Neck involvement and disease recurrence in adenoid cystic carcinoma of the minor salivary glands: the role of surgery in primary and progressive disease.

The aim of this study was to analyse the rates of metastatic events and clinical outcomes of patients with adenoid cystic carcinoma (ACC) of the minor salivary glands and to critically evaluate the role of surgical therapy. A retrospective cohort study was designed including all patients with ACC of the oral minor salivary glands treated in the study department during the years 2010-2017. Relevant clinicopathological data were analysed to determine factors with an impact on overall survival (OS) and progression-free survival (PFS). Forty-one patients with primary ACC of the oral cavity and the oropharynx were included. Cervical metastases were found in 14 patients (34.1%) and were shown to have a significant negative impact on OS (P=0.009) and PFS (P=0.03). Sixteen patients developed disease recurrence during follow-up (39.0%) and most patients exhibited local disease recurrence with or without regional or distant metastases (14/16, 87.5%). Local recurrence was treated successfully with surgery in five cases. We recommend surgical therapy for patients with ACC of the minor salivary glands, including elective neck dissection and microvascular reconstruction, to optimize the planning of adjuvant therapy.

The prognostic significance of the lymph node ratio in oral cancer differs for anatomical subsites.

The aim of this study was to validate the prognostic significance of the lymph node ratio (LNR) in patients suffering from oral squamous cell carcinoma in regard to different anatomical subsites. A cohort of 430 patients was investigated to determine the rates of primary metastasis and local and regional disease recurrence. Correlation analysis of the LNR with relevant clinical and pathological parameters was performed. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the prognostic impact for different subsites. Significantly differing rates of primary metastasis and loco-regional disease recurrence were found for cancer of different anatomical subsites of the head and neck. Furthermore, ROC curve analysis suggested that LNR has prognostic relevance in subsets of cancer (tongue, P< 0.001; alveolar process, P= 0.04; maxilla, P= 0.03; buccal mucosa, P= 0.02). The LNR of cancer located in the soft palate (P= 0.6) and floor of the mouth (P= 0.11) showed little or no association with the clinical outcome. There is the need for a more sensitive consideration of the LNR as a factor in the assessment of risk and the treatment decision, as the anatomical subsite plays a crucial role in its impact on the clinical outcome.

Long-term donor site morbidity in head and neck cancer patients and its impact on quality of life: a cross-sectional study.

Modern head and neck reconstructive surgery offers a multitude of different reconstructive options. In such cases, donor site morbidity is an important factor in the affected patient's decision-making. The aim of this study was to perform an objective comparison of donor site morbidity for the five most frequent microvascular donor sites in head and neck reconstructive surgery (radial forearm, anterolateral thigh, fibula, iliac crest, and scapula) using a uniform testing system. In this cross-sectional study, 117 donor sites were analyzed (106 for malignant disease and 11 for non-malignant disease): 73 radial forearm, 14 scapula, 12 anterolateral thigh, 10 fibula, and eight iliac crest. Testing consisted of range of motion, muscle strength, and sensation. The non-affected side served as the control. Quality of life was assessed using the Washington Quality of Life Questionnaire version 4 in its German translation. Range of motion was restricted in 15 cases (12.8%). Muscle strength was decreased in 58 cases (49.6%). Sensation was reduced in 70 cases (60%). Concerning quality of life, 31.2% of patients were limited in their daily activities. The scapula flap showed the highest incidence of overall donor site morbidity. However, correlation between objective and subjective donor site impairment was weak and the majority of patients experienced only minor limitations.

Carbon ion therapy (C12) for high-grade malignant salivary gland tumors (MSGTs) of the head and neck: do non-ACCs profit from dose escalation?

PURPOSE: To evaluate the use of high-dose radiotherapy using carbon ions (C12) on non-adenoid cystic malignant salivary gland tumors (MSGT). PATIENTS AND METHODS: Between 2009 and 2013, patients with biopsy-proven non-ACC MSGT histologies of the head and neck received a combined regimen of IMRT plus C12 boost. Treatment toxicity (CTC v3), response (RECIST 1.1), control and survival rates were retrospectively analyzed. RESULTS: 40 patients with pathologically confirmed non-ACC MSGT (T4: 45 %; N+: 40 %; gross residual: 58 %; mucoepidermoid carcinoma (MEC): 45 %; adenocarcinoma: 20 %) were treated with a median of 74 GyE (80 Gy BED). Chemoradiation was given in 5 patients with MEC. Grade III acute toxicity was observed in up to 15 % (mucositis, dermatitis, dysphagia), no higher-grade late toxicity occurred to date. At a follow-up of 25.5 months, LC, and PFS at 2 and 3 years are 81.5 % (LC) and 66.8 % (PFS), OS at 2 and 3 years is 83.6 % and 72.8 %. Most frequent site of disease progression was distant metastasis. Histologic subtype correlated with LC and PFS. Resection status (gross vs microscopic disease) had no significant effect on LC, PFS, or OS. CONCLUSION: The treatment is well tolerated, no higher grade late effects were observed. Considering the negative pre-selection, LC, PFS and OS are promising. While histology and site of origin significantly influenced control and survival rates, resection status did not, potentially due to the effect of dose escalation.

[Therapeutic strategies for the reconstruction of extensive mandibular defects]. / Behandlungskonzepte zur Rekonstruktion bei ausgedehnten Unterkieferdefekten.

Tumours of the mandibular bone or adjacent soft tissue often necessitate mandibular resection. Subsequent primary bone reconstruction to achieve optimal functional and aesthetic results has been made possible by microvascular surgical techniques and now represents the international gold standard. Microvascular reanastomosis of autologous bone grafts from the iliac crest or fibula is the most common procedure for reconstruction of the mandible. The localisation and extent of the expected defect, as well as a patient's overall condition and ability to tolerate long surgical procedures must be carefully considered before deciding upon the course of treatment. Additional microvascular reanastomosis of soft tissue flaps and stereolithographic models facilitate preoperative planning and broaden the surgical spectrum. Following successful reconstruction of the bone, insertion of dental implants and prosthetic rebuilding are required to complete rehabilitation, including restoration of the patient's ability to chew and speak. The authors recommend specialised oncologic centres for such complex surgical reconstructions.

Ki-67 expression predicts radiosensitivity in oral squamous cell carcinoma.

The prognostic relevance of Ki-67 expression in oral squamous cell carcinoma (OSCC) is still controversial. As proliferating cells are more susceptible to ionizing radiation, the authors investigated if a high proliferation rate reflected by Ki-67 expression, predicts radiosensitivity in OSCC patients. In 52 patients with OSCC who received primary surgery followed by radiation therapy, the proliferation rate was assessed by Ki-67 immunhistochemistry and correlated to recurrent free survival and overall survival. Low proliferative carcinomas showed a significantly shorter mean time to recurrence of 27.5 months compared to 49.5 months of high proliferative tumours (p=0.048). The 5-year survival rate of low proliferative tumours was 49% compared to 80% for high proliferative tumours (p=0.042). This study indicates that tumours with high proliferative activity are more susceptible to radiation therapy. Ki-67 might be used as a marker to predict the response to radiation therapy in patients with OSCC.

[Surgically assisted rapid maxillary expansion. Effects on the nasal airways and nasal septum]. / Chirurgisch unterstützte transversale Oberkieferdistraktion. Auswirkungen auf Nasenwege und Nasenseptum.

BACKGROUND: Surgically assisted rapid maxillary expansion (SARME) is a standardized method to treat cross bites in maxillofacial surgery. Changes to the nasal airways are assumed due to the anatomic dependence between the palate and the nasal floor. PATIENTS AND METHODS: In this study 19 patients with a transverse deficit of the upper jaw underwent SARME. CT scans were performed 1 month pre- and 6 months postoperatively. Effects to the lower nasal airways, the nasal septum and the hard palate were subsequently evaluated. RESULTS: The mean distraction width of the upper jaws was 5.84 mm (SD 2.19) postoperatively. In addition to the dentoalveolar gain in width, a significant increase in the nasal floor was observed (p<0.001). The anterior part of the nasal floor was increased by 14.11%. An anterior-caudal tilt of the upper jaw was observed in the anterior part measuring 1.5 mm (SD 1.05). No significant deviation of the nasal septum occurred. CONCLUSION: SARME has a significant effect on ear, nose and throat medicine. Nasal airways enlarge significantly, while no significant deviation of the nasal septum is observed.

[Activation of sonic hedgehog signaling in keratocystic odontogenic tumors]. / Aktivierung des Sonic-hedgehog-Signalwegs in keratozystischen odontogenen Tumoren.

BACKGROUND: Keratocystic odontogenic tumors are benign neoplasms of the viscerocranium that occur sporadically as well as in association with Gorlin-Goltz syndrome. Multiple basal cell carcinomas of the skin are another typical feature of Gorlin-Goltz syndrome. Aberrant activation of sonic hedgehog signaling has been reported for sporadic and hereditary basal cell carcinoma caused by specific genetic mutations, but for keratocystic odontogenic tumors, the role of aberrant sonic hedgehog signaling has not yet been evaluated in detail. MATERIALS AND METHODS: In the present study, 131 keratocystic odontogenic tumors were analyzed by immunohistochemistry for the expression of sonic hedgehog signaling proteins SHH, PTCH1, SMO, GLI1, and NMYC on tissue microarray sections. RESULTS: High expression of the analyzed proteins-between 67.3% (PTCH1) and 92.9% (SHH)-was found in the epithelial compartment of the keratocystic odontogenic tumors analyzed. In the stromal compartment of the tumors, high expression of the target proteins was found significantly less frequently (all p-values <0.001). CONCLUSION: Aberrant sonic hedgehog signaling is critically involved in the molecular pathogenesis of keratocystic odontogenic tumors. This finding underlines the neoplastic character of this intraosseous lesion. Because of high recurrence rates after local excision, more radical surgical approaches are recommended for treating keratocystic odontogenic tumors.

Intermediate short-term tourniquet use during the preparation of a free vascularised fibula flap for mandibular reconstruction. A case report.

First described by Taylor et al. in 1975, the fibula flap is well established as a universal method for reconstruction of defects in several medical fields. Mostly a tourniquet is kept on during the whole procedure of harvesting the fibula flap. In some hospitals the operation is performed without tourniquet. The outcome is mostly described as successful, but functional impairment and donor site morbidity should not be neglected and severe complications are not frequently reported. In this article we describe a modification of the standard harvesting techniques to minimise the ischaemia time of the flap as well as the danger of severe blood loss. The tourniquet was only activated during the final disconnection of the fibular artery and was released immediately after the successful harvesting of the fibula flap. This method combines the safety of a tourniquet during the critical disconnection procedure and the advantages of a long perfusion of the donor site and the graft.

Amplification of Cyclin L1 is associated with lymph node metastases in head and neck squamous cell carcinoma (HNSCC).

Overrepresentation of chromosomal bands 3q25-q29 has been associated with shortened disease-specific survival in head and neck squamous cell carcinoma (HNSCC). To assess the prevalence of copy number gains (>4 signals per cell) and high-level amplifications (>8 signals per cell) from putative oncogenes in this chromosomal region (CCNL1, SNO, PIK3CA, TP73L), tissue microarray analysis was applied on 280 HNSCCs by fluorescence in situ hybridization. Overall frequency of additional copy numbers was 34.3% for CCNL1, 31.8% for SNO, 39.0% for PIK3CA and 38.3% for TP73L, respectively. In general, gains were more frequently detected in stage IV compared to stage I-III tumours. Performing multivariate logistic regression analysis, a significant association of CCNL1 gains and the presence of lymph node metastases was found, which was independent of anatomical site and T-stage of the primary tumour (P=0.049). Site-specific subgroup analysis further showed that copy number gains of CCNL1 and SNO occurred more frequently in oral carcinomas in advanced clinical stages as compared to N0 oral lesions (CCNL1: P=0.03; SNO: P=0.03). Finally, Kaplan-Meier analysis revealed that high-level amplifications of CCNL1 correlated with shorter overall survival of the patients. Our results indicate that CCNL1 plays a critical role in the loco-regional progression of HNSCC and may serve as an indicator for occult advanced tumour stages.

[Opportunities and chances for tissue chip microarrays in head and neck surgery. A novel technique for the rapid evaluation of potentially novel biomarkers]. / Möglichkeiten und chancen der Gewebechiptechnologie bei Kopf-Hals-Tumoren. Eine neue Technik zur schnellen Analyse von potenziellen Tumormarkern.

Oral squamous cell carcinomas (OSCC) are malignant tumors with a poor prognosis and low long-term survival rates, even when using modern adjuvant and neoadjuvant therapy forms in addition to surgery. For the clinical estimation of each tumor, it is necessary to define stage-dependent molecular and/or cellular parameters as it is known that OSCC develop along a multistep pathway including the loss of tumor suppressor genes and the amplification of oncogenes which result in changes in protein expression. In order to establish a reliable pattern of molecular and cellular biomarkers, a large number of tumor specimens from different stages of the disease need to be analysed. In this study, biopsies of a collective of 293 OSCC in different stages were screened with the novel technique of tissue chip microarrays by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). FISH-analysis was performed on the oncogene cyclin D1 and IHC-analysis on the proteins cyclin D1, p53, p16, cdk4, bcl2, mdm2 and rb. Tissue chip technology was shown to facilitate rapid screening for molecular and cellular alterations in different stages of OSCC and revealed reliable and reproducible results that may allow the definition of a multistep pathway model for tumor progression in OSCC.

Genetic and environmental influences on coping styles: a twin study.

OBJECTIVE: Coping styles are generally considered to be environmentally driven, primarily by family influences. However, because personality traits are commonly influenced by genetic effects, we hypothesized that heredity is also important for coping. METHODS: We tested this hypothesis by assessing 19 coping styles, as well as four secondary coping factors, by questionnaire in 212 pairs of monozygotic and dizygotic twins. We then examined heredity by structural equation modeling. RESULTS: All coping styles showed evidence of genetic influences. The coping styles shared one common genetic factor. In addition, each coping style was also influenced by other separate genetic factors. Shared environment had no significant influence on coping styles. Three of 19 more specific coping styles showed shared environmental effects as well as genetic influences, 14 were solely under genetic influences, and two showed only shared environment effects. CONCLUSIONS: We suggest that hereditary effects on certain coping style preferences cannot be explained solely by genetic influences on major personality traits and temperament. An analysis of the relationships between coping and personality in twin subjects may elucidate the distinction between genetic and environmental effects.

[Silent thrombosis and total hip endoprosthesis]. / Stumme Thrombosen und Totalendoprothesenplastik der Hüfte.

In patients looking out for a total hip replacement so called "silent thrombosis" were recognised (8 of 168 examined patients) by the help of preoperative unilateral phlebography of the leg. Postponing these patients from operation the decrease of postoperative complication (thrombo-embolism) was only small. After critical analysis our invasive method cannot recommended as a screening. In a modified way we will continue this method in high risk patients.