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Objective S-1 and modified FOLFIRINOX (mFFX) were often used as the second-line chemotherapies after failure of gemcitabine plus nab-paclitaxel (GnP) in unresectable pancreatic cancer (UPC) until nanoliposomal irinotecan plus 5-fluorouracil/leucovorin therapy was approved as an alternative in Japan in 2020. However, the clinical outcomes of S-1 and mFFX after GnP have scarcely been reported. Therefore, we retrospectively studied them. Methods We extracted the clinical data of 86 patients with UPC who received second-line chemotherapy after GnP between 2015 and 2020. Among the patients who had a good organ functions and no massive ascites, 41 patients treated with S-1 and 21 treated with mFFX were enrolled. Results Compared to S-1, mFFX tended to be used for younger patients with a good general condition (median age, 63 vs. 71 years, p0.01; and performance status 0, 67% vs. 37%, p0.05). The median progression-free and overall survival were similar between the S-1 (3.7 and 7.2 months, respectively) and mFFX (3.3 and 7.4 months, respectively) groups. The response rate in patients with measurable lesions was 4% (n=1/23) in the S-1 group and 17% (n=2/12) in the mFFX group. The incidence of grade 3 or 4 adverse events was 20% in the S-1 group and 57% (neutrophil count decreased in 43%) in the mFFX group (p0.01). Conclusion S-1 and mFFX were both acceptable second-line chemotherapies after GnP therapy for UPC, although attention should be paid to myelosuppression during mFFX treatment. Further studies involving nanoliposomal irinotecan plus 5-fluorouracil/leucovorin therapy are necessary to facilitate the selection of the optimal regimen for each patient.

Malnutrition and risk of malnutrition continues to be a common finding in elders, yet its association with oral function in hospitalised patients remains unclear.Patients aged 70 years or over who had been hospitalised for non-acute rehabilitation were recruited. Nutritional risk was screened using the Mini-Nutritional Assessment Short Form (MNA-SF) and Nutritional Risk Screening (NRS) scores. Malnutrition was assessed according to the Global Leadership Initiative on Malnutrition (GLIM) criteria. All participants underwent the oral hypofunction test battery, evaluating oral hygiene, oral dryness, occlusal force, tongue-lip motor function, tongue pressure, masticatory and swallowing function. Statistical analyses comprised Mann-Whitney or Kruskal-Wallis tests. Bivariate associations between categorical variables were tested using the Pearson chi-square test; for continuous variables, the Spearman correlation was calculated. A P-value .05 was considered statistically significant.Sixty patients aged a mean 82.5 ± 7.0 years participated. Some 88.3% were diagnosed with oral hypofunction, and this was more common in older patients (P = .020). Analysing the 7 oral hypofunction tests as an interval variable (NiOF) revealed additional correlations with number of teeth (ρ = 0.477) as well as the nutritional risk, evaluated by the MNA-SF (ρ = -0.284) and NRS (ρ = 0.317) scores. NiOF scores were higher among denture wearers (P = .003). GLIM did not confirm the correlation with NiOF. Biomarkers such as serum albumin and CRP were not associated with the NiOF score.In this sample, the association between oral function and nutritional state is more obvious in nutritional risk scores than in the malnutrition diagnosis by GLIM.

Background/purpose Burning mouth syndrome (BMS) is a chronic condition presenting as intraoral burning or dysesthesia, with a high preponderance in menopausal women. This study aimed to examine the association between somatosensory dysfunction and BMS in premenopausal, early postmenopausal, and late postmenopausal patients, using a standardized Quantitative Sensory Testing (QST) protocol, and to determine the predictive value of thermal or mechanical perception by QST for detecting BMS. Materials and methods An observational case–control study was performed with 36 female participants with BMS (12 premenopausal, 10 early postmenopausal, and 14 late postmenopausal) and 42 age- and sex-matched healthy volunteers (21 premenopausal, 10 early postmenopausal, and 11 late postmenopausal). Neurophysiological tests were used to evaluate somatosensory dysfunction at the tongue. Results Z-score in the late postmenopausal BMS group revealed a gain of function for the cold pain threshold and heat pain threshold (Z = 2.08 and 3.38, respectively). In the multiple regression analysis with the Visual Analog Scale as the dependent variable, the vibration detection threshold predicted the severity of burning mouth sensation in the premenopausal group. Conclusion Late postmenopausal patients with BMS showed an increased response of the tongue to noxious thermal stimuli. This supports the theory that changes in sex hormones may affect trigeminal somatosensory function, particularly during the late postmenopausal stage in patients with BMS.

BACKGROUND Masticatory function declines with age or disease, implicating a poor chewing efficiency and an often-unconscious change for a less healthy, yet easy to chew diet. Timely screening of masticatory function may foster an early-onset diagnosis and potential treatment. The aim of this study was to compare alternative diagnostic tools for masticatory function to a Jelly-scan test. MATERIALS AND METHODS Patients aged 70 years and older who were hospitalized for rehabilitation were recruited for this study. A total of four different tests for masticatory function were administered. The Japanese Society of Gerodontology glucose extraction test (Jelly-scan) was used as reference to compare a colour-changing gum test (Gum1-colour) as well as a mixing ability test with a visual (Gum2-visual) and opto-electronical (Gum2-digital) analyses. Receiver operating characteristic (ROC) curves were used to establish the discriminative value, kappa-values were used to estimate individual agreements and correlations were verified using Spearman's tests. RESULTS Sixty-one patients (Men n=23, Women n=38) aged 82.4±6.8 years participated in the experiments. The average number of natural teeth was 16.5 ± 10.5, 34.4% of the participants wore removable dentures. For all tests, the sum of sensitivity and specificity was >150%. All test correlated with Jelly-scan (absolute Rho >0.5). With Jelly-scan 51 participants (83.6%) were diagnosed with "masticatory hypofunction". After reducing the cut-off value of the test from 100 mg/dl to 65 mg/dl, only 33 participants (54%) fulfilled the diagnosis. This post-hoc analysis increased the sensitivity of the Gum2-tests and the agreement to kappa >0.5 for all three tests. CONCLUSION All three tests can be considered useful screening alternatives. In its original version, Jelly-scan may tend to over-diagnose masticatory hypofunction, hence a novel cut-off with better agreement between tests is suggested.

Clinical evidence is sparse on whether dentures fabricated by computer-aided design and computer-aided manufacturing (CAD-CAM) methods afford superior fit and retention when compared with those fabricated conventionally.The purpose of this clinical controlled crossover study was to evaluate the peak retention force and fit of CAD-CAM manufactured (3D-printed and milled) maxillary complete denture bases and conventional heat-polymerized bases (control).Twenty participants with edentulous maxillary arches were recruited. Impressions were made with a border-molded custom tray, and the resulting definitive cast was scanned. The conventional base was manufactured on the definitive cast with a hook and a 45-degree platform with a central notch and 2 lateral notches. The scan of the definitive cast was used for the fabrication of a milled and a printed base. The platform and hook position on the conventional base were transferred digitally to the milled and printed bases. All bases were scanned. A traction dynamometer was orientated into the notches, and retention was evaluated in the post dam and tuberosity areas. Scans were imported into a comparison software program which matched scans to their corresponding reference and performed a 3-dimensional comparison. The Friedman and Wilcoxon tests were used to compare between groups (confidence interval: 95%, α=.05).Nineteen participants with a mean ±standard deviation age of 64.1 ±14.7 years completed all clinical sessions. No significant difference in peak retention was measured between milled (MB1), printed (PB1), and conventional (CB) bases in the post dam (CB: 12.44 ±9.62 N, PB1: 16.08 ±15.28 N, MB1: 14.52 ±17.07 N) and right tuberosity area (CB: 8.99 ±7.82 N, PB1: 11.28 ±9.57 N, MB1: 11.99 ±12.10 N). In the left tuberosity area, peak retention was lower for CB (10.03 ±8.39 N) than PB1 (14.98 ±14.72 N) and MB1 (13.55 ±15.53 N; P=.05). Compared with the definitive cast, the fit of the conventional base (0.18 ±0.01 mm) was closer than the printed (0.21 ±0.03 mm) and milled bases (0.21 ±0.02 mm) (P.001).The CD bases manufactured by CAD-CAM techniques provided retention and fit similar to that of conventionally manufactured bases and can therefore be considered suitable techniques.

Aim Portal hypertension induces pancreatic congestion and impaired insulin secretion in patients with liver cirrhosis (LC). However, its mechanism is unclear, with no established noninvasive imaging method for the evaluation of its pathogeneses. The present study focused on pancreas stiffness, as assessed by shear wave elastography (SWE), and examined its association with portal hypertension and insulin secretion. Methods SWE and contrast-enhanced ultrasonography (CE-US) were utilized to evaluate pancreas stiffness and congestion, respectively. A glucagon challenge test was employed for insulin secretion assessment. Furthermore, rat models of carbon tetrachloride (CCl4 )-induced LC and portal hypertension were used to identify the direct effects of pancreatic congestion. Immunohistochemistry staining of the pancreas was performed on human autopsy samples. Results Pancreas stiffness measured by SWE was higher in patients with LC than that in controls and showed significant correlation with pancreatic congestion. The glucagon challenge test indicated a lower value for the change in C-peptide immunoreactivity in the LC group, which was inversely correlated with pancreas stiffness and congestion. Additionally, portal hypertension and insulin secretion dysfunction were confirmed in CCl4 rat models. Autopsy of human samples revealed congestive and fibrotic changes in the pancreas and the relationship between insulin secretion and their factors in patients with LC. Conclusions In patients with LC, pancreas stiffness measured by SWE could be a potential non-invasive test for evaluating pancreatic congestion and fibrosis due to portal hypertension. Moreover, it was associated with impaired insulin secretion, and aid in guiding the treatment for hepatogenous diabetes. This article is protected by copyright. All rights reserved.

Background To provide updates on clinical practice of acute pancreatitis (AP) in Japan, we conducted a nationwide epidemiological survey. Methods This study consisted of a two-staged survey; the number of AP patients was estimated by the first-stage survey and their clinical features were examined by the second-stage survey. We surveyed AP patients who had visited hospitals in 2016. Results The estimated number of AP patients in 2016 was 78,450, with an overall incidence of 61.8 per 100,000 persons. We obtained detailed clinical information of 2994 AP patients, including 706 (23.6%) severe cases classified according to the Japanese severity criteria. The male-to-female sex ratio was 2.0, and the mean age at onset was 59.9 years in males and 66.5 years in females. Alcohol was the most common etiology (42.8%) in males and gallstones in females (37.7%). The AP-associated mortality was 6.1% in severe AP cases, which was decreased by 40% compared to the 2011 survey. Antibiotics were administered to most cases, with carbapenem being frequently used. Enteral nutrition was given in 31.8% of severe cases, but majority cases received after 48 h. Among the 107 patients who received intervention for walled-off necrosis, five patients received surgery-first approach, 66 received endoscopic ultrasound-guided transluminal drainage, and 19 underwent step-up approach. Conclusions We clarified the current status of AP in Japan including the significant reduction of mortality in severe cases, shift to endoscopic approaches for walled-off necrosis, and poor compliance of the recommendations in the guidelines including management of enteral nutrition and antibiotic administration.

Objective The long-term effect of the ABO blood type on the clinical course of patients with pancreatic cancer (PC) is inconclusive. This study aimed to determine whether or not the ABO blood type influences the long-term outcomes of PC in Japanese patients. Methods The medical records of Japanese patients with PC were reviewed. Data, including the age, sex, and outcomes, from the Ehime Pancreato-Cholangiology Study Group were analyzed. Results The mean age of the 406 patients was 71.0±10.5 years, and 220 (54.2%) were men. A total of 44.6%, 20.7%, 22.4%, and 12.3% had blood type A, B, O, and AB, respectively. The median survival time (MST) of patients with A alleles was shorter than that of patients with non-A alleles (p=0.048), especially among those who underwent resection (p=0.031). In contrast, no marked difference in the MST was noted among those who underwent chemotherapy and palliative care. Finally, a multivariate analysis confirmed A alleles as an independent factor associated with the long-term outcome of PC (p

To investigate the predictive power of depression and anxiety for conditioned pain modulation (CPM) and to examine the relationships of CPM at 40°C and CPM at 47°C with age, disease-related pain, pain duration, and psychosocial factors in burning mouth syndrome (BMS).A total of 22 patients with BMS and 22 healthy female controls participated in this study. Temporal summation was used as the test stimulus for CPM, and subsequent exposure either to a nonpainful (40°C) or a painful (47°C) Peltier thermode was used as the conditioning stimulus. CPM was calculated as the difference in pain perception following the conditioning stimulus. Psychosocial factors were examined using the Profile of Mood States (POMS) and the State-Trait Anxiety Inventory (STAI).State anxiety and tension-anxiety scores were significantly higher for patients with BMS than for control participants. Multiple regression analyses showed that CPM47°C was affected by vigor, fatigue, confusion, and trait anxiety (adjusted RIncreases in trait anxiety reduced the CPM effect. These findings suggest that CPM impairments and increases in trait anxiety are involved in the development of BMS.

Although the intraoral scanning of edentulous ridges is feasible, clinical evidence that the resulting denture retention is equivalent to that achieved with conventional impressions is lacking.The purpose of this clinical study was to determine the retention of complete denture bases fabricated from digital intraoral scans versus conventional impressions by using border molding and posterior palatal seal compression.Twenty volunteers with an edentulous maxilla were recruited. An intraoral scan of the maxilla and a conventionally border-molded impression with a custom tray were made. The conventional impression was poured; the definitive cast was scanned. Three-dimensionally (3D) printed (PB1) and milled bases (MB1) were fabricated based on the scan of the definitive cast. Based on the intraoral scan, a 3D-printed (PB2) and a milled base (MB2) were fabricated. On each base, a platform with a hook consisting of a central notch orienting the force against the post dam (PD) and 2 lateral notches orienting the forces against the left (LT) and right (RT) tuberosities was set in the center of the outer surface of the base. A traction dynamometer was inserted in the hook and oriented into the corresponding notch by applying force until dislodgement. All bases were subsequently stored in artificial saliva for 2 weeks and scanned. Retention testing was repeated by using the same procedure. To evaluate trueness and to visualize the differences on a color map, the scan of the definitive cast and the intraoral scans were matched and compared in 3 dimensions. The Wilcoxon tests were used to compare the retention of the different bases (95% confidence interval, α=.05).Nineteen participants with a mean ±standard deviation age of 64.1 ±14.7 years completed the 4 study sessions. The retention of printed bases (PD: 16.08 ±15.28 N; LT: 14.98 ±14.72 N; RT: 11.28 ±9.57 N) and milled bases (PD:14.52 ±17.07 N; RT: 11.99 ±12.10 N; LT: 13.55 ±15.53 N) fabricated from conventional impressions presented significantly higher retentive forces than those printed (PD: 6.21 ±4.72 N; RT:5.12 ±2.78 N; LT: 4.45 ±2.77 N) and milled (PD: 6.58 ±4.92 N; RT: 4.65 ±2.63 N; LT: 5.02 ±3.58 N) from the intraoral scans (P.05). The differences were significant in all directions of dislodgement, as well as after storage in artificial saliva for 2 weeks. Comparison of the 3D distances between the intraoral scan and the definitive cast revealed a mean deviation of 0.45 ±0.11 mm.Conventional impressions of the edentulous maxilla, including the clinical steps of border molding and posterior palatal seal compression, provide better retention than digital intraoral scans with both milled and 3D-printed denture bases.

INTRODUCTION Reduced tongue pressure may render eating and swallowing difficult. The purpose of this study was to investigate whether the tongue training device can also be used as a diagnostic device and whether its sensitivity and specificity are equal to the numerical tongue pressure measuring device. MATERIAL AND METHODS The target group is patients aged 70��years and over who are hospitalised for rehabilitation. Tongue pressure was measured by both, a tongue pressure measuring instrument and a tongue training tool. The diagnosis of the reduced tongue pressure was made with the tongue pressure measuring instrument and set the verified with the novel tongue training tool. RESULTS Sixty-two participants were included in the study. Forty-five were classified by the tongue pressure measuring device and 53 by the tongue training device as 'low tongue pressure'. Spearman correlation confirmed a positive correlation between the tongue pressure measuring device and the tongue training device rs ��=��0.800, p��=��0.01��level (2-tailed). The tongue training device test identified sensitivity was 100%, and its specificity was 52.9%. The AUC of the ROC curve is 0.901. CONCLUSION The tongue training device seems a simple, safe and readily available alternative to the tongue pressure measuring device for the diagnosis of low tongue pressure, with an excellent sensitivity and very good specificity.

The cause of burning mouth syndrome (BMS) is unknown. Although no effective treatment has been established, BMS patients frequently chew gum to alleviate pain. To identify the cause and new treatments for BMS, this study investigated the psychophysical and pharmacological properties of gum chewing to better understand its pain-relieving effects. In this prospective, blinded study, plasma catecholamine and serotonin levels and Profile of Mood States (POMS) scores were assessed after gum chewing or simulated chewing in 40 women (20 BMS patients and 20 age-matched controls). Visual analogue scale (VAS) scores for pain decreased significantly in BMS patients after gum chewing and simulated chewing. Moreover, resting VAS scores of BMS patients were significantly positively correlated with plasma adrenaline level. Furthermore, gum chewing was significantly correlated with lower plasma adrenaline level, VAS score, and tension-anxiety score. These results suggest that adrenaline is important in the pathogenesis of BMS pain and that the analgesic effect of gum chewing is induced through the potential effects of anxiety reduction, although this effect might not be specific to BMS. In addition, the analgesic effect of gum chewing was not induced solely by chewing motion.

Although xerostomia can cause persistent oral pain, the mechanisms underlying such pain are not well understood. To evaluate whether a phosphorylated p38 (pp38)-TRPV4 mechanism in trigeminal ganglion (TG) neurons has a role in mechanical hyperalgesia of dry tongue, a rat model of dry tongue was used to study the nocifensive reflex and pp38 and TRPV4 expression in TG neurons. The head-withdrawal reflex threshold for mechanical stimulation of the tongue was significantly lower in dry-tongue rats than in sham rats. The numbers of TRPV4- and pp38-immunoreactive cells in the TG were significantly higher in dry-tongue rats than in sham rats. Many TRPV4-IR cells were also pp38-immunoreactive. The number of TRPV1-IR cells was unchanged in the TG after induction of tongue dryness. Local injection of a TRPV4 blocker attenuated tongue mechanical hypersensitivity in dry-tongue rats. Intraganglionic injection of a selective p38 MAP kinase inhibitor eliminated tongue hypersensitivity in dry-tongue rats and suppressed TRPV4 expression in TG neurons. The present findings suggest that TRPV4 activation via p38 phosphorylation in TG neurons is involved in mechanical hypersensitivity associated with dry tongue. These mechanisms may have a role in pain associated with xerostomia.

Objective To evaluate whether patients with hepatitis B virus (HBV)– and hepatitis C virus (HCV)–related chronic liver disease were diagnosed as having pancreatic cancer (PC) at an early stage during abdominal imaging surveillance for hepatocellular carcinoma (HCC). Patients and Methods We retrospectively examined 447 patients with PC diagnosed at Ehime University Hospital and affiliated centers (2011-2013). Data were collected regarding HBV and HCV status, likelihood of PC diagnosis, and Union for International Cancer Control (UICC) stage. Intergroup comparisons were performed using the χ2 test. Results The UICC stage distribution in the HCC surveillance group (n=16) was stage 0 (n=2, 12.5%), stage IA (n=3, 18.8%), stage IB (n=2, 12.5%), stage IIA (n=2, 12.5%), stage IIB (n=2, 12.5%), stage III (n=1, 6.3%), and stage IV (n=4, 25%). The UICC stage distribution in the nonsurveillance group (n=431) was stage 0 (n=4, 0.9%), stage IA (n=28, 6.5%), stage IB (n=27, 6.3%), stage IIA (n=86, 20.0%), stage IIB (n=48, 11.1%), stage III (n=56, 13.0%), and stage IV (n=182, 42.2%). The HCC surveillance group had significantly more patients with stage 0 disease than with stages IA through IV (P=.02). Similar results were observed when including stages IA (P=.007) and IB (P=.004) as early stages but not stage IIA (P=.10). A dilated pancreatic duct led to a PC diagnosis in all 6 patients with stage 0 disease. Conclusion Patients with HBV- and HCV-related chronic liver disease had an early PC diagnosis during HCC surveillance. Careful evaluation of the pancreas is warranted during HCC surveillance.

Trigeminal nerve injury is known to cause severe persistent pain in the orofacial region. This pain is difficult to diagnose and treat. Recently, many animal studies have reported that rewiring of the peripheral and central nervous systems, non-neuronal cell activation, and up- and down-regulation of various molecules in non-neuronal cells are involved in the development of this pain following trigeminal nerve injury. However, there are many unknown mechanisms underlying the persistent orofacial pain associated with trigeminal nerve injury. In this review, we address recent animal data regarding the involvement of various molecules in the communication of neuronal and non-neuronal cells and examine the possible involvement of ascending pathways in processing pathological orofacial pain. We also address the clinical observations of persistent orofacial pain associated with trigeminal nerve injury and clinical approaches to their diagnosis and treatment.

Background: This study aimed to examine the association between somatosensory dysfunction and burning mouth syndrome (BMS) in premenopausal, early postmenopausal, and late postmenopausal patients, using a standardized Quantitative Sensory Testing (QST) protocol, and to determine the predictive value of thermal or mechanical perception by QST for detecting BMS.Methods: The study included 36 female participants with BMS (12 premenopausal, 10 early postmenopausal, and 14 late postmenopausal) and 42 age- and sex- matched healthy volunteers (21 premenopausal, 10 early postmenopausal, and 11 late postmenopausal). Neurophysiological tests were used to evaluate somatosensory dysfunction at the tongue.Results: Z-scores in the late postmenopausal BMS group revealed a gain of function for the cold pain threshold and heat pain threshold (Z=2.08 and 3.38, respectively). In the multiple regression analysis with the Visual Analogue Scale as the dependent variable, the vibration detection threshold predicted severity of burning mouth sensation in the premenopausal group.Conclusions: Late postmenopausal patients with BMS showed an increased response of the tongue to noxious thermal stimuli. This supports the theory that changes in sex hormones may affect trigeminal somatosensory function in particular, during the late postmenopausal stage in patients with BMS.

OBJECTIVES Tongue pressure (TP) is used for the diagnosis of oral hypofunction; however, the impact of several variables on TP is unclear. Therefore, the current systematic review and meta-analysis aimed to analyse the variability in tongue pressure among healthy individuals aged ≥60 years vs

© 2020 John Wiley & Sons LtdObjective: To develop a beta version of a preliminary set of empirically derived research diagnostic criteria (RDC) for burning mouth syndrome (BMS) through expert consensus, which can then be taken into a test period before publication of a final RDC/BMS. Design: A 6 round Delphi process with twelve experts in the field of BMS was used. The first round formed a focus group during which the purpose of the RDC and the definition of BMS was agreed upon, as well as the structure and contents. The remaining rounds were carried out virtually via email to achieve a consensus of the beta version of the RDC/BMS. Results: The definition of BMS was agreed to be ‘an intraoral burning or dysaesthetic sensation, recurring daily for more than 2 hours per day over more than 3 months, without evident causative lesions on clinical examination and investigation’. The RDC was based upon the already developed and validated RDC/TMD and formed three main parts: patient self-report; examination; and psychosocial self-report. A fourth additional part was also developed listing aspirational biomarkers which could be used as part of the BMS diagnosis where available, or to inform future research. Conclusion: This Delphi process has created a beta version of an RDC for use with BMS. This will allow future clinical research within BMS to be carried out to a higher standard, ensuring only patients with true BMS are included. Further validation studies will be required alongside refinement of the RDC as trialling progresses.

Burning mouth syndrome (BMS) is classified into idiopathic orofacial pain conditions. Although central and peripheral neuropathic mechanisms are believed to be involved, the etiology remains to be fully elucidated. The present study examined temporal brain responses to an ongoing hot stimulus to investigate the pain modulating system in patients with BMS. The thermal stimulation sequence comprised baseline (32°C, 40 s) to warm (40°C, 32 s) to baseline (32°C, 40 s) to hot (49°C, 32 s), which was repeated four times using a Peltier thermode. These warm and hot stimuli were applied on the right palm and right lower lip in two separate sessions. Functional magnetic resonance imaging data were acquired by recording echo-planar images with a block design. Brain activity induced by purely hot stimulation (49°C vs. 40°C) applied to the palm was more pronounced than that induced by lip stimulation and in patients with BMS compared with controls. Comparison of brain activity between the first 16 s and second 16 s of the stimulus revealed pronounced time-dependent facilitation in patients with BMS during lip stimulation. These findings indicate that the pain modulating system in patients with BMS is dysregulated and that the brain in BMS is highly sensitized to pain information originating from the trigeminal system.

Burning mouth syndrome (BMS) is one of the most frequently seen idiopathic pain conditions in a dental setting. Peri- and postmenopausal women are most frequently affected, and patients who experience BMS complain of persistent burning pain mainly at the tip and the bilateral border of the tongue. Recent studies have assessed whether BMS is a neuropathic pain condition, based on morphologic changes in biopsied tongue specimens, and whether there are abnormal pain responses in patients with this disease. Somatosensory studies have reported some abnormal findings in sensory and pain detection thresholds with inconsistency; however, the most distinct finding was exaggerated responses to painful stimuli. Imaging and electrophysiologic studies have suggested the possibility of dysregulation of the pain-modulating system in the central nervous system, which may explain the enhanced pain responses despite the lack of typical responses toward quantitative sensory tests. Basic studies have suggested the possible involvement of neuroprotective steroids, although the underlying mechanisms of this condition have not been elucidated. Experimental studies are looking for preferable supportive therapies for BMS patients despite the obscure pathogenesis.

We herein report a 55-year-old woman who presented with erythema and bilateral hilar lymphadenopathy 4 months prior to the detection of pancreatic lesions on an ultrasound. A skin biopsy showed evidence of sarcoidosis. The largest lesion in the tail of the pancreas was hypoechoic on endoscopic ultrasonography (EUS). The lesion was initially iso-enhanced on contrast enhanced-EUS (CE-EUS) but subsequently became hypoenhanced. The lesion revealed heterogeneous components of both soft and hard tissue on EUS elastography. She was ultimately diagnosed with pancreatic sarcoidosis based on the presence of noncaseating granulomas seen on pancreatic tissue retrieved through an EUS-guided fine needle aspiration biopsy.

Most patients with pancreatic cancer are ineligible for curative resection at diagnosis, resulting in poor prognosis. This study aimed to evaluate the prognostic factors in patients with unresectable pancreatic cancer. We retrospectively collected clinical data from 196 patients with unresectable pancreatic cancer who received palliative chemotherapy (N = 153) or palliative care alone (N = 43) from January 2011 to December 2013. Patients’ background data and overall survival were analyzed using the Cox proportional hazard regression model. In patients receiving palliative chemotherapy (gemcitabine-based regimen, 88.2%) and palliative care alone, the median (range) ages were 68 (43–91) and 78 (53–90) years, and metastatic diseases were present in 80% (N = 123) and 86% (N = 37), respectively. Multivariate analysis in the palliative chemotherapy patients showed that liver metastasis (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.58–3.20, P 4.5 vs ≤4.5; HR 3.45, 95% CI 2.22–5.36, P

Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is often associated with type 1 autoimmune pancreatitis, and the frequency of isolated IgG4-SC seems to be quite low, making the diagnosis of isolated IgG4-SC challenging. A 63-year-old male was admitted to our hospital for frequent fever. Abdominal magnetic resonance cholangiopancreatography showed diffuse narrowing of the common bile duct and post-stenotic dilatation of the right posterior bile duct. Laboratory tests showed abnormalities in the levels of hepatobiliary enzymes and serum IgG4 levels. Endoscopic retrograde cholangiopancreatography showed diffuse narrowing of intrahepatic bile ducts and post-stenotic dilatation of the right posterior bile duct but no abnormalities in the pancreas. Intraductal ultrasonography showed symmetric circumferentially thickened walls of both narrowed and non-narrowed common bile ducts. Histologic examination of the common bile duct mucosa showed infiltration of IgG4-positive plasma cells. Laparoscopic observations showed discoloration with red lobular markings and multiple small depressed lesions. Liver histology showed mild cholangitis with infiltration of IgG4-positive plasma cells around the bile ducts. From these findings, the patient was diagnosed with isolated IgG4-SC. After treatment with a steroid, bile duct dilatations improved. Laparoscopy and intraductal ultrasonography were useful to diagnose isolated IgG4-SC.

Although it is well known that migraine pain is enhanced by photic stimulation of the eye, the mechanisms underlying this response are not yet understood. Noxious stimulation to the dura is known to activate trigeminal spinal subnucleus caudalis and upper cervical spinal cord (Vc/C1) neurons, causing migraine pain. Intense photic stimulation to the eye is also known to activate certain Vc/C1 neurons, thus increasing migraine pain. In this study, we hypothesized that Vc/C1 neurons receiving noxious dural input would be further activated by intense photic stimulation, resulting in the enhancement of migraine pain. However, mechanisms underlying the interactions between dural and photic sensory information in Vc/C1 neurons is unknown. To evaluate the above hypothesis, we studied phosphorylated extracellular signal-regulated kinase (pERK) -immunoreactive (IR) cells in Vc/C1 in dural mustard oil (DMO)-administrated rats. The change in neuronal excitability of Vc/C1 nociceptive neurons receiving input from the dura in DMO rats was examined and tested if those neurons were modulated by intense flush light stimulation. There were many pERK-IR cells in the lateral portion of Vc/C1 after MO administration to the dura. Flashlight presentation to the eye in DMO rats caused an enhancement of ERK phosphorylation in Vc/C1 neurons and pERK-IR cells were significantly suppressed after intracisternal administration of MEK1 inhibitor PD98059. Dura-light sensitive (DL) neurons were recorded in the lateral portion of Vc/C1 and photic responses of DL neurons were significantly enhanced following dural MO administration. These findings indicate that DL Vc/C1 neurons in DMO rats intensified their responses to intense photic stimulation and that ERK phosphorylation in Vc/C1 neurons receiving noxious dural input increased with intense photic stimulation, suggesting that Vc/C1 nociceptive neurons are involved in the enhancement of dural nociception associated with intense light stimulation.

Burning mouth syndrome (BMS) is a chronic intraoral pain syndrome featuring idiopathic oral pain and burning discomfort despite clinically normal oral mucosa. The etiology of chronic pain syndrome is unclear, but preliminary neuroimaging research has suggested the alteration of volume, metabolism, blood flow, and diffusion at multiple brain regions. According to the neuromatrix theory of Melzack, pain sense is generated in the brain by the network of multiple pain-related brain regions. Therefore, the alteration of pain-related network is also assumed as an etiology of chronic pain. In this study, we investigated the brain network of BMS brain by using probabilistic tractography and graph analysis. Fourteen BMS patients and 14 age-matched healthy controls underwent 1.5T MRI. Structural connectivity was calculated in 83 anatomically defined regions with probabilistic tractography of 60-axis diffusion tensor imaging and 3D T1-weighted imaging. Graph theory network analysis was used to evaluate the brain network at local and global connectivity. In BMS brain, a significant difference of local brain connectivity was recognized at the bilateral rostral anterior cingulate cortex, right medial orbitofrontal cortex, and left pars orbitalis which belong to the medial pain system; however, no significant difference was recognized at the lateral system including the somatic sensory cortex. A strengthened connection of the anterior cingulate cortex and medial prefrontal cortex with the basal ganglia, thalamus, and brain stem was revealed. Structural brain network analysis revealed the alteration of the medial system of the pain-related brain network in chronic pain syndrome.

Migraine is a common, debilitating, primary headache disorder that can cause and be affected by odontalgia.A 49-year-old woman(Patient 1) presented with pulsating pain in the left maxillary molar area, and a history of unsuccessful root canal treatment. She was ultimately diagnosed with menstrually related migraine without aura and zolmitriptan was prescribed, which reduced her headache and toothache together. A 45-year-old woman (Patient 2) presented with throbbing pain in the right maxillary molar and cheek area. Past repeated endodontic therapy had been unsuccessful. She was then diagnosed with menstrually related migraine without aura, and sumatriptan significantly reduced her headache and toothache. A 40-year-old woman (Patient 3) presented with pulsating pain near the left maxillary molar region. Pulpectomy was performed after she had previously received a diagnosis of pulpitis in the left maxillary second molar, but her pain did not subside. Patient 2 and 3 were misdiagnosed as pulpitis by dental practitioners and the pain did not relive after pulpectomy. All patients were diagnosed as migraine by headache specialists and were treated with triptans, which resulted in satisfactory pain relief.A thorough history and examination, as well as an understanding of migraine headaches, is necessary to differentiate odontogenic pain and migraine headaches. Key Words: menstrually related migraine, orofacial pain, ICHD-3, headache.

Objectives The aim of this study was to examine temporal summation (TS) and conditioned pain modulation (CPM) in patients with burning mouth syndrome (BMS) and healthy controls using intra-epidermal electrical stimulation (IES). Materials and methods Twenty-six female patients with BMS and 27 healthy female controls participated in this study. A single stimulus with electrical stimulation followed by a train of 10 successive stimuli was administered to the right chin of participants in both the BMS and control groups. CPM was evaluated with the changes of TS calculated from the difference in numerical pain scale data between these two test stimuli and the following warm (40°C) and hot (47°C) conditioning stimuli applied at the non-dominant hand in both the BMS and control groups. Results TS was present in both the BMS and control groups. CPM in the BMS group was significantly less efficient at the 47°C condition than that in the control group, while no significant difference was observed in the CPM between the BMS and the control groups at the 40°C condition. Conclusion These findings indicate that BMS is associated with a deficit inhibitory CPM and implicate the involvement of the central nervous system in the pathophysiology of BMS.

Classical trigeminal neuralgia with concomitant persistent facial pain responds poorly to conservative treatment. The authors describe the effects of microvascular decompression and radiofrequency thermocoagulation for patients with classical trigeminal neuralgia and concomitant persistent facial pain.Case 1 was a 61-year-old man with dull, continuous, aching pain in the left maxillary and mandibular molar area. Case 2 was a 68-year-old woman with aching pain in the maxillary right molar. Case 3 was a 67-year-old woman with severe pain in the right upper lip and maxillary right second premolar. Case 4 was a 42-year-old man with orofacial pain of 14 months' duration. Cases 1 and 2 underwent radiofrequency thermocoagulation and reported good relief of symptoms. Cases 3 and 4 underwent microvascular decompression and attained excellent relief.Microvascular decompression may be more effective than radiofrequency thermocoagulation for patients with classical trigeminal neuralgia with concomitant persistent facial pain.

Background and Overview The authors report the case of a patient with mixed connective tissue disease (MCTD) and Sjogren syndrome, showing signs and symptoms of bilateral trigeminal neuropathy and aseptic meningitis. The patient was assessed by means of quantitative sensory testing (QST) according to the German Research Network on Neuropathic Pain standards, in both the gingiva and forearm, and the results were compared with those of healthy control participants. Case Description A 27-year-old woman, who had received a diagnosis of MCTD and Sjogren syndrome from a rheumatologist, sought treatment at an orofacial pain clinic for bilateral electriclike pain in the maxillary anterior gingiva, eyelids, and cheeks. QST indicated allodynia and hyperalgesia in response to mechanical and thermal stimuli in both her gingiva and forearm, and cold hyperalgesia in her forearm only. She had been prescribed an oral corticosteroid (prednisone, 7 milligrams per day) by the rheumatologist, and was given lidocaine gel and systemic pregabalin (400 mg/d) at the clinic. Conclusions and Practical Implications The cause of trigeminal neuropathy in MCTD and Sjogren syndrome (SS) is unknown. The QST data in this case showed that the somatosensory disturbance severity was higher in the gingiva than in the forearm, suggesting that the trigeminal nerve may be more susceptible than other parts of the nervous system in patients with MCTD. If reproducible in future studies, the finding of greater hypersensitivity in the gingiva than in the forearm may provide an opportunity for dentists to play a role in the detection, diagnosis, or both of MCTD and SS. Dentists must be sufficiently familiar with MCTD and SS to include them in their differential diagnoses and should consider performing simple neurosensory testing such as via intraoral cotton swab or pinprick test.

We investigated the effect of botulinum neurotoxin type A (BoNT-A) on mechanical allodynia and hyperalgesia associated with infraorbital nerve constriction (ION-CCI) in rats. ION-CCI rats received a subcutaneous BoNT-A injection into the whisker pad area on day 7 postoperatively and underwent pain assessment on days 14 and 21 postoperatively. Rats were assigned to one of four treatment groups (n=5 each): ION-CCI+BoNT-A 20pg (low-dose group), ION-CCI+BoNT-A 200pg (high-dose group), ION-CCI+saline, and Sham. Mechanical allodynia and hyperalgesia were evaluated preoperatively (baseline) and on days 7, 14, and 21 postoperatively. After noxious mechanical stimulation of whisker pad skin, the number and distribution pattern of the phosphorylated extracellular signal-regulated kinase (pERK)-immunoreactive (IR) neurons were analyzed in the trigeminal spinal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2). On day 21, nocifensive behavior was attenuated by high-dose but not low-dose BoNT-A administration. In addition, after noxious mechanical stimulation of whisker pad skin, the numbers of pERK-IR cells in the superficial laminae of Vc and C1-C2 were significantly lower in the high-dose BoNT-A group than in the ION-CCI+saline group. The present findings suggest that, by suppressing Vc neuronal activity, high-dose intradermal injection of BoNT-A at the site of ION innervation alleviates mechanical facial allodynia and hyperalgesia associated with ION-CCI.

Burning mouth syndrome (BMS) is an idiopathic orofacial pain condition. Although the pathophysiology of BMS is not clearly understood, central and peripheral neuropathic mechanisms are thought to be involved. The authors compared brain response to noxious heat stimuli in 16 right-handed women with primary BMS and 15 sex- and age-matched right-handed healthy female controls. A thermal stimulus sequence of 32 °C to 40 °C to 32 °C to 49 °C was repeated 4 times in a cycle. Warm and noxious heat stimuli were delivered with a Peltier thermode placed on the right palm or right lower lip for 32 s each in a session. Functional magnetic resonance imaging data were obtained by recording echoplanar images with a block design. Statistical Parametric Mapping 8 software was used to analyze the data. Patients and controls both reported feeling more pain during palm stimulation than during lip stimulation. Repetition of noxious heat stimulus on the lower lip but not on the palm induced habituation in brain activity in the cingulate cortex without reduction in pain perception. Multiple regression analysis revealed a correlation between perceived pain intensity and suppression of brain activity in the anterior cingulate cortex when the repeated thermal sequence was applied at the lower lip. Furthermore, the response of the parahippocampal area differed in BMS patients and controls when the same repeated thermal sequence was applied at the palm. The authors’ findings indicate that BMS patients show specific brain responses due to impaired function of the central and peripheral nervous systems (clinical trial registration: UMIN000015002).

Trigeminal nerve injury causes a distinct time window of glial activation in the trigeminal spinal subnucleus caudalis (Vc), which are involved in the initiation and maintenance phases of orofacial neuropathic pain. Microglia-derived factors enable the activation of astrocytes. The complement component C1q, which promotes the activation of astrocytes, is known to be synthesized in microglia. However, it is unclear whether microglia&ndash, astrocyte communication via C1q is involved in orofacial neuropathic pain. Here, we analyzed microglia-astrocyte communication in a rat model with infraorbital nerve injury (IONI). The orofacial mechanical hypersensitivity induced by IONI was significantly attenuated by preemptive treatment with minocycline. Immunohistochemical analyses revealed that minocycline inhibited the increase in c-Fos immune-reactive (IR) cells and the fluorescence intensity of both Iba1 and glial fibrillary acidic protein (GFAP) in the Vc following IONI. Intracisternal administration of C1q caused orofacial mechanical hypersensitivity and an increase in the number of c-Fos-IR cells and fluorescence intensity of GFAP. C1q-induced orofacial mechanical hypersensitivity was completely abrogated by intracisternal administration of fluorocitrate. The present findings suggest that the enhancement in the excitability of Vc nociceptive neurons is produced by astrocytic activation via the signaling of C1q released from activated microglia in the Vc following IONI, resulting in persistent orofacial neuropathic pain.