A modified pull-through approach with a pedicled bone flap for oral and oropharyngeal cancer resection: a feasibility study.

PURPOSE: Compromised swallowing, speaking, and local complications are the major disadvantages of established approaches to the posterior tongue and oropharynx. The mandibular split involves an esthetically unpleasant bipartition of the lower lip and is prone to bony non-union or sequestration. The conventional pull-through technique on the other hand lacks the secure reattachment of the lingually released soft tissues. METHODS: The feasibility of a new modified pull-through approach was tested on three anatomical specimens. CAD/CAM cutting guides were used to design a retentive bone flap to properly refixate the genioglossus and geniohyoid muscles after the procedure. The radiographic assessment and treatment planning was performed on 12 cadavers. The entire procedure was tested surgically via dissection in three of those cases. This procedure was then applied in a clinical case. RESULTS: Precise repositioning and dynamic compression of bony segments was possible reproducibly and without injury to adjacent structures. In all dissected cases, a median lingual foramen was found and in two cases vessels entering it could be dissected Radiologic anatomical landmarks were sufficient in all 12 cases to perform the clinical planning procedure. Clinically, the osteotomized segment demonstrated good blood supply and plateless repositioning was verified postoperatively via cone beam scan. CONCLUSION: The method presented is safe and easy to perform. Individual cutting guides improve the safety and accuracy of the procedure, potentially eliminating the need for osteosynthesis. We provide the anatomical and radiologic basis for clinical evaluation of this pedicled bone flap procedure and present the clinical application of this modified pull-through approach.

Prognostic value of lymph node involvement in oral squamous cell carcinoma.

OBJECTIVES: Different parameters have been identified in patients with oral squamous cell carcinomas (OSCC) that have a serious impact on survival, including residual tumour and extracapsular spread. Moreover, other factors, including the lymph node ratio (LNR) and lymph node yield (LNY), have been suggested as prognostic markers. MATERIAL AND METHODS: This retrospective study included patients diagnosed with OSCC and cervical lymph node metastases during the years 2010-2020. Patients' records were evaluated regarding lymph node status, final therapy regime, tumour recurrence, time to death, tumour association with death, disease-free survival (DSF), and overall survival (OS). RESULTS: In 242 patients with a mean age of 63.57 ± 11.24 years, treated either by selective neck dissection (SND; n = 70) or by modified radical neck dissection (MRND; n = 172), 5772 lymph nodes were detected. The LNR and LNY were identified as independent risk factors in OS and DFS. The optimal cut-off point for the LNY was ≥ 17 lymph nodes in the SND and ≥ 27 lymph nodes in the MRND group. The metastatic lymph node clearance (MLNC) was established as a score to relate the LNR and LNY to the extent of lymph node removal. Survival analysis showed statistically significant differences among score levels. CONCLUSIONS: As information about the extent of nodal dissection is excluded from LNR and LNY, we propose the use of a new scoring system comprising individual cut-off values for LNY and LNR with regard to the extent of neck dissection. CLINICAL RELEVANCE: MLNC might help to identify high-risk OSCC patients with metastatic lymph nodes.

Modified McLaughlin's Dynamic Muscle Support in the 21st Century? A Retrospective Study With a Prospective Follow-Up Analysis for Patients With Long Standing Facial Paralysis.

INTRODUCTION: Facial nerve paralysis can dramatically affect the life of a patient as it leads to significant alterations of the facial symmetry and functional limitations. Various methods exist including free neuromuscular flaps to reanimate patients suffering from uni- or even bilateral facial nerve paralysis. The more than 60-year-old technique described by McLaughlin continues to offer an alternative with distinct advantages for the individual patient. The present study aimed to evaluate clinical outcome and satisfaction of patients treated with a modified McLaughlin's Dynamic Muscle Support. MATERIALS AND METHODS: A total of 13 patients (mean age of 58.4 years) who received a modified McLaughlin's Dynamic Muscle Support due to uni- or bilateral long-standing facial paralysis were included. Medical records were reviewed retrospectively, and patients were contacted for additional follow-up. Patients who agreed to participate in the follow-up study were asked to answer a self-developed questionnaire. RESULTS: In all patients, a rehabilitation of facial symmetry with an improvement of the mimic expression could be achieved. Mean length of inpatient stay was 6.5 days and average duration of surgery was 121 minutes. No surgical site infection occurred. Mean follow-up was 23 months. Most of the patients were fully satisfied with the result and could experience functional and esthetic improvement.Patients who participated in the prospective follow-up study were very satisfied with the esthetic result and functional outcome. CONCLUSIONS: Even in times of advanced microsurgical techniques, McLaughlin's Dynamic Muscle Support appears to be a good alternative for the successful treatment of long-standing facial paralysis.

Oxidative and Nitrosative Stress in Oral Squamous Cell Carcinoma.

INTRODUCTION: The incidence of oral squamous cell carcinoma (OSCC) shows a constant increase, while the long-term outcome remains poor over the last decades. Radical oxygen and nitrogen species (RONS) - initially released by carcinogens, such as alcohol and tobacco, and later maintained by the tumor microenvironment - appear to be strongly associated to chronic inflammation, tumor induction, progression, and metastatic spread. The aim of this study was to evaluate the role of oxidative and nitrosative stress in primary OSCC compared to healthy tissue specimens and to identify their impact on tumor carcinogenesis. MATERIALS AND METHODS: In this basic research study, tissue samples of 30 patients with primary OSCC were evaluated for the expression of pAKT, pERK, 3-NT, NOS1, NOS3, MAPK1, and IP-8 by immunohistochemistry and RT-PCR and compared to those of a healthy control group (n = 30). RESULTS: The results showed a significantly increased expression of pAKT (p < 0.001), pERK (p = 0.01), 3-NT (p = 0.039), NOS1 (p = 0.025), NOS3 (p = 0.046), and MAPK1 (p = 0.032) in OSCC tissue samples compared to healthy controls. CONCLUSION: The results of this study prove the tested stable degradation products to be suitable for the detection of RONS in OSCC. Moreover, the significantly increased expression underlines the role of RONS in carcinogenesis of OSCC, suggests specific mechanisms of detection, and anticipates supplementary research.

Following in the footsteps of Hippocrates-interrelation between the incidence of odontogenic abscess and meteorological parameters.

OBJECTIVES: Although many physicians in daily practice assume a connection between odontogenic infections and meteorological parameters, this has not yet been scientifically proven. Therefore, the aim of the present study was to evaluate the incidence of odontogenic abscess (OA) in relation to outdoor temperature and atmospheric pressure. PATIENTS AND METHODS: An analysis of patients with an odontogenic abscess who presented at the emergency department within a period of 24 months was performed. Only patients who had not received surgical or antibiotic treatment prior to presentation and who lived in Berlin/Brandenburg were included. The OA incidence was correlated with the mean/maximum outdoor temperature and atmospheric pressure starting from 14 days before presentation. The statistical analysis was carried out using Poisson regression models with OA incidence as dependent and meteorological parameters as independent variables. RESULTS: A total of 535 patients (mean age 39.4 years; range 1 to 95 years) with 538 cases were included. Of these, 227 were hospitalized. The most frequent diagnosis was a canine fossa abscess. A significant association between mean (p = 0.0153) and maximum temperature (p = 0.008) on the day of the presentation and abscess incidence was observed. Furthermore, a significant correlation between OA incidence and maximum temperature 2 days before presentation was found (p = 0.034). The deviation of the mean temperature on the day of the presentation from the monthly mean temperature had a significant influence (p = 0.021) on the incidence of OA. In contrast to temperature, atmospheric pressure had no significant influence on the incidence of OA. CONCLUSION: This study supports a relationship between the incidence of odontogenic abscess and outdoor temperature, but not atmospheric pressure. A significantly higher frequency of patients with an OA presented at our emergency department on days with (comparably) low and high outdoor temperatures. Furthermore, a significant correlation between incidence and maximum temperature 2 days before presentation was found. CLINICAL RELEVANCE: The treatment of odontogenic infections has become a significant economic burden to public health care facilities. The results of this study may help to adapt the numbers of doctors/dentists on duty in relation to different weather conditions. In any case, it is an impetus to think outside the box.

[Frequency and management of complex facial fractures-an oral and maxillofacial surgical assessment]. / Häufigkeit und Management von Gesichtsschädelfrakturen ­ eine MKG-chirurgische Einschätzung.

INTRODUCTION: The treatment of facial fractures is an integral part of the oral and maxillofacial surgical treatment spectrum. In the case of complex fractures that involve multiple levels of the facial skeleton associated with severe concomitant injuries, an individual and interdisciplinary treatment approach is needed, which requires the infrastructure of a national trauma center. OBJECTIVE: The aim of this study was to analyze the incidence and management of patients with complex facial fractures and considering the concomitant injury pattern. MATERIAL AND METHODS: A retrospective analysis of patients with complex facial fractures during the years 2009-2015 admitted to the emergency surgical department of a national trauma center was carried out. The identification of appropriate patient cases was based on the International Statistical Classification of Diseases and Related Health Problems (ICD) coding of electronic patient data. Only patients with at least a combination of mandibular and midfacial fractures (2-level fractures) were considered. Patients with mainly dentoalveolar fractures and simple nasal bone fractures were not included. The evaluation of the electronic medical records included the etiology, fracture pattern, associated severe injuries on the basis of the injury severity score (ISS), treatment regimen as well as the length of the hospital stay. RESULTS: In the 7­year study period, 3382 patients were identified with facial fractures. Of these, 128 patients (3.78%) presented with a complex fracture pattern with a combination of mandibular fractures and fractures of the midface. The majority of these patients (n = 92) had less severe concomitant injuries (ISS ≤ 16), while 36 patients showed severe concomitant injuries (ISS > 16). The incidence of a 3-level fracture involving the mandible, midface and anterior skull base was only 0.47% and could be detected in 16 patients, of which 10 were classified as polytrauma (ISS > 16). CONCLUSION: The incidence of complex fractures of the facial skeleton was comparatively low with almost 4%. More than one in four patients with complex injury patterns of the facial skeleton exhibited severe concomitant life-threatening injuries, necessitating an interdisciplinary management with the specialized infrastructure of a nationwide trauma center.

Clinical outcome after orbital floor fracture reduction with special regard to patient's satisfaction.

PURPOSE: Primary reconstruction via transconjunctival approach is a standardized treatment option for orbital floor fractures. The aim of this study was to compare the findings of specific ophthalmologic assessment with the patient's complaints after fracture reduction. METHODS: A retrospective medical chart analysis was performed on patients who had undergone transconjunctival orbital floor fracture reduction for fracture therapy with resorbable foil (ethisorb sheet or polydioxanone foil). A follow-up assessment including ophthalmological evaluation regarding visual acuity (eye chart projector), binocular visual field screening (Bagolini striated glasses test) and diplopia (cover test, Hess screen test) was conducted. Additionally, a questionnaire was performed to assess patients' satisfaction. RESULTS: A total of 53 patients with a mean follow-up of 23 months (ranging from 11 to 72) after surgical therapy were included. Diplopia was present preoperatively in 23 (43.4%) and reduced in follow-up examination (n = 12, 22.6%). Limitations in ocular motility reduced from 37.7% to 7.5%. The questionnaire about the patient's satisfaction revealed excellent outcomes in relation to the functional and esthetical parameters. CONCLUSION: Transconjunctival approach is a safe approach for orbital fracture therapy. Postoperative diplopia is nearly never perceptible for the individual and differs to pathologic findings in the ophthalmic assessment.

Treatment of Wound Healing Disorders of Radial Forearm Free Flap Donor Sites Using Cold Atmospheric Plasma: A Proof of Concept.

PURPOSE: The treatment of wound healing disturbances of the radial forearm free flap donor site after reconstructive surgery is typically long and burdensome and often requires additional surgery. Cold atmospheric plasma is a promising approach to overcome these impairments. The aim of this proof of concept study was to evaluate the clinical outcome of plasma irradiation in patients with wound healing disorders with exposed brachial tendons of the radial forearm. PATIENTS AND METHODS: Four patients (mean age 64.2 years, range 44 to 80) who had undergone radial forearm free flap procedures and developed wound healing disturbance leading to exposed flexor tendons were included in the present prospective case series. In addition to routine wound care, all sites were irradiated with cold atmospheric plasma. The primary outcome variable was complete wound closure. RESULTS: In all patients, complete wound repair in terms of the absence of tendon exposure was observed within a mean treatment time of 10.1 weeks (range 4.9 to 16). No undesirable side effects were observed, and no inflammation or infection occurred. CONCLUSIONS: Cold atmospheric plasma could offer a reliable conservative treatment option for complicated wound healing disturbances. This was exemplarily shown in the case of radial forearm free flap donor site morbidity with exposed flexor tendons in the present study.

Drill-related root injury caused by intraoperative intermaxillary fixation: an analysis of 1067 screw applications.

BACKGROUND/AIMS: Intermaxillary fixation is a standard procedure for the treatment of mandibular fractures or in orthognathic surgery. Predrilling for screws poses the risk of accidental tooth root injury, potentially leading to further pathological processes. Limited evidence about accidental tooth injury during intermaxillary fixation is available due to heterogenous study designs. The aim of this study was to evaluate the risk of root trauma using predrilled transgingival fixation screws and the clinical consequences for the affected teeth. MATERIALS AND METHODS: In this retrospective study, the data of open reduction and internal fixation surgery files with intraoperative application of predrilled intermaxillary fixation screws were analysed. The postoperative radiographic images were evaluated for the occurrence of tooth root injury. Patients diagnosed with root injury were clinically followed up with respect to the dental health for the affected teeth. RESULTS: A total of 133 radiologically diagnosed tooth root injuries were recorded (12.5% of screws). The median follow-up interval was 16 months (range: 3-77 months). The return rate was 49.5% for all patients. Of these, four of the injured teeth (3%) needed endodontic treatment. No toothache was reported, no tooth was lost, and no negative impact on periodontal health was clinically evident. CONCLUSION: Intermaxillary fixation with predrilled transgingival screws is a safe way to manage mandibular fractures. The incidence of tooth root injury is not uncommon, but the adverse side effects are rare and the health of the affected teeth is mostly not compromised.

Age-Related Changes of the Orolabial Region in Caucasian Women: An Anthropometric Analysis.

PURPOSE: Anthropometric data can provide valuable support for the attending physician in planning surgical and nonsurgical esthetic procedures with regard to a patient's age. The purpose of the present study was to identify age-related orolabial changes in younger and older Caucasian women. MATERIALS AND METHODS: In the present cross-sectional study, anthropometric landmarks were identified using indirect anthropometry (2-dimensional photometry) in younger (≤35 yr) and older (≥50 yr) Caucasian women to analyze age-related parameters and proportions of the orolabial region, especially of the lower and upper lip vermilion areas. The Mann-Whitney U test was applied to compare the results between the younger and older populations. RESULTS: The study population consisted of 45 women. The cohort was divided into a younger population (24 participants; mean age, 27.4 yr) and an older population (21 participants; mean age, 58 yr) to evaluate age-related differences. Increases of upper lip height, cutaneous height of the upper lip, and cutaneous height of the lower lip were observed in older women. In contrast, the vermilion height of the lower lip decreased significantly with increasing age. CONCLUSION: These results show changes of the orolabial region occur in Caucasian women with increasing age. The statistically relevant decrease of the vermilion height of the lower lip should be given particular attention for (age-appropriate) diagnostic, esthetic, and prosthetic treatment planning.

Severe tooth loss after root damage caused by predrilled intermaxillary fixation screw: a case report.

Intermaxillary fixation (IMF) with screws is routinely used as a conservative therapy or to obtain normal occlusion during the surgical procedure of open reduction and internal fixation for treating mandibular fractures. The risk of iatrogenic dental damage caused by interdental drilling is widely known. Several side effects are described, including loss of response to pulp sensibility testing, root fracture, and, loss of the tooth. This is a case report about a young man who had undergone temporary IMF treatment with a single proven root damage. The patient did not appear for follow-up but he presented 5 years afterward with local purulent osteomyelitis concerning the affected and the adjacent teeth. Osteotomy and extraction of two premolars and one molar were necessary for rehabilitation. This case report illustrates the importance of careful use of predrilled IMF screws and the necessity of frequent follow-ups in cases of proven tooth root damage due to IMF treatment.

A teaching intervention in a contouring dummy run improved target volume delineation in locally advanced non-small cell lung cancer: Reducing the interobserver variability in multicentre clinical studies.

INTRODUCTION: Interobserver variability in the definition of target volumes (TVs) is a well-known confounding factor in (multicentre) clinical studies employing radiotherapy. Therefore, detailed contouring guidelines are provided in the prospective randomised multicentre PET-Plan (NCT00697333) clinical trial protocol. This trial compares strictly FDG-PET-based TV delineation with conventional TV delineation in patients with locally advanced non-small cell lung cancer (NSCLC). Despite detailed contouring guidelines, their interpretation by different radiation oncologists can vary considerably, leading to undesirable discrepancies in TV delineation. Considering this, as part of the PET-Plan study quality assurance (QA), a contouring dummy run (DR) consisting of two phases was performed to analyse the interobserver variability before and after teaching. MATERIALS AND METHODS: In the first phase of the DR (DR1), radiation oncologists from 14 study centres were asked to delineate TVs as defined by the study protocol (gross TV, GTV; and two clinical TVs, CTV-A and CTV-B) in a test patient. A teaching session was held at a study group meeting, including a discussion of the results focussing on discordances in comparison to the per-protocol solution. Subsequently, the second phase of the DR (DR2) was performed in order to evaluate the impact of teaching. RESULTS: Teaching after DR1 resulted in a reduction of absolute TVs in DR2, as well as in better concordance of TVs. The Overall Kappa(κ) indices increased from 0.63 to 0.71 (GTV), 0.60 to 0.65 (CTV-A) and from 0.59 to 0.63 (CTV-B), demonstrating improvements in overall interobserver agreement. CONCLUSION: Contouring DRs and study group meetings as part of QA in multicentre clinical trials help to identify misinterpretations of per-protocol TV delineation. Teaching the correct interpretation of protocol contouring guidelines leads to a reduction in interobserver variability and to more consistent contouring, which should consequently improve the validity of the overall study results.

Survival analysis of dental implants and implant-retained prostheses in oral cancer patients up to 20 years.

OBJECTIVES: The purpose of this study was to evaluate the long-term survival rate and potential influencing factors of dental implants and implant-retained prostheses in oral cancer patients who had undergone surgical tumor resection. MATERIAL AND METHODS: In the present study, 157 patients (95 females and 62 males with a mean age of 53.7 years) with 830 implants were included. All patients were diagnosed with a malignant tumor in the oral cavity and had undergone ablative surgery. In 55 patients (292 implants), the surgical procedure was followed by an additional radiochemotherapy (RCT) before implant placement. Nicotine users who received RCT were excluded from this study. Patients were clinically examined every 6 or 12 months according to a standard procedure. RESULTS: Of the 830 examined implants, 450 were placed in the maxilla and 380 in the mandible. A total of 65 implants were lost, 36 in the maxilla and 29 in the mandible; of these, 42 implants (65%) were documented as lost due to the patient's death. The mean observation period was 121 months. The cumulative survival rate was 94.9% at 3 years and 92.5% at 7 years. With an observation period up to 20 years, the cumulative survival rate remained constant after 11 years with 90.8%. Age, gender, and localization (maxilla/mandible) of implants did not show any influence on the survival of the implants. However, radiochemotherapy was determined as a significant factor influencing the survival rate. CONCLUSIONS: The results of this study demonstrate that the survival rate of implants was significantly lower in oral cancer patients who had been treated by ablative surgery and additional radiochemotherapy than in patients without RCT. Since there is no significant difference in the mortality rate of patients with additional RCT compared to patients who underwent sole ablative surgery, the higher loss ratio is due to a late failure of osseointegration. CLINICAL RELEVANCE: Dental implants in oral cancer patients who had been treated by ablative surgery show a high and steady cumulative survival rate after 11 years. Implant survival of patients with additional RCT is significantly lower. Non-smoking-irradiated patients seem to have a better implant survival.

Diagnostic pitfalls in pediatric orbital entrapment fractures.

Prompt diagnosis and management of orbital entrapment fractures in the pediatric patient have been advocated. This retrospective study analyzed a cohort of orbital entrapment fractures in pediatric patients with regard to diagnostic pitfalls, treatment and outcomes in a Level I trauma center in Germany. Based on medical records and radiological imaging, patients under the age of 18 years who presented with orbital fractures during 2009-2021 were analyzed. Overall, 125 patients presented with orbital fractures, of whom 29 patients (23.2%) had orbital entrapment fractures. The majority of patients presented with monocle hematoma (n = 23), diplopia (n = 20), and/or restricted extraocular eye movement (n = 14). While all patients with orbital entrapment fractures underwent three-dimensional imaging, 10 radiological reports (34.5%) did not include findings on orbital entrapment fractures. All patients underwent surgical exploration in less than 24 h. In 12 patients, clinical symptoms such as diplopia and restricted ocular elevation were documented upon postoperative evaluation before discharge. Considering the significant proportion of orbital entrapment fractures that are not noted on radiological imaging, prompt clinical examination should be initiated in pediatric patients at risk for orbital fractures. Urgent surgical intervention should be recommended in entrapment fractures.

Exogenous Estrogen in the Development of Head and Neck Cancer.

Importance: Sex differences in head and neck cancer (HNC) incidence suggest a potential contribution of sex hormones. Objective: To assess the role of exogenous estrogen exposure in the development of HNC in female patients. Design, Settings, and Participants: This large multicenter cohort study using clinical records from the TriNetX real-world database included 20 years of data (through May 31, 2023) from 87 health care organizations. The TriNetX database was searched for medical records for female patients with and without exogenous estrogen exposure according to their chronological age. Cohort 1 included 731 366 female patients aged 18 to 45 years old with regular oral contraceptive (OC) intake and cohort 2 included 3 886 568 patients in the same age group who did not use OC. Cohort 3 comprised 135 875 female patients at least 50 years old receiving hormone replacement therapy (HRT), whereas cohort 4 included 5 875 270 patients at least 50 years old without HRT. Propensity score matching was performed for the confounders age, alcohol dependence, and nicotine dependence. Data analyses were performed in May 2023. Main Outcome and Measures: Diagnosis of HNC (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision: C00-C14), and after propensity score matching (1:1 nearest-neighbor greedy matching), a risk analysis to investigate risk differences and risk ratios (RRs) with a 95% CI. Results: Among the 718 101 female patients in each of cohorts 1 and 2 (mean [SD] age at diagnosis, 25.9 [6.7] years), those with OC intake had a higher risk of an HNC diagnosis (RR, 1.47; 95% CI, 1.21-1.78) than those without OC use. Among the 131 835 female patients in each of cohorts 3 and 4 (mean [SD] age, 67.9 [12.0] years), those with postmenopausal HRT intake had a lower risk of an HNC diagnosis (RR, 0.77; 95% CI, 0.64-0.92) than those without HRT use. Conclusions and Relevance: The findings of this cohort study illustrate a positive association between OC and a negative association between HRT and the development of HNC in female patients. Given the limitations of the TriNetX database, future research should include detailed information on the intake of OC and HRT and reproductive health information (eg, age at menarche/menopause, number of pregnancies) to more accurately define the strength and direction of the possible association between exogeneous estrogen exposure and the development of HNC in female patients.

Quantifying bone healing after mandibular displacement in orthognathic surgery.

Impaired bony healing following bilateral sagittal split osteotomy (BSSO) is a major unmet medical need for affected patients, and rare occurrences can hinder the identification of underlying risk factors. We hypothesised that osseous union following BSSO can be quantified using volumetric analysis, and we aimed to identify the risk factors for impaired bone healing. The percentage change in bony volume was measured in orthognathic patients following BSSO using two consecutive postoperative cone-beam computed tomography scans. Patients' characteristics and treatment parameters were documented, and correlation and regression analyses of these variables performed. Thirty-six patients (23 men and 13 women) with a mean (SD) age of 33.28 (11.86) years were included. The gap site (lingual versus buccal) (p < 0.01) had a significant impact on the change in volume. Age (p = 0.06) showed a trend towards significance. Initial width of the osteotomy gap, sex, and indication for surgery did not influence osseous healing. Increased age at surgery and the side of the buccal osteotomy are independent risk factors for impaired osseous healing following BSSO.

Resection status and margin control in intraoperative frozen sectioning analysis of oral squamous cell carcinoma.

PURPOSE: Intraoperative frozen section analysis (IFSA) is a well-established procedure for determining the intraoperative soft tissue resection status in patients with oral squamous cell carcinoma (OSCC). Margin status is a major predictor of the patient´s outcome, histologically free margins of ≥ 5 mm are demanded. This study evaluates the accuracy of IFSA, the impact of margin status and the impact of intraoperative margin revision on disease-free survival (DFS) and overall survival (OS). METHODS: This retrospective study included 213 patients with OSCC. IFSA results were compared with definitive histopathological reports, Kaplan-Meier analysis was performed. Cut-off values were calculated for resection margins considering known risk factors. RESULTS: IFSA showed positive margins in 8 cases (3.8%). Kaplan-Meier analysis revealed no significant differences for OS or DFS if R0-status was achieved by initial resection or immediate re-resection. Final histopathological evaluation revealed false-positive IFSA in 3/8 cases (37.5%) and false-negative IFSA in 1/205 cases (0.5%). Sensitivity was 83.3% and specificity was 98.6%. Analysis of optimal cut-off values showed no general need for larger resection margins in patients with risk factors. Cut-off values were slightly higher for patients with the risk factor alcohol consumption (7 mm for OS and DFS) or pN + ECS- disease (7 mm for DFS). Optimal cut-off values for tumour-margin-distance were around 6 mm. CONCLUSION: IFSA provides a valuable assessment method for intraoperative soft tissue resection margins. Risk factors seemingly do not significantly influence the extent of tumour resection.

The impact of time between surgery and adjuvant chemoradiotherapy in advanced oral cavity squamous cell carcinoma.

Objective: In advanced oral squamous cell carcinoma (OSCC), adjuvant therapy (AT) is an important part of the treatment to ensure extended locoregional control after primary surgical resection. The impact of the time interval between surgery and AT on the oncological prognosis remains unclear, particularly in high-risk constellations. The aim of this study is to categorize treatment delays and to determine their impact on the oncological prognosis within the context of the histopathological risk parameters of patients with advanced OSCC. Methods: In this single-institutional retrospective cohort study, all patients treated for OSCC between 2016 and 2021 and who received postoperative chemoradiation (POCRT) were included. Patients were divided into two groups: Group I: ≤ 6 weeks between surgery and POCRT; and Group II: > 6 weeks between surgery and POCRT. Results: Overall, 202 patients were included (Group I: 156 (77.2%) vs. Group II: 46 (22.8%)). There were no statistically significant differences in epidemiological aspects and histopathological risk factors between the two groups. The maximum time to initiation of POCRT was 11 weeks. Delayed POCRT initiation had no statistically significant influence on the 5-year OS (61.6% vs. 57.3%, p = 0.89), locoregional control rate (38.6% vs. 43.3%, p = 0.57), and RFS (32.3% vs. 30.4%, p = 0.21). On multivariate analysis, extracapsular spread (HR: 2.21, 95% CI: 1.21 - 4.04, p = 0.01) and incomplete surgical resection (HR: 2.01, 95% CI: 1.10 - 3.69, p = 0.02) were significantly correlated with OS. For RFS, ECS (HR: 1.82, 95% CI: 1.15 - 2.86, p = 0.01), incomplete resection (HR: 1.67, 95% CI: 1.04 - 2.71, p = 0.04), and vascular infiltration of the tumor (V-stage; HR: 2.15, 95% CI: 1.08 - 4.27, p = 0.03) were significant risk predictors. Conclusion: Delays in POCRT initiation up to 11 weeks after surgical resection for advanced OSCC were not statistically significantly associated with impaired survival. In cases of prolonged surgical treatment due to management of complications, a small delay in AT beyond the recommended time limit may be justified and AT should still be pursued.

Differentiation of opioid drug effects by hierarchical multi-site phosphorylation.

Differences in the ability of opioid drugs to promote regulated endocytosis of µ-opioid receptors are related to their tendency to produce drug tolerance and dependence. Here we show that drug-specific differences in receptor internalization are determined by a conserved, 10-residue sequence in the receptor's carboxyl-terminal cytoplasmic tail. Diverse opioids induce receptor phosphorylation at serine (S)375, present in the middle of this sequence, but opioids differ markedly in their ability to drive higher-order phosphorylation on flanking residues [threonine (T)370, T376, and T379]. Multi-phosphorylation is required for the endocytosis-promoting activity of this sequence and occurs both sequentially and hierarchically, with S375 representing the initiating site. Higher-order phosphorylation involving T370, T376, and T379 specifically requires GRK2/3 isoforms, and the same sequence controls opioid receptor internalization in neurons. These results reveal a biochemical mechanism differentiating the endocytic activity of opioid drugs.

Worse prognosis in females with new onset of depression after oral cancer diagnosis: a retrospective case-control study.

Background: Sex-related discrepancies in the prognosis of oral cancer patients have not been clarified. This study aimed to assess survival outcomes and potential prognostic factors in female and male patients with oral cancer. Methods: A retrospective search of the TriNetX network (TriNetX, Cambridge, Massachusetts, USA) was conducted to identify patients diagnosed with oral cancer (International Classification of Diseases (ICD)-10 codes C02-C06), within the past 20 years from the access date April 21, 2023. Patients were categorized according to sex (female vs. male). Following matching for age and risk factors such as nicotine dependence and alcohol abuse, Kaplan-Meier analysis was performed and risk, odds, and hazard ratios were calculated. Outcome variables were five-year disease-free survival (DFS) and overall survival (OS). Additionally, the female and male patient cohort were compared with regard to the novel diagnosis of depression (depressive episode, major depressive disorder, dysthymic disorder) after the tumor diagnosis. Results: A total of 77,348 patients were assessed. After propensity score matching, 26,578 male and 26,578 female patients were included in each group (mean age 63 years). DFS (71.92% in females vs. 68.29% in males; hazard ratio (HR) 0.870; p < 0.001) and OS (77.08% in females vs. 71.74% in males; HR 0.793; p < 0.001) were significantly higher in the female cohort. However, in patients diagnosed with depression after the initial cancer diagnosis (N = 4,824), survival was worse in female patients compared to male patients (82.48% in females vs. 86.10% in males; HR 1.341; p < 0.001). Conclusion: This retrospective case-control study showed that females with oral cancer had a better DFS and OS than males. However, survival in females with a newly diagnosed depression after the oral cancer diagnosis was worse compared to those of male oral cancer patients. Depression may be a relevant prognostic factor that contributes to sex disparities in oral cancer patients.