Two-stage palatal repair in non-syndromic CLP patients using anterior to posterior closure is associated with minimal need for secondary palatal surgery.

OBJECTIVE: The aim of the present study was to assess the need for secondary palatal corrective surgery in a concept of palate repair that uses a protocol of anterior to posterior closure of primary palate, hard palate and soft palate. METHODS: A data base of patients primarily operated between 2001 and 2021 at the Craniofacial and Cleft Care Center of the University Goettingen was evaluated. Cleft lips had been repaired using Tennison Randall and Veau-Cronin procedures in conjunction with alveolar cleft repair. Cleft palate repair in CLP patients was accomplished in two steps with repair of primary palate and hard palate first using vomer flaps at the age of 10-12 months and subsequent soft palate closure using Veau/two-flap procedures 3 months later. Isolated cleft palate repair was performed in a one-stage operation using Veau/two-flap procedures. Data on age, sex, type of cleft, date and type of surgery, occurrence and location of oronasal fistulae, date and type of secondary surgery performed for correction of oronasal fistula (ONF)and / or Velophyaryngeal Insufficiency (VPI) were extracted. The rate of skeletal corrective surgery was registered as a proxy for surgery induced facial growth disturbance. RESULTS: In the 195 patients with non-syndromic complete CLP evaluated, a total number of 446 operations had been performed for repair of alveolar cleft and cleft palate repair (Veau I through IV). In 1 patient (0,5%), an ONF occurred requiring secondary repair. Moreover, secondary surgery for correction of VPI was required in 1 patient (0,5%) resulting in an overall rate of 1% of secondary palatal surgery. Skeletal corrective surgery was indicated in 6 patients (19,3%) with complete CLP in the age group of 15 - 22 years (n = 31). CONCLUSIONS: The presented data have shown that two-step sequential cleft palate closure of primary palate and hard palate first followed by soft palate closure has been associated with minimal rate of secondary corrective surgery for ONF and VPI at a relatively low need for surgical skeletal correction.

Optimizing the structure of interdisciplinary tumor boards for effective cancer care.

Introduction: Multi-professional interdisciplinary tumor boards (ITB) are essential institutions to discuss all newly diagnosed, relapsed or complex cancer patients in a team of specialists to find an optimal cancer care plan for each individual patient with regard to national and international clinical practice guidelines, patient´s preference and comorbidities. In a high-volume cancer center, entity-specific ITBs take place at least once a week discussing a large number of patients. To a high level of expertise and dedication, this also requires an enormous amount of time for physicians, cancer specialists and administrative support colleagues, especially for radiologists, pathologists, medical oncologists and radiation oncologists, who must attend all cancer-specific boards according to certification requirements. Methods: In this 15-month prospective German single-center analysis, we examined the established structures of 12 different cancer-specific ITBs at the certified Oncology Center and demonstrate tools helping to optimize processes before, during and after the boards for optimal, time-saving procedures. Results: By changing pathways, introducing revised registration protocols and new digital supports we could show that the workload of preparation by radiologists and pathologists could be reduced significantly by 22.9% (p=<0.0001) and 52.7% (p=<0.0001), respectively. Furthermore, two questions were added to all registration forms about the patient´s need for specialized palliative care support that should lead to more awareness and early integration of specialized help. Discussion: There are several ways to reduce the workload of all ITB team members while maintaining high quality recommendations and adherence to national and international guidelines.

Semi-quantitative assessment of environmental tobacco smoke exposure and its association with the development of oral squamous cell carcinoma: A pilot study.

INTRODUCTION: Two known major risk factors for oral squamous cell carcinoma are smoking and alcohol consumption. Environmental tobacco smoke (also known as secondhand smoke) has been proven to be associated with the occurrence of lung and breast carcinoma. This study aimed to assess exposure to environmental tobacco smoke and its association with the development of oral squamous cell carcinomas. METHODS: Using a standardized questionnaire, 165 cases and 167 controls were asked about their demographic data and risk behaviors, including environmental tobacco smoke exposure. An environmental tobacco smoke score (ETS-score) was developed to semi-quantitatively record the previous exposure to ETS. Statistical analyses were performed with χ2 test or Fishers exact test, and with ANOVA or Welch's t-test as appropriate. An analysis was done using multiple logistic regression. RESULTS: Cases had a significantly increased previous exposure to environmental tobacco smoke compared to the controls (ETS-score: 36.69 ± 26.34 vs 13.92 ± 12.44; p<0.0001). Comparing only the groups without additional active risk factors, exposure to environmental tobacco smoke was associated with a more than threefold higher likelihood of oral squamous cell carcinoma (OR=3.47; 95% CI: 1.31-10.55). Statistically significant differences in ETS-score were found for different tumor locations (p=0.0012) and different histopathological gradings (p=0.0399). A multiple logistic regression analysis confirmed exposure to environmental tobacco smoke as an independent risk factor for the development of oral squamous cell carcinomas (p<0.0001). CONCLUSIONS: Environmental tobacco smoke is an important but yet underestimated risk factor for the development of oral squamous cell carcinomas. Further studies are needed to confirm the results, including the usefulness of the developed environmental tobacco smoke score for exposure.

Gender and risk-taking behaviors influence the clinical presentation of oral squamous cell carcinoma.

OBJECTIVE: The common risk factors for oral squamous cell carcinoma (OSCC) are smoking and alcohol abuse. A small percentage of patients, mostly women, are demonstrating oral cancer without the common risk behavior. This study investigates how gender and different patterns of lifestyle factors influence the clinical presentation of OSCC. PATIENTS AND METHODS: From this retrospective study, demographical and tumor-specific data and lifestyle factors were analyzed. Statistical analyses were performed using the χ2 test or Fisher's exact test for categorical analysis and the t test, ANOVA test, or Kruskal-Wallis test for continuous variables. The influence of the respective lifestyle factors together with their interactions with the gender on tumor characteristics has been tested using logistic and ordinal cumulative link regression models. RESULTS: Among a total of 308 patients, men represented the majority of smokers (87.2%) and the female cohort were largely non-smokers and non-drinkers (64.9%). For age, tumor site and N-stage it looks like that differences of men and women are driven by the different risk behavior. But if the lifestyle factors are taken into account, we observe contrary effects between men and women for T-, N-, and UICC-stage. For different cancer locations we saw opposite effects with gender and risk profile. These effects are not dose-dependent explainable for gender. CONCLUSION: Some but not all differences in the development of OSCC for men and women are explainable by the respective difference in lifestyle behavior. Some further investigations are necessary to find explanations for the obvious differences between men and women in developing OSCC.

Cotransplantation of mesenchymal stromal cells and endothelial cells on calcium carbonate and hydroxylapatite scaffolds in vivo.

This study investigated the cotransplantation of bone marrow mesenchymal stromal cells (BMSC) and human umbilical cord endothelial cells (HUVEC), and evaluated their contribution to vascular and bone tissue engineering in vivo. To evaluate the success of osteogenic differentiation and timely vascularization of different osteoconductive scaffolds in vivo, we transferred BMSC and HUVEC pre-cultivated calcium carbonate (CaCO3) and hydroxylapatite (HA) matrices into immunocompromised RNU-rats, and analyzed mineralization, expression of osteopontin, and vascular integration via new vessel formation. After in vivo transplantation, pre-cultivated scaffolds demonstrated overall improved mineralization of 44% for CaCO3 (p = 0.01, SD ± 14.3) and 34% for HA (p = 0.001, SD ± 17.8), as well as improved vascularization of 5.6 vessels/0.1 mm2 on CaCO3 (p < 0.0001, SD ± 2.0) and 5.3 vessels/0.1 mm2 on HA (p < 0.0001, SD ± 2.4) compared with non-pre-cultivated controls. However, no significant differences between the implantation of BMSC-only, HUVEC-only, or BMSC + HUVEC cocultures could be observed. There is an increasing demand for improved bone regeneration in tissue engineering. Cotransplantation of mesenchymal stromal cells and endothelial cells often demonstrates synergistic improvements in vitro. However, the benefits or superiority of cotransplantation was not evident in vivo and so will require further investigation.

Association of the Preoperative Body Mass Index With Postoperative Complications After Treatment of Oral Squamous Cell Carcinoma.

PURPOSE: Nutritional status is believed to influence surgical outcome. Because of a lack of actual reports in the literature, this study evaluated the surgical outcome of patients after treatment for oral squamous cell carcinoma (OSCC), with special focus on the preoperative body mass index (BMI). PATIENTS AND METHODS: This retrospective cohort study investigated the association between preoperative BMI and surgical outcome for patients with OSCC, focusing on local and medical complications. This research also analyzed common clinical and demographic parameters, such as age, gender, TNM stage, tumor differentiation, risk behavior, Karnofsky Index, duration of operation, and length of hospital stay. Statistics were performed using the χ2 test or Fisher exact test for categorical analysis and the t test or analysis of variance and Pearson correlation test for continuous variables. Multivariate analysis was computed for BMI with a multivariate linear regression model and for local and medical complications with multivariate Poisson regression. RESULTS: In the sample of 419 patients with OSCC, 8.6% were underweight, 54.7% were normal weight, and 36.8% were overweight (overall mean BMI, 24.28 kg/m2). BMI was significantly associated with age (P = .0017), consumption of nicotine (P = .0178) and alcohol (P = .0008), dental status (P = .0163), tumor differentiation (P = .0288), and tumor status (P = .0005). Underweight in particular was negatively correlated with local postoperative complications (P = .0047). Local complications were associated with the need for operative revisions (P < .0001) and an increase of hospital length of stay (P < .0001) using multivariable analysis. CONCLUSION: These results indicate that evaluation of preoperative morbidity and nutritional status, especially in underweight patients, is worthwhile to improve medical and economic postoperative outcomes after surgical therapy of OSCC.

Degree of Keratinization Is an Independent Prognostic Factor in Oral Squamous Cell Carcinoma.

PURPOSE: Keratinization is a routinely reported histologic feature in head and neck cancer. In contrast to numerous clinicopathologic parameters, the prognostic value of keratinization in oral squamous cell carcinoma (OSCC) is rarely reported in the literature. The purpose of this study was to review the outcome of patients with OSCC with a special focus on the degree of keratinization. PATIENTS AND METHODS: In this retrospective cohort study, we evaluated the medical records at the Department of Oral and Maxillofacial Surgery, Jena University Hospital, and investigated the outcome of patients with OSCC with disease-free survival and disease-specific survival according to the degree of keratinization. This research also analyzed common clinical and histologic parameters such as age, gender, tumor site, T category, N category, resection margin, lymphovascular invasion, and extracapsular spread. Descriptive statistics were performed, and survival was calculated by the Kaplan-Meier method. Prognostic factors were analyzed by multivariate Cox analysis. RESULTS: In the sample of 151 OSCC patients, with a median age of 57.5 years and a male-female ratio of 4.03:1, 119 had tumors with no or low keratinization (K0 to K2) and 32 had tumors with good or high keratinization (K3 or K4). More recurrences were seen in patients with OSCC with low keratinization (P = .0008). The 5-year disease-free survival rate was significantly decreased for OSCC with low keratinization (52.9%) compared with good or high keratinization (93.2%) (P = .0008). The 5-year disease-specific survival rate was reduced to 66.1% (P = .0136) for patients with OSCC with low keratinization. Multivariate analysis showed that extracapsular spread (P = .001) and keratinization (P = .002) are independent, significant prognostic factors for recurrence in OSCC. CONCLUSIONS: Besides extracapsular spread, the degree of keratinization seems to be an important prognostic factor for recurrence and survival in OSCC. Our results indicate that the degree of keratinization should be considered in decisions regarding treatment and prognosis for OSCC.

Genetic disruption of Pten in a novel mouse model of tomaculous neuropathy.

'Tomacula' and myelin outfoldings are striking neuropathological features of a diverse group of inherited demyelinating neuropathies. Whereas the underlying genetic defects are well known, the molecular mechanisms of tomacula formation have remained obscure. We hypothesized that they are caused by uncontrolled, excessive myelin membrane growth, a process, which is regulated in normal development by neuregulin-1/ErbB2, PI3 Kinase signalling and ERK/MAPK signalling. Here, we demonstrate by targeted disruption of Pten in Schwann cells that hyperactivation of the endogenous PI3 Kinase pathway causes focal hypermyelination, myelin outfoldings and tomacula, even when induced in adult animals by tamoxifen, and is associated with progressive peripheral neuropathy. Activated AKT kinase is associated with PtdIns(3,4,5)P(3) at paranodal loops and Schmidt-Lanterman incisures. This striking myelin pathology, with features of human CMT type 4B1 and HNPP, is dependent on AKT/mTOR signalling, as evidenced by a significant amelioration of the pathology in mice treated with rapamycin. We suggest that regions of non-compact myelin are under lifelong protection by PTEN against abnormal membrane outgrowth, and that dysregulated phosphoinositide levels play a critical role in the pathology of tomaculous neuropathies.

Elevated phosphatidylinositol 3,4,5-trisphosphate in glia triggers cell-autonomous membrane wrapping and myelination.

In the developing nervous system, constitutive activation of the AKT/mTOR (mammalian target of rapamycin) pathway in myelinating glial cells is associated with hypermyelination of the brain, but is reportedly insufficient to drive myelination by Schwann cells. We have hypothesized that it requires additional mechanisms downstream of NRG1/ErbB signaling to trigger myelination in the peripheral nervous system. Here, we demonstrate that elevated levels of phosphatidylinositol 3,4,5-trisphosphate (PIP3) have developmental effects on both oligodendrocytes and Schwann cells. By generating conditional mouse mutants, we found that Pten-deficient Schwann cells are enhanced in number and can sort and myelinate axons with calibers well below 1 microm. Unexpectedly, mutant glial cells also spirally enwrap C-fiber axons within Remak bundles and even collagen fibrils, which lack any membrane surface. Importantly, PIP3-dependent hypermyelination of central axons, which is observed when targeting Pten in oligodendrocytes, can also be induced after tamoxifen-mediated Cre recombination in adult mice. We conclude that it requires distinct PIP3 effector mechanisms to trigger axonal wrapping. That myelin synthesis is not restricted to early development but can occur later in life is relevant to developmental disorders and myelin disease.