Immunomodulatory aspects in the progression and treatment of oral malignancy

Inflammation substantially affects the risk of oral malignancy. Pro-inflammatory cytokine, interferon (IFN)-γ, confers anti-tumor activity using several different mechanisms. Conversely, higher expression of interleukin (IL)-17 is associated with worse prognosis. Monocyte chemotactic protein (MCP)-1 correlates positively with poor long-term survival of head and neck squamous cell carcinoma (HNSCC) patients. IL-1α affects cancer associated fibroblasts and macrophages, and promote several malignant phenotypes including immune suppression. Some anti-inflammatory cytokines, including IL-10 and transforming growth factor (TGF)-β, relate to pro-tumoral activities.Among immune checkpoint modulators, programmed death (PD-)1 and PD-ligand (L)1 facilitate oral squamous cell carcinoma (OSCC) cell evasion from immune surveillance, and the expression status of these has a prognostic value.OSCCs contain tumor associated macrophages (TAMs) as major stromal cells of their tumor microenvironment. Among the two distinctive states, M2 macrophages support tumor invasion, metastasis and immune suppression. Crosstalk between TAMs and OSCC or cancer-associated fibroblasts (CAF) plays an important role in the progression of OSCC.Clinical trials with blocking antibodies against IL-1α or melanoma-associated antigens have been reported as therapeutic approaches against OSCCs. The most promising approach activating antitumor immunity is the blockade of PD-1/PD-L1 axis. Manipulating the polarization of pro-tumorigenic macrophages has been reported as a novel therapeutic approach.     

Association of Increased Indoleamine 2, 3‐Dioxygenase With Impaired Natural Killer Cell Activity in Hemodialysis Patients

Indoleamine 2, 3‐dioxygenase (IDO) suppresses adaptive immune response. However, there was no study to examine whether IDO activity is associated with immune parameters in dialysis patients. In this study, we estimated serum IDO activity by the kynurenine/tryptophan ratio (KTR), and compared KTR with natural killer (NK) cell activity, soluble interleukin‐2 receptor (sIL‐2R) and serum levels of trace elements such as selenium (Se) and zinc (Zn) that affect T‐cell function in 28 hemodialysis (HD) patients (age: 72 ± 13 years old, time on HD: 79 ± 89 months). NK cell activity was decreased in 35.7% of the patients. KTR values were almost 10‐times higher in HD patients (380.81 ± 385.46 mM/M) than those in the referred controls (32.9 ± 9.10 mM/M). KTR was lower in patients with impaired NK cell activity than those without (279 ± 111 vs. 565 ± 603 mM/M, P = 0.07). There was no relationship between KTR and sIL‐2R and Zn, while KTR was significantly and negatively correlated with serum Se levels that can impair cellular immunity (r = ?0.41, P < 0.05). Our findings suggest that increased IDO activity with Se deficiency may be associated with impaired NK cell function in HD patients.     

Esophageal motor dysfunction plays a key role in GERD with globus sensation - Analysis of factors promoting resistance to PPI therapy

Abstract Objective. Patients with gastroesophageal reflux disease (GERD) also have various extra-esophageal symptoms. Laryngopharyngeal reflux disease (LPRD) is a subtype of GERD associated with globus sensation, but proton pump inhibitor (PPI) therapy achieves disappointing results. This study investigated esophageal motility in GERD patients with globus sensation who were resistant to PPI therapy. Design. The subjects were 350 patients with globus sensation. All patients underwent both laryngoscopy and upper gastrointestinal endoscopy to exclude organic disease. After 4 weeks of treatment with rabeprazole sodium (20 mg daily), the patients were divided into PPI-responsive and PPI-resistant groups. Then we investigated esophageal motility in the PPI-resistant group by a multichannel intraluminal impedance and manometry study. Results. A total of 119 patients (55.6%) were resistant to PPI therapy, among whom 57 patients (47.9%) had abnormal esophageal motility. They included 36 patients (66.4%) with ineffective esophageal motility, 9 patients (14.4%) with achalasia, 6 patients (9.6%) with diffuse esophageal spasm, 5 patients (8%) with nutcracker esophagus, and 1 patient (1.6%) with hypertensive lower esophageal sphincter. There were significant differences of upper esophageal sphincter pressure and esophageal body peristalsis between the patients with PPI-resistant LPRD and healthy controls matched for age and sex. Conclusion. Among patients with PPI-resistant LPRD, 47.9% had abnormal esophageal motility.     

Diabetic ketoacidosis accompanied by hypothermia: a case report

Diabetic ketoacidosis (DKA) is an acute, life-threatening complication of diabetes mellitus and is caused by insulin insufficiency. Hypothermia is defined as a core temperature of less than 35°C and is sometimes accompanied by DKA. We report two patients with diabetes who were admitted for DKA accompanied by hypothermia.     

Resequencing and association analysis of MIR137 with schizophrenia in a Japanese population

MicroRNA may play a role in the pathophysiology of schizophrenia. A recent meta‐analysis of genome‐wide association studies indicated a significant association between schizophrenia and a common intronic variation in MIR137HG (microRNA 137 host gene) encoding the primary microRNA‐137. To explore additional risk variations for schizophrenia, we resequenced MIR137 and performed an association analysis in 1321 Japanese individuals. By resequencing, we detected four sequence variations in the 5' and 3' flanking regions. There were no significant associations between these variations and schizophrenia. Our resequencing and association analysis of MIR137 failed to find additional risk variations for schizophrenia.     

Influence of preoperative dental procedures on the prognosis of patients with squamous cell carcinoma of the gingiva

Our aim was to investigate the prognosis of patients with squamous cell carcinoma (SCC) of the gingiva who had preoperative dental operations. We studied 102 patients who were being operated on for SCC of the gingiva with special reference to the effects of preoperative dental operations on the prognosis. Twenty-six patients had dental procedures such as tooth extraction, or incision, or curettage before they visited our hospital, while the remaining 76 had no such interventions. The percentage of patients with advanced T stage disease (T3 or T4) was higher among those who had interventions (17/26, 65%) than among those who had not (35/76, 46%). The difference was not significant. Histopathologically invaded nodes were detected in half the patients in the intervention group (13/26), while they were found in only 18/76 (24%) of those in the no intervention group (p < 0.02). The incidence of nodal metastases with extranodal spread was significantly higher in the intervention group than in the no intervention group (p < 0.05), and those in the intervention group were more likely to develop distant metastases than those in the other group (p < 0.001). The 5-year survival in the two groups was 65% and 92%, respectively (p < 0.01). Preoperative dental operations such as tooth extraction, incision, or curettage possibly lead to regional and distant metastases and therefore a poor prognosis in patients with SCC of the gingiva.     

The observational study of delayed wound healing after tooth extraction in patients receiving oral bisphosphonate therapy

IntroductionIn this study, we investigated whether such a discontinuation of oral bisphosphonate (BP) for 3 months might influence the incidence of BP-related osteonecrosis of the jaw (BRONJ) and wound healing after tooth extraction in patients receiving oral BP therapy.Material and methodsThere were a total of 434 teeth in 201 patients (18 males and 183 females). The patients were divided into two groups depending on whether or not they underwent a 3-month discontinuation of BP therapy (BP? and BP+) before tooth extraction. In this observational study investigated delayed wound healing after tooth extraction in patients receiving oral BP therapy.ResultsIn all cases of the BP? group, there were no BRONJ although there was delayed wound healing in two cases. However, in one case of the BP+ group, oral BP was continued because it was deemed high risk to discontinue treatment by the patient's physician. In this case, an intraoral fistula was still present with bone exposure at 120 weeks after extraction (BRONJ stage 1).ConclusionThis study supports the idea of a drug holiday and encourages further clinical research on this topic of tooth extraction in patients receiving oral BP therapy.