A narrative review and clinical anatomy of herpes zoster infection following COVID-19 vaccination.

INTRODUCTION: In this review, cases of herpes zoster (HZ) infection following receipt of COVID-19 vaccines will be analyzed. We also present two cases of oral HZ following the COVID-19 vaccine and discuss this clinical anatomy. MATERIALS AND METHODS: A database search using PubMed was conducted in August 2021 and 20 articles were found to be eligible for review. Patient data and vaccine information were analyzed. In addition, two cases of oral HZ infection following the receipt of COVID-19 vaccines are presented. RESULTS: A total of 399 cases were identified. The affected dermatomes mimicked the regular distribution of HZ. For the dermatomes of the face, the various reports used different ways to describe the areas involved; CNV, CNV1, CNV2, CNV3, lower jaw, forehead, and under the eyebrow (CNV, 2 cases; CNV1, 4 cases; CNV2, 3 cases; and CNV3, 3 cases). Some patients who had a history of varicella zoster virus vaccination had HZ following the COVID-19 vaccination. Two patients with oral HZ following vaccination were found to have involvement of the greater palatine nerve. CONCLUSIONS: Vaccine-related HZ cases have been reported worldwide. Although many studies with a larger number of cases are ongoing, detailed information can be obtained from case reviews as reported herein.

The potential for facial artery injury during mandibular third molar extraction. An anatomical study using contrast-enhanced computed tomography.

The purpose of this study was to evaluate the risk of injury to the facial (FA) and related arteries during mandibular third molar (MTM) extraction using contrast-enhanced computed tomography (CE-CT). CE-CT images of the MTM region were retrospectively reviewed. The area of the MTM was equally divided into three zones in the coronal images from mesial to distal, that is, zone 1, zone 2, and zone 3. The FA, submental artery (SMA), and sublingual artery (SLA) were identified. The distance from the mandible to FA, SMA, and SLA and the diameter of the FA, SMA, and SLA was measured in three zones, respectively. The thickness of the facial soft tissues and width of the mandible were measured at their maximum. The mean distance from the FA to the buccal cortical bone in zone 1, zone 2 and zone 3 was 2.24 mm, 2.39 mm and 1.67 mm, respectively. The SMA and SLA were found to be distal to the mandible. The mean diameter of the FA was 1.26 mm in males and 1.04 mm in females, respectively (p < 0.0001). The distance between the FA and buccal cortical bone of the mandible, and the patients' weight showed moderate correlation in zones 1 and 2. Based on our findings, the FA can be damaged if the surgical invasion reaches the facial soft tissues during MTM surgery. The patients' weight might be a good predictor for FA injury when CE-CT is not available.

Factors associated with severe oral mucositis and candidiasis in patients undergoing radiotherapy for oral and oropharyngeal carcinomas: a retrospective multicenter study of 326 patients.

PURPOSE: The present retrospective multicenter study intended to investigate the factors associated with severe oral mucositis and candidiasis in patients undergoing radiotherapy for oral and oropharyngeal carcinomas. METHODS: A total of 326 patients who underwent radiotherapy for oral and oropharyngeal cancers were enrolled in the study. The patients' age, sex, body mass index, primary site, diabetes, serum albumin, creatinine, hemoglobin, leukocyte and lymphocyte, concurrent cisplatin or cetuximab, method of radiation, total radiation dose, feeding route, use of spacers, pilocarpine hydrochloride, and corticosteroid ointment were examined, and the associations of each variable with oral mucositis and candidiasis were analyzed by multivariate Cox regression analysis. RESULTS: Grade 3 oral mucositis occurred in 136 (41.7%) patients. Male sex, oropharyngeal cancer, low hemoglobin levels, low leukocytes or lymphocytes, concurrent cisplatin or cetuximab, and oral feeding were found to be significantly associated with a higher incidence of severe oral mucositis. Oral candidiasis occurred in 101 (31.0%) patients. Oropharyngeal cancer, low leukocyte count, and oral mucositis of grade 2 or higher were found to be significantly associated with a higher incidence of oral candidiasis. The use of a topical steroid ointment was not found to be a risk factor for oral candidiasis. CONCLUSIONS: The present retrospective study demonstrated that certain factors may predispose patients with oral and oropharyngeal cancers receiving radiotherapy to develop severe oral mucositis and oral candidiasis. A preventive strategy for severe oral mucositis needs to be established in the future for high-risk cases.

Clinical significance of periosteal reaction as a predictive factor for treatment outcome of medication-related osteonecrosis of the jaw.

Regarding treatment strategies for medication-related osteonecrosis of the jaw (MRONJ), surgical therapy has recently been reported to be more effective than conservative therapy. However, some patients did not achieve complete healing, even when extensive surgery was performed. Periosteal reaction in MRONJ patients is often observed by the CT examination. Tssshe purpose of this study was to investigate the relationship between periosteal reaction and treatment outcome of MRONJ. A total of 164 surgeries in 136 patients with MRONJ at two hospitals were included in the study. Correlations between various clinical and radiographic factors and treatment outcome were examined with Cox regression analysis. The results showed that the presence of periosteal reaction, as well as primary disease involving malignant tumor, were independent risk factors related to poor outcome. Furthermore, we examined factors related to the occurrence of the periosteal reaction and found that 4 variables were significantly correlated with periosteal reaction by multivariate analysis: gender (female), site (lower jaw), primary disease (malignant tumor), and osteosclerosis (severe). The present study clarified that the cure rate after surgical treatment decreased in cases with periosteal reaction, suggesting that it is necessary to review the treatment method.

Multimodal Prediction of Cervical Lymph Node Metastasis and Recurrence in Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) is the most common malignancy in the head/neck region, and cervical lymph node (CLN) metastasis is a strong poor-prognosis factor. In addition, many patients with OSCC experience recurrence despite multidisciplinary treatment. We sought to identify factors associated with CLN metastasis and recurrence in patients with OSCC. PATIENTS AND METHODS: We evaluated a total of 45 patients and 233 target CLNs. The longest diameter of the target CLN, the shortest diameter of the target CLN (LS), the area of the target CLN, and the relative computed tomography (CT) values of the target CLNs calculated based on the CT values of the internal jugular vein (LCT) were obtained from preoperative CT images, and the maximum standardized uptake values of the primary tumor (pSUV) and target CLN (nSUV) were obtained from preoperative 18F-fluorodeoxyglucose-positron emission tomography/CT images. We performed immunohistochemical staining for cytokeratin 13 (CK13) and 17 (CK17) on neck dissection tissues. RESULTS: A discrimination equation was used that can predict CLN metastasis with a 92.2% discrimination rate using LS, LCT, pSUV, and nSUV. The CLNs were divided into discrimination and non-discrimination groups based on discriminant equations and CK13 and CK17 were used as the objective variables. A significantly higher recurrence rate was observed in the non-discrimination group (CK13: 5-year recurrence rate 28.6% vs. 64.3%, p<0.01; CK17: 5-year recurrence rate 28.0% vs. 76.0%, p<0.01). CONCLUSION: CLN metastases in OSCC can be assessed by combining preoperative imaging. The combined use of CK13 and CK17 expression with imaging findings offers an integrated approach to predict OSCC recurrence.

EpEX, the soluble extracellular domain of EpCAM, resists cetuximab treatment of EGFR-high head and neck squamous cell carcinoma.

OBJECTIVES: Cetuximab (Cmab) is a molecularly targeted monoclonal antibody drug for head and neck squamous cell carcinoma (HNSC), although cetuximab resistance is a serious challenge. Epithelial cell adhesion molecule (EpCAM) is an established marker for many epithelial tumors, while the soluble EpCAM extracellular domain (EpEX) functions as a ligand for epidermal growth factor receptor (EGFR). We investigated the expression of EpCAM in HNSC, its involvement in Cmab action, and the mechanism by which soluble EpEX activated EGFR and played key roles in Cmab resistance. MATERIALS AND METHODS: We first examined EPCAM expression in HNSCs and its clinical significance by searching gene expression array databases. We then examined the effects of soluble EpEX and Cmab on intracellular signaling and Cmab efficacy in HNSC cell lines (HSC-3 and SAS). RESULTS: EPCAM expression was found to be enhanced in HNSC tumor tissues compared to normal tissues, and the enhancement was correlated with stage progression and prognosis. Soluble EpEX activated the EGFR-ERK signaling pathway and nuclear translocation of EpCAM intracellular domains (EpICDs) in HNSC cells. EpEX resisted the antitumor effect of Cmab in an EGFR expression-dependent manner. CONCLUSION: Soluble EpEX activates EGFR to increase Cmab resistance in HNSC cells. The EpEX-activated Cmab resistance in HNSC is potentially mediated by the EGFR-ERK signaling pathway and the EpCAM cleavage-induced nuclear translocation of EpICD. High expression and cleavage of EpCAM are potential biomarkers for predicting the clinical efficacy and resistance to Cmab.

Oral surgery in patients with antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by recurrent thrombosis, other associated autoimmune disease, and/or obstetrical morbidity along with persistent production of antiphospholipid antibodies. Because of the nature of this systemic disease, most patients are medicated with antithrombotic agents and abundant glucocorticoids. This study reports a cohort of 16 patients with APS, who underwent oral surgery between 2010 and 2017 at the Nagasaki University Hospital. Because oral antithrombotic therapy was continued in the perioperative period, all wounds were strictly closed by suturing to prevent postoperative bleeding. Perioperative laboratory dates and medications were assessed. All patients achieved local postoperative hemostasis and did not exhibit systemic complications. Moreover, there were no postoperative systemic and/or local infections. Oral surgeons should suture oral wounds and ensure local hemostasis to prevent postoperative bleeding. Because patients with APS are likely to develop thrombosis despite continued administration of antithrombotic medications, strict perioperative examination of blood coagulation is needed. Furthermore, it is important to consider the damage and stress caused due to oral surgery. Moreover, when necessary, glucocorticoid therapy should be carefully administered, in accordance with the degree of invasion and judgment of the attending physician.

Restoration of fragile histidine triad expression restores Chk2 activity in response to ionizing radiation in oral squamous cell carcinoma cells.

Early in tumorigenesis, a DNA damage-response network is activated in preneoplastic cells that delays or prevents cancer. Activation of the Chk2 G(2)/M checkpoint kinase and loss of fragile histidine triad (Fhit) tumor suppressor expression increase cellular susceptibility to DNA-damaging 'oncogenic' stressors, particularly in precursor or precancerous lesions. To understand the mechanism of oral carcinogenesis, we assessed the association between phosphorylated Chk2 (pChk2) and Fhit expression in oral squamous cell carcinoma. Loss of Fhit expression was an early event during oral carcinogenesis, whereas a decrease in the number of pChk2-positive cells was associated with tumor progression. Although tyrosine 114 is known to be essential to Fhit's tumor-suppressing activity, both wild-type and tyrosine 114 mutant Fhit increased the population of subG(1) DNA-containing HSC-3 OSCC cells with elevated pChk2 levels. In particular, when cells were exposed to ionizing radiation, pChk2 levels were upregulated dramatically, as were those of its downstream target Cdc25C. Knockdown of Fhit with FHIT small interfering RNA diminished the ionizing radiation-induced Chk2 phosphorylation in HEK293 cells. Furthermore, Fhit-deficient mice demonstrated a decrease in the number of pChk2-positive cells not only in dysplastic lesions but also in N-nitrosobenzylamine-induced papilloma of the forestomach, suggesting that lack of Fhit expression and the resultant defects of the ataxia telangiectasia mutated-Chk2 pathway can cause a difference in the incidence of N-nitrosobenzylamine-induced forestomach lesions. These findings suggest that Fhit plays a key role in the regulation of the ataxia telangiectasia mutated-Chk2 DNA damage response during oral carcinogenesis.

Increased wild-type p53-induced phosphatase 1 (Wip1 or PPM1D) expression correlated with downregulation of checkpoint kinase 2 in human gastric carcinoma.

Phosphorylation of checkpoint kinase 2 (Chk2) at Thr68 (pChk2) induced by DNA double-strand breaks is required for inhibition of cell cycle progression in the G(2) phase. The purpose of the present paper was to investigate the expression of wild-type p53-induced phosphatase 1 (Wip1 or PPM1D), a negative regulator of Chk2, to better understand its role in human gastric cancer. In non-neoplastic gastric mucosa, most epithelial cells exhibited Wip1-positive and pChk2-negative immunoreactivity, whereas an inverse pattern of protein expression was detected at the surface of the foveolar epithelium. In tumor tissues, 74% of 53 gastric cancers had intense Wip1 immunoreactivity and close correlation with both tumor size (P = 0.0497) and Chk2 dephosphorylation (P = 0.0213). In MKN-74 gastric cancer cells, ionizing radiation (IR)-induced Wip1 upregulation was detected at protein levels, but the Chk2-mediated cell cycle regulatory mechanism was disrupted. In addition, protease inhibitor Z-Leu-Leu-Leu (ZLLL) effectively upregulated Wip1 levels in the presence or absence of IR, suggesting that Wip1 expression can be modulated post-transcriptionally. Understanding the Wip1-mediated signaling pathway in gastric cancer may provide useful information for the development of new chemo- and radiotherapies.