Osseointegrated Oral Implants in Head and Neck Cancer Patients

After cancer treatment in the head and neck area, mastication and speech are often affected. Some of the problems encountered can be solved by adequate dental rehabilitation. However, dental rehabilitation is often compromised for various reasons. The change in anatomy due to surgery often results in lack of denture-bearing mucosa. The effects of radiotherapy on the salivary glands and the mucosa result in dry oral tissue and diminished retention of removable dentures. Osseointegrated oral implants can help to solve these problems. Although implant treatment for patients with cancer of the head and neck is covered by the Dutch national health insurance, and there is therefore no financial obstacle, implants have not, so far, been widely used with these patients. In order to establish the possible reasons for this, an analysis was performed. Retrospective data on 95 consecutive patients were collected from records. The indication for the use of oral osseointegrated implants was reviewed. Analysis of the data showed that 45% did not need specific prosthetic rehabilitation. An indication for the use of osseointegrated implants was found in 25% of the patients. For various reasons, only 3% actually received implants. In striving to completely rehabilitate a cancer patient, the possible use of osseointegrated oral implants should be evaluated before the initial oncological treatment begins. The insertion of implants during the initial surgical procedure should be considered more often, with a view to reducing the number of surgical procedures.     

Nerve maintenance and regeneration in the damaged cochlea

Following the onset of sensorineural hearing loss, degeneration of mechanosensitive hair cells and spiral ganglion cells (SGCs) in humans and animals occurs to variable degrees, with a trend for greater neural degeneration with greater duration of deafness. Emergence of the cochlear implant prosthesis has provided much needed aid to many hearing impaired patients and has become a well-recognized therapy worldwide. However, ongoing peripheral nerve fiber regression and subsequent degeneration of SGC bodies can reduce the neural targets of cochlear implant stimulation and diminish its function. There is increasing interest in bio-engineering approaches that aim to enhance cochlear implant efficacy by preventing SGC body degeneration and/or regenerating peripheral nerve fibers into the deaf sensory epithelium. We review the advancements in maintaining and regenerating nerves in damaged animal cochleae, with an emphasis on the therapeutic capacity of neurotrophic factors delivered to the inner ear after an insult. Additionally, we summarize the histological process of neuronal degeneration in the inner ear and describe different animal models that have been employed to study this mechanism. Research on enhancing the biological infrastructure of the deafened cochlea in order to improve cochlear implant efficacy is of immediate clinical importance.     

Oromandibular reconstruction with free peroneal flap and osseointegrated implants

Free fibula flaps have proved to be one of the most versatile for oromandibular reconstruction due to the available length of bone and the possibility of incorporating a long skin paddle to cover intraoral soft tissues. The use of a osseointegrated dental implants is an important technique for the oral rehabilitation of these patients. Osseointegrated implants provide the most rigid prosthetic stabilization available to withstand masticatory forces. These implants can be placed immediately or in second time procedure. In our case, implantation in the fibula free flap is done after 6-9 months because of the large amount of osteosynthesis material required for the fixation of the flap. Four or six months later, when osseointegration has taken place, the implants are loaded with a dental rehabilitation. We analize 10 cases of mandibular reconstruction with fibula free flap and their aesthetic and functional rehabilitation with osseointegrated implants with a 2 year follow up. Forty-six dental implants were placed developing all of them but one a correct osseointegration. All these patients recovered masticatory function and underwent a considerable improvement in labial competence, salivary continence, speech articulation and facial harmony.     

Nerve regeneration in the peripheral nervous system versus the central nervous system and the relevance to speech and hearing after nerve injuries

Schwann cells normally form myelin sheaths around axons in the peripheral nervous system (PNS) and support nerve regeneration after nerve injury. In contrast, nerve regeneration in the central nervous system (CNS) is not supported by the myelinating cells known as oligodendrocytes. We have found that: 1) low frequency electrical stimulation can be used to elevate cAMP thereby promoting regeneration of CNS axons and 2) a conditioning lesion, created by a crush of the peripheral branch of the dorsal root ganglion sensory neurons along with a simultaneous cut of these axons in the CNS, promotes even greater neural outgrowth than electrical stimulation. The effectiveness of the lesion results from both an acceleration of axon outgrowth and an increase in the rate of axon growth. However, electrical stimulation remains a more viable treatment of nerve injuries to stimulate regeneration and has been successfully used to promote development of the auditory pathways in children with severe to profound deafness who use cochlear implants. Without nerve regeneration, there is only a random reinnervation of affected muscles. An example occurs when the laryngeal nerve attempts to reinnervate the vocal cords after injury, causing deficits in speech. Synkinesis occurs when reinnervation of antagonistic muscles effectively paralyze the vocal cords and, in turn, severely compromises speech. The misdirection of laryngeal nerve reinnervation can be alleviated surgically by strategies favoring inspiratory abduction.Learning outcomesReaders of this article will gain an understanding of (1) the potential for axon regeneration in the central nervous system and (2) problems and possible solutions for random reinnervation of laryngeal muscles for speech.     

Long-term results of fittig subperiosteal implants: report of twelve patient cases]

The subperiosteal dental implantation implant was orginally described in the 1940s. The inadequate long-term results of subperiosteal implants are in contrast to the excellent results documented for endosseus oral implants. Consequently, subperiosteal implants and other soft-tissue-anchored implants should not be used presently. The present report documented twelve patient cases with complications after treatment with subperiosteal implants. Typical complications of SI are implant exposure, inflammation, infection, fistula formation and implant mobility. After removing the SI severe atrophic bone was seen. The placement of osseointegrated oral implants was mostly not possible without autogenous bone grafting. The present report is in conclusion with other studies, that a regular control of patients with subperiosteal implants is necessary. Subperiosteal implants should definitely be removed, if continuous periods of complication occur. The complete oral rehabilitation requires further surgical treatment in the field of preprosthetic surgery.     

Extra-oral implants and irradiation: current trends

Recommended treatment for head and neck cancer associates surgery and radiotherapy. Indication for bone-anchored epitheses in irradiated patients is also a common situation. The outcome of the implant appears to be improved with a special protocol for hyperbaric oxygen therapy, antibiotic therapy and calcitherapy. The problem of radiotherapy in patients with titanium osseointegrated implants is also discussed.     

骨整合在耳廓畸形和缺损修复中的临床应用

目的探讨骨整合修复耳廓畸形和缺损的临床意义。方法采用Branemark种植系统的常规操作方法，对先天性和后天性共20例(21耳)耳廓畸形和缺损进行骨整合及假体修复。Ⅰ期手术骨整合，Ⅱ期用固定可卸式假体修复。随访时间0．5～3年。结果骨整合假体修复1次成功率为100％，满意度90．5％(19／21)，骨整合支架与皮肤组织接触之问的感染率14．3％(3／21)，修复体的稳定率为100％。结论骨整合及假体修复耳廓畸形和缺损具有良好的临床效果。     

Extraoral implants in irradiated pacients

The aim of this study is to analyze the success of extraoral osseointegrated implants used to support and contain prosthesis designed to rehabilitate craniofacial deformities.MethodThis study was based on the retrospective assessment of charts from 59 patients submitted to cancer surgery and who received 164 extraoral implants to contain facial prosthesis.ResultsAmong 164 implants, 42 were fixed in previously irradiated regions. Eight of the implants did not have osseointegration; and from these, 2 were fixed in irradiated bone. The result show 116 (95.1%) successfully osseointegrated implants in non-irradiated sites. The success rate among 42 implants fixed in previously irradiated bones was 40 (95.3%) osseointegrated implants.ConclusionThe use of extraoral craniofacial implants represents a safe and effective approach to treat facial deformities as a support for the rehabilitation prosthesis. Radiotherapy treatment does not prevent osseointegration.     

A novel drug therapy for recurrent laryngeal nerve injury using T-588

OBJECTIVES/HYPOTHESIS: We have previously shown that gene therapy using Insulin-like growth factor (IGF)-I, glial cell line-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF), or a combination of these trophic factors, is a treatment option for recurrent laryngeal nerve (RLN) palsy. However, there remain some difficulties preventing this option from becoming a common clinical therapy for RLN injury. Thus, we need to develop novel treatment option that overcomes the problems of gene therapy.R(-)-1-(benzothiophen-5-yl)-2-[2-N,N-diethylamino]ethoxy]ethanol hydrochloride (T-588), a synthetic compound, is known to have neuroprotective effects on neural cells. In the present study, the possibility of new drug treatments using T-588 for RLN injury was assessed using rat models. STUDY DESIGN: Animal study. METHODS: Animals were administered T-588 for 4 weeks. The neuroprotective effects of T-588 administration after vagal nerve avulsion and neurofunctional recovery after recurrent laryngeal nerve crush were studied using motoneuron cell counting, evaluation of choline acetyltransferase immunoreactivity, the electrophysiologic examination, and the re-mobilization of the vocal fold. RESULTS: T-588 administration successfully prevented motoneuron loss and ameliorated the choline acetyltransferase immunoreactivity in the ipsilateral nucleus ambiguus after vagal nerve avulsion. Significant improvements of motor nerve conduction velocity of the RLN and vocal fold movement were observed in the treatment group when compared to controls. CONCLUSION: These results indicate that oral administration of T-588 might be a promising therapeutic option in treating peripheral nerve injury.     

Peri-implantitis or squamous cell carcinoma?

INTRODUCTION: Squamous cell carcinoma developed around dental implants has seldom been described. It simulates peri-implantitis. The authors present two cases and a literature review. CASE REPORTS: A 70 year-old woman presented with an exophytic tumor developed around dental implants placed in the anterior part of the mandible. Panoramic X-rays showed major osteolysis, especially around the distal abutment implants. A 72 year-old patient, smoker, presented with chronic lichen planus; he was carrying two implants supporting an overdenture with ball-attachments, placed 15 years before. He presented with an ulcerated symphyseal tumor, bone loss around implant in position 43. The implant had been spontaneously pushed out. In both cases the diagnosis was squamous cell carcinoma. DISCUSSION: Few cases of squamous cell carcinoma developed around dental implants have been reported. They initially mimic peri-implantitis. The carcinogenic role of the implant has never been established. Another hypothesis is the migration of malignant cells, originating from a mucosal tumor, through the sulcus. Risk factors for squamous cell carcinoma (smoking or alcohol consumption, precancerous lesions) are an indication for a permanent follow-up. Biopsies will prove the diagnosis.     

Effect of platelet rich plasma and fibrin sealant on facial nerve regeneration in a rat model

OBJECTIVE: To investigate the effects of platelet rich plasma (PRP) and fibrin sealant (FS) on facial nerve regeneration. STUDY DESIGN: Prospective, randomized, and controlled animal study. METHODS: Experiments involved the transection and repair of facial nerve of 49 male adult rats. Seven groups were created dependant on the method of repair: suture; PRP (with/without suture); platelet poor plasma (PPP) (with/without suture); and FS (with/without suture) groups. Each method of repair was applied immediately after the nerve transection. The outcomes measured were: 1) observation of gross recovery of vibrissae movements within 8-week period after nerve transection and repair using a 5-point scale and comparing the left (test) side with the right (control) side; 2) comparisons of facial nerve motor action potentials (MAP) recorded before and 8 weeks after nerve transection and repair, including both the transected and control (untreated) nerves; 3) histologic evaluation of axons counts and the area of the axons. RESULTS: Vibrissae movement observation: the inclusion of suturing resulted in overall improved outcomes. This was found for comparisons of the suture group with PRP group; PRP with/without suture groups; and PPP with/without suture groups (P < .05). The PRP without suture group had a significantly greater degree of recovery than the PPP without suture group (P < .05), but it did not have better performance than suture group (P > .05). The movement recovery of the suture group was significantly better than the FS group (P = .014). The recovery of function of the PRP groups was better than that of the FS groups, although this did not reach statistical significance (P = .09). Electrophysiologic testing: there was a significantly better performance of the suture group when compared with the PRP and PPP without suture groups in nerve conduction velocity (P < .05). The PRP with suture group had the best results when compared with the suture as well as the PPP with suture groups in duration and latency-2 of MAP (P < .05). For the FS groups, no results were found demonstrating a biological effect. The PRP with suture group demonstrated the best performance in the latency-2 and the area under the curve of MAP when compared with the suture and FS with suture groups (P < .05). Histomorphometric analysis: PRP with suture demonstrated the greatest increase in axon counts when compared with suture, FS with suture, and PPP with suture groups (P < .05). There was no statistically significant difference seen in axon diameter. CONCLUSION: The best results for the return of function in our rat facial nerve axotomy models occurred when the nerve ends were sutured together. At the same time, the data demonstrated a measurable neurotrophic effect when PRP was present, with the most favorable results seen with PRP added to suture. There was an improved functional outcome with the use of PRP in comparison with FS or no bioactive agents (PPP). FS showed no benefit over conventional suturing in facial nerve regeneration. Our study provides the potential of a new clinical application for PRP in peripheral nerve regeneration.     

Biologische Therapien in der Otologie

Millions of people worldwide suffer from hearing loss. Current treatment for patients with severe to profound hearing loss consists of cochlear implants. Providing the cochlear nerve is intact, patients generally benefit enormously from this intervention, frequently achieving significant improvements in speech comprehension. There are, however, some cases where current technology does not provide patients with adequate benefit. New therapeutic concepts based on cell transplantation and gene therapy are developing rapidly, at least in the research sector. Compared to the wealth of basic research available in this area, translation of these new experimental approaches into clinical application is presently at a very early stage. The current review focuses on translatable treatment concepts and discusses the barriers that need to be overcome in order to translate basic scientific research into clinical reality. Furthermore, the first examples of clinical application of biological therapies in severe hearing loss are presented, particularly in connection with cochlear implants.     

Histological and histomorphometric results of implantation of dental implants by early and late implantation]

In this study, a histologic and histomorphometric analysis of delayed and immediate-placed implants was performed. An implantation of 16 self-cutting conical titanium screw implants was carried out in 8 beagle dogs. Of these implants, 8 were placed immediately after extraction of the second premolar and 8 implants were placed after 6 months of healing after extraction. For dynamic histomorphometry, fluorochrome bone markers were injected at two different times prior to euthanasia. The specimens were examined macroscopically and microscopically 8 months after implantation. A histologic, dynamic, and static histomorphometry was performed with the aid of different computer programs. A mean surface of osseointegration of 75.7% and a mean soft tissue implant contact surface of 24.2% was seen in immediate-placed implants. For delayed implantation, an osseointegrated surface of 80.7% and a soft tissue covering of 19.3% was examined. The fibrogenic structures in the cervical implant part were more dense and there were more adhesive epithelial elements (hemidesmosomes) around delayed implants. The result of the dynamic and static histomorphometry showed no significant differences in the two groups (P < 0.1). In conclusion, it can be stated that a new steady-state of the soft and hard tissue around dental implants was seen 8 months after implant insertion in both groups. There was a pseudoankylotic healing in the osseous part. The lower level of osseointegration in immediate-placed implants was caused by early resorption of bone in the crestal part. Thus, a larger part of the implant was surrounded by soft tissue and a long epithelial attachment resulted.     

Osseointegrated implants in the management of childhood ear abnormalities: with particular emphasis on complications

Little has been published about the difficulties encountered during the insertion of osseointegrated implants for the attachment of bone anchored hearing aids (BAHA) and auricular prostheses in children. This study examines this issue in the first 51 children implanted at our centre. During surgery, the most common problem encountered was the presence of thin bone resulting in incomplete insertion of fixtures. Five fixtures had failed to integrate and six fixtures were lost in the long-term, however, only five children required revision surgery. The reason why few patients require revision was due to the judicious insertion of 'sleeper' fixtures. At follow-up, seven children required counselling for psychological problems. It is apparent from this study that osseointegrated implants in children are associated with difficulties, re-emphasizing that a paediatric osseointegration programme requires significant investment, and should only be undertaken by institutions that are committed to its success.     

鼠神经生长因子治疗单侧突发性聋的疗效分析

目的 观察鼠神经生长因子治疗突发性聋的疗效.方法 回顾性分析2013年11月至2015年2月期间诊治的124例单侧突发性聋患者的临床资料,其中,治疗组59例,对照组65例,根据不同的听阈曲线,两组患者又进一步分为低中频下降型、中高频下降型、平坦型、全聋型4个亚组.对照组依据不同听力曲线类型给予相应的常规治疗,治疗组在对照组治疗的基础上,辅予鼠神经生长因子肌肉注射,疗程均为10天,比较两组及各亚组间治疗后的总有效率.结果 治疗组总有效率为64.41%(38/59),对照组总有效率为44.62%(29/65),治疗组的总有效率高于对照组(x2=4.877,P=0.032<0.05).治疗组低中频下降型、中高频下降型、平坦型、全聋型患者的有效率分别为82.35%、42.1%、72.27%、66.67%,对照组分别为61.11%、28.57%、50%、41.67%,两组间各听力曲线亚组间的疗效差异均无统计学意义(x2值分别为1.933、0.803、1.326、1.510,均为P>0.05).治疗过程中两组患者均未出现不良反应.结论 鼠神经生长因子治疗突发性聋有较好的临床疗效,且对各型听阈曲线的突发性聋均有效,无不良反应,是一种治疗突发性聋安全有效的药物.     

Regeneration des N. facialis im Vergleich zu anderen peripheren Nerven

Despite increasing knowledge of cellular and molecular mechanisms determining the success or failure of peripheral nerve regeneration, no effective treatments for peripheral nerve injury exist. Newly developed and validated approaches for precise numerical assessment of motor deficits have recently allowed testing of novel strategies in experimental animals. One of these approaches is the daily manual stimulation of the denervated musculature. This treatment is effective in cases of cranial nerve lesions with preservation of the sensory input (facial or hypoglossal nerve) and has the potential of direct translation in clinical settings. However, manual stimulation appears to be ineffective for the treatment of mixed peripheral nerve injuries. Generally, no long-term improvement of functional recovery is achieved by electrical stimulation in rodents. While short-term post-traumatic stimulation of the proximal nerve stump has no negative effects, direct electrical stimulation of the muscle during the period of de- and reinnervation appears to hinder muscle fibre reinnervation. Finally, experimental evidence suggests that application of peptides known as glycomimetics, which mimic functional properties of carbohydrate molecules, may provide significant benefits after injuries of mixed peripheral nerves.     

Iliac crest internal oblique osteomusculocutaneous free flap reconstruction of the postablative palatomaxillary defect.

BACKGROUND: Traditionally, restoration of extensive palatomaxillary defects have been achieved by prosthetic restoration, often with suboptimal functional results. More recently, vascularized bone-containing free flaps have been used for this purpose. OBJECTIVE: To describe 6 patients who underwent palatomaxillary reconstruction using the composite iliac crest-internal oblique osteomusculocutaneous free flap. METHODS: Six cases of iliac crest osteomusculocutaneous free flap reconstruction of extensive postablative palatomaxillary defects were retrospectively reviewed with clinical follow-up. We reviewed these cases for pathologic findings, defect size, dental restoration, oral rehabilitation, and speech. RESULTS: Pathologic findings included squamous cell carcinoma (n = 4), osteogenic sarcoma (n = 1), and sinonasal hemangiopericytoma (n = 1). Mean follow-up was 14.5 months (range, 10-25 months). Four patients underwent resection and reconstruction primarily and 2 underwent reconstruction secondarily. Two patients required reconstruction of a cutaneous defect using the iliac skin paddle. The hard palate and lateral nasal wall were reconstructed in all 6 patients, and the orbital rim and zygomatic body were reconstructed in 4. One patient underwent reconstruction with an orbital prosthesis supported by osseointegrated implants. There was 1 donor site complication and 1 recipient site infection, which was treated successfully with oral antibiotics. Four patients were rehabilitated with osseointegrated implants, and all 6 patients maintain an unrestricted oral diet. All 6 patients have normal speech without velopharyngeal or oronasal insufficiency. CONCLUSION: For extensive palatomaxillary defects, the iliac crest-internal oblique osteomusculocutaneous free flap offers a reliable method of primary reconstruction, allowing for complete orodental rehabilitation without the use of a prosthetic obturator.     

Osteonecrosis of the jaws by long term therapy with bisphosphonates]

For several decades bisphosphonates have been used to reduce skeletal related events in patients with both osteoporosis or bone metastases. Under long term application, besides the known therapy side effects, a new clinical picture has been described within the last few years. This is osteonecrosis of the jaws, which is characterized by its difficulty in treatment. Besides exposed jaw bone, the start of the disease usually lacks any symptoms. The typical clinical symptoms then are foetor ex ore, swelling, exsudation, loosening of teeth, pain or paresthesia. Later oro-antral/nasal or oro-cutaneous fistula can develop. The X-ray shows persisting tooth sockets after extractions and later cloudy radio-lucency, sequestra or fractures. The patient exposed to bisphosphonate can be grouped according to the risk for osteonecrosis: high risk patients with intravenous bisphosphonate therapy and additional chemo-, radiation or corticoid therapy--predominantly patients with a malignant underlying disease and bone metastases low risk patients with an oral bisphosphonate therapy without additional chemo-, radiation or corticoid therapy--preferably patients with non-corticoid-induced osteoporosis. Before starting a bisphosphonate therapy possible causes of infection should be treated and risk of injuries to the mucosa should be reduced according to the individual risk profile. This is supplemented by information of the patient about the risk of necrosis and the possibilities for prevention. Regular dental recall under bisphophonate therapy is emphasised for early recognition of possible problems. Prophylaxis is recommended for the prevention of periodontal infection combined with a follow up of removable denture for possible ulcera. Generally, conservative treatment measures are preferred to surgical ones. Inevitable operations are carried out non-traumatically using broad spectrum antibiotic prophylaxis until the day of suture removal (not before day 10). Long term follow up examinations are recommended.Patients with dental implants inserted before a bisphophonate therapy should be subject to intensive recall examinations. For patients undergoing or following a bisphosphonate therapy the indication for dental implants should be as strict as for patients following head and neck radiation therapy. In the present for patients with osteonecrosis, even after healing, dental implants are regarded as contra-indication. Therapy of the necrosis often requires general anaesthesia, hospitalisation, naso-gastral feeding tube and intravenous, systemic antiinfective treatment. The necrosis is removed completely and a tension free wound closure with vascularised tissue is intended. A literature review shows the metabolic effect of biphosphonates, the known pathogenesis of the bisphosphonate-induced jaw necrosis. It is essential to develop interdisciplinary communication, aiming at a joint care for this group of concerned patients and involving not only those medical disciplines, which order and use bisphosphonates, but especially dentists and maxillofacial surgeons.     

Neue Rekonstruktionsm?glichkeiten von ausgedehnten Kieferdefekten mit vorbereiteten mikrovaskul?ren Fibulatransplantaten und ITI-Implantaten

The reconstruction of extensive jaw defects is frequently only possible with microvascular bone flaps. Here we are presenting an operative technique using prefabricated fibular flaps and osseointegrated implants. In a first operation, the fibula is prepared with implants, split skin graft, and a nonresorbable membrane. The jaw defect is reconstructed 6 weeks later and can be treated directly with a prosthesis thanks to osseointegrated implants. The technique is described with reference to 5 patients already operated according to this technique and the initial findings are evaluated.     

Delayed nerve repair is associated with diminished neuroenhancement by FK506

OBJECTIVES/HYPOTHESIS: The immunosuppressive agent FK506 has been shown in many studies to enhance nerve regeneration and to accelerate functional recovery after immediate nerve repair. However, in clinical practice the diagnosis and treatment of patients with peripheral nerve injuries is often delayed. The study investigated whether FK506 would retain its neuroregenerative properties when nerve repair and initiation of FK506 therapy were delayed for 7 days. STUDY DESIGN: In vivo laboratory study. METHODS: Thirty-two Lewis rats underwent tibial nerve transection and were randomly assigned to four experimental groups: immediate repair with FK506 treatment, immediate repair without FK506 treatment, 7-day delayed repair with FK506 treatment, and 7-day delayed repair without FK506 treatment. Treated animals received daily subcutaneous injections of 2 mg/kg FK506. Serial walking track measurements were performed at 14, 16, and 18 days after nerve repair. On day 18 after repair, peripheral nerves were injected with a fluorescent tracer for retrograde labeling. On day 21, peripheral nerves and spinal cords were harvested for histomorphometric analysis and motor neuron cell body counts, respectively. RESULTS: Animals that underwent immediate repair with FK506 had significantly higher fiber counts and percentages of nerve than the other three groups (P <.05) but did not show statistically significant earlier functional recovery. The remaining three groups had intermediate levels of nerve regeneration that were not significantly different. Retrograde abled motor neurons counts were decreased in animals with delayed nerve repair that received no FK506 (P <.05). CONCLUSION: In a rat tibial nerve transection model, the neuroregenerative effects of FK506 diminished markedly when repair and initiation of FK506 therapy were delayed by 7 days.