Application of Scanning Acoustic Microscopy for Detection of Dental Caries Lesion

Introduction: A scanning acoustic microscope (SAM) is an apparatus for imaging acoustic properties. This apparatus can non-invasively and rapidly evaluate the hardness of materials in the elastic region. This device shows great potential for the diagnosis of dental caries in the clinical setting. However, since the tissue elastic modulus measured using a SAM is a property of the elastic region and the Knoop hardness is a property of the plastic region, the hardness properties differ completely. Therefore, we investigated whether the acoustic impedance measured using a SAM is related to the Knoop hardness, which is used as the standard for removal of carious dentin. Method: Polished sections were prepared from 20 extracted carious wisdom teeth. The acoustic impedance and Knoop hardness were measured for each section. In addition to comparing carious and healthy dentin in SAM images, we evaluated the difference between the carious and healthy dentin in terms of the acoustic impedance and Knoop hardness. We also evaluated the correlation between the Knoop hardness and acoustic impedance. Results: The SAM images were visualized as two-dimensional color images based on the acoustic impedance values. The mean acoustic impedance of carious dentin was significantly lower than that of healthy dentin, showing a similar trend as Knoop hardness. A strong correlation was observed between the two. Discussion: The acoustic impedance values obtained through acoustic microscopy differed significantly between carious and sound dentin. Both types of dentins were visualized using two-dimensional color images. A strong correlation was observed between the acoustic impedance value, which indicates the hardness of the elastic region, and the Knoop hardness, which indicates the hardness of the plastic region. The results of the present study indicate that acoustic impedance accurately reflects the hardness of dentin.

Case of clear-cell hepatocellular carcinoma that developed in the normal liver of a middle-aged woman

A 36-year-old woman was admitted to our department for close examination of a liver tumor that was found during a medical checkup. Abdominal US, CT and MRI showed a tumor in segment 7 (S7) of the liver. Although imaging suggested hepatocellular carcinoma, laboratory tests showed no abnormality in liver function, hepatitis virus markers were negative, and tumor markers including protein induced by vitamin K absence or antagonist Ⅱ (PIVKA-Ⅱ), α-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) were all within normal ranges. Upon aspiration biopsy of the liver, the histopathological diagnosis was moderately differentiated hepatocellular carcinoma. Therefore, right hepatectomy was performed. Although a part of the tumor was necrotic, about 60% of the viable part showed a clear-cell variant. Consequently, it was diagnosed as clear-cell hepatocellular carcinoma. It was noted that the background liver tissue was normal. This case is worthy of reporting because development of clear-cell hepatocellular carcinoma in the normal liver of a middle-aged woman is rarely seen.

Centrilobular necrosis in acute presentation of Japanese patients with type 1 autoimmune hepatitis

AIM: To compare clinicopathological features of acute presentation of type 1 autoimmune hepatitis (AIH) with or without centrilobular necrosis (CN). METHODS: Our study comprised 41 patients with biopsy-proven acute presentation (acute exacerbation phase 36, acute hepatitis phase 5) of type 1 AIH at our hospital from 1975 to 2009. Elevated serum alanine aminotransferase (ALT) (> 5x upper limit of normal) identified acute presentation of the disease. We compared clinicopathological features of these AIH patients with or without CN. The data used for analysis included patient background (age, sex, type of disease, presence of complications with other autoimmune diseases, human leukocyte antigen, and International Autoimmune Hepatitis Group score), clinical parameters at presentation (ALT, alkaline phosphatase, IgG, anti-nuclear antibodies, and anti-smooth muscle antibodies), histology and therapy. RESULTS: CN was found in 13 (31.7%) patients with acute presentation (acute exacerbation phase 10, acute hepatitis phase 3) of AIH. Serum IgG levels of patients with CN were significantly lower than those of patients without CN (mean: 2307 mg/dL vs 3126 mg/dL, P < 0.05), while antinuclear antibody-negative rates were significantly higher (30.7% vs 3.5%, P < 0.05). However, other clinical features were similar between the two groups. The frequency of advanced fibrosis in patients with CN was significantly lower than in patients without CN (F0-2: 84.6% vs 35.7%, F3-4: 15.4% vs 64.3%, P < 0.05). Other histological features were similar between the two groups. Although there was no significant difference between groups when evaluated using the revised original score (12 vs 14), the simplified AIH score of patients with CN was significantly lower (6 vs 7, P < 0.05). Frequency of DR4 was similar between patients with and without CN. CONCLUSION: CN is observed in both Japanese patients with acute hepatitis phase and acute exacerbation phase of type 1 AIH, although AIH with CN often shows clinical features of the genuine acute form.

Contrast uptake in primary hepatic angiosarcoma on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging in the hepatobiliary phase

Primary hepatic angiosarcoma is the most common malignant mesenchymal tumor of the liver. It has a poor prognosis and various appearances on magnetic resonance(MR) images. We report a case of hepatic angiosarcoma with a characteristic appearance on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)-enhanced MR imaging in the hepatobiliary phase. A 72-year-old man was admitted with a complaint of abdominal pain. Gd-EOBDTPA-enhanced MR imaging revealed a liver tumor that showed slight hyperintensity in the hepatobiliary phase. These findings suggested Gd-EOB-DTPA uptake in the tumor. An autopsy revealed the solid proliferation and sinusoidal spreading of hepatic angiosarcoma cells. Immunohistochemistry indicated that the tumor was negative for OATP1B3. Gd-EOB-DTPA uptake in the liver tumor in the hepatobiliary phase suggested sinusoidal tumor invasion with residual normal hepatocytes.

Relationship between clinicopathological features and mucin phenotypes of advanced gastric adenocarcinoma

AIM: To investigate a relationship between the clinicopathological features and mucin phenotypes in advanced gastric adenocarcinoma (AGA). METHODS: Immunohistochemical staining was performed to determine the mucin phenotypes in 38 patients with differentiated adenocarcinomas (DACs), 9 with signet-ring cell carcinomas (SIGs), and 48 with other diffuse-type adenocarcinomas (non-SIGs) of AGA. The mucin phenotypes were classified into 4 types: gastric (G), gastrointestinal (GI), intestinal, and unclassified. RESULTS: The G-related mucin phenotypes were highly expressed in all the histological subtypes of AGA. The expression of the GI phenotype in SIG patients was lower than that in DAC patients (P = 0.02), and this phenotype was observed in 56% of the non-SIG patients in the intramucosal layer. Among non-SIG cases, the expression of the GI phenotype was significantly higherin patients with extended adenocarcinomas and those with positive rates of lymph node metastasis. There was no difference between the expressions of the G and other GI phenotypes factors. Among DAC and non-SIG patients, there were no differences between the survival rates of the corresponding patient groups. CONCLUSION: The GI phenotype might possess more invasive characteristics than the G phenotype in nonSIG. Neither of the phenotypes indicated a poor prognosis of DAC and non-SIG.

A case of advanced intrahepatic cholangiocarcinoma successfully treated with chemosensitivity test-guided systemic chemotherapy

Intrahepatic cholangiocarcinoma （ICC） is a relatively rare and highly fatal neoplasm that arises from the biliary epithelium. Prognosis is generally poor and survival is limited to a few months. Here we present a case of advanced ICC successfully treated by chemosensitivity test-guided systemic chemotherapy combining S-1 and cisplatin （CDDP）. A 65-year-old woman with a liver tumor was referred to our hospital on November 21, 2007. Abdominal ultrasonography and computed tomography （CT） showed low-density masses of 50 and 15 mm in diameter, respectively in segment w of the liver and in the enlarged lymph node in the para-aorta. Ultrasonography-guided fine needle biopsy diagnosed the tumors as ICC. Since the patient was inoperable for lymph node metastasis, she underwent systemic chemotherapy with gemcitabine. Six months afcer initiation of chemotherapy, CT revealed ICC progression in the liver and pleural dissemination with pleural effusion. The patient was admitted to our hospital for anticancer drug sensitivity testing on June 9, 2008. Based on the sensitivity test results, we elected to administer systemic chemotherapy combining S-1 and CDDP. Two months into the second chemotherapy treatment, CT revealed a reduction of the tumors in the liver and lymph node and a decrease in pleural effusion.After eight cycles of the second chemotherapy, 17 mo after ICC diagnosis, she is alive and well with no sign of recurrence. We conclude that chemosensitivity testing may effectively determine the appropriate chemotherapy regimen for advanced ICC.

A case of primary biliary cirrhosis complicated by Behcet's disease and palmoplantar pustulosis

A 46-year-old woman was diagnosed with palmoplantar pustulosis （PPP） at the Department of Dermatology, Fukushima Medical University Hospital in 2000, and was treated with ointment. However, because liver dysfunction developed in 2003, she was referred to our department, where primary biliary cirrhosis （PBC） was also diagnosed on the basis of clinical findings. One year later, at the age of 49, she developed manifestations of Behcet＇s disease （BD）, including erythema nodosum in the lower extremities. Because she had a history of uveitis, recurrent oral ulceration was present, and the HLA typing was positive for B51, BD was additionally diagnosed. Liver function normalized within three months of the start of treatment with ursodesoxycholic acid （UDCA）. This is the first case of PBC associated with BD and PPP.

Who needs further evaluations to diagnose upper urinary tract urothelial cancers among patients with abnormal findings by enhanced CT?

Objective:We evaluated who would need further evaluations such as retrograde pyelography(RP)and/or ureteroscopy to diagnose upper urinary tract urothelial cancers(UUTUCs)when abnormal findings for the upper urinary tract(UUT)were detected by enhanced computed tomography(CT).Methods:We retrospectively analyzed 125 patients who underwent enhanced CT for various reasons and had abnormal findings for the UUT.Patients whose tumors were suspected to be of extraureteral origin were excluded.All patients received RP and/or ureteroscopy to evaluate the UUTUCs.Results:The median age of the 125 patients was 70 years and gross hematuria(26.4%)was the most frequently observed symptoms.RP,ureteroscopy and both were performed for 121,59 and 55 patients,respectively.CT revealed tumor-like lesions in 58 patients and the other patients had non-tumor-like lesions.UUTUCs were found in 43(34.4%)of the 125 patients.All of them had tumor-like lesions on CT.In 58 patients who had tumor-like lesions on CT,univariate and multivariate analyses revealed that tumor diameter and tumor enhancement were significant predictive factors for UUTUCs.ROC curve analysis of enhanced CT to diagnose UUTUCs revealed that a tumor diameter of 18 mm was the best cutoff point.The sensitivity,specificity and accuracy were 90.0%,98.8% and 92.7% for RP and 95.5%,100% and 97.1%for ureteroscopy,respectively.Both of them had high sensitivity,specificity and accuracy.Conclusion:We should decide to evaluate the UUT according to the tumor diameter on enhanced CT.When we evaluate the UUT in patients with tumor diameters of less than 20 mm,ureteroscopy is recommended.

Investigation of the Aroma Profile of Green Tea Leaves Using Organic Synthesis and Conventional Analytical Techniques

Although many aroma components have been identified in green tea leaves, the aroma compounds contributing to green tea＇s characteristic odor have not yet been reported. The authors recently reported that aroma components with a matcha-like odor are present in both green tea and black tea prepared from the Sayamakaori tea cuttivar. This matcha-like odor is similar to the odor of commercial available matcha （high-quality powdered green tea）, and is a specific odor feature of green tea leaves. At present, the green-tea odor is thought to arise from the combination of a large number of constituents. Recent reports indicate that a complex interaction between olfactory receptors and odorants is important for the evaluation of the odors. Taking into consideration these findings, the authors investigated the aroma profile of green tea, focusing on the characteristic molecular structures of the constituents that give matcha-like odor. Using a combination of organic synthesis and gas chromatography-mass spectrometry plus gas chromatography-olfactometry, the authors identified aroma components with matcha-like odors in five other tea cultivars. This investigation also revealed that several compounds with a formyl group were important constituents of the aroma of green tea leaves, although the odor of each constituent was not individually similar to the tea＇s overall aroma. The authors found for the first time a group of key components that have the matcha-like odor.

Development of autoimmune hepatitis type 1 after pulsed methylprednisolone therapy for multiple sclerosis: A case report

A 43-year-old woman with multiple sclerosis （MS） was treated with pulsed methylprednisolone and interferon 13 at a hospital. Four weeks after initiating treatment, liver dysfunction occurred and she was referred and admitted to our hospital. Clinical and laboratory findings were consistent with and fulfilled the criteria for drug-induced hepatitis, but not for autoimmune hepatitis （AIH）. She was successfully treated with corticosteroids. As ataxia developed after i year, she was treated with pulsed methylprednisolone for 3 days, then readmitted to our hospital when liver dysfunction occurred. Clinical and laboratory findings led to the diagnosis of AIH. To the best of our knowledge, this is the second case of AIH developed after pulsed methylprednisolone for MS.

Influence of DAP1 Genotype and Psychosocial Factors on Posttraumatic Stress Disorder in Thai Tsunami Survivors: A GxE Approach

Background: Posttraumatic Stress Disorder (PTSD) is a psychiatric disorder found in individuals afflicted by a traumatic event including the natural disaster. “Tsunami” occurred in Andaman coast of Thailand on December 26, 2004, in which 33.6% of survivors were diagnosed as PTSD. This study aimed to explore the single nucleotide polymorphism (SNP). rs267943 genotype is located on chromosome 5 in the intron of the death-associated protein 1 (DAP1) gene and psychosocial factors for PTSD. Methods: Participants (N = 1970) were recruited from volunteers who have complete data both of DAP1 gene and psychosocial factor. Results: Using a binary logistic regression model, significant gene-environment interactions were found for the single nucleotide polymorphism (SNP) rs267943 and psychosocial factors including depression (adj. OR = 6.0, 95% CI = 4.29 - 8.39), neurotic personality (adj. OR = 2.73, 95% CI = 2.18 - 3.42), planning (adj. OR = 1.52, 95% CI = 1.20 - 1.93), use of emotional support (adj. OR = 1.32, 95% CI = 1.21 - 1.94) with statistical significant p Conclusion: This study demonstrated that GxE studies can be utilized to shed light on the origins of PTSD.

Genome-Wide Association Study in Thai Tsunami Survivors Identified Risk Alleles for Posttraumatic Stress Disorder

Posttraumatic stress disorder (PTSD) is a psychiatric disorder found in individuals afflicted by a traumatic event. Multiple environmental and genetic factors can contribute to PTSD susceptibility. Since it is rare to find members of the same family afflicted by the same catastrophic event, it is not practical to determine PTSD susceptibility genes by a gene linkage analysis. A natural disaster, such as the 2004 Tsunami, provided us with a rare chance for a genetic analysis of PTSD. To identify SNPs associated with PTSD susceptibility, we conducted a genome-association study (GWAS) in Thai-Tsunami survivors. Initial phase of the study with 396 chronic PTSD patients and 457 controls, we identified top ninety SNPs (P -4), which were further assessed in the second phase with 395 chronic PTSD patients and 798 controls. Two SNPs (rs267950 and rs954406), were identified in the second phase, and subjected to fine mapping using a data set from both phases. SNP rs267943 showed the strongest association with PTSD susceptibility and was in complete linkage disequilibrium with SNP rs267950 with P = 6.15 × 10-8, OR = 1.46 and 95% CI = 1.19 - 1.79, reaching genome-wide significance. SNP rs267943 is located on chromosome 5 in the intron of the death-associated protein 1 (DAP1) gene and, when linked to a synthetic promoter, could regulate transcription. To our knowledge, this is the first GWAS for PTSD susceptibility in an Asian population which could provide an important insight into the genetic contribution of PTSD and may lead to new treatment strategies for PTSD.

Which characteristics are associated with changes in medication status for lower urinary tract symptoms among patients with prostate cancer receiving external beam radiotherapy?

Background:We clarified the predictive factors for changes in the status ofmedications for lower urinary tract symptoms(LUTS)2 years after local radiotherapy for nonmetastatic prostate cancer.Materials and methods:We retrospectively included patients who underwent local external radiotherapy for nonmetastatic prostate cancer in 8 institutions between April 2001 and March 2016.Patients were divided into themedication and no-medication group based on the use of drugs for LUTS before radiotherapy.We defined improvement of LUTS as when the patient did not require medication for LUTS at 24 months after radiotherapy in the medication group and as deterioration whenmedication was required in the no-medication group.Logistic regression analysis was used to evaluate predictive factors for changes in medication status.Results:Altogether,505 patients were divided into a no-medication group(n=352)and a medication group(n=153).The number of patients with deterioration and improvement in LUTS was 49(14%)and 36(23%),respectively.In the multivariate analysis,the predictive variables for deterioration were the International Prostate SymptomScore(≥8;odds ratio[OR],2.21;p=0.014)and the biopsy Gleason score(≤3+4=7;OR,2.430;p=0.008)in the no-medication group,whereas those for improvement were age(<75 years old;OR,5.81;p=0.002),the quality of life score(<3;OR,3.15;p=0.028),and a positive biopsy core rate(≥50%;OR,2.530;p=0.027)in the medication group.Conclusions:These predictive factors for changes in the status ofmedications for LUTS at 2 years after external radiotherapymay help determine the definitive therapy for nonmetastatic prostate cancer.

Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome-wide association and whole genome sequencing analyses

Dear editor,Lung carcinoma is responsible for the highest fatal-ity rate among cancer-related deaths globally,with lung adenocarcinoma(LADC)emerging as the prevailing sub-type.

Difference in symptom manifestation between postmenopausal and premenopausal women in acute uncomplicated cystitis:A multi-institutional pilot study

Objectives:We aimed to prospectively compare lower urinary tract symptoms in premenopausal and postmenopausal women with acute uncomplicated cystitis before and after antibiotic therapy.Materials and methods:This study included adult women with acute uncomplicated cystitis who visited 4 institutions between 2019 and 2020.After registration,we administered oral antibiotics and prospectively documented the changes in lower urinary tract symptoms from the first visit to a follow-up visit at 1 week using the Core Lower Urinary Tract Symptoms Score(CLSS)questionnaire.Results:After treatment,pyuria disappeared in 60 of the 66 patients(14 premenopausal and 46 postmenopausal).The CLSS total score(range)changed from 13(3-29)to 4(0-18)with a significant improvement in all CLSS items.At baseline,nocturia,urgency,and urgency incontinence were more prominent in postmenopausal women than in premenopausal women.In contrast,baseline urethral pain and quality of life index were more severe in premenopausal women than in postmenopausal women.After treatment,the CLSS total score was still higher in postmenopausal women,as reflected by the relatively higher scores for nocturia and urgency,irrespective of the comparable scores for urethral pain and the quality of life index in the 2 groups.Conclusions:Our results suggest that if storage symptoms persist,they should be carefully interpreted according to menopausal status.