A new standardized critical size bone defect model in the pig forehead for comparative testing of bone regeneration materials.

OBJECTIVES: The preclinical study aimed to establish a standardized preclinical model to investigate osseous graft consolidation in defect configurations of limited regenerative capacity. MATERIAL AND METHODS: Critical size defects (CSD) were prepared and titanium tubes inserted for defect separation from local bone in the forehead area of 18 pigs. Defects were filled with demineralized bovine bone mineral (DBBM) or served as empty controls and were covered with a resorbable collagen membrane (CM) or left untreated. Six randomly selected pigs were sacrificed after 4, 8 and 12 weeks. Specimens were histologically and histomorphometrically analysed focusing on newly formed bone (NFB), demineralized bovine bone mineral (DBBM) and soft tissue (ST) proportions. RESULTS: Four weeks after defect preparation, no statistically significant difference concerning NFB quantity could be detected within the groups. Defects covered with the CM showed lower amounts of DBBM. After 6 and 12 weeks, defects augmented with DBBM in combination with a CM (8 weeks: 43.12 ± 4.31; 12 weeks: 43.05 ± 3.01) showed a statistically significant higher NFB rate compared to empty control defects covered with 8 weeks: 7.66 ± 0.59; 12 weeks or without a CM; 8 weeks: 8.62 ± 2.66; 12 weeks: 18.40 ± 2.40. CM application showed no significant impact on osseous defect regeneration or soft tissue formation. Superior NFB could be detected for basal aspect for several evaluation time points. CONCLUSIONS: The modification of CSD with titanium tubes represents a suitable model to imitate a one-wall defect regeneration situation. CLINICAL RELEVANCE: The established model represents a promising method to evaluate graft consolidation in one-wall defect configuration.

Correction to: Anatomical locations in the oral cavity where surgical resections of oral squamous cell carcinomas are associated with a close or positive margin-a retrospective study.

The following note was inadvertently omitted from the published paper: This work was performed in (partial) fulfillment of the requirements for the first author's obtaining the degree Dr. med. dent.

Anatomical locations in the oral cavity where surgical resections of oral squamous cell carcinomas are associated with a close or positive margin-a retrospective study.

OBJECTIVES: This study aimed to identify anatomical areas where resections of oral squamous cell carcinomas (OSCC) are significantly associated with close or positive margins. MATERIALS AND METHODS: This retrospective study included 330 patients with a primary OSCC from 2010 to 2015. Patient and tumour data were categorised into three groups by R-status (R0 [clear], ≥ 5 mm, 185 patients [56.06%]; R1 [positive], < 1 mm, 24 patients [7.27%]; and R0 [close], 1-5 mm, 121 patients [36.67%]). RESULTS: Areas where resections were significantly associated with close or positive margins were the hard palate (p < 0.001), buccal mucosa (p = 0.03), floor of the mouth (p = 0.004), lower alveolar ridge (p = 0.01), retromolar triangle (p = 0.005), and dorsal tongue (p = 0.02). CONCLUSIONS: Anatomical areas were identified in the oral cavity where it is challenging to resect OSCCs with an adequate safety margin. CLINICAL RELEVANCE: These results may enable surgeons to achieve a postulated safe distance during tumour resection, leading to a survival benefit for patients.

Does formalin fixation influence MSCT/CBCT accuracy?

PURPOSE: Advanced imaging modalities, such as multi-slice computed tomography (MSCT) and cone beam computed tomography (CBCT), greatly facilitate diagnostic medicine. In radiological research, it is important to know how accurately a scanned object is visualized, and whether the methodology leads to image distortion. The objective of this study was to evaluate whether formalin fixation impacted the accuracy of virtual 3D bone models generated via CBCT and MSCT using a software-based evaluation method that excluded human measurement errors. METHODS: A head specimen, with and without formalin preservation, was subjected to MSCT and CBCT scans using the manufacturers' predefined scanning protocols. Digital models of the lower jaw were constructed and superimposed with a master model generated based on optical scanning with an industrial non-contact scanner. Means and standard deviations were calculated to assess accuracy, and a t test was used for comparisons between the fixed and unfixed specimens. RESULTS: The extent of discrepancy between the fixed and unfixed specimens was analyzed using a total of 200 points (n = 200) in each specimen state. The mean deviation between states was 0.01 mm for MSCT (at both 80 and 140 kV). Mean values from CBCT at 0.4 voxel did not differ between states. CONCLUSIONS: Our results suggest that formalin fixation of an anatomical specimen does not substantially affect the accuracy of a three-dimensional image generated with CBCT and MSCT. Thus, fixed specimen can be used in future investigations of 3D models without concerns regarding the accuracy.

Development and validation of a classification and scoring system for the diagnosis of oral squamous cell carcinomas through confocal laser endomicroscopy.

BACKGROUND: Confocal laser endomicroscopy (CLE) is an optical biopsy method allowing in vivo microscopic imaging at 1000-fold magnification. It was the aim to evaluate CLE in the human oral cavity for the differentiation of physiological/carcinomatous mucosa and to establish and validate, for the first time, a scoring system to facilitate CLE assessment. METHODS: The study consisted of 4 phases: (1) CLE-imaging (in vivo) was performed after the intravenous injection of fluorescein in patients with histologically confirmed carcinomatous oral mucosa; (2) CLE-experts (n = 3) verified the applicability of CLE in the oral cavity for the differentiation between physiological and cancerous tissue compared to the gold standard of histopathological assessment; (3) based on specific patterns of tissue changes, CLE-experts (n = 3) developed a classification and scoring system (DOC-Score) to simplify the diagnosis of oral squamous cell carcinomas; (4) validation of the newly developed DOC-Score by non-CLE-experts (n = 3); final statistical evaluation of their classification performance (comparison to the results of CLE-experts and the histopathological analyses). RESULTS: Experts acquired and edited 45 sequences (260 s) of physiological and 50 sequences (518 s) of carcinomatous mucosa (total: 95 sequences/778 s). All sequences were evaluated independently by experts and non-experts (based on the newly proposed classification system). Sensitivity (0.953) and specificity (0.889) of the diagnoses by experts as well as sensitivity (0.973) and specificity (0.881) of the non-expert ratings correlated well with the results of the present gold standard of tissue histopathology. Experts had a positive predictive value (PPV) of 0.905 and a negative predictive value (NPV) of 0.945. Non-experts reached a PPV of 0.901 and a NPV of 0.967 with the help of the DOC-Score. Inter-rater reliability (Fleiss` kappa) was 0.73 for experts and 0.814 for non-experts. The intra-rater reliability (Cronbach's alpha) of the experts was 0.989 and 0.884 for non-experts. CONCLUSIONS: CLE is a suitable and valid method for experts to diagnose oral cancer. Using the DOC-Score system, an accurate chair-side diagnosis of oral cancer is feasible with comparable results to the gold standard of histopathology-even in daily clinical practice for non-experienced raters.

Chronic recurrent multifocal osteomyelitis in association with pyoderma gangraenosum.

BACKGROUND: Chronic recurrent multifocal osteomyelitis (CRMO) is a rare acquired inflammatory skeletal disorder of unknown origin. CRMO was first described by Gideon in 1972 and mainly affects children and young adults of female gender. The CRMO is part of the clinical picture of non-bacterial Osteomyelitis (NBO) and typically presents a relapsing recurring course with both remission and spontaneous exacerbation. CRMO is typically encountered in the limbs and the metaphysis of long bones in particular. Usually the clinical symptoms include painful swellings of the affected regions. This case report describes the rare case of a CRMO of the mandible in association with pyoderma gangraenosum. CASE PRESENTATION: A 14-year old female caucasian patient, residing in the south of Germany, presented in the oncological outpatient clinic of our Department of Paediatrics and Adolescent Medicine in June 2014 complaining of increasing neck pain and progressive swelling at her left cheek ongoing for about 6 weeks. These symptoms had been occurring quarterly for 4 years, but had never been as pronounced. Blood biochemistry showed a moderately elevated CRP (35 mg/l) and a significantly increased blood sedimentation rate (BSR 48/120 mm). The panoramic radiograph, however, revealed a bone alteration in the left mandibular region. Further investigations confirmed the diagnosis of CRMO. CONCLUSION: The present case underlines the fact that rare diseases might occasionally present with even more rare symptoms. These occasions can obviously be considered to present a considerable diagnostic challenge.

Case report: Upper arm metastasis of an oral squamous cell carcinoma.

BACKGROUND: The Oral Squamous Cell Carcinoma (OSCC) frequently metastasizes lymphogenously. Haematogenous dissemination is less common. This report describes a rare case of a metastatic OSCC of the floor of the mouth to the patients' left upper arm. To our knowledge this is the first of such case described in the literature. CASE PRESENTATION: Twelve months after R0 tumor resection surgery, including microvascular reconstruction of the lower jaw followed by adjuvant radiotherapy, the patient was admitted for osteosynthesis plates removal. During clinical examination a tumor located at his left upper arm was detected. According to the patient the tumor has demonstrated rapid growth. Macroscopic appearance and conventional imaging led to the differential diagnosis of an abscess. MR-imaging could not differentiate between a tumor of soft tissue origin and a metastasis. A biopsy was taken and the pathological examination confirmed the diagnosis of an OSCC metastasis. The postoperative interdisciplinary tumor board recommended radiation therapy. CONCLUSION: Due to the fact that patients with regional lymph node metastases have a higher probability to develop distant metastasis a more detailed screening might be considered--especially when hemangiosis carcinomatosa was histologically or macroscopically found.

The outcome after surgical therapy of bisphosphonate-associated osteonecrosis of the jaw--results of a clinical case series with an average follow-up of 20 months.

OBJECTIVES: The present case series evaluates the success rate of osteotomy and primary wound closure in patients with bisphosphonate-associated osteonecrosis of the jaw (BRONJ). MATERIALS AND METHODS: Eighty patients suffering from BRONJ were included in the study. All patients received intravenous bisphosphonate therapy and underwent osteotomy and primary wound closure according to a standardised protocol. After discharge, the patients were reviewed on a regular basis over an average time period of 20 months. RESULTS: During follow-up in 11 patients, a recurrence of BRONJ occurred in the former operation field. Seventeen patients died due to their underlying disease. The success rate of osteotomy and primary wound closure in the treatment of BRONJ was calculated at 84.2 % 20 months after surgery. The results showed non-significant difference concerning the outcome of surgery in the different clinical stages of BRONJ. CONCLUSIONS: In accordance with previous studies, stage-independent osteotomy and primary wound closure combined with antibiotics shall be deemed a viable treatment option in patients suffering from BRONJ. CLINICAL RELEVANCE: With a high success rate, osteotomy in combination with primary wound closure seems to be a viable alternative to more conservative protocols in the treatment of BRONJ.

Dental treatment on a German warship during a three-month deployment.

INTRODUCTION: Despite routine dental screenings and treatments before military deployments, dental emergencies may arise due to acute infections, trauma or failed restorations. The purpose of this study is to evaluate the dental service during a three-month deployment on a German warship. METHODS: A retrospective analysis of dental attendances and treatments in a German naval task group of three ships with an average total of 650 soldiers. Diagnosis, treatments performed, percentage of emergencies, routine procedures and numbers of appointments were recorded. RESULTS: Out of 650 soldiers, there were 71 patients (10.92%) with a mean age of 25.1 ±5 .3 years. Out of 136 treatments, 17.65% were for emergency treatment, which is equivalent to 3.69% of all servicemen of the task group. Combining the reasons for dental emergencies, 95.84% were caused by caries. CONCLUSIONS: The pre-screening of sailors before an overseas deployment is necessary to avoid severe dental treatments. Caries remains the main cause for dental emergencies, and medical doctors should be trained to treat caries lesions if a dentist is not on board.

Mandibular reconstruction using intraoral microvascular anastomosis following removal of an ameloblastoma.

Ameloblastoma is a histologically benign, locally aggressive tumor arising from the odontogenic ectoderm. It accounts for 1% of all oral tumors and for 9% to 11% of all odontogenic tumors. In up to 96.6%, the tumor can be found in the mandible, predominantly in the molar region. High recurrence rates of up to 90% have been described with conservative treatment. Recurrences most often occur after 2 to 5 years. After radical resection, significantly lower recurrence rates have been reported, sometimes as low as 3.6%. As a consequence, when recurrence rate is the main concern, there is a tendency to prefer radical resection of the ameloblastoma. Microvascular segmental reconstruction of the mandible that uses an intraoral anastomosis technique has not been described in the current literature. Therefore, the present study aimed at extending the armamentarium of bony microvascular reconstruction in cases of segmental mandibulectomy by describing an intraoral microvascular anastomosing technique.

Intraoral microvascular anastomosis for segmental mandibular reconstruction following removal of an ameloblastoma.

Cases of immediate bony microvascular reconstruction following segmental mandibulectomy in children are hard to find in the current literature. Moreover, microvascular segmental mandibular reconstruction that adopts an intraoral anastomosis technique has not been described so far. Therefore, the present clinical report aims at extending the armamentarium of bony microvascular reconstruction in pediatric cases of segmental mandibulectomy by highlighting an intraoral microvascular anastomosing technique.A 6-year-old boy, who suffered from an ameloblastoma of the mural type in the mandible, received a radical segmental mandibular resection because of the high recurrence rate of this tumor entity. Immediate reconstruction was carried out with a fibular double-barrel graft. Microvascular anastomoses were performed in an end-to-end fashion with the facial artery and vein as recipient vessels. The postoperative course was uneventful. There was no impairment of speech, deglutition, mastication, and facial nerve function. The facial appearance remained unobtrusive. On removal of the reconstruction plate 3 months after the reconstruction procedure, bleeding from the reconstructed mandibular segment indicated vascularization of the graft.It seems that segmental mandibulectomy and simultaneous microvascular bony reconstruction do not necessarily lead to impaired function as far as speech, deglutition, and mastication are concerned. Instead, the intraoral anastomosis technique allows waiving extraoral skin incisions and subsequent scarring, leaving the facial appearance unchanged and unobtrusive. Especially, the potential risk of stigmatization of the patient is avoided. Therefore, decision making in the choice of 1 or the other reconstruction option following segmental mandibulectomy should always consider the adoption of an intraoral anastomosing technique.

The diameter of anodic TiO2 nanotubes affects bone formation and correlates with the bone morphogenetic protein-2 expression in vivo.

INTRODUCTION: Recently, it has been demonstrated that the nanoscale environment is a critical factor for cellular behaviour. It has been shown that the diameter of TiO2 nanotube layers controls the cellular behaviour of cells involved in the bone-forming process in vitro. Therefore, the aim of the present study was to investigate the effects of the diameter of TiO2 nanotubes on peri-implant bone formation and the expression of bone matrix proteins in vivo. MATERIALS AND METHODS: Ninety experimental implants with a nanotube diameter ranging from 15 up to 100 nm were placed in the frontal skulls of six domestic pigs, whereas untreated implants served as controls. The bone-implant contact (BIC) as well as the expression of bone morphogenetic protein (BMP)-2, collagen type-I and osteocalcin were histomorphometrically and immunohistochemically analysed after 30 days. RESULTS: Evaluating the BIC, a significant higher value, could be found for the 50, 70 and 100 nm groups compared with the controls, whereas a correlation with the BMP-2 expression was present. The BMP-2 expression within the 50, 70 and 100 nm groups was statistically different compared with the control group. Significant difference was found for the osteocalcin expression in the 70 nm group. No statistical difference was found evaluating collagen type-I. SEM evaluation of the specimen surfaces revealed that the nanotube coatings do resist shearing forces evoked by implant insertion. CONCLUSION: The nanotube diameter can be designed to support cellular functions of osteoblasts and osteoclasts in vivo, including differentiation and protein expression and therefore offer a powerful tool for the controlled formation of peri-implant bone around medical implant devices.

Diabetes mellitus negatively affects peri-implant bone formation in the diabetic domestic pig.

AIM: Diabetes mellitus is classified as a relative contraindication for implant treatment, and higher failure rates have been seen in diabetic patients. The aim of the present study was to investigate the effect of diabetes on peri-implant bone formation in an animal model of human bone repair. MATERIALS AND METHODS: Diabetes was induced by an intra-venous application of streptozotocin (90 mg/kg) in 15 domestic pigs. Implants were placed after significant histopathological changes in the hard and soft tissues were verified. The bone-implant contact (BIC), peri-implant bone mineral density (BMD), and expression of collagen type-I and osteocalcin proteins were qualitatively evaluated 4 and 12 weeks after implantation. Fifteen animals served as healthy controls. RESULTS: Diabetes caused pathological changes in the soft and hard tissues. The BIC and BMD were significantly reduced in the diabetic group after 4 and 12 weeks. Collagen type-I was increased in the diabetic group at both time points, whereas osteocalcin was reduced in the diabetic group. CONCLUSIONS: Poorly controlled diabetes negatively affects peri-implant bone formation and bone mineralization. These findings have to be taken into consideration for diabetic patients with an indication for implant therapy.

The effect of combined delivery of recombinant human bone morphogenetic protein-2 and recombinant human vascular endothelial growth factor 165 from biomimetic calcium-phosphate-coated implants on osseointegration.

OBJECTIVES: The delivery of growth factors for enhanced osseointegration depends on the effectiveness of the carrier systems at the bone-implant interface. This study evaluated the effect of solo and dual delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human vascular endothelial growth factor (rhVEGF(165) ) from biomimetically octacalcium phosphate-coated implants on osseointegration. MATERIALS AND METHODS: Biomimetic implants, bearing either a single growth factor (BMP or VEGF) or their combination (BMP+VEGF), were established, and compared with acid-etched (AE, control) and biomimetic implants without growth factor (CAP). Implants were placed into frontal skulls of nine domestic pigs. The quality of osseointegration was evaluated using microradiographic and histomorphometric analysis of bone formation inside four defined bone chambers of the experimental implant at 1, 2 and 4 weeks. RESULTS: Biomimetic implants, either with or without growth factor, showed enhanced bone volume density (BVD) values after 2 and 4 weeks. This enhancement was significant for the BMP and BMP+VEGF group compared with the control AE group after 2 weeks (P<0.05). All biomimetic calcium-phosphate (Ca-P) coatings exhibited significantly enhanced bone-implant contact (BIC) rates compared with the uncoated control surface after 2 weeks (P<0.05). However, the combined delivery of BMP-2 and VEGF did not significantly enhance BIC at the final observation period. CONCLUSION: It was concluded that the combined delivery of BMP-2 and VEGF enhances BVD around implants, but not BIC. Therefore, it may be assumed that changes in the surface characteristics should be considered when designing growth factor-delivering surfaces.

Clinical outcome of patients with orbital fractures treated with patient specific CAD/CAM ceramic implants - A retrospective study.

The aim of this study was to determine whether patients benefit from a secondary reconstruction since it carries the risks of no improvement or worsening of their current situation. Patients treated with individual computer-aided-design/computer-aided-manufacturing (CAD/CAM) ceramic implants were reviewed. To ascertain changes throughout the secondary reconstruction, the study investigators reviewed ophthalmological examinations, took volumetric measurements of the orbits and asked the patients for evaluation of their situation before and after the reconstruction. Points addressed were double vision, visual acuity, field of vision, limitations in daily life and aesthetic considerations. A total of 14 patients were reviewed and 11 answered the questionnaire. Ophthalmological examinations showed that the physical integrity of the eye was maintained. Volumetric measurements preopeatively (33.94 ± 3.24 cm3) and postoperatively (30.67 ± 2.07 cm3) showed that a statistically significant overcorrection of orbital volume leads to good functional and aesthetic outcomes. Patients' subjective opinions were that they greatly benefitted, especially concerning limitations in daily life, which improved by 4.4 ± 2.8 points out of 10 possible points, and aesthetics, with an improvement of 5.9 ± 1.78 points. Based on these findings, we conclude that secondary reconstructions contribute to improvement of the patients' quality of life and therefore should be considered as an option to improve patients' condition.

Establishment of a streptozotocin-induced diabetic domestic pig model and a systematic evaluation of pathological changes in the hard and soft tissue over a 12-month period.

OBJECTIVE: The number of diabetic patients in need of medical treatment is growing steadily. Therefore, a diabetic animal model with high degree of similarities with humans, which is suitable for the systematic evaluation of biomaterials and medical devices, is needed. MATERIALS AND METHODS: Twenty domestic pigs were used for the study. Fifteen received Streptozotocin (STZ) to induce diabetes mellitus. Internal parameters were measured and bone as well as soft tissues biopsies were taken after 0, 6 and 12 months and evaluated qualitatively and quantitatively by means of scanning electronic microscopy, light microscopy and microradiography. RESULTS: The results of the clinical internal parameters, determined by the American Diabetes Association for the definition of diabetes mellitus could be fulfilled. Pathological changes of the skin vasculatures were already visible after 6 months with a significant wall thickening in the diabetic group. The bone mineralization was lower in the diabetic group after 6 months and with a significant difference after 12 months. CONCLUSION: From the present results, it can be concluded that a STZ dosage of 90 mg/kg body weight in the domestic pig is suitable for the induction of an apparent diabetes, leading to histolopathological changes in the hard and soft tissues already after 6 months. The high degree of similarities with humans makes it an interesting diabetic animal model for biomaterial research in a compromised animal model.

The influence of nanoporous anodic aluminum oxide on the initial adhesion of Streptococcus mitis and mutans.

The use of nanoscale surface modifications offers a possibility to regulate the bacterial adherence behavior. The aim of this study was to evaluate the influence of nanoporous anodic aluminum oxide of different pore diameters on the bacterial species Streptococcus mitis and Streptococcus mutans. Nanoporous anodic aluminum oxide (AAO) surfaces with an average pore diameter of 15 and 40 nm, polished pure titanium and compact aluminum oxide (alumina) samples as reference material were investigated. S. mitis and mutans were evaluated for initial adhesion and viability after an incubation period of 30 and 120 min. After 30 min a significantly reduced growth of S. mitis and mutans on 15 nm samples compared to specimens with 40 nm pore diameter, alumina and titanium surfaces could be observed (p < .001). Even after 120 min incubation there was a significant difference between the surfaces with 15 nm pore diameter and the remaining samples (p < .001). AAO surfaces with a small pore diameter have an inhibitory effect on the initial adhesion of S. mitis and mutans. The use of such pore dimensions in the area of the implant shoulder represents a possibility to reduce the adhesion behavior of these bacterial species.

In vitro behavior of layer-by-layer deposited molecular oligoelectrolyte films on Ti-6Al-4V surfaces.

Layer-by-layer self-assembled films of molecular oligoelectrolytes were used to modify Ti-6Al-4V surfaces in order to test their ability as potential drug delivery system. With regard to medical application the in vitro behavior of the modified material was investigated. The Ti-6Al-4V (6% aluminium, 4% vanadium) material was treated in a layer-by-layer (LbL) process with 2, 4, 6 and 8 layers of molecular oligoelectrolytes 1 and 2 and thereby doped with a fluorescent reporter molecule 2. Human osteoblasts were cultured for a period up to 5 days on the modified material. Ti-6Al-4V surfaces without modification were used as control. In order to investigate the in vitro behavior of the coating as well as the influence of components of the coating on osteoblastic cells, respectively, cell proliferation, differentiation and attachment of hFOB cells were observed by means of cell number, osteoblastic gene expression and fluorescence microscopy. Degradation behavior of the OEM (oligoelectrolyte multilayer film) was examined using optical spectroscopy. Measurement data imply that the layer-by-layer coating was successfully assembled on the Ti surface and endures steam sterilization. The fluorescence signal in cell culture medium increased strictly linear with increasing pre-assembled number of layers on the surface. Proliferation rates of the cells in experimental groups did not differ significantly from each other (P >or= 0.783). Differentiation pattern was not significantly changed by the coating. The fluorescent reporter component of the film was absorbed by osteoblastic cells and was detected by fluorescence microscopy.

Antiseptic negative pressure instillation therapy for the treatment of septic wound healing deficits in oral and maxillofacial surgery.

INTRODUCTION: Impaired wound healing, chronic wounds and extended soft tissue defects present a crucial problem in reconstructive surgery of the head and neck region, even more after radiation therapy. In such cases the standard is a prolonged open wound treatment. The negative pressure instillation therapy might present an alternative therapy option. MATERIAL AND METHODS: In this study the effects of negative pressure instillation therapy on the healing of chronic wounds in 15 patients diagnosed with impaired wound healing were investigated. These based upon infected osteoradionecrosis and osteomyelitis of the jaw. The parameters investigated as markers of the therapeutic success were serum inflammatory parameters i.e. white blood cell counts, wound smear results and wound surface reduction. RESULTS: The use of negative pressure instillation therapy lead to a reduction of the bacterial load and formation of a stabile granulation tissue in all but one case. The mean inpatient time of the patients was 13.33 ± 4.62 days. Between 2 and 8 dressing changes were needed to reach clinical sufficient wound healing results. Secondary intention wound healing could be obtained in 14 out of 15 cases. The crucial part for the successful application was a watertight enoral suturing as oro-cutaneous fistulae were present in most cases. CONCLUSION: The negative pressure instillation therapy poses a good treatment for wound healing problems and extended size soft tissue defects, even when oro-cutaneous fistulae were present. Especially in cases that contraindicate micro-vascular reconstruction, negative pressure instillation therapy could be a good alternative.