Tumor Microenvironment, HLA Class I and APM Expression in HPV-Negative Oral Squamous Cell Carcinoma.

Progression of oral squamous cell carcinoma (OSCC) has been associated with an escape of tumor cells from the host immune surveillance due to an increased knowledge of its underlying molecular mechanisms and its modulation by the tumor microenvironment and immune cell repertoire. In this study, the expression of HLA class I (HLA-I) antigens and of components of the antigen processing machinery (APM) was analyzed in 160 pathologically classified human papilloma virus (HPV)-negative OSCC lesions and correlated to the intra-tumoral immune cell response, IFN-γ signaling and to the patient's outcome. A heterogeneous but predominantly lower constitutive protein expression of HLA-I APM components was found in OSCC sections when compared to non-neoplastic cells. Tumoral HLA-I APM component expression was further categorized into the three major phenotypes HLA-Ihigh/APMhigh, HLA-Ilow/APMlow and HLA-Idiscordant high/low/APMhigh. In the HLA-Ihigh/APMhigh group, the highest frequency of intra-tumoral CD8+ T cells and lowest number of CD8+ T cells close to FoxP3+ cells were found. Patients within this group presented the most unfavorable survival, which was significantly evident in stage T2 tumors. Despite a correlation with the number of intra-tumoral CD8+ T cells, tumoral JAK1 expression as a surrogate marker for IFN-γ signaling was not associated with HLA-I/APM expression. Thus, the presented findings strongly indicate the presence of additional factors involved in the immunomodulatory process of HPV-negative OSCC with a possible tumor-burden-dependent complex network of immune escape mechanisms beyond HLA-I/APM components and T cell infiltration in this tumor entity.

Immune Escape Mechanisms and Their Clinical Relevance in Head and Neck Squamous Cell Carcinoma.

Immunotherapy has been recently approved for the treatment of relapsed and metastatic human papilloma virus (HPV) positive and negative head and neck squamous cell carcinoma (HNSCC). However, the response of patients is limited and the overall survival remains short with a low rate of long-term survivors. There exists growing evidence that complex and partially redundant immune escape mechanisms play an important role for the low efficacy of immunotherapies in this disease. These are caused by diverse complex processes characterized by (i) changes in the expression of immune modulatory molecules in tumor cells, (ii) alterations in the frequency, composition and clonal expansion of immune cell subpopulations in the tumor microenvironment and peripheral blood leading to reduced innate and adaptive immune responses, (iii) impaired homing of immune cells to the tumor site as well as (iv) the presence of immune suppressive soluble and physical factors in the tumor microenvironment. We here summarize the major immune escape strategies of HNSCC lesions, highlight pathways, and molecular targets that help to attenuate HNSCC-induced immune tolerance, affect the selection and success of immunotherapeutic approaches to overcome resistance to immunotherapy by targeting immune escape mechanisms and thus improve the HNSCC patients' outcome.

Clinical Performance of Short Expandable Dental Implants for Oral Rehabilitation in Highly Atrophic Alveolar Bone: 3-year Results of a Prospective Single-Center Cohort Study.

BACKGROUND AND OBJECTIVES: Oral health-related quality of life (OHRQOL) is compromised during the post-implant healing period, especially when vertical augmentation is required. A long-term trial sought to evaluate a short dental implant system with an apically expandable macro-design. MATERIALS AND METHODS: Over 4.5 years, patients with limited vertical alveolar bone were consecutively recruited into this prospective cohort study. Implant success rate, OHRQOL (Oral Health Impact Profile (OHIP)-14), implant stability, and crestal bone changes were evaluated. RESULTS: Data from 30 patients (mean age: 64.6 years, range 44-83) were analyzed, which related to 104 implants (53 in the maxilla, 51 in the mandible). Over the mean follow-up (42.6 ± 16.4 months), the implant success rate was 94.7% in the mandible (two implants lost) and 83.6% in the maxilla (four implants lost; p = 0.096), and the prosthetic success rate was 100%. The median OHIP-14 scores improved from 23 (interquartile range (IQR) 9-25.5) to 2 (IQR 0-5; p < 0.001). The mean implant stability quotient (ISQ) was 71.2 ± 10.6 for primary stability and 73.7 ± 13.3 (p = 0.213) for secondary stability, without significant maxilla-versus-mandible differences (p ≥ 0.066). Compared to the baseline, median crestal bone changes after loading were 1.0 mm (IQR 0-1.3) and 1.0 mm (IQR 0.2-1.2) in the maxilla and mandible (p = 0.508), respectively, at the end of the first year, 1.1 mm (IQR 0-1.3) and 1.0 mm (IQR 0.1-1.2) (p = 0.382), respectively, at the end of the second year, and 1.2 mm (IQR 0-1.9) and 1.1 mm (IQR 0.1-1.2) (p = 0.304), respectively, at the end of the third year. CONCLUSIONS: In patients with limited vertical bone height, short implants with optimized macro-design constitute a reliable method for functional rehabilitation, avoiding extensive alveolar bone augmentation.

Lower eyelid ectropion as a sequela of different underlying diseases in maxillo-facial surgery: Diagnostics and treatment approaches.

PURPOSE: This study investigated the outcome of lower eyelid ectropion (LEE) treatment in patients with another primary periorbital or mid-facial pathology. MATERIALS AND METHODS: This 18-year monocentric retrospective cohort study included patients admitted for various leading mid-facial pathologies and presenting with a LEE. The primary diagnosis, surgical pretreatment, ectropion type, ectropion severity score (ESS), and surgical techniques were recorded. The primary endpoint was the postoperative ESS score. RESULTS: Overall, 40 patients (female n = 16, male n = 24, average age 70.8 years), primarily with periorbital skin cancer (n = 21, 52.5%), facial palsy (n = 7, 17%), trauma (n = 6, 15%), or other pathologies (n = 6, 15%), were included. Surgical procedures mostly addressed a correction of anterior and posterior lamellae (n = 22, 55%), with isolated anterior lamellae in only a few cases (n = 10, 25%). The ESS score significantly decreased from 4.8 ± 1.8 to 1.3 ± 1.3 (paired t-test, p < 0.001) after a mean follow-up of 23.8 months. CONCLUSION: LEE constitutes a relevant problem. Due to preexisting canthal ligament laxity in patients undergoing oncologic or traumatic midface surgery, the risk of ectropion has so far been underestimated. Bilamellar approaches in elderly patients are likely to be obligatory in any case.

[Upper Jaw Malignoma: Results of a Monocentric Study Over 45 Years]. / Oberkiefermalignome ­ Ergebnisse einer monozentrischen Studie über 45 Jahre.

BACKGROUND: Malignancies originating from the upper jaw are comparatively rare. This study aimed to evaluate the histological features, grading and staging in upper jaw carcinomas. MATERIALS AND METHODS: A total of 199 malignancies of the maxillary sinus were analysed over 45 years and matched for age, gender, tumour size, and histological differentiation. Cases of squamous cell carcinomas were classified based on the TNM system, grading and five-year survival time. RESULTS: Squamous cell carcinomas (60%) were the most frequent malignant tumours. The five-year survival rate of squamous cell carcinomas was more than 60% and hence superior to that of other oral squamous cell carcinomas, although approximately ⅔ of these tumours were T4 cases. More than 60% of squamous cell carcinomas were highly differentiated and characterised as G1 tumours. G2 and G3 tumours were considerably less common. CONCLUSION: The risk of local recurrence was inversely disproportional to the grade of histological differentiation. All in all, an optimal surgical and radiological treatment may lead to good aesthetic and satisfactory functional results.

Novel expandable short dental implants in situations with reduced vertical bone height-technical note and first results.

PURPOSE: Short implants often have the disadvantage of reduced primary stability. The present study was conducted to evaluate the feasibility and safety of a new expandable short dental implant system intended to increase primary stability. METHODS: As a "proof of concept", a prospective clinical cohort study was designed to investigate intraoperative handling, primary and secondary implant stability (resonance frequency analysis), crestal bone changes, implant survival and implant success, of an innovative short expandable screw implant. From 2014 until 2015, 9 patients (7-9-mm vertical bone height) with 30 implants (length 5-7 mm, diameter 3.75-4.1 mm) were recruited consecutively. RESULTS: All 30 implants in the 9 patients (age 44 to 80 years) could be inserted and expanded without intraoperative problems. Over the 3-year follow-up period, the implant success rate was 28/30 (93.3%). The mean implant stability quotients (ISQ) were as follows: primary stability, 69.7 ± 10.3 ISQ units, and secondary stability, 69.8 ± 10.2 ISQ units (p = 0.780), both without significant differences between the maxilla and mandible (p ≥ 0.780). The mean crestal bone changes after loading were (each measured from the baseline) as follows: in the first year, 1.0 ± 0.9 mm in the maxilla and 0.7 ± 0.4 mm in the mandible, and in the second year, 1.3 ± 0.8 mm and 1.0 ± 0.7 mm, respectively. CONCLUSIONS: Compared to other prospective studies, in this indication, the success rate is acceptable. Implant stability shows high initial and secondary stability values. The system might present an extension of functional rehabilitation to the group of elderly patients with limited vertical bone height. Further long-term investigations should directly compare this compressive implant with standard short implants.

Complex functional and epithetic rehabilitation after ablation of recurrent retroauricular basal cell carcinoma - a case study.

The reconstruction of extended defects of the concha poses a complex challenge for plastic surgeons. In cases of subtotal ablation, an alternative method designed especially for elderly oncological patients consists of epithetic rehabilitation. However, inserting an implant-retained concha epithesis proves challenging in patients with antecedents of deep resections involving the mastoid process. In the present case study, we report on the long-term treatment course (2009-2017) of a 79-year-old male patient suffering from a recurrent basal cell carcinoma of the retroauricular region. Following tumor resection, along with lateral mastoidectomy, reconstruction, and adjuvant radiotherapy, functional and esthetic deficits primarily due to peripheral facial nerve palsy were successfully managed using a multistep procedure. The procedure was completed by inserting an implant-retained concha epithesis, resulting in improved quality of life. Due to prior lateral mastoidectomy, ultra-short implants (4 mm) were inserted, partially at atypical positions. For maintaining healthy periimplant soft tissue, aftercare comprised cold plasma treatment. This oncologic case demonstrates the therapeutic necessity of using a broad spectrum of reconstructive procedures, along with their limitations, in a critical anatomic region. Specific features include the presentation of a workflow using ultra-short implants in a compromised mastoid region. Surgeons should consider alternative implant positions in the event of any compromised mastoid process. A particular emphasis has been put on meticulous aftercare to preserve healthy periimplant soft tissues.

Maxillofacial trauma - Underestimation of cervical spine injury.

Undiagnosed cervical spine injury can have devastating results. The aim of this study was to analyse patients with primary maxillofacial trauma and a concomitant cervical spine injury. It is hypothetised that cervical spine injury is predictable in maxillofacial surgery. A monocentric clinical study was conducted over a 10-year period to analyse patients with primary maxillofacial and associated cervical spine injuries. Demographic data, mechanism of injury, specific trauma and treatments provided were reviewed. Additionally a search of relevant international literature was conducted in PubMed by terms "maxillofacial" AND "cervical spine" AND "injury". Of 3956 patients, n = 3732 (94.3%) suffered from craniomaxillofacial injuries only, n = 174 (4.4%) from cervical spine injuries only, and n = 50 (1.3%) from both craniomaxillofacial and cervical spine injuries. In this study cohort the most prevalent craniofacial injuries were: n = 41 (44%) midfacial and n = 21 (22.6%) skull base fractures. Cervical spine injuries primarily affected the upper cervical spine column: n = 39 (58.2%) vs. n = 28 (41.8%). Only in 3 of 50 cases (6%), the cervical spine injury was diagnosed coincidentally, and the cervical spine column was under immobilised. The operative treatment rate for maxillofacial injuries was 36% (n = 18), and for cervical spine injuries 20% (n = 10). The overall mortality rate was 8% (n = 4). The literature search yielded only 12 papers (11 retrospective and monocentric cohort studies) and is discussed before our own results. In cases of apparently isolated maxillofacial trauma, maxillofacial surgeons should be aware of a low but serious risk of underestimating an unstable cervical spine injury.

Surgical treatment of bisphosphonate-associated osteonecrosis: Prognostic score and long-term results.

Over a century after the first synthesis of bisphosphonates (1897) and a decade (2003) since the initial report on bisphosphonate-related osteonecrosis of the jaw (ONJ), this osteopathy remains a serious clinical challenge. A single center longitudinal study (2005-2014) was carried out to prospectively characterize inpatients with manifest ONJ and to evaluate their outcomes. The data recorded were: medical history, bisphosphonate treatment, localization, imaging, treatment, histomorphological features, and complications. A prognostic score (modified UCONN-Score) was adopted to predict outcomes. Eighty patients were included (mean age 69.4 years; 40 male, 40 female). Breast cancer (n = 25), multiple myeloma (n = 16), and prostate cancer (n = 15) were the three most common malignancies; and cardiovascular disease (n = 31), diabetes mellitus (16), and renal disorders (6) were the most important comorbidities. The severity of ONJ was stage I in three patients, stage II in 37, and stage III in 40, being predominantly localized in the posterior mandible and needing gradual resection. The average duration of bisphosphonate treatment was 38.3 months. The typical histological aspects of ONJ were predominantly osteonecrosis, bone marrow fibrosis, and bacterial colonization (Actinomyces) with suppurative inflammation. Within the resected jawbone a primary malignancy was diagnosed in two cases. The overall success rate was 83.6% (follow-up 23.5 months), with a UCONN-Score ≥15 predicting unfavorable treatment results (OR = 5.2). The past decade has enhanced experience with ONJ treatment and knowledge about its pathogenesis, which seems to be a multistep process. This study demonstrates the importance of bone and multilayer soft tissue management, preferably as an early intervention. The UCONN-Score might help to assess individual prognosis in ONJ surgery and the potential benefit of an antiresorptive drug holiday. To our knowledge it is the first use of a prognostic score in ONJ surgery.

A huge infiltrating squamous cell carcinoma of the neck 46 years after radiotherapy of a haemangioma.

BACKGROUND: There is a higher risk for malignant tumours in patients who underwent any kind of radiotherapy. MAIN OBSERVATIONS: An 87-year-old patient with an extended squamous cell carcinoma of the neck was referred to our hospital. The large ulcerated tumour showed a deep infiltration of the para-vertebral muscles and the spinal processes C6-C7. The tumour was known since about six years and appeared about 46 years after low-dose radiotherapy of a cervical haemangioma of the neck in 1961. The large dimension of the tumour leaded to a radical surgical removal and a sufficient fast reconstruction strategy. The extended defect was covered by a pedicled lower musculocutaneous trapezius flap. No postoperative complications like partial necrosis, infection or movement disorders of the shoulder or a shoulder drop syndrome were seen. Ten weeks after the operation the patient showed a good functional and aesthetic result with no limitation of arm mobility. Two and a half years after radical intended surgery the patient was still alive and showed no recurrence of the tumour. CONCLUSIONS: In conclusion there is a need for a life-time lasting dermatological supervision in patients with a history of radiotherapy in the past, because the handling of patients with such an enlarged tumour is complicated.

Orthognathic surgery in a case of infantile facioscapulohumeral muscular dystrophy with macroglossia.

INTRODUCTION: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder with a shortened fragment of a D4Z4 repeat on chromosome 4q35. The infantile form of FSHD is relatively rare. CASE REPORT: Within this case report, we describe the orthognatic surgery in a patient with infantile FSHD to diminish the functional and esthetic disturbances in the orofacial region. We saw a 20-year-old female patient suffering from infantile FSHD with remarkable macroglossia and frontal open bite. Diagnosis was based on molecular genetic investigations. To improve the functions of the stomatognathic system, we performed a tongue reduction and a segment osteotomy in the frontal aspect of the mandible. The patient was satisfied with the functional and esthetic results. Lip competence and occlusion were significantly improved. Thus, orthognatic surgery can enhance oral function, facial esthetics, and general quality of life.

Risk factors for a bad split during sagittal split osteotomy.

One of the operative complications during sagittal split osteotomy (SSO) in orthognatic surgery is a bad split, meaning an undesired fracture of the mandible during osteotomy. The aim of this study was to find out if there is a relation between the occurrence of bad splits during SSO and the presence of third molars, the patient's age, or the surgeon's experience. Clinical notes of 110 consecutive patients who had had a total of 220 SSOs using the Obwegeser/Dal Pont technique were evaluated and divided into three groups: 1 missing third molar (n=168); 2 retained or impacted third molar that was removed during the SSO (n=23); and 3 third molar left in place during SSO (n=29). There were a total of 12 (6%) bad splits. 9 (5%) in group 1, two (9%) in group 2, and one (3%) in group 3. There were no significant differences between groups 1-3, in particular the surgeon's qualification had no influence on the incidence. Older patients seemed more at risk of a bad split than younger ones.