A multivariable normal tissue complication probability model for predicting radiation-induced hypothyroidism in nasopharyngeal carcinoma patients in the modern radiotherapy era.

Radiation-induced hypothyroidism (RHT) is a common long-term complication for nasopharyngeal carcinoma (NPC) survivors. A model using clinical and dosimetric factors for predicting risk of RHT could suggest a proper dose-volume parameters for the treatment planning in an individual level. We aim to develop a multivariable normal tissue complication probability (NTCP) model for RHT in NPC patients after intensity-modulated radiotherapy or volumetric modulated arc therapy. The model was developed using retrospective clinical data and dose-volume data of the thyroid and pituitary gland based on a standard backward stepwise multivariable logistic regression analysis and was then internally validated using 10-fold cross-validation. The final NTCP model consisted of age, pretreatment thyroid-stimulating hormone and mean thyroid dose. The model performance was good with an area under the receiver operating characteristic curve of 0.749 on an internal (200 patients) and 0.812 on an external (25 patients) validation. The mean thyroid dose at ≤45 Gy was suggested for treatment plan, owing to an RHT incidence of 2% versus 61% in the >45 Gy group.

Relationship of the Degree of Nerve Exposure and Surgical Manipulation and Short-Term Neurosensory Disturbance Following Sagittal Split Ramus Osteotomy: A Prospective Study.

BACKGROUND: Neurosensory disturbance (NSD) is a common complication after sagittal split ramus osteotomy (SSRO) due to inferior alveolar nerve (IAN) injury. The impact of intraoperative nerve manipulation on NSD remains debated. PURPOSE: The purpose of this study was to evaluate the influence of IAN exposure and manipulation during SSRO on functional sensory recovery (FSR). STUDY DESIGN: This was a single-center, prospective cohort study of 40 patients undergoing SSRO at Mahidol University from December 2020 to December 2021. The inclusion criteria were patients aged 20-34, ASA Class I-II. The exclusion criteria were patients with systemic bone disease, history of head and neck or neurological pathology, previous SSRO, or incomplete data collection. PREDICTOR VARIABLE: Degree of intraoperative nerve manipulation was divided by the attending surgeon as follows; 1) Nerve fully encased in distal segment and not visible (NS); 2) Nerve encased in distal segment but partially visible (DS); and 3) Nerve partially encased in proximal segment and fully dissected free (PS). OUTCOME VARIABLES: The area of interest was divided into the lip and chin. The primary outcome was time to FSR. The secondary outcome was subjective patient report, using a visual analogue scale, compared to FSR. COVARIATES: The covariates were sex, age, skeletal diagnosis, degree of movement, and concomitant genioplasty/subapical procedure. ANALYSES: Kaplan-Meier survival analysis, Cox proportional hazards regression, and Mcnemar test were utilized. P-value < .05 was significant. RESULTS: In the lip, the median times to FSR were NS, 2 days; DS, 45 days; PS, 102 days. (Interquartile range: 77,127, 114, respectively) In the chin, the median times to FSR were NS, 23 days; DS, 92 days; PS, 87 days. (Interquartile range: 77, 161, 101, respectively.) Nerve manipulation significantly affected FSR in the lip and chin (P = .001, <0.001, respectively. Cox hazard ratios for DS and PS were lower compared to NS. Patients consistently reported more NSD compared to FSR as per Mcnemar test. CONCLUSION AND RELEVANCE: After SSRO, FSR in the lip is prolonged when the IAN is partially encased in the proximal segment and released. This raises the question of the efficacy of surgically releasing a partially encased IAN.

Histopathological and risk factor analyses of oral potentially malignant disorders and oral cancer in a proactive screening in northeastern Thailand.

BACKGROUND: Lip and oral cavity cancer has been reported as the 10th most common cancer in Thailand. Recently, a screening program for oral potentially malignant disorders (OPMDs) and oral cancer was conducted in the northeastern Thailand which took into consideration a total of 371,911 people who resided in the provinces of Buriram, Chaiyaphum, Nakhon Ratchasima, and Surin. METHODS: A total of 330,914 subjects were consecutively screened for risk factors of oral cancer by village health volunteers (VHVs) using a questionnaire (S1). Then, 186,710 subjects with one or more risk factors for oral cancer were referred for oral screening by dental auxiliaries or dentists at sub-district level hospitals (S2) where 86,941 subjects were subsequently screened. Afterwards, 1576 subjects with suspicious oral lesions for OPMDs or oral cancer attended local hospitals for further investigation and treatment. Oral medicine specialists, oral surgeons, and local dentists at the district level hospitals performed biopsies and the samples were sent for histopathological analysis. The objectives of the study were to report the histopathology findings from the biopsies obtained from these subjects and the associated risk factors. RESULTS: Out of 427 subjects who received biopsies, complete diagnostic results were obtained from 409 patients (462 specimens). The 5 most common histopathological results from these specimens were mild epithelial dysplasia (27.3%), fibroepithelial hyperplasia (14.5%), oral lichen planus/oral lichenoid reactions (11.5%), moderate epithelial dysplasia (8%), and acanthosis with or without hyperkeratosis (5%). Oral squamous cell carcinoma was detected in 14 subjects and 11 other forms of oral cancer were revealed. Among the analyzed risk factors, habitual betel quid chewing was established as a statistically significant risk factor associated with OPMDs and oral cancer. CONCLUSION: The most frequently observed histopathological results of clinically suspected oral cancer and OPMDs included mild epithelial dysplasia, fibroepithelial hyperplasia, oral lichen planus/oral lichenoid reactions, moderate epithelial dysplasia, and acanthosis with or without hyperkeratosis. Betel quid chewing habit was found to be associated with OPMDs and oral cancer.

Machine learning-based normal tissue complication probability model for predicting albumin-bilirubin (ALBI) grade increase in hepatocellular carcinoma patients.

PURPOSE: The aim of this study was to develop a normal tissue complication probability model using a machine learning approach (ML-based NTCP) to predict the risk of radiation-induced liver disease in hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: The study population included 201 HCC patients treated with radiotherapy. The patients' medical records were retrospectively reviewed to obtain the clinical and radiotherapy data. Toxicity was defined by albumin-bilirubin (ALBI) grade increase. The normal liver dose-volume histogram was reduced to mean liver dose (MLD) based on the fraction size-adjusted equivalent uniform dose (2 Gy/fraction and α/ß = 2). Three types of ML-based classification models were used, a penalized logistic regression (PLR), random forest (RF), and gradient-boosted tree (GBT) model. Model performance was compared using the area under the receiver operating characteristic curve (AUROC). Internal validation was performed by 5-fold cross validation and external validation was done in 44 new patients. RESULTS: Liver toxicity occurred in 87 patients (43.1%). The best individual model was the GBT model using baseline liver function, liver volume, and MLD as inputs and the best overall model was an ensemble of the PLR and GBT models. An AUROC of 0.82 with a standard deviation of 0.06 was achieved for the internal validation. An AUROC of 0.78 with a standard deviation of 0.03 was achieved for the external validation. The behaviors of the best GBT model were also in good agreement with the domain knowledge on NTCP. CONCLUSION: We propose the methodology to develop an ML-based NTCP model to estimate the risk of ALBI grade increase.

Anatomical Variations of the Anterior Belly of the Digastric Muscle in Thai Cadavers: A Cross-Sectional Study.

Aim: Because the digastric muscle is considered as an anatomical landmark, its variations may emphasize clinicians to be cautious during surgery. However, previous studies from different ethnicities reported a wide range of occurrence and several types of this muscle variation, pointing the necessity of the data from local population to better treatment decisions. Thus, this study aimed to explore the variations of the anterior belly of the digastric muscle in Thai cadavers. Materials and Methods: This cross-sectional study investigated the submental region of 91 cadavers by convenient sampling method. The characteristics of the variation in the anterior belly were recorded in accordance with sex and side of the cadavers. Multiple logistic regression was calculated for determining the association of occurrence of muscle variation with sexes and sides (α = 0.05). Results: Among 91 cadavers, the accessory bundles were observed in 16 cadavers (10 males and 6 females). The presence of the additional belly was sex and side independent. Three variation types were observed; the arrowhead type and the double-headed type have been previously reported, whereas the asymmetrical fan-shaped type is the new variant that has never been described before. Conclusions: The variation of the anterior belly of the digastric muscle including the new variant can be seen in Thais with low occurrence. To our knowledge, the present study is the first report of the aberrations of the digastric muscle in the Southeast Asian population. Therefore, our study provides the basis for anatomical study of muscular variants and helps surgeons plan the operation to prevent iatrogenic injuries.

Fungicidal Effect of Lemongrass Essential Oil on Candida albicans Biofilm Pre-established on Maxillofacial Silicone Specimens.

AIMS: This in-vitro study aimed to evaluate the efficacy of lemongrass (Cymbopogon citratus) essential oil in eradicating Candida albicans biofilm pre-established on the maxillofacial silicone specimens. MATERIALS AND METHODS: Two maxillofacial silicones, namely, MDX4-4210 and Multisil Epithetik, were used for the fabrication of 6 mm diameter disks (n = 21 for each brand of silicone). A 48-h mature C. albicans ATCC 10231 biofilm was pre-established on sterile silicone specimen. These disks were then exposed to various concentrations of lemongrass essential oil ranging from 0.31% to 5% (v/v), 20% (v/v) nystatin, and RPMI-1640 medium for 18-20 h. After exposure, the remaining viable fungal biofilm was examined by the XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide]-reduction assay. All data were analyzed by using a regression coefficient and a post hoc Tukey HSD multiple comparisons test (α = 0.05). RESULTS: Different brands of silicone used for fabrication did not significantly affect the formation of mature C. albicans biofilm (P =0.302). A 5% (v/v) lemongrass essential oil significantly eliminated fungal biofilm by approximately 95% (P =0.031). However, less than 50% of the fungal biofilm was eliminated by the tested oil at a concentration as low as 0.31% (v/v). Furthermore, the fungicidal efficacy against C. albicans biofilm of lemongrass essential oil at 2.5% (v/v) was as potent as that of 20% (v/v) nystatin suspension (P = 0.99). CONCLUSION: Lemongrass essential oil expressed fungicidal effect on C. albicans biofilm pre-established on the disks fabricated from different brands of silicone. Additionally, the fungicidal effectiveness of the oil against the mature fungal biofilm was dose-dependent.

Assessment of the confidence interval in the multivariable normal tissue complication probability model for predicting radiation-induced liver disease in primary liver cancer.

We developed a confidence interval-(CI) assessing model in multivariable normal tissue complication probability (NTCP) modeling for predicting radiation-induced liver disease (RILD) in primary liver cancer patients using clinical and dosimetric data. Both the mean NTCP and difference in the mean NTCP (ΔNTCP) between two treatment plans of different radiotherapy modalities were further evaluated and their CIs were assessed. Clinical data were retrospectively reviewed in 322 patients with hepatocellular carcinoma (n = 215) and intrahepatic cholangiocarcinoma (n = 107) treated with photon therapy. Dose-volume histograms of normal liver were reduced to mean liver dose (MLD) based on the fraction size-adjusted equivalent uniform dose. The most predictive variables were used to build the model based on multivariable logistic regression analysis with bootstrapping. Internal validation was performed using the cross-validation leave-one-out method. Both the mean NTCP and the mean ΔNTCP with 95% CIs were calculated from computationally generated multivariate random sets of NTCP model parameters using variance-covariance matrix information. RILD occurred in 108/322 patients (33.5%). The NTCP model with three clinical and one dosimetric parameter (tumor type, Child-Pugh class, hepatitis infection status and MLD) was most predictive, with an area under the receiver operative characteristics curve (AUC) of 0.79 (95% CI 0.74-0.84). In eight clinical subgroups based on the three clinical parameters, both the mean NTCP and the mean ΔNTCP with 95% CIs were able to be estimated computationally. The multivariable NTCP model with the assessment of 95% CIs has potential to improve the reliability of the NTCP model-based approach to select the appropriate radiotherapy modality for each patient.

Differential Expression of EZH2 and H3K27me3 in Oral Verrucous Carcinoma and Oral Verrucous Hyperplasia.

Enhancer of zeste homolog 2 (EZH2), a component of the polycomb repressive complex 2 that catalyzes trimethylation of H3K27 (H3K27me3), has been shown to promote tumor development and progression. Expression of EZH2 is associated with cell cycle regulation and cell proliferation in various neoplasms. Oral verrucous hyperplasia (OVH) and Oral verrucous carcinoma (OVC) are rare entities and share several clinical and histopathologic features. Problems distinguishing these lesions are added by a lack of adjacent normal tissue of the biopsy samples and poorly oriented tissue sections. The aim of this study was to investigate the expression of EZH2 and H3K27me3 in OVH and OVC and comparing the expression with normal oral mucosa and oral squamous cell carcinoma (OSCC). Seventy-eight samples, including 25 cases of OVC, 8 cases of OVH, 35 cases of OSCC and 10 cases of normal oral mucosa, were retrieved and submitted for immunohistochemical staining. The results demonstrated that the mean labeling indices (LIs) of EZH2 and H3K27me3 expression were highest in OSCC, followed by the OVC, OVH, and normal mucosa. Statistical differences in EZH2 LI were observed among these lesions whereas H3K27me3 LI was significantly different among OSCC, OVH and normal mucosa. EZH2 LI was found to have a sensitivity of 72.00% and specificity of 87.50% in distinguishing OVH from OVC, and a sensitivity of 57.14% and specificity of 84.00% in distinguishing OVC from OSCC. A positive correlation between EZH2 and H3K27me3 expression was significantly found in OVC but not in OVH and OSCC. These findings highlight the involvement of epigenetic regulation by EZH2-mediated H3K27me3 in the pathogenesis of OVH and OVC, and EZH2 expression indicates disease progression of these verrucous lesions. Diagnostic test analysis further suggests that EZH2 may be used as an additional test for differentiating OVH from OVC in questionable cases.