Relationship between temporomandibular joint pain and magnetic resonance imaging findings in patients with temporomandibular joint disorders.

The purpose of this study was to evaluate abnormal magnetic resonance imaging (MRI) findings related to temporomandibular joint (TMJ) pain. This study included 245 joints of 152 patients with temporomandibular disorders with anterior disc displacement; of these, 129 joints had joint pain whereas 116 joints had no joint pain. MRI was used to evaluate the reduction of anterior disc displacement, joint effusion, mandible condylar morphology, bone marrow oedema of the mandibular condyle, and signal intensity of the posterior disc attachment (PDA) on fat-suppressed T2-weighted images. The odds ratio (OR) for each MRI variable for the pain group versus the no pain group was computed using logistic regression analysis. Univariate logistic regression analysis showed significant correlations between TMJ pain and all MRI findings. Multivariate logistic regression analysis showed significant correlations with joint effusion (P=0.03, OR 2.21), bone marrow oedema (P<0.001, OR 11.75), and signal intensity of the PDA (P<0.001, OR 6.21). These results suggest that bone marrow oedema, high signal intensity of the PDA on fat-suppressed T2-weighted images, and joint effusion, in descending order of influence, are factors related to TMJ pain.

Removal of carbon contamination in ETEM by introducing Ar during electron beam irradiation.

Organic materials, including carbon, exist inside the transmission electron microscope (TEM) chamber and are adsorbed onto samples under observation during TEM. When these adsorbed organic materials are irradiated by an electron beam, the adsorbed gas is decomposed. Carbon atoms remain on the sample and bond with each other forming a material with an amorphous structure. Due to the carbon deposition on the observation area of the sample, it is contaminated and the TEM image quality is decreased. Ar was introduced into environmental TEM (ETEM) to purge organic material from the sample chamber to reduce contamination growth. After Ar gas was introduced, the contamination was gradually removed. The contamination removal rate was dependent on the Ar pressure. Moreover, it was clear that Ar was ionised by electron beam irradiation and the Ar ions were produced in the ETEM during electron beam irradiation. It is proposed that the Ar ions removed the carbon contamination. LAY DESCRIPTION: Organic materials, including carbon, exist inside the transmission electron microscope (TEM) chamber and are adsorbed onto samples under observation during TEM. When these adsorbed organic materials are irradiated by an electron beam, the adsorbed gas is decomposed. Carbon atoms remain on the sample and bond with each other forming a material with an amorphous structure. Due to the carbon deposition on the observation area of the sample, it is contaminated and the TEM image quality is decreased. Ar was introduced into environmental TEM (ETEM) to purge organic material from the sample chamber to reduce contamination growth. After Ar gas was introduced, the contamination was gradually removed. The contamination removal rate was dependent on the Ar pressure. Moreover, it was clear that Ar was ionised by electron beam irradiation and the Ar ions were produced in the ETEM during electron beam irradiation. It is proposed that the Ar ions removed the carbon contamination.

Rikkunshito simultaneously improves dyspepsia correlated with anxiety in patients with functional dyspepsia: A randomized clinical trial (the DREAM study).

BACKGROUND: Functional dyspepsia (FD), a heterogeneous disorder, involves multiple pathogenetic mechanisms. Developing treatments for FD has been challenging. We performed a randomized, placebo-controlled, double-blind clinical trial to determine the efficacy of rikkunshito, a Japanese herbal medicine, in FD patients. METHODS: FD patients (n = 192) who met the Rome III criteria without Helicobacter pylori infection, predominant heartburn, and depression were enrolled at 56 hospitals in Japan. After 2 weeks of single-blind placebo treatment, 128 patients with continuous symptoms were randomly assigned to 8 weeks of rikkunshito (n = 64) or placebo (n = 61). The primary efficacy endpoint was global assessment of overall treatment efficacy (OTE). The secondary efficacy endpoints were improvements in upper gastrointestinal symptoms evaluated by the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM), the Global Overall Symptom scale (GOS), and the modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (m-FSSG), and psychological symptoms evaluated by the Hospital Anxiety and Depression Scale (HADS). KEY RESULTS: Rikkunshito increased OTE compared to placebo at 8 weeks (P = .019). Rikkunshito improved upper gastrointestinal symptoms (PAGI-SYM, GOS, and m-FSSG) at 8 weeks, especially postprandial fullness/early satiety (P = .015 and P = .001) and bloating (P = .007 and P = .002) of the PAGI-SYM subscales at 4 weeks and 8 weeks. Improvement of HADS at 8 weeks (P = .027) correlated with those of PAGI-SYM (r = .302, P = .001), GOS (r = .186, P = .044), and m-FSSG (r = .462, P < .001), postprandial fullness/early satiety (r = .226, P = .014), dyspepsia (r = .215, P = .019), and PDS (r = .221, P = .016). CONCLUSION & INFERENCES: Rikkunshito may be beneficial for FD patients to simultaneously treat gastrointestinal and psychological symptoms.

Crystalline structure of pulverized dental calculus induces cell death in oral epithelial cells.

BACKGROUND AND OBJECTIVE: Dental calculus is a mineralized deposit attached to the tooth surface. We have shown that cellular uptake of dental calculus triggers nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation, leading to the processing of the interleukin-1ß precursor into its mature form in mouse and human phagocytes. The activation of the NLRP3 inflammasome also induced a lytic form of programmed cell death, pyroptosis, in these cells. However, the effects of dental calculus on other cell types in periodontal tissue have not been investigated. The aim of this study was to determine whether dental calculus can induce cell death in oral epithelial cells. MATERIAL AND METHODS: HSC-2 human oral squamous carcinoma cells, HOMK107 human primary oral epithelial cells and immortalized mouse macrophages were exposed to dental calculus or 1 of its components, hydroxyapatite crystals. For inhibition assays, the cells were exposed to dental calculus in the presence or absence of cytochalasin D (endocytosis inhibitor), z-YVAD-fmk (caspase-1 inhibitor) or glyburide (NLRP3 inflammasome inhibitor). Cytotoxicity was determined by measuring lactate dehydrogenase (LDH) release and staining with propidium iodide. Tumor necrosis factor-α production was quantified by enzyme-linked immunosorbent assay. Oral epithelial barrier function was examined by permeability assay. RESULTS: Dental calculus induced cell death in HSC-2 cells, as judged by LDH release and propidium iodide staining. Dental calculus also induced LDH release from HOMK107 cells. Following heat treatment, dental calculus lost its capacity to induce tumor necrosis factor-α in mouse macrophages, but could induce LDH release in HSC-2 cells, indicating a major role of inorganic components in cell death. Hydroxyapatite crystals also induced cell death in both HSC-2 and HOMK107 cells, as judged by LDH release, indicating the capacity of crystal particles to induce cell death. Cell death induced by dental calculus was significantly inhibited by cytochalasin D, z-YVAD-fmk and glyburide, indicating NLRP3 inflammasome involvement. In permeability assays, dental calculus attenuated the barrier function of HSC-2 cell monolayers. CONCLUSION: Dental calculus induces pyroptotic cell death in human oral epithelial cells and the crystalline structure plays a major role in this process. Oral epithelial cell death induced by dental calculus might be important for the etiology of periodontitis.

The effect of glucose-dependent insulinotropic polypeptide (GIP) variants on visceral fat accumulation in Han Chinese populations.

OBJECTIVES: We aim to validate the effects of glucose-dependent insulinotropic polypeptide (GIP) on fat distribution and glucose metabolism in Han Chinese populations. METHODS: We genotyped six tag single-nucleotide polymorphisms (SNPs) of GIP and four tag SNPs of glucose-dependent insulinotropic polypeptide receptor (GIPR) among 2884 community-based individuals from Han Chinese populations. Linear analysis was applied to test the associations of these variants with visceral fat area (VFA) and subcutaneous fat area (SFA) quantified by magnetic resonance imaging as well as glucose-related traits. RESULTS: We found that the C allele of rs4794008 of GIP tended to increase the VFA and the VFA/SFA ratio in all subjects (P=0.050 and P=0.054, respectively), and rs4794008 was associated with the VFA/SFA ratio in males (P=0.041) after adjusting for the BMI. The VFA-increasing allele of rs4794008 was not related to any glucose metabolism traits. However, rs9904288 of GIP was associated with the SFA in males as well as glucose-related traits in all subjects (P range, 0.004-0.049), and the GIPR variants displayed associations with both fat- and glucose-related traits. CONCLUSIONS: The results could provide the evidence that GIP might modulate visceral fat accumulation via incretin function or independent of incretin.

Lafutidine, a histamine H2 receptor antagonist with mucosal protective properties, attenuates 5-fluorouracil-induced intestinal mucositis in mice through activation of extrinsic primary afferent neurons.

Intestinal mucositis accompanied by severe diarrhea is one of the most common side effects during cancer chemotherapy. Lafutidine, a histamine H2 receptor antagonist with mucosal protective properties via sensory afferent neurons, is used for the treatment of upper gastrointestinal diseases. The present study investigated the effects of lafutidine on 5-fluorouracil (5-FU)-induced intestinal mucositis induced in mice. Male C57BL/6 wild-type (WT), sensory deafferented mice, and transient receptor potential vanilloid subfamily 1 knockout (TRPV1KO) mice were used. Animals were administered 5-FU once daily, while lafutidine and famotidine were administered twice daily for 6 days. Repeated administration of 5-FU caused severe intestinal mucositis, characterized by shortening of villi and destruction of crypts and was accompanied by diarrhea and body weight loss. Daily administration of lafutidine reduced the severity of intestinal mucositis, diarrhea and body weight loss in a dose-dependent manner, while famotidine had no effect on intestinal mucositis. The preventive effects of lafutidine were completely abolished in sensory deafferented and TRPV1-KO mice. Lafutidine significantly suppressed 5-FU-increased MPO activity and inflammatory cytokine expression on day 6, but not apoptosis induction in intestinal crypts on day 1. Lafutidine induced Alcian Blue and PAS-positive mucus production in the small intestine. These findings suggest that lafutidine attenuates 5-FU-induced intestinal mucositis, most likely by increasing mucus production via activation of sensory afferent neurons. Furthermore, intact TRPV1 signaling is essential for the activation of sensory afferent neurons induced by lafutidine. Therefore, lafutidine is more useful than other common antacids for the treatment of intestinal mucositis during cancer chemotherapy.

Actinomyces denticolens colonisation identified in equine tonsillar crypts.

Recently, submandibular abscesses associated with Actinomyces denticolens have been reported in horses. The actinomycotic clumps have been observed in the tonsillar crypts. The aim of this study was to demonstrate colonisation of A denticolens in equine tonsils. Twelve equine tonsils obtained from a slaughterhouse were divided into two parts for histopathological examination and for isolation of A denticolens. When actinomycotic clumps were found in these tonsillar crypts, immunohistochemistry using hyperimmune serum against A denticolens (DMS 20671) was performed on the serial sections. To determine whether Actinomyces-like bacteria isolated using immunoantigenic separation technique were A denticolens, the isolates were analysed for the 16S rRNA gene sequence. Actinomycotic clumps were found in the tonsillar crypts of 11 (91.7 per cent) horses. The clumps were of the saprophytic type accompanied with the feedstuffs, but a few clumps were surrounded by inflammatory cells. A denticolens antigens were immunodetected not only in the clumps of 11 (100 per cent) tonsils, but also in the tonsillar parenchyma. Six isolates obtained from four tonsils showed 99.7-99.9 per cent similarity to A denticolens in the 16S rRNA gene sequence. In horses, the colonisation sites of A denticolens are the tonsils, thus the authors suggest that the tonsils provide the intrinsic infection site for A denticolens.

Axonal TDP-43 aggregates in sporadic amyotrophic lateral sclerosis.

AIMS: Axonal aggregates of phosphorylated (p-) transactive response DNA-binding protein 43 kDa (TDP-43) in sporadic amyotrophic lateral sclerosis (sALS) were examined in relation to propagation of the protein in the nervous system. METHODS: Brains and spinal cords of Japanese patients with sALS and control subjects were examined immunohistochemically using formalin-fixed paraffin-embedded specimens with special reference to the topographical distribution, microscopic features, presynaptic aggregates, and correlation between the aggregates in axons and the clinical course. RESULTS: (i) Aggregates of p-TDP-43 were frequently present in axons of the hypoglossal and facial nerve fibres and the spinal anterior horn cells. (ii) Aggregates of p-TDP-43 in the axons showed two characteristic microscopic features - dash-like granuloreticular aggregates (GRAs) and massive aggregates (MAs). (iii) MAs were surrounded by p-neurofilaments, but p-neurofilament immunnoreactivity decreased at the inside of axons with GRAs. (iv) Patients showing MAs and GRAs had a relatively shorter clinical course than patients without the aggregates. (v) Some neurones in the red nucleus in patients were surrounded by synapses containing p- and p-independent (i)-TDP-43, and almost all neurones had lost their nuclear TDP-43 immunoreactivity; 17% of those neurones in the red nucleus also had TDP-43-immunopositive neuronal cytoplasmic inclusions, but no postsynaptic p-TDP-43 deposition was evident. CONCLUSIONS: There are two types of axonal p-TDP-43 aggregates, MAs and GRAs, located predominantly in the facial and hypoglossal nuclei and anterior horn cells. These aggregates may influence the function of neurones, and presynaptic aggregates of the protein induce loss of p-i-TDP-43 in the nuclei of postsynaptic neurones.

NFκB2 Gene as a Novel Candidate that Epigenetically Responds to Interval Walking Training.

Physical fitness has been reported to decrease the risk of lifestyle-related diseases. The present study evaluated genome-wide methylation under the hypothesis that interval walking training (IWT) imparted beneficial effects on health, particularly by epigenetically ameliorating susceptibility to inflammation. We screened DNA from peripheral blood samples via genome-wide microarray for genes whose methylation was affected by IWT, paying special attention to promoter regions, and identified over 40 hyper- or hypo-methylated genes following IWT that were not witnessed in controls. We next selected genes in which the degree of methylation change in the promoter region was correlated with energy consumption following IWT. In this way, we found the NFκB2 gene to have increased methylation in multiple regions of its promoter sequence following participation in an exercise regimen. Next, IWT-induced NFκB2 hyper-methylation was confirmed by a quantitative PyroSequencing assessment of methylation in samples obtained from independent subjects who also underwent IWT. The increase in NFκB2 gene promoter methylation by IWT indicates that this regimen may suppress pro-inflammatory cytokines. Thus, these results provide an additional line of evidence that IWT is advantageous in promoting health from an epigenetic perspective by ameliorating susceptibility to inflammation.

Protective effect of hypotaurine against oxidative stress-induced cytotoxicity in rat placental trophoblasts.

INTRODUCTION: Hypotaurine is a precursor of taurine and an antioxidant, and is concentrated in fetal plasma compared to maternal plasma. Hypotaurine is significantly decreased in fetal plasma of ezrin (Vil2) knock-out mice, and fetuses show intrauterine growth retardation. The aim of this study was to characterize the mechanism through which cellular hypotaurine level is maintained in placental trophoblasts, and the effect of hypotaurine on oxidative stress induced by hydrogen peroxide (H2O2). METHODS: Hypotaurine transfer from extracellular fluid and antioxidant effect of hypotaurine were analyzed in rat placental trophoblast TR-TBT 18d-1 cells. RESULTS: We found that hypotaurine is concentrated into rat placental trophoblast TR-TBT 18d-1 cells, and the level of hypotaurine was markedly reduced by culture in medium supplemented with dialyzed fetal bovine serum (FBS) instead of normal FBS. The hypotaurine level recovered almost completely when hypotaurine was added to the culture medium, indicating that intracellular hypotaurine is predominantly supplied by transport across the plasma membrane from extracellular fluid rather than by biosynthesis. Hypotaurine showed a cytoprotective effect against H2O2-induced oxidative damage in TR-TBT 18d-1 cells. Hypotaurine treatment of TR-TBT 18d-1 cells increased antioxidant capacity against hydroxyl radical and peroxyl radical. The concentration of intracellular hydroxyl radical induced by H2O2 in TR-TBT 18d-1 cells was significantly reduced by hypotaurine treatment. DISCUSSION: These results indicate that intracellular hypotaurine is mainly supplied to placental trophoblasts by transfer from extracellular fluid across the plasma membrane, and may play a role in cell protection by scavenging reactive oxygen species.

Diagnostic value of blood gene expression signatures in active tuberculosis in Thais: a pilot study.

Tuberculosis (TB) is a major global health problem. Routine laboratory tests or newly developed molecular detection are limited to the quality of sputum sample. Here we selected genes specific to TB by a minimum redundancy-maximum relevancy package using publicly available microarray data and determine level of selected genes in blood collected from a Thai TB cohort of 40 active TB patients, 38 healthy controls and 18 previous TB patients using quantitative real-time PCR. FCGR1A, FCGR1B variant 1, FCGR1B variant 2, APOL1, GBP5, PSTPIP2, STAT1, KCNJ15, MAFB and KAZN had significantly higher expression level in active TB individuals as compared with healthy controls and previous TB cases (P<0.01). A mathematical method was applied to calculate TB predictive score, which contains the level of expression of seven genes and this score can identify active TB cases with 82.5% sensitivity and 100% specificity as compared with conventional culture confirmation. In addition, TB predictive scores in active TB patients were reduced to normal after completion of standard short-course therapy, which was mostly in concordant with the disease outcome. These finding suggested that blood gene expression measurement and TB Sick Score could have potential value in terms of diagnosis of TB and anti-TB treatment monitoring.

Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naïve patients with advanced gastric cancer.

BACKGROUND: We evaluated the efficacy and safety of S-1 plus oxaliplatin (SOX) as an alternative to cisplatin plus S-1 (CS) in first-line chemotherapy for advanced gastric cancer (AGC). PATIENTS AND METHODS: In this randomized, open-label, multicenter phase III study, patients were randomly assigned to receive SOX (80-120 mg/day S-1 for 2 weeks with 100 mg/m(2) oxaliplatin on day 1, every 3 weeks) or CS (S-1 for 3 weeks with 60 mg/m(2) cisplatin on day 8, every 5 weeks). The primary end points were noninferiority in progression-free survival (PFS) and relative efficacy in overall survival (OS) for SOX using adjusted hazard ratios (HRs) with stratification factors; performance status and unresectable or recurrent (+adjuvant chemotherapy) disease. RESULTS: Overall, 685 patients were randomized from January 2010 to October 2011. In per-protocol population, SOX (n = 318) was noninferior to CS (n = 324) in PFS [median, 5.5 versus 5.4 months; HR 1.004, 95% confidence interval (CI) 0.840-1.199; predefined noninferiority margin 1.30]. The median OS for SOX and CS were 14.1 and 13.1 months, respectively (HR 0.958 with 95% CI 0.803-1.142). In the intention-to-treat population (SOX, n = 339; CS, n = 337), the HRs in PFS and OS were 0.979 (95% CI 0.821-1.167) and 0.934 (95% CI 0.786-1.108), respectively. The most common ≥grade 3 adverse events (SOX versus CS) were neutropenia (19.5% versus 41.8%), anemia (15.1% versus 32.5%), hyponatremia (4.4% versus 13.4%), febrile neutropenia (0.9% versus 6.9%), and sensory neuropathy (4.7% versus 0%). CONCLUSION: SOX is as effective as CS for AGC with favorable safety profile, therefore SOX can replace CS. CLINICAL TRIAL NUMBER: JapicCTI-101021.

Randomised clinical trial: prevention of recurrence of peptic ulcers by rabeprazole in patients taking low-dose aspirin.

BACKGROUND: Few studies have evaluated the effects of rabeprazole on low-dose aspirin (LDA)-induced gastroduodenal injuries. AIM: To conduct a randomised, double-blind, triple-dummy, active-controlled, multicentre trial, named the PLANETARIUM study, to assess the efficacy, dose-response relationship and safety of rabeprazole for peptic ulcer recurrence in Japanese patients on long-term LDA therapy. METHODS: Eligible patients had a history of endoscopically confirmed peptic ulcers and were receiving long-term LDA (81 or 100 mg/day) therapy for cardiovascular or cerebrovascular protection. Subjects were randomly segregated into three groups receiving rabeprazole 10 mg once daily (standard dose in Japan), rabeprazole 5 mg once daily, or teprenone (geranylgeranylacetone; mucosal protective agent commercially available in Japan) 50 mg three times per day as an active control. The primary endpoint was recurrence of peptic ulcers over 24 weeks. RESULTS: Among 472 randomised subjects, 452 subjects (n = 151, 150, 151, respectively) constituted the full analysis set. The cumulative recurrence rates of peptic ulcers over 24 weeks in the 10- and 5-mg rabeprazole groups were 1.4% and 2.8%, respectively, both of which were significantly lower than that in the teprenone group (21.7%). The cumulative occurrence rate of bleeding ulcers over 24 weeks in the teprenone group was 4.6%, while bleeding ulcers were not observed in the 10- or 5-mg rabeprazole groups. Rabeprazole was well tolerated at both doses. CONCLUSION: Rabeprazole prevents the recurrence of peptic ulcers with no evidence of a major dose-response effect in subjects on low-dose aspirin therapy.

Transmission of systemic AA amyloidosis in animals.

Amyloidoses are a group of protein-misfolding disorders that are characterized by the deposition of amyloid fibrils in organs and/or tissues. In reactive amyloid A (AA) amyloidosis, serum AA (SAA) protein forms deposits in mice, domestic and wild animals, and humans that experience chronic inflammation. AA amyloid fibrils are abnormal ß-sheet-rich forms of the serum precursor SAA, with conformational changes that promote fibril formation. Extracellular deposition of amyloid fibrils causes disease in affected animals. Recent findings suggest that AA amyloidosis could be transmissible. Similar to the pathogenesis of transmissible prion diseases, amyloid fibrils induce a seeding-nucleation process that may lead to development of AA amyloidosis. We review studies of possible transmission in bovine, avian, mouse, and cheetah AA amyloidosis.

An evaluation of the effectiveness of engaging Canadian clients as partners in in-home care.

This exploratory quasi-experimental evaluation assessed the effectiveness of the use of a concrete discussion guide to promote organisation-wide application of a partnering approach to engage older home-care clients with chronic disease/disabilities as care partners. A post-test-only design with an independent pre-test sample was used to compare selected outcomes with those of standard in-home care. The theoretically informed discussion guide portrayed how to go about the process of empowering partnering by using language and open-ended conversational leads to construct partnering, partnering effort and health as a resource for everyday living through social interaction. The discussion guide was provided to all providers for use with all clients in one home-care programme in Ontario, Canada and this organisation was compared with a similar but geographically distanced organisation, also in Ontario. Seven hundred and ninety-one randomly selected clients (mean age = 72.5 years) receiving 3+ months of in-home care for chronic conditions/disabilities from the two home-care programmes between September 2007 and May 2010 completed a researcher-administered questionnaire at either baseline, 1 year or 2 years. Instruments included the Client's Partnering Experience, Health-Promoting Partnering Effort, a modified version of Locus of Authority in Decision-Making, the Medical Outcomes Survey Self-Rated Health Scale, Health and Social Services Utilization and a modified Functional Independence Measure. Analysis of covariance revealed that the use of the concrete discussion guide to promote organisation-wide application of a partnering approach achieved significantly greater client partnering experience and health-promoting partnering effort over time than did the usual approach to in-home-care interactions. Using the discussion guide enhanced client/provider partnering, hence, interdependence, contributing positively to promoting clients' health as a resource for everyday living.

Factors associated with the presence of multiple Lugol-voiding lesions in patients with esophageal squamous-cell carcinoma.

Multicentric squamous dysplasia of the esophagus is characterized by multiple Lugol-voiding lesions (LVLs) on Lugol chromoendoscopy. Multiple LVLs are associated with a very high risk of multiple cancers arising in the esophagus as well as the head and neck. To gain insight into the pathogenesis of multiple LVLs of the esophageal mucosa, we studied risk factors for the development of such lesions in 76 patients who had a current or previous diagnosis of esophageal squamous cell carcinoma. All patients underwent Lugol chromoendoscopy of the esophageal mucosa. The history of tobacco and alcohol use was documented. Polymorphisms of the aldehyde dehydrogenase type 2 (ALDH2) gene were identified by polymerase chain reaction using sequence-specific primers. Clinical factors related to multiple LVLs were analyzed. All patients with multiple LVLs were drinkers. On univariate analysis, male sex (odds ratio [OR] 15, 95% confidence interval [CI] 1.84-122.45: P = 0.011), presence of the ALDH2-2 allele (OR 4.5, 95% CI 1.55-13.24: P = 0.006), and smoking index ≥1000 (OR 2.6, 95% CI 1.02-6.6: P = 0.045) were associated with multiple LVLs. On multivariate analysis, male sex (OR 10.02, 95% CI 1.13-88.44: P = 0.038) and presence of the ALDH2-2 allele (OR 4.56, 95% CI 1.4-14.82: P = 0.012) were associated with multiple LVLs. Among drinkers, a daily alcohol intake of ≥100 g pure ethanol with the ALDH2-2 allele (OR 17.5, 95% CI 1.97-155.59: P = 0.01) and a daily alcohol intake of <100 g pure ethanol with the ALDH2-2 allele (OR 8.85, 95% CI 1.68-46.69: P = 0.01) more strongly correlated with multiple LVLs than did a daily alcohol intake of <100 g pure ethanol without the ALDH2-2 allele, whereas a daily alcohol intake of ≥100 g pure ethanol without the ALDH2-2 allele (OR 4.0, 95% CI 0.54-29.81: P = 0.18) did not. In conclusion, male sex and the ALDH2-2 allele are associated with an increased risk for multiple LVLs of the esophageal mucosa in patients with esophageal squamous cell carcinoma. Among drinkers with the ALDH2-2 allele, the risk of multiple LVLs increased in parallel to the daily alcohol intake.