Tilo Schlittenbauer

Major histocompatibility complex class II polymorphisms are associated with the development of anti-resorptive agent-induced osteonecrosis of the jaw

The aetiology of anti-resorptive agent-induced osteonecrosis of the jaw (ARONJ) is still under debate. Clinical and genetic risk factors are currently being investigated to help understand its pathogenesis. This case-control study analysed a large number of cancer patients (n = 230) under therapy with intravenous bisphosphonates, half of which were diagnosed with ARONJ. Multiple myeloma, greater patient age and the use of more than one bisphosphonate were identified as clinical risk factors on logistic regression analysis. In addition, 204 patients were genotyped for HLA-DRB1 and DQB1 and the allele frequencies were compared between ARONJ (n = 94) and unaffected cancer patients (n = 110). For the HLA class II alleles, a strong increase in the frequency of DRB1*15, DQB1*06:02, DRB1*01 and DQB1*05:01 was observed in the ARONJ group. These results were reinforced on analysis of the respective haplotypes, with DRB1*15-DQB1*06:02 being significantly associated with the development of ARONJ (odds ratio [OR] 2.5; 95% confidence interval [CI] 1.3-5.0). The presence of at least one of the haplotypes DRB1*15-DQB1*06:02 and DRB1*01-DQB1*05:01 was highly associated with the development of ARONJ (OR 3.0; 95% CI 1.7-5.5). The data in this study of a large number of cancer patients receiving intravenous bisphosphonates suggest that MHC class II polymorphisms represent genetic risk factors for the development of ARONJ. This result supports recent findings that inflammation and infection might play an important role in the pathogenesis of ARONJ.

Implant-based rehabilitation in oncology patients can be performed with high long-term success.

PURPOSE Radiotherapy and compromised vital bone and/or surrounding soft tissue can be a challenge to the successful osseointegration of dental implants. We evaluated the long-term results of dental implants in patients with oral cancer. MATERIALS AND METHODS To address the research purpose, we designed and implemented a retrospective cohort study that included patients with oral cancer who had received dental implants from 2003 to 2011. The data were collected from a clinical oncology database. The predictor variables included a set of heterogeneous variables grouped into logical sets of demographics, surgical treatment, dental rehabilitation, radiotherapy type, and tumor entity. The primary outcome variable was implant survival; the secondary outcome variable was peri-implantitis. The descriptive statistics, survival time analysis, Kaplan-Meier implant survival curves, and Cox hazard proportional modeling were computed. RESULTS The study sample included 59 patients with oral cancer (20 women [33.9%], 39 men [66.1%]; mean age at tumor diagnosis, 55 years), who had had 272 implants placed during the study period. The mean follow-up period was 30.9 months (range 3 to 82). Of the 272 implants, 269 (98.9%) and 264 (97.1%) had survived for 2 and 5 years, respectively. During the observation period, 10 implants were lost (3.7%). Of the implant failures, 82% occurred in transplanted bone (4 fibula flaps, 4 iliac crests, and 2 native mandibles). We observed peri-implantitis caused by insufficiently attached gingiva and bone loss in 182 of the implants (67%). The factors associated with implant failure were peri-implantitis, insufficient soft and hard tissue, muscle dysfunction, and xerostomia. CONCLUSIONS Implant-based rehabilitation in oncology patients can achieve a high long-term success rate, although risk factors such as impaired muscle function and a high frequency of peri-implantitis can affect healing.

Assessment of free microvascular flap perfusion by intraoperative fluorescence angiography in craniomaxillofacial surgery

Microsurgical tissue transfer represents a standard technique for reconstruction in craniomaxillofacial surgery. The transferred tissue is anastomosed to vessels of varying diameters and different physiological conditions. The aim of this study was to evaluate the blood flow in free flaps at their origin and compare this with the flow after reperfusion. In 24 patients undergoing microsurgical procedures (13 radial forearm free flaps (RFFF) and 11 parascapular/scapular free flaps (PSFF)), blood flow was evaluated by intraoperative fluorescence angiography after flap raising and again after reperfusion in the neck area (Flow800, Carl Zeiss AG, Oberkochen, Germany). Flow is expressed by the blood flow index (BFI), maximum intensity (MaxInt) and half-time to MaxInt (t1/2) and was measured in the flap pedicle itself, as well as in the supplying vessels. Following anastomosis of the free flaps in the head and neck area, both the arterial and the venous BFI and MaxInt significantly increased, whereas t1/2 decreased significantly. There was no significant difference in the perfusion parameters between RFFF and PSFF. Intraoperative fluorescence angiography is a reliable method for assessing the perfusion of free microvascular flaps. In the head and neck area, free flaps undergo a significant increase in perfusion but show no differences between varying flap types.

Positron emission tomography–computed tomography versus positron emission tomography–magnetic resonance imaging for diagnosis of oral squamous cell carcinoma: A pilot study

Diagnostic imaging of head and neck cancer has made enormous progress during recent years. Next to morphological imaging modalities (computed tomography [CT] and magnetic resonance imaging [MRI]), there are also hybrid imaging systems that combine functional and morphological information (positron emission tomography [PET]/CT and PET/MRI). The aim of this study was to compare the diagnostic accuracy of PET/MRI in the diagnosis of head and neck cancer with other imaging modalities (MRI, CT, PET/CT). Ten patients (nine male and one female) with histologically proven oral squamous cell carcinoma participated in an 18 F-FDG-PET/CT scan and an additional 18 F-FDG PET/MRI scan prior to surgery. The morphological and functional results were compared with the histological results. Inclusion criteria were histologically proven oral squamous cell carcinoma and no prior surgical intervention, medical therapy, or local external radiation. There was no significant correlation between tumor differentiation and maximum standard uptake values. Functional imaging showed a slightly better correlation with the measurement of the maximal tumor diameter, whereas pure morphological imaging showed a better correlation with the measurement of infiltration depth. Only with PET/MRI could correct lymph node staging be reached; the other imaging tools showed false-negative or false-positive results. In conclusion, we showed in our limited patient cohort that PET/MRI is superior to the morphological imaging modalities, especially for lymph node staging.

Macrophage polarization differs between apical granulomas, radicular cysts, and dentigerous cysts

ObjectivesApical periodontitis can appear clinically as apical granulomas or radicular cysts. There is evidence that immunologic factors are involved in the pathogenesis of both pathologies. In contrast to radicular cysts, the dentigerous cysts have a developmental origin. Macrophage polarization (M1 vs M2) is a main regulator of tissue homeostasis and differentiation. There are no studies comparing macrophage polarization in apical granulomas, radicular cysts, and dentigerous cysts.Materials and methodsForty-one apical granulomas, 23 radicular cysts, and 23 dentigerous cysts were analyzed in this study. A tissue microarray (TMA) of the 87 consecutive specimens was created, and CD68-, CD11c-, CD163-, and MRC1-positive macrophages were detected by immunohistochemical methods. TMAs were digitized, and the expression of macrophage markers was quantitatively assessed.ResultsRadicular cysts are characterized by M1 polarization of macrophages while apical granulomas show a significantly higher degree of M2 polarization. Dentigerous cysts have a significantly lower M1 polarization than both analyzed periapical lesions (apical granulomas and radicular cysts) and accordingly, a significantly higher M2 polarization than radicular cysts. Macrophage cell density in dentigerous cysts is significantly lower than in the periapical lesions.ConclusionsThe development of apical periodontitis towards apical granulomas or radicular cysts might be directed by macrophage polarization. Radicular cyst formation is associated with an increased M1 polarization of infiltrating macrophages. In contrast to radicular cysts, dentigerous cysts are characterized by a low macrophage infiltration and a high degree of M2 polarization, possibly reflecting their developmental rather than inflammatory origin.Clinical relevanceAs M1 polarization of macrophages is triggered by bacterial antigens, these results underline the need for sufficient bacterial clearance during endodontic treatment to prevent a possible M1 macrophage-derived stimulus for radicular cyst formation.

Skeletal stability and complications in transantral maxillary distraction in patients with cleft lip and palate.

AbstractThe current prospective study aimed at assessing skeletal stability and complications arising from transantral maxillary distraction adopted for advancements of less than 12 mm in patients with cleft lip, alveolus, and palate malformations.The recruited patients with cleft lip, alveolus, and palate were followed up for 12 months. Lateral skull radiographs were obtained before surgery (T0), at the end of the activation period of the distractors (T1), and after completion of the follow-up interval (T2). Length and height of the maxilla were assessed at the different points of time. The relapse rate of maxillary advancement was calculated. Complications such as infections, distractor breakage and loosening, nonunions, and the need for reoperation were documented.Seven patients were included in this study (mean [SD] age, 19.5 [2.6] y). The length of the maxilla significantly increased by 6.4 ± 1.1 mm at T1 (P = 0.018) but showed a significant relapse by 7.5% at T2 (P = 0.018). As a complication, a case of infection of the cheek occurred during the consolidation period, which could be treated conservatively. In an additional patient, there was a loosening of a distractor at the end of the distraction period, which required reoperation with conventional fixation of the maxilla in the intended position. At the time of removal of the distractors and the conventional osteosynthesis plates, no cases of nonunion could be identified.It seems that the low horizontal relapse rate of transantral maxillary distraction in patients with cleft lip and palate outweighs the possible complications of this procedure in cases of limited distances of advancement of less than 12 mm.

Masticatory Rehabilitation of a Patient With Cleft Lip and Palate Malformation Using a Maxillary Full-Arch Reconstruction With a Prefabricated Fibula Flap

For full-arch reconstruction of an atrophied cleft maxilla with missing premaxilla, a prefabricated microvascular free bony flap is a relevant option. A fibula flap was prefabricated in a cleft patient who received six dental implants and an epithelial layer. Six weeks later, maxillary reconstruction was performed. The inpatient period could be confined to 2 weeks. A fixed provisional prosthesis was delivered after an additional 2 weeks. A prefabricated flap allows for the reduction of the interval without a dental prosthesis to only a few weeks, even when a complex full-arch reconstruction of the maxilla is required.