Drug holiday clinical relevance verification for antiresorptive agents in medication-related osteonecrosis cases of the jaw.

Treatment strategies of medication-related osteonecrosis of the jaw (MRONJ) are controversial. Recently, surgical treatment has been reported as superior to nonsurgical treatment, but the contribution discontinued antiresorptive agent use during MRONJ treatment remains unclear. This study aimed to evaluate the efficacy of drug holidays and treatment strategies in MRONJ cases. Four-hundred and twenty-seven patients with MRONJ treated at nine hospitals from 2009 to 2017 were included in this multicenter retrospective study. Multivariate Cox regression analysis showed that the primary disease (osteoporosis or malignant tumor), diabetes, serum albumin, and treatment method (surgical or nonsurgical) were significantly correlated with the cure rate. The cumulative 1-year cure rates in the surgical and nonsurgical treatment groups were 64.7% and 18.2%, respectively. However, discontinuing antiresorptive agents did not influence the treatment outcome in the cohort overall, or in 230 patients after performing propensity score matching among the discontinuation and continuation groups. When stratifying by treatment method, antiresorptive agent discontinuation significantly increased the cure rate in patients with osteoporosis who underwent nonsurgical treatment. In patients with malignant tumors undergoing nonsurgical therapy, discontinuing the antiresorptive agent was associated with a better treatment outcome, but not with statistical significance. In contrast, drug holidays showed no effect on improving outcomes in patients with both osteoporosis and malignant tumors who underwent surgical therapy. Thus, regardless of the primary disease, discontinuing antiresorptive agents during treatment for MRONJ may not be necessary and may be helpful in some cases. Future prospective trials should examine this question further.

Prevalence of and risk factors for postoperative hemorrhage after lower third molar extraction on warfarin therapy: a multicenter retrospective study in Japan.

Postoperative hemorrhage after tooth extraction is a critical and clinically important issue for clinicians and patients receiving anticoagulants. The purpose of the present study was to investigate the prevalence of and risk factors for postoperative hemorrhage after lower third molar extraction in Japanese patients receiving warfarin therapy. A total of 142 patients who underwent lower third molar extraction between January 2010 and December 2016 were included, and their medical records were retrospectively reviewed. The prevalence of and risk factors for postoperative hemorrhage were investigated. The prevalence of postoperative hemorrhage after lower third molar extraction was significantly higher in patients receiving warfarin than in healthy subjects (21.8% vs 0.7%, P < 0.001). The cutoff value for PT-INR was 2.11 based on a receiver-operating characteristic analysis. A multivariate analysis indicated that an elevated PT-INR value [hazard ratio (HR) 3.798, 95% confidence interval (CI) 1.400-10.467, P < 0.01], preoperative antibiotic administration (HR 4.434, 95% CI 1.591-14.775, P < 0.01), difficulties with intraoperative hemostasis (HR 16.298, 95% CI 2.986-110.677, P < 0.01), and higher serum creatinine levels (HR 7.465, 95% CI 1.616-39.576, P < 0.05) are significant predictors of postoperative hemorrhage after lower third molar extraction. Multivariate correlations were observed between risk factors including an elevated PT-INR value, preoperative antibiotic administration, and higher serum creatinine levels, and postoperative hemorrhage after lower third molar extraction in patients receiving warfarin therapy. Clinicians need to consider these risk factors for postoperative hemorrhage after the lower third molar extraction and monitor PT-INR in patients receiving warfarin therapy.

Comparison of Subjective and Objective Assessments of Neurosensory Function after Lingual Nerve Repair.

OBJECTIVE: Mandibular third molar extractions are important in oral maxillofacial surgery. Damage to the lingual nerves, although rare, is a possible complication. There are reports of postoperative recovery after lingual nerve repair, but few reports have compared subjective and objective assessments of neurosensory function. Therefore, this study aims to compare subjective and objective assessments of neurosensory function after lingual nerve repair. SUBJECTS AND METHODS: This retrospective cohort study comprised 52 patients with lingual nerve anesthesia after third molar extraction at the Department of Oral and Maxillofacial Surgery, Wakayama Medical University Hospital, Wakayama, Japan, between December 2008 and December 2015. We recorded pre- and postoperative (6 months and 12 months) neurosensory examinations. RESULTS: Patient's subjective assessments of neurosensory function suggested improvement between the preoperative period and 12 months postoperation, although this difference was not significant. Objective assessment based on examination and testing, on the other hand, showed a significant difference in improvement (p < 0.05). CONCLUSIONS: There was no evidence that improvement of subjective preoperative and postoperative assessments was significantly associated with improvement of objective neurosensory assessments after lingual nerve repair. Overall physical condition and background were thought to affect subjective evaluation. Subjective assessment is important in conjunction with objective evaluation because it may reveal dysesthesia that would otherwise be missed. In the future, we will examine those cases in whom subjective assessments showed no improvement although objective assessments showed improvement.

Recovery of Impaired Somatosensory Evoked Fields After Improvement of Tongue Sensory Deficits With Neurosurgical Reconstruction.

Somatosensory evoked fields (SEFs) induced by tongue stimulation can be useful as an objective parameter to assess sensory disturbances in the tongue. However, whether tongue SEFs can be useful as a clinical, objective follow-up assessment method of tongue sensation after oral surgery is unknown. We describe 2 cases in which tongue SEFs were successfully used in clinical assessment. Two patients with unilateral tongue sensory deficits caused by lingual nerve injury during lower third molar extraction were recruited. Both patients underwent surgery to repair the damaged nerve, and all tongue sensory evaluations were performed once before and once after surgery. SEFs were recorded by stimulating the affected and unaffected sides of the tongue separately, and cortical activity was evaluated over the contralateral hemisphere. The unilaterality of the deficit also was assessed. In both patients, stimulation of the unaffected side evoked reproducible cortical responses before and after surgery. Both patients also recovered some sensation after surgery, given that presurgery stimulation of the affected side failed to evoke cortical activity whereas postsurgery stimulation evoked cortical activity on both sides. Sensation was initially highly lateralized in both patients but was restored to approximately normal in the postsurgery evaluation. Finally, both patients rated their subjective tongue sensations on the affected side over 50% better after the surgical intervention. These cases indicate that tongue SEFs may have a clinical use as an objective parameter for assessing the course of tongue sensory recovery.

Outcome following lingual nerve repair with vein graft cuff: a preliminary report.

PURPOSE: The object of this study was to assess the effects of an inside-out vein graft as a cuff after direct suture on human lingual nerve regeneration and recovery after iatrogenic lingual nerve injury. PATIENTS AND METHODS: Ten patients with unilateral lingual nerve anesthesia as a complication of iatrogenic injury after third molar extraction underwent microneurosurgical procedures for the injured lingual nerve under general anesthesia. The patients were randomized into 2 groups. In group A, after removing the neuromas and peripheral scars surrounding the torn nerves, the 2 nerve ends were sutured without tension. In group B, after the same procedure, including the same suturing procedure, an inside-out vein graft was placed as a cuff after the direct suture. Each group was followed at least once every 6 months for 1 year after the procedure. Postoperative outcomes were evaluated using the Pogrel criteria, the Sunderland grade, and the British Medical Research Council Scale (MRCS). RESULTS: There were no particular differences between groups A and B at 6 and 12 months after the operation. However, based on the MRCS criteria, there was a clearly better result in group B than in group A at 6 and 12 months after the operation, and the recovery of gustatory sensation tended to be better in group B than in group A 1 year after the operation. CONCLUSION: This inside-out vein graft as a cuff after direct suturing may facilitate faster lingual nerve regeneration than the traditional direct suture approach. The inside-out vein graft as a cuff may provide the advantages of preventing axonal escape at the suture lines, minimizing nerve entrapment, and preventing neuroma formation in the space between the sutured nerves.

Application of Tinel's test combed with clinical neurosensory test distinguishes spontaneous healing of lingual nerve neuropathy after mandibular third molar extraction.

BACKGROUND: Extraction of the mandibular third molar, the most frequent and important surgical procedure in the clinical practice of oral surgery, is associated with the risk of injury of the lingual nerve. Neuropathy of the lingual nerve poses diagnostic challenges regarding the transient or permanent nature of the injury. No consensus or criteria have been established regarding the diagnosis of lingual nerve neuropathy. We applied both Tinel's test and clinical neurosensory testing together, which can be easily used at the bedside in the early stages of injury. Therefore, we propose a new method to differentiate between lesions with the ability to heal spontaneously and those that cannot heal without surgery. RESULTS: Thirty-three patients (29 women,  4 men; mean age, 35.5 years) were included in this study. For all patients, the median interval between nerve injury and initial examination was 1.6 months and that between nerve injury and the second examination before determining the need for surgical management was 4.5 months. The patients were assigned to either group A or B. The spontaneous healing group (group A, n = 10) revealed a tendency for recovery within 6 months after tooth extraction. In this group, although there were individual differences in the degree of recovery, a remarkable tendency for recovery was observed based on clinical neurosensory testing in all cases. None of the patients were diagnosed with allodynia. In seven cases, the Tinel test result was negative at the first inspection, and in three cases, the result changed to negative at the second inspection. Conversely, in group B(n = 23), no recovery trend was observed with regard to clinical neurosensory testing, and nine patients had allodynia. Further, the Tinel test result was positive for all patients in both examinations. CONCLUSIONS: Our findings indicate that in case of transient lingual nerve paralysis, clinical neurosensory testing findings deteriorate immediately after tooth extraction and gradually recover, while Tinel's test shows a negative result. Using Tinel's test and clinical neurosensory testing together enabled early and easy identification of the severity of the lingual nerve disorder and of lesions that would heal spontaneously without surgical management.

Positive impact of perioperative oral management on the risk of surgical site infections after abdominal surgery: Sixteen universities in Japan.

Surgical site infections (SSI) are associated with increased morbidity and mortality rates. This study aimed to investigate the ability of perioperative oral management (POM) to reduce the risk of SSI in abdominal surgery Real-world data collected from 16 university hospitals in Japan were reviewed. The medical records of consecutive 2782 patients (1750 men and 1032 women) who underwent abdominal surgery under general anesthesia at 16 university hospitals were retrospectively reviewed. Detailed information about SSI was assessed and compared between patients with and without POM in univariate and multivariate analyses. SSI were observed in 275 patients (incidence rate:9.9%), and POM was administered to 778 patients (28.0%). Univariate analyses revealed that diabetes mellitus, Eastern Cooperative Oncology Group performance status, American Society of Anesthesiologists classification, surgical site, preoperative Prognostic Nutritional Index score, POM, extent of surgery, operation time, and intraoperative blood loss were significantly associated with postoperative SSI (Chi-square or Mann-Whitney U test, P < .01). Multivariate analysis revealed that POM had significant preventive effects against postoperative SSI (estimate: -0.245, standard error: 0.080, P < .01). Surgical site, American Society of Anesthesiologists classification, and operation time were also significant and independent clinical predictors of SSI. The analysis of real-world data from 16 university hospitals revealed that, regardless of the content and degree of the problem, the addition of POM has significant beneficial effects in reducing the risk of SSI in patients who undergo abdominal surgery. Medical records from each hospital and data from the Health Care Payment Fund were collected and analyzed retrospectively.

Comparison of prognosis in two methods for the lingual nerve repair: direct suture with vein graft cuff and collagen allograft method.

BACKGROUND: No studies have compared the outcomes of direct perineurial suture with vein graft cuff repair and indirect collagen allograft repair of the lingual nerve following an injury. Therefore, we evaluated and compared the outcomes of each over a 1-year observation period. We retrospectively assessed 20 patients who had undergone microneurosurgical repair of unilateral lingual nerve injuries at the Wakayama Medical University Hospital between May 2015 and March 2019. We utilized two different methods for lingual nerve repair, i.e., direct perineurial repair with a vein graft cuff and interpositional collagen allograft repair. Sensory and taste function in the lingual nerve were preoperatively evaluated using a static two-point discrimination test, superficial pain/tactile sensation test, tests for the pressure pain threshold (Semmens-Weinstein monofilament), test for thermal discrimination hot and cold sensation, and a taste discrimination test. These tests were performed again at 6 and 12 months postoperatively. RESULTS: Compared to the preoperative conditions, all patients showed improved sensory reactions. Functional sensory recovery outcomes were defined by Pogrel's criteria, Medical Research Council Scale grades, and functional sensory recovery. In each group, all patients improved after the operation. However, the operation time was significantly shorter for an interpositional collagen allograft repair as compared to that for a direct perineurial repair with a vein graft cuff. CONCLUSIONS: There were no statistically significant differences between the two repair Methods, except for the operation time. Both methods led to satisfactory results for all criteria. From an economic point of view, direct perineurial repair with a vein graft cuff is meaningful; however, the esthetic effect on the donor site should be considered. Conversely, interpositional collagen allograft repair has the advantage of a greatly shortened operation time.

Usefulness of myofascial flap without skin in contemporary oral and maxillofacial reconstruction.

PURPOSE: Pedicle myofascial graft should be considered in contemporary oral and maxillofacial reconstruction for the following reasons: 1) the pedicle myofascial unit is reliable and easily handled; 2) on the grafted myofascia in the oral cavity, the mucosa regenerates naturally with regard to suppleness and surface characteristics; and 3) vascularized myofascial coverage of tissues or materials is useful in some clinical situations. The purpose of this retrospective study was to evaluate the usefulness of this graft material. PATIENTS AND METHODS: Using myofascial flaps from the pectoralis major muscle in 15 patients and from the platysma muscle in 11 patients, several types of reconstructive procedures were conducted in the Department of Oral and Maxillofacial Surgery, Wakayama Medical University. RESULTS: Myofascial tissue was used to cover the surgical defect and for regeneration of oral mucosa (24 patients), to prevent exposure of the mandibular reconstruction plate (4 patients), for prevention of wound breakdown and secondary infection in the oral cavity (2 patients), for vascularized coverage of free grafted autologous bone (2 patients), and for protection of large vessels after radical neck dissection (9 patients). Although partial flap necrosis or wound dehiscence was noticed in 3 patients with a platysma-myofascial graft, the healing process of all patients was favorable and required no additional operations. This procedure is most suitable for the reconstruction of small to medium-sized soft tissue defects in the oral cavity, because it induces the formation of nearly normal mucosa through epithelial regeneration without clear scar formation. CONCLUSIONS: Myofascial flap is a useful option in certain oral and maxillofacial reconstruction cases in which mucosal regeneration and/or vascularized soft tissue coverage are required.

The effects of perioperative oral management on perioperative serum albumin levels in patients treated surgically under general anesthesia: A multicenter retrospective analysis in Japan.

ABSTRACT: The purpose of the present study was to investigate the efficacy of perioperative oral managements (POMs) on perioperative nutritional conditions in patients undergoing surgery with general anesthesia. Medical records were retrospectively reviewed and the effects of POMs were investigated based on a large number of cases using a multicenter analysis. The profile of serum albumin levels was assessed and compared between patients with and without POMs using the multivariate analysis. Seventeen Eleven thousand and one hundred sixty patients (4,873 males and 6,287 females) were reviewed. Of these, 2710 patients (24.3%) had undergone POMs. The results of a multivariate analysis revealed the significant positive effect of POMs on perioperative serum albumin level (change between at admission and discharge, (Estimate: 0.022, standard error: 0.012, P < .0001). Patient gender, age, surgical site, performance status, the American Society of Anesthesiologists (ASA) physical status classification, operation time, amount of blood loss, and serum albumin level at admission were also significant predictors. Adjusted multivariate analysis of the effects of POMs on perioperative change of serum albumin level in all subjects reveled the significance of POMs intervention (estimate: 0.022, standard error: 0.012, P < .0001). These results suggest that POMs exerts significant positive effects on perioperative serum albumin levels in patients underwent surgery under general anesthesia.

Identification of cisplatin-resistance related genes in head and neck squamous cell carcinoma.

Resistance to cisplatin is a major obstacle to successful treatment of head and neck squamous cell carcinoma (HNSCC). To investigate the molecular mechanism of this resistance, we compared the gene expression profiles between the cisplatin-sensitive SCC cell lines (Sa-3, H-1 and KB) and the cisplatin-resistant cell lines established from them (Sa-3R, H-1R and KB-R) using Affymetrix U133 Plus 2.0 microarray. We identified 199 genes differentially expressed in each group. To identify important functional networks and ontologies to cisplatin resistance, the 199 genes were analyzed using the Ingenuity Pathway Analysis Tool. Fifty-one of these genes were mapped to genetic networks, and we validated the top-10 upregulated genes by real-time reverse transcriptase-polymerase chain reaction. Five novel genes, LUM, PDE3B, PDGF-C, NRG1 and PKD2, showed excellent concordance with the microarray data. In 48 patients with oral SCC (OSCC), positive immunohistochemical staining for the five genes correlated with chemoresistance to cisplatin-based combination chemotherapy. In addition, the expression of the five genes predicted the patient outcomes with chemotherapy. Furthermore, siRNA-directed suppressed expression of the five genes resulted in enhanced susceptibility to cisplatin-mediated apoptosis. These results suggested that these five novel genes have great potential for predicting the efficacy of cisplatin-based chemotherapy against OSCC. Global gene analysis of cisplatin-resistant cell lines may provide new insights into the mechanisms underlying clinical cisplatin resistance and improve the efficacy of chemotherapy for human HNSCC.

Change in allodynia of patients with post-lingual nerve repair iatrogenic lingual nerve disorder.

PURPOSE: Mandibular third molar extractions are common treatment in oral maxillofacial surgery, but risk disturbance of the lingual nerves causing anesthesia, eating difficulty and allodynia, which can seriously reduce patient quality of life. This study investigates the change in allodynia before and after repair in patients with lingual nerve disorder. SUBJECTS AND METHODS: This retrospective cohort study comprises the 52 patients with affected lingual nerve after third molar extraction at our hospital over a 7-year period. Pre- and postoperative (6 months and 12 months) neurosensory records were analyzed. RESULTS: Fifty-two patients underwent lingual nerve repair and returned for at least 1 year of follow-up. Mean age was 36.8 ± 11.9. Median interval between injury and surgery was 5 (4, 8) months. In 92.9% of those with pain before surgery, allodynia disappeared postoperatively. CONCLUSIONS: This study shows that microsurgical lingual reconstructions are effective in patients with preoperative allodynia, but a small number of patients may have remaining allodynia after surgery. Large-scale, more detailed analysis of such cases is required.

A multicenter retrospective investigation on the efficacy of perioperative oral management in cancer patients.

Patients develop a number of oral complications during cancer treatments. Oral bacteria are associated with the onset of dental focal infections and the progression of oral mucositis. Dental focal infections are frequently associated with the systemic onset of bacteremia, sepsis, and pneumonia. The degeneration of oral function with these complications may become an obstacle to cancer treatments. Although comprehensive oral management, including oral care, the removal of dental focal infections, and improvements in oral function with dentures, is conducted for cancer patients in Japan, few studies have assessed its efficacy.The aim of the present study was to investigate the incidence of dental/oral complications in cancer patients with perioperative oral managements (POMs) based on a large number of case series with a multicenter retrospective analysis.The medical records of cancer patients with POMs were retrospectively reviewed and the incidence of oral complications and efficacy of oral management were investigated.A total of 2744 cancer patients with POMs (1684 males and 1080 females, mean age 65.9 ±â€Š13.0 years) were included and investigated in the present study. Among these patients, 2097 (76.4%) started POM before the initiation of cancer treatments, with 2130 (77.6%) receiving oral care only and 391 (14.2%) being subjected to invasive treatments, such as tooth extraction. The incidence of dental focal infections during the period of cancer treatments was 8.2%. The most frequent infection was acute periodontitis, including alveolar abscesses (112 patients, 4.1%). The incidence of grade 2 and 3 oral mucositis was 2.8%. Prolonged fever was observed in 113 patients (4.1%), with 7 having dental focal infections (6.2%). These incidence rates were lower than those reported previously.Based on analyses of a large number of patients, the present results support the efficacy of oral management in cancer patients. However, further studies are needed to establish adequate oral management guidelines for cancer patients.

Cross-resistance of platinum derivatives in H-1R, a cisplatin-resistant cell line.

We previously established H-1R cells, a cisplatin (CDDP)-resistant cell line, from H-1 cells, a CDDP-sensitive oral carcinoma cell line. The aim of this study was to identify the molecular mechanism of cross-resistance to antitumor drugs containing a platinum agent in H-1R cells. The 3-(3,4-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay and clonogenecity assay indicated that H-1R cells showed strong cross-resistance to carboplatin, nedaplatin and oxaliplatin. The expression status of the copper transporter and organic cation transporters was confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction. The transporters ATP7A, ATP7B, hCtr1, hOCT1 and hOCT2 were up-regulated, whereas hOCT3 was down-regulated. The cellular glutathione level was elevated 2-fold in H-1R cells compared with H-1 cells. Our results suggested that H-1 and H-1R cells may be useful in searching for candidate genes responsible for cross-resistance to platinum derivatives and for further studies to understand the mechanism of platinum resistance.

A case report of a long-term abandoned torn lingual nerve injury repaired by collagen nerve graft induced by lower third molar extraction.

BACKGROUND: The lingual nerve plays an important role in multiple functions, including gustatory sensation and contact sensitivity and thermosensitivity. Misdiagnosed conservative treatments for serious lingual nerve (LN) injuries can induce the patient to serious mental disability. After continuous observation and critical diagnosis of the injury, in cases involving significant disruption of lingual nerve function, microneurosurgical reconstruction of the nerve is recommended. Direct anastomosis of the torn nerve ends without tension is the recommended approach. However, in cases that present significant gaps between the injured nerve ends, nerve grafts or conduits (tubes of various materials) are employed. Recently, various reconstruction materials for peripheral nerves were commercially offered especially in the USA, but the best method and material is still unclear in the world. There currently exists no conventional protocol for managing LN neurosensory deficiency in regard to optimal methods and the timing for surgical repair. In Japan, the allograft collagen nerve for peripheral nerves reconstruction was permitted in 2017, and we tried to use this allograft nerve and got a recommendable result. CASE PRESENTATION: This report is a long-term abandoned torn LN reconstructed with allograft nerve induced by the lower third molar extraction. CONCLUSIONS: In early sick period, with the exact diagnosis, the LN disturbance should be managed. In a serious condition, the reconstruction with allograft nerve is one of the recommendable methods.

Risk of lingual nerve injuries in removal of mandibular third molars: a retrospective case-control study.

BACKGROUND: Through the analysis of clinical data, we attempted to investigate the etiology and determine the risk of severe iatrogenic lingual nerve injuries in the removal of the mandibular third molar. METHODS: A retrospective chart review was performed for patients who had undergone microsurgical repair of lingual nerve injuries. The following data were collected and analyzed: patient sex, age, nerve injury side, type of impaction (Winter's classification, Pell and Gregory's classification). Ratios for the respective lingual nerve injury group data were compared with the ratios of the respective data for the control group, which consisted of data collected from the literature. The data for the control group included previous patients that encountered various complications during the removal of the mandibular third molar. RESULTS: The lingual nerve injury group consisted of 24 males and 58 females. The rate of female patients with iatrogenic lingual nerve injuries was significantly higher than the control groups. Ages ranged from 15 to 67 years, with a mean age of 36.5 years old. Lingual nerve injury was significantly higher in the patient versus the control groups in age. The lingual nerve injury was on the right side in 46 and on the left side in 36 patients. There was no significant difference for the injury side. The distoangular and horizontal ratios were the highest in our lingual nerve injury group. The distoangular impaction rate in our lingual nerve injury group was significantly higher than the rate for the control groups. CONCLUSION: Distoangular impaction of the mandibular third molar in female patients in their 30s, 40s, and 50s may be a higher risk factor of severe lingual nerve injury in the removal of mandibular third molars.

Effect of duration from lingual nerve injury to undergoing microneurosurgery on improving sensory and taste functions: retrospective study.

BACKGROUND: The prognosis of recovery following microneurosurgery for injured lingual nerves varies among individual cases. This study aimed to investigate if recovery ratios of sensory and taste functions are improved by the microneurosurgery within 6 months after lingual nerve injury. METHODS: We retrospectively assessed 70 patients who underwent microneurosurgery at the Wakayama Medical University Hospital for lingual nerve injuries between July 2004 and December 2016. Sensory and taste functions in lingual nerves were preoperatively evaluated using a static two-point discrimination test, an intact superficial pain/tactile sensation test, and a taste discrimination test. They were evaluated again at 12 and at 24 months postoperatively. The abundance ratio of Schwann cells in the excised traumatic neuromas was analyzed with ImageJ software following immunohistochemistry with anti S-100ß antibody. RESULTS: In early cases (microneurosurgery within 6 months after the injury), recovery ratios of sensory and taste functions were not significantly different at 24 months after microneurosurgery compared with later cases (microneurosurgery more than 6 months after the injury). Meanwhile, the ratio of patients with taste recovery within 12 months after microneurosurgery was significantly decreased in late cases compared with early cases. The abundance ratio of Schwann cells in traumatic neuroma was also significantly lower in later cases. CONCLUSION: Microneurosurgery more than 6 months after lingual nerve injury did not lead to decreased recovery ratio of sensory and taste functions, but it did lead to prolonged recovery of taste. This delay may be associated with a decrease in the abundance ratio of Schwann cells in traumatic neuromas.

Differential expression of claudin­4, occludin, SOX2 and proliferating cell nuclear antigen between basaloid squamous cell carcinoma and squamous cell carcinoma.

Basaloid squamous cell carcinomas (BSCCs) in oral lesions are extremely rare, and the histology is not well understood. Histologically, they are often similar to conventional squamous cell carcinoma (SCC). The present study was designed with an aim to distinguish BSCC from SCC using claudin­4, occludin, SRY­box 2 (SOX2) and proliferating cell nuclear antigen (PCNA) immunoreactivities and staining patterns. Three BSCCs (with abundant, with moderate, and without squamous components) specimens and 20 SCC specimens were selected for comparison of their immunoreactivity. These specimens were stained with claudin­4, occludin, SOX2 and PCNA. In addition to histological analysis, the expression of claudin­4, occludin and PCNA was determined in oral cancer HSC2 and HSC3 cells with or without SOX2 overexpression, and cell proliferation was determined by XTT assay. Claudin­4 had strong and occludin had weak immunoreactivity as detected in the membrane of squamous components of BSCC but not in cancer cells. No obvious detection of squamous components and cancer cells were observed in SCC. SOX2 and PCNA immunoreactivities in SCC had dot­like staining patterns in the nuclei of partial and marginal cancer cells. In contrast, in BSCCs, SOX2 and PCNA had diffuse staining patterns in almost all cancer cells. SOX2 overexpression had little effect on the expression levels of claudin­4, occludin and PCNA. It also had little effect on the cell proliferation of HSC2 and HSC3 cells. Differences in immunoreactivity and staining pattern may be valuable to distinguish between BSCC and SCC in diagnosis.

PD-L1 expression correlated with p53 expression in oral squamous cell carcinoma.

BACKGROUND: Programmed cell death ligand 1 (PD-L1) is an immune checkpoint molecule that attenuates the immune response. PD-L1 contributes to failed antitumor immunity; thereby, blockade of PD-L1 with monoclonal antibody enhances the immune response. Recently, it was reported that PD-L1 was regulated by protein 53 (p53). Besides, cytokeratin 17 (CK17) is thought to be a diagnostic marker of oral squamous cell carcinoma (OSCC). Our aim was to evaluate the correlation between the immunohistochemical expression of PD-L1, p53 and CK17 with clinicopathological characteristics and disease-specific survival in patients with OSCC. METHODS: A total of 48 patients with OSCC were included in this study. Immunohistochemical staining was performed to evaluate the correlation among the expressions of PD-L1, p53 and CK17, and furthermore the correlation among various clinicopathological factors, PD-L1, p53 and CK17. RESULTS: The positive rate of p53, CK17, PD-L1 (tumor cells) and PD-L1 (tumor-infiltrating lymphocytes) was 63.2%, 91.7%, 48.9% and 57.1%. A statistically significant correlation between p53 expression and T stage and TNM stage (p = 0.049, p = 0.03, respectively) was observed. Also, a statistically significant correlation between p53 and PD-L1 (TCs) expression (p = 0.0009) was observed. Five-year disease-specific survival rate was not significantly correlated with gender, TNM stage, p53 expression, PD-L1 expression and CK17 expression. CONCLUSION: The expression of p53 and PD-L1 shows significantly positive correlation in oral squamous cell carcinoma in tumor cells. Also, a significant correlation between p53 expression and T stage and TNM stage was observed. No other significant correlation between PD-L1 staining or CK17 and clinical or pathologic characteristics was identified.

EGFR inhibitor enhances cisplatin sensitivity of oral squamous cell carcinoma cell lines.

Epidermal growth factor receptor (EGFR) is involved in multiple aspects of cancer cell biology. EGFR has already been identified as an important target for cancer therapy, with various kinds of EGFR inhibitors currently used in treatment of several human cancers. Recently, EGFR and its downstream signaling pathways were identified as being associated with cisplatin sensitivity. In addition, EGFR inhibitors have shown significant promise for patients who failed cisplatin-based therapy. In this study, we investigated whether treatment with an EGFR inhibitor improves cisplatin sensitivity in oral squamous cell carcinoma (OSCC) cell lines. The effects of a combination of AG1478, a specific EGFR tyrosine kinase inhibitor, with cisplatin were evaluated in cultured OSCC cell lines and cisplatin-resistant sublines. Higher expression of EGFR and p-EGFR was found in the two cisplatin-resistant cell lines compared with the corresponding parental cell lines. In addition, augmented inhibition of OSCC cell growth by the combination of AG1478 with cisplatin was found in both cell lines. These results suggest that the combination of an EGFR inhibitor and cisplatin may be useful as a rational strategy for the treatment of patients with oral cancer with acquired cisplatin resistance.