Major influencing factors on routine implementation of shared decision-making in cancer care: qualitative process evaluation of a stepped-wedge cluster randomized trial.

BACKGROUND: Shared decision-making (SDM) is highly relevant in oncology but rarely implemented in routine care. In a stepped-wedge cluster randomized implementation trial, the outcome evaluation of a theoretically and empirically based multi-component SDM implementation program did not show a statistically significant effect on patient-reported SDM uptake. Within this SDM implementation trial, a thorough a priori planned process evaluation was conducted. Thus, the aim of this study was to investigate factors influencing SDM implementation in the context of a multi-component SDM implementation program. METHODS: We conducted qualitative process evaluation of a stepped-wedge SDM implementation trial. Qualitative data included interviews with nurses and physicians of participating departments, field notes by the study team, and meeting minutes. Data were analyzed via deductive and inductive qualitative content analysis on basis of the Consolidated Framework for Implementation Research (CFIR). RESULTS: Transcripts of 107 interviews with 126 nurses and physicians, 304 pages of field note documentation, and 125 pages of meeting minutes were analyzed. Major factors influencing SDM implementation were found for all domains of the CFIR: a) four regarding characteristics of the individuals involved (e.g., perceived personal relevance, individual motivation to change), b) eleven regarding the inner setting (e.g., leadership engagement, networks and communication, available resources, compatibility with clinical practice), c) two regarding the outer setting (e.g., culture of health care delivery), d) eight regarding characteristics of the intervention (e.g., relative advantage, adaptability), and e) three regarding the implementation process (e.g., integration into existing structures). Furthermore, we found strong interrelations between several of the influencing factors within and between domains. CONCLUSIONS: This comprehensive process evaluation complements the outcome evaluation of the SDM implementation trial and adds to its interpretation. The identified influencing factors can be used for planning, conducting, and evaluating SDM implementation in the future. TRIAL REGISTRATION: clinicaltrials.gov, NCT03393351, registered 8 January 2018, https://clinicaltrials.gov/ct2/show/NCT03393351.

Parotid sparing and quality of life in long-term survivors of locally advanced head and neck cancer after intensity-modulated radiation therapy.

PURPOSE: Intensity-modulated radiation therapy (IMRT) enables radiation oncologists to optimally spare organs at risk while achieving homogeneous dose distribution in the target volume. Despite great advances in technology, xerostomia is one of the most detrimental long-term side effects after multimodal therapy in patients with locally advanced head and neck cancer (HNC). This prospective observational study examines the effect of parotid sparing on quality of life in long-term survivors. PATIENTS AND METHODS: A total of 138 patients were grouped into unilateral (n = 75) and bilateral (n = 63) parotid sparing IMRT and questioned at 3, 24, and 60-month follow-up using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-H&N35 questionnaires. Treatment-related toxicity was scored according to the RTOG/EORTC toxicity criteria. Patients' QoL 24 and 60 months after IMRT was analyzed by ANCOVA using baseline QoL (3 months after IMRT) as a covariate. RESULTS: Patients with bilateral and unilateral parotid-sparing IMRT surviving 60 months experience similar acute and late side effects and similar changes in QoL. Three months after IMRT, physical and emotional function as well as fatigue, nausea and vomiting, pain, dyspnea, and financial problems are below (function scales) or above (symptom scales) the threshold of clinical importance. In both groups, symptom burden (EORTC H&N35) is high independent of parotid sparing 3 months after IMRT and decreases over time in a similar pattern. Pain and financial function remain burdensome throughout. CONCLUSION: Long-term HNC survivors show a similar treatment-related toxicity profile independent of unilateral vs. bilateral parotid-sparing IMRT. Sparing one or both parotids had no effect on global QoL nor on the magnitude of changes in function and symptom scales over the observation period of 60 months. The financial impact of the disease and its detrimental effect on long-term QoL pose an additional risk to unmet needs in this special patient population. These results suggest that long-term survivors need and most likely will benefit from early medical intervention and support within survivorship programs.

Combination of Rigid and Nonrigid Fixation Versus Nonrigid Fixation for Bilateral Mandibular Fractures: A Multicenter Randomized Controlled Trial.

PURPOSE: We aimed to compare complication rates and functional outcomes in patients with bilateral mandibular fractures treated with different degrees of internal fixation rigidity. PATIENTS AND METHODS: This international, multicenter randomized controlled trial included adults with bilateral mandibular fractures located at either the angle and body, angle and symphysis, or body and symphysis. Patients were treated with either a combination of rigid fixation for the anterior fracture and nonrigid fixation for the posterior fracture (mixed fixation) or nonrigid fixation for both fractures. The primary outcome was complications within 6 weeks after surgery. Secondary outcomes were complications within 3 months, Helkimo dysfunction index, and mandibular mobility at 6 weeks and 3 months after surgery. RESULTS: Of the 315 patients enrolled, 158 were randomized to the mixed fixation group and 157 to the nonrigid fixation group. The overall complication rate at 6 weeks in the intention-to-treat population was 9.6% (95% confidence interval [CI], 5.3% to 15.6%) in the mixed fixation group and 7.8% (95% CI, 4.0% to 13.5%) in the nonrigid fixation group. With an unadjusted odds ratio of 1.25 (95% CI, 0.51 to 3.17), there were no statistically significant differences in complication rates between the 2 groups (P = .591). A multivariable model for complication risk at 6 weeks found no significant differences between treatment groups, but patients with moderate or severe displacement had a higher complication rate than those with no or minimal displacement (adjusted odds ratio, 4.58; 95% CI, 1.16 to 18.06; P = .030). There were no significant between-group differences in complication rates at 3 months. Moreover, no significant differences in Helkimo dysfunction index and mandibular mobility index at 6 weeks and 3 months were found between groups according to treatment allocated and treatment received. CONCLUSIONS: A combination of rigid and nonrigid fixation in patients with bilateral mandibular fracture has similar complication rates and functional outcomes to nonrigid fixation for both fractures.

Analysis of outcome for elderly patients after microvascular flap surgery: a monocentric retrospective cohort study.

OBJECTIVES: Increasingly, aging societies pose a challenge, particularly in the most developed countries. This trend leads to an increasing group of old and very old patients presenting unique requirements and challenges. One of these challenges consists in reassessment and adaption of established treatment strategies for the elderly patients. There is an ongoing discussion taking place among cranio-maxillo-facial surgeons about the appropriate extent of reconstructive flap surgery for old patients. MATERIALS AND METHODS: This monocentric retrospective cohort study investigated 281 reconstructions with microvascular flaps by comparing the risk for a negative outcome, which was defined as revision, flap loss, and patient death, between three subgroups of elderly patients and younger patients. The three subgroups of elderly patients were defined as-1: young old (65-74 years), 2: old (75-84 years), and 3: oldest old (≥ 85 years). The group of the younger patients was defined by age between 50 and 64 years. Data were obtained within a defined period of 42 months. RESULTS: Significant correlations with a negative outcome were found for the variables stay on IMC/ICU, multiple flaps, and radiotherapy prior surgery. Our data showed no significant correlation between age and a higher risk for a negative outcome. CONCLUSION: Defect reconstruction with microvascular flaps in old patients is not related with a higher risk for a negative outcome. CLINICAL RELEVANCE: Independently of age, treatment with microvascular flaps is an option for all operable patients, with an indication for oncologic surgery. For optimal therapy planning, individual patient resources and preferences should be considered instead of chronologic age.

Survivin expression in head and neck squamous cell carcinomas is frequent and correlates with clinical parameters and treatment outcomes.

OBJECTIVES: Strong expression of survivin is associated with worse survival in many different tumours, and in cell culture, a correlation between radiation resistance and survivin expression can be seen. The potential of survivin expression as a prognostic/predictive marker or therapeutic target has not been examined in head and neck squamous cell carcinomas (HNSCC) yet. MATERIAL AND METHODS: Retrospective study of 452 tissue samples and clinical data from patients with squamous cell carcinomas of the larynx/hypopharynx (LSCC), oral cavity (OSCC) and oropharynx (OPSCC) treated in the University Medical Centre Hamburg-Eppendorf between 2002 and 2006. The expression patterns were detected by tissue microarray technique and correlated with clinical parameters (sex, age, tumour location, TNM 7th edition, grading, recurrence-free and overall survival). RESULTS: 222 OSCC, 126 OPSCC and 105 LSCC tumours of 118 females and 335 males with a mean follow-up of 41.3 months were examined. Survivin expression correlates with pN, cM, pT and overall survival. CONCLUSION AND CLINICAL RELEVANCE: The potential of survivin as a prognostic/predictive marker is very high. The findings have to be confirmed in a larger cohort of HNSCC esp. in those tumours treated primarily with radio/radiochemotherapy.

Evaluation of long-term functional donor-site morbidity after deep circumflex iliac crest artery bone flap harvest.

PURPOSE: Free flap surgery can be associated with donor-site morbidity. The purpose of this study was to analyze long-term functional outcomes at the donor site after deep circumflex iliac artery (DCIA) bone flap harvesting. METHODS: Fourteen patients (8 men and 6 women, mean age 53.9 years; range 22-87 years) with mandible resection (8 carcinomas, 4 ameloblastomas, 1 osteonecrosis, and 1 myxofibroma) and DCIA flap reconstruction were included in an observational study. Ranges of motion in the hip and lumbar spine, Harris hip score (HHS), jumping mechanography, chair rising, and balance testing were performed on a ground force reaction plate (Leonardo Mechanograph, Novotec Medical GmbH, Germany). The primary outcome was the Esslinger fitness index (EFI, maximum peak power in W/kg normalized to age and gender). RESULTS: Functional assessment was performed preoperatively and 29.0 months postoperatively (range 12-51 months). Mean DCIA flap length was 6.3 cm (range 3.3-10.1 cm). Jaw reconstruction was successful in all cases. HHS (99.2 vs. 97.7 points, P = .004) and all ranges of motion in the lumbar spine and hip joint except for dorsal extension were significantly reduced postoperatively (range -4° to -11.0°). There was no significant difference between pre- and postoperative EFI (77.9% vs. 74.28%, P = .591) and body sway (1.25 cm2 vs. 2.01 cm2 , P = .806). Sensory deficits (n = 5), load dependent pain (n = 3), and limitations of daily activities (n = 3) were subjective complaints. CONCLUSION: Functional donor site morbidity after DCIA harvesting can be expected to be low in the long-term.

EZH2 overexpression in head and neck cancer is related to lymph node metastasis.

BACKGROUND: Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the polycomb repressive complex 2, plays an important role in tumor development and progression by interacting with histone and non-histone proteins. EZH2 represents a putative therapeutic target and has been suggested as a prognostic marker in several cancer types. MATERIAL AND METHODS: This study investigates the prognostic relevance of immunohistochemical EZH2 expression in head and neck squamous cell carcinoma. Tissue microarray sections with 667 cancers of oral cavity, oro- and hypopharynx and larynx were analyzed for EZH2 expression. RESULTS: Nuclear EZH2 staining was recorded in 322 (81.8%) of 394 cases. Staining was weak in 33 (10.2%), moderate in 128 (39.6%), and strong in 103 (32.0%) cancers. The prevalence of EZH2 expression in tumors of the oral cavity and the orohypopharynx was higher as compared to cancers of the larynx (P = .0023). EZH2 expression was correlated to presence of lymph node metastasis (P = .0089) but was unrelated to histological grade, tumor stage, surgical margin, or distant metastasis. EZH2 expression had no impact on patient survival. CONCLUSION: The high prevalence of EZH2 expression in head and neck squamous cell carcinoma stresses its capability as a therapeutic target.

Changes in surface characteristics of titanium and zirconia after surface treatment with ultraviolet light or non-thermal plasma.

Positive effects of irradiation with ultraviolet (UV) light or treatment with non-thermal plasma on titanium and zirconia surfaces have been described in various studies. The aim of this study was to assess and compare the changes in the physicochemical surface conditions of titanium and zirconia surfaces after a short treatment with UV light or with non-thermal plasmas of argon or oxygen. Titanium and zirconia samples with moderately rough surfaces were treated for 12 min either in a UV-light oven or in a non-thermal plasma reactor that generates non-thermal plasmas of oxygen or argon. Changes in surface conditions were assessed by confocal microscopy, dynamic contact angle measurement, and X-ray photoelectron spectroscopy (XPS). No changes in roughness occurred. Ultraviolet irradiation and non-thermal plasma significantly increased the wettability of the titanium and zirconia surfaces. X-ray photoelectron spectroscopy showed an increase of oxygen and a significant decrease of carbon after treatment with either method. Thus, ultraviolet light and non-thermal plasma were found to be able to improve the chemical surface conditions of titanium and zirconia following a short exposure time. However, further in vitro and in vivo studies are needed to determine the relevance of the results.

Postoperative bleeding risk for oral surgery under continued rivaroxaban anticoagulant therapy.

OBJECTIVES: The purpose of this study was to assess the risk of postoperative bleeding complications after oral procedures performed under continued mono or dual anticoagulation therapy with rivaroxaban (and aspirin). METHODS: This retrospective single-center observational study included 52 oral procedures performed under continued oral anticoagulant therapy with rivaroxaban (20 mg/day). Among them, two procedures were performed under continued dual therapy with aspirin (100 mg/day) added to the regimen. Postoperative bleeding events were compared with 285 oral procedures in patients without any anticoagulation/antiplatelet therapy. RESULTS: Postoperative bleeding complications after oral surgery occurred significantly more often in patients under continued rivaroxaban therapy (11.5 %) than in the control cases without anticoagulation/antiplatelet medication (0.7 %). All of the bleeding events were manageable: Two of them were treated with local compression, three by applying new fibrin glue with (one case) or without (two cases) secondary sutures, one occurred during a weekend and was therefore treated under inpatient conditions with suture replacement. All postoperative bleeding episodes occurred during the first postoperative week. CONCLUSIONS: According to our data, continued anticoagulation therapy with rivaroxaban significantly increases postoperative bleeding risk for oral surgical procedures, although the bleeding events were manageable. CLINICAL RELEVANCE: Oral surgeons, cardiologists, general physicians, and patients should be aware of the increased bleeding risk after oral surgical procedures. Close observation up to 1 week postoperatively is advisable to prevent excessive bleeding.

Linear accuracy and reliability of volume data sets acquired by two CBCT-devices and an MSCT using virtual models: a comparative in-vitro study.

OBJECTIVE: To discriminate clinically relevant aberrance, the accuracy of linear measurements in three-dimensional (3D) reconstructed datasets was investigated. MATERIALS AND METHODS: Three partly edentulous human skulls were examined. Landmarks were defined prior to acquisition. Two CBCT-scanners and a Quad-slice CT-scanner were used. Actual distances were physically measured with calipers and defined as a reference. Subsequently, from digital DICOM datasets, 3D virtual models were generated using maximum intensity projections (MIPs). Linear measurements were performed by semi-automated image analysis. Virtual and analogue linear measurements were compared using repeated measurements in a mixed model (p ≤ 0.05). RESULTS: No significant difference was found among all of the digital measurements when compared to one another, whereas a significant difference was found in matched-pairs analysis between CBCT and calipers (p = 0.032). All digitally acquired data resulted in lower mean values compared to the measurements via calipers. A high level of inter-observer reliability was obtained in the digital measurements (inter-rater correlation = 0.988-0.993). CONCLUSIONS: The reconstructed datasets led to highly consistent values among linear measurements. Yielding sub-millimeter precision, these modalities are assumed to reflect reality in a clinically irrelevant altered manner. During data acquisition and evaluation, a maximum of precision must be achieved.

Localized thermal tumor destruction using dye-enhanced photothermal tumor therapy.

BACKGROUND AND OBJECTIVE: In an attempt to develop a new therapeutic approach for highly localized thermal destruction of tissue targets that lack natural pigmentation, the potential of in-vivo dye-enhanced photothermal therapy (PTT) was investigated. PTT involves the application of an exogenous absorber, which accumulates in metabolically active tissues, followed by non-invasive light irradiation, using appropriate wavelengths, exposure durations, and irradiances. The chromophore used, palladium(II) octabutoxynaphthalocyanine (PdNc(OBu)8 ), strongly absorbs in the near infrared wavelength range which thus permits good penetration depth of the exciting light. The predominant de-excitation routes of the chromophore are radiationless thermal processes. MATERIALS AND METHODS: Using a BALB/c mouse model with a subcutaneously implanted syngeneic EMT6 adenocarcinoma, 96-100 hours after intraperitoneal application of PdNc(OBu)8 , tumor, and surrounding tissue were irradiated with a 830 nm continuous wave diode laser applying 30 Wcm(-2) for 10-20 seconds. Treatment parameters were based on theoretical calculations. RESULTS: Histological evaluation of thermal effects on tumor and normal tissue showed that after PdNc(OBu)8 -enhanced photothermal treatment, highly localized and selective thermal damage of the tumors was achieved. The necrotic tumor area was invaded by inflammatory cells, including neutrophils, macrophages, mast cells, and lymphocytes, thus reflecting a prominent host immune response. In tumors treated with PTT for 15 or 20 seconds, respectively, only few surviving tumor cells were detected underneath the epidermis. Adjacent peripheral normal tissue including skin and muscle remained completely unaffected. CONCLUSION: This study highlights the potential of achieving irreversible thermal tissue damage closely localized to the target tissue when PdNc(OBu)8 is used in combination with continuous-wave light.

Virtual planning of complex head and neck reconstruction results in satisfactory match between real outcomes and virtual models.

OBJECTIVES: The reconstruction of large facial bony defects using microvascular transplants requires extensive surgery to achieve full rehabilitation of form and function. The purpose of this study is to measure the agreement between virtual plans and the actual results of maxillofacial reconstruction. MATERIALS AND METHODS: This retrospective cohort study included 30 subjects receiving maxillofacial reconstruction with a preoperative virtual planning. Parameters including defect size, position, angle and volume of the transplanted segments were compared between the virtual plan and the real outcome using paired t test. RESULTS: A total of 63 bone segments were transplanted. The mean differences between the virtual planning and the postoperative situation were for the defect sizes 1.17 mm (95 % confidence interval (CI) (-.21 to 2.56 mm); p = 0.094), for the resection planes 1.69 mm (95 % CI (1.26-2.11); p = 0.033) and 10.16° (95 % CI (8.36°-11.96°); p < 0.001) and for the planes of the donor segments 10.81° (95 % CI (9.44°-12.17°); p < 0.001) The orientation of the segments differed by 6.68° (95 % CI (5.7°-7.66°); p < 0.001) from the virtual plan; the length of the segments differed by -0.12 mm (95 % CI (0.89-0.65 mm); not significant (n.s.)), respectively, while the volume differed by 73.3 % (95 % CI (69.4-77.6 %); p < 0.001). The distance between the transplanted segments and the remaining bone was 1.49 mm (95 % CI (1.24-1.74); p < 0.001) and between the segments 1.49 mm (95 % CI (1.16-1.81); p < 0.001). CONCLUSIONS: Virtual plans for mandibular and maxillofacial reconstruction can be realised with excellent match. CLINICAL RELEVANCE: These highly satisfactory postoperative results are the basis for an optimal functional and aesthetic reconstruction in a single surgical procedure. The technique should be further investigated in larger study populations and should be further improved.

Her2 expression and gene amplification is rarely detectable in patients with oral squamous cell carcinomas.

PURPOSE: Her2 (ErbB2) transforms cells when overexpressed and is an important therapeutic target in breast cancer. Contrary to breast cancer, studies on Her2 overexpression and gene amplification in squamous cell carcinomas of the head and neck region described largely different results. This study was undertaken to learn more on the prevalence and clinical significance of HER2 amplification and overexpression in squamous cell carcinomas of the head and neck. MATERIALS AND METHODS: Her2 expression and gene amplification was analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) on two tissue microarrays composed of 427 squamous cell carcinomas of the head and neck region and 222 oral squamous cell carcinomas. Results were compared with clinicopathological features. RESULTS: Her2 expression and gene amplification was rarely detectable in squamous cell carcinomas of the head and neck region and unrelated to tumor phenotype or survival of the patients with oral squamous carcinoma. DISCUSSION: Our results demonstrate that Her2 protein and gene amplification was only detectable in a small subset of squamous cell carcinomas of the head and neck region as well as oral squamous cell carcinomas. However, it can be speculated that those few patients with Her2 overexpressing and gene amplificated tumors may possibly benefit from an anti-Her2 therapy.

CCND1 amplification and cyclin D1 immunohistochemical expression in head and neck squamous cell carcinomas.

OBJECTIVES: Gene products, which show a significant association to cell proliferation and cell cycle control, are of high scientific interest, because genes as well as gene products could be possible targets for a specific therapeutic approach and eventually be prognostic markers. MATERIALS AND METHODS: Cyclin D1 expression and amplification as well as the Ki-67 expression status were examined in a two tissue microarray analysis for head and neck squamous cell carcinoma (HNSCC) including 546 patients. A tumour site-specific analysis and a survival analysis of 222 oral squamous cell carcinoma (OSCC) patients were performed. Cyclin D1 amplification status was examined with fluorescence in situ hybridisation analysis, while cyclin D1 expression and Ki-67 expression status were examined with IHC. RESULTS: Amplification of the CCND1 gene and immunohistochemical expression of cyclin D1 and Ki-67 were examined in 546 tumours of the head and neck region in two tissue microarrays. CCND1 amplification was significantly more frequent in pharyngeal carcinomas (63%) than in laryngeal (37%) and oral (25%) carcinomas. Among the 222 cases of OSCCs, both CCND1 amplification and cyclin D1 expression were significantly associated with overall survival of the patients (p = 0.0127 and p = 0.0004, respectively). Ki-67 expression was significantly associated with cyclin D1 expression and with amplification of the CCND1 gene (p = 0.0002 and p = 0.0015, respectively) but not with patient overall survival. CONCLUSION: Our results suggest the prognostic value of CCND1 amplification and cyclin D1 expression for patients with OSCC and highlight the genetic differences in HNSCC of different subanatomic localisation. CLINICAL RELEVANCE: Cyclin D1 expression and CCND1 amplification seem to have a prognostic value for OSCC. Further studies of HNSCC should always consider subanatomic genetic differences.

P53 immunohistochemical expression does not correlate with clinical features in 207 carcinomas of the oral cavity and in the head and neck region.

OBJECTIVES: The present study aims to investigate the relevance of immunohistochemical p53 expression in carcinomas of the oral cavity and of the head and neck region. Long-term clinical and histopathological follow-up findings as well as HPV status are correlated with the results of this examination. MATERIALS AND METHODS: Sections made from two tissue arrays composed of 222 oral squamous cell carcinomas and 427 squamous cell carcinomas of the head and neck region, respectively, were examined for p53 expression and Ki-67 index by means of immunohistochemistry. Correlation of long-term clinical findings of the patients and pathological features of tumours with laboratory results were examined statistically. RESULTS: No significant correlation was found between the p53 immunohistochemical expression in the 207 oral carcinomas and features of the tumours and patient outcomes. There was no significant association between the Ki-67 labelling index and the p53 expression. DISCUSSION: Our failure in detecting any association of the p53 immunohistochemical expression regardless of HPV status with clinical features of these tumours suggests it lacks a prognostic value for squamous cell carcinomas of the oral cavity. CLINICAL RELEVANCE: The prognostic value of p53 immunostaining in oral squamous carcinoma is not clarified yet. In the present study, there is no impact on any prognostical item nor even a correlation with cell proliferation (Ki-67) regardless of HPV status.

Imaging of the midfacial and orbital trauma.

The severity of midfacial and orbital injuries depends on the one hand on cause, force vector, load point, or area and on the other hand on the bony and soft tissue resistance as well as individual anatomy. These variables result in a variety of possible injuries of the midfacial and orbital complex. The time critical choice of an adequate imaging modality of these injuries is influenced by the possible severity of concomitant injuries. Besides the confirmation of a clinical diagnosis, the need for high-resolution three-dimensional imaging for preoperative planning of facial reconstruction using intraoperative navigation has become more and more important in the past years. To achieve optimal functional and esthetic outcomes, the anatomical complexity of the midface has to be addressed and the adequate imaging modality has to be chosen keeping the upcoming surgical treatment in mind. The current imaging modalities for midfacial and orbital trauma are presented and critically evaluated depending on the indications. Furthermore, new strategies to support surgeons in achieving best possible midfacial reconstructions are discussed. An algorithm to choose the adequate imaging modality in midfacial and orbital traumatology is provided.

Immunohistochemical analysis of p16 expression, HPV infection and its prognostic utility in oral squamous cell carcinoma.

OBJECTIVES: Functional inactivation of p16 is an early and frequent event in the carcinogenesis of tumours of the head and neck region. However, the prognostic relevance of p16 protein expression for these tumours has been controversial. This study aims to examine immunohistochemical expression of p16 and HP virus in a large number of oral carcinomas, and possible correlation with clinical features of the tumours and survival of the patients. METHODS: Two tissue microarrays composed of 222 oral carcinomas and 427 squamous cell carcinomas of the head and neck region were used for this study. Sections were stained immunohistochemically (anti-p16), and PCR analysis (HPV status) was carried out. Correlation of p16 expression/HPV status with features of tumours and with survival of the patients was analysed by means of Chi-squared test and using Kaplan-Meier analysis, respectively. RESULTS: p16 expression was found immunohistochemically in 74% of tumours, but was not significantly correlated with features of the tumours, but recurrence-free survival of the patients (P = 0.009) if located predominantly nuclear. On the other hand neither intensity of p16 expression (P = 0.41) nor HPV status (P = 0.82) had any effect on these two aspects. CONCLUSION: Immunohistochemical expression of p16 alone provides a limited tool for diagnosis and prognosis of carcinomas of the head and neck region. Immunohistochemical analysis of p16 depending on its intracellular location might serve as a surrogate marker for HPV infection.

Primary and secondary leiomyosarcoma of the oral and perioral region--clinicopathological and immunohistochemical analysis of a rare entity with a review of the literature.

PURPOSE: Leiomyosarcoma (LMS) rarely occurs in the head and neck region. These tumors present with a wide range of clinical features, so the diagnosis is predicated on conventional microscopic findings coupled with immunohistochemical analysis. PATIENTS AND METHODS: Clinical and histologic data of 7 patients with LMS of the head and neck were recorded retrospectively. In addition to routine immunohistochemistry, staining for cell cycle regulator proteins p16 and p21 was performed. RESULTS: Five LMSs (4 intraoral, 1 dermal cheek) occurred primarily in the oral and perioral region. Two LMSs (parietal and sinonasal) were diagnosed as metastases originating from the uterus and pelvis. Treatment of the primary LMSs consisted of radical tumor resection with clear margins. Distant metastases from LMSs were irradiated or excised as palliative treatment. Three of 5 patients (60%) with primarily excised LMS developed recurrence after an average of 7 months, with lung metastases occurring after 17 months. In 1 patient, cervical lymph node metastases were detected after 10 months. Of all patients, 5 died after an average survival period of 2.4 years. The mean survival period of the 5 patients with primary LMS of the head and neck was 3.3 years. All tumors were positive for vimentin and α-smooth muscle actin, with 57% of tumors showing positive nuclear expression of p16 and 71% of p21. Lack of p16 nuclear expression was associated with a shorter mean survival time (1.3 vs 4.3 yr for p16 positivity). CONCLUSION: Lung and cervical lymph node metastases often occur in LMS of the head and neck. Presurgical staging, including gynecologic examination, whole-body computed tomography, and sometimes positron-emission or computed tomography, to rule out LMS metastasis is mandatory. Surgical resection of the tumor should be given top priority. Lack of p16 reactivity may have a prognostic value for LMS because it was related to a trend toward poorer survival.

Long-term in vivo observations show biocompatibility and performance of ZX00 magnesium screws surface-modified by plasma-electrolytic oxidation in Göttingen miniature pigs.

Bioabsorbable magnesium implants for orthopedic fixation of bone have recently become available for different fields of indication. While general questions of biocompatibility have been answered, tailoring suitable degradation kinetics for specific applications as well as long-term tissue integration remain the focus of current research. The aim of this study was the evaluation of the long-term degradation behavior and osseointegration of Mg-Ca-Zn (ZX00MEO) based magnesium implants with plasma-electrolytic oxidation (PEO) surface modification (ZX00MEO-PEO) in comparison to non-surface modified implants in vivo and in vitro. Besides a general evaluation of the biological performance of the alloy over a prolonged period, the main hypothesis was that PEO surface modification significantly reduces implant degradation rate and improves tissue interaction. In vitro, the microstructure and surface of the bioabsorbable screws were characterized by SEM/EDS, cytocompatibility and degradation testing facilitating hydrogen gas evolution, carried out following ISO 10993-5/-12 and ASTM F3268-18a/ASTM G1-03 (E1:2017). In vivo, screws were implanted in the frontal bone of Minipigs for 6, 12, and 18 months, following radiological and histomorphometric analysis. A slower and more uniform degradation and improved cytocompatibility could be shown for the ZX00MEO-PEO group in vitro. A significant reduction of degradation rate and enhanced bone formation around the ZX00MEO-PEO screws in vivo was confirmed. Proficient biocompatibility and tissue integration could generally be shown in vivo regardless of surface state. The tested magnesium alloy shows generally beneficial properties as an implant material, while PEO-surface modification further improves the bioabsorption behavior both in vitro and in vivo. STATEMENT OF SIGNIFICANCE: Devices from bioabsorbable Magnesium have recently been introduced to orthopedic applications. However, the vast degradation of Magnesium within the human body still gives limitations. While reliable in-vivo data on most promising surface treatments such as Plasma-electrolytic-Oxidation is generally scarce, long-time results in large animals are to this date completely missing. To overcome this lack of evidence, we studied a Magnesium-Calzium-Zinc-alloy with surface enhancement by PEO for the first time ever over a period of 18 months in a large animal model. In-vitro, surface-modified screws showed significantly improved cytocompatibility and reduction of degradation confirmed by hydrogen gas evolution testing, while in-vivo radiological and histological evaluation generally showed good biocompatibility and bioabsorption as well as significantly enhanced reduction of degradation and faster bone regeneration in the PEO-surface-modified group.

Leech therapy in reconstructive maxillofacial surgery.

PURPOSE: Corrective plastic surgery is indicated after accidents, burns, cancer surgery, or postoperative wound healing disorders with large tissue defects. The range of reconstructive techniques includes local skin flaps, pedicle grafts, and microvascular anastomosed flaps in the case of large defects. Main complications such as arterial and venous insufficiency caused by a vessel collapse or a vascular spasm are reported regularly in the area of anastomosed vessels and are the concern of any surgeon. Today, leeches are used if wound healing is at risk because of hemodynamic imbalance or a venous insufficiency. PATIENTS AND METHODS: A retrospective evaluation of 148 patients who underwent medical leech therapy in the case of local or pedicaled flaps and some patients who had undergone reconstruction with microvascular flaps from 2005 and 2010 was conducted. Our sample had the typical symptoms of venous congestions of their flaps, despite suture removal, relief of pressure on the flap, and the elimination of a hematoma beyond the flap after surgery. Medical leech therapy was used in these cases. RESULTS: Our series has confirmed the excellent and predictable healing after medical leech therapy for local and microsurgical anastomosed flaps in the case of venous congestion. CONCLUSION: Leech therapy should be considered as a reliable additional procedure and an advantage in maxillofacial and plastic reconstructive surgery to remedy complications resulting from a hemodynamic imbalance or venous insufficiency in the immediate postoperative period.