on 3-dimensional visualization of a computed tomography scan. After the resection of remaining pathologic bone from earlier surgical procedures, the alloplastic implant was inserted to achieve functional coverage of the brain. Due to anatomic variation of donor site vessels during anterolateral thigh flap preparation, the authors performed a vastus intermedius free flap as a new muscular flap for craniofacial reconstruction. The authors achieved excellent functional and esthetic results. The muscular vastus intermedius free flap in combination with a split skin graft proves to be a new alternative to the anterolateral thigh flap for soft tissue reconstruction of the neurocranium.