The tumour/normal tissue ratio of Keap1 protein is a predictor for lymphovascular invasion in colorectal cancer: a correlation study between the Nrf2 and KRas pathways.

PURPOSE: Oxidative stress has impacts on the KRas and Nrf2/Keap1 pathways, which have multiple interactions with each other and play important roles in colorectal cancer (CRC). This study investigated the expressions of proteins in the KRas and Nrf2/Keap1 pathways and their associations with clinicopathological features in CRC. METHODS: The protein levels of Nrf2, Keap1, Bach1, p62, HO1, KRas, Erk, Raf1 and PI3K in both the tumour and normal tissues of 60 CRC subjects were determined by Western blot and their T/N (tumour/normal tissue) ratios were correlated with clinicopathological features. RESULTS: The T/N ratios of proteins in the KRas and Nrf2/Keap1 pathways had correlation patterns and proximity profiles in cluster dendrograms different in CRC with different status of lymphovascular invasion (LVI) or lymph node/distant metastases. The Keap1 protein T/N ratio was a significant predictor (odd ratio: 2.24; 95% confidence interval: 1.26 - 4.38) of LVI, which in turn predicted metastases (11.0; 3.49 - 39.8). CONCLUSION: The interactions between the KRas and Nrf2/Keap1 pathways may be affected differently by LVI and metastases, and the protein T/N ratio of Keap1 may be helpful for predicting LVI in CRC.

A rare epidermal growth factor receptor (EGFR) gene mutation in small cell lung carcinoma patients.

AIM: Activating mutations in the epidermal growth factor receptor (EGFR) are predominantly detected in pulmonary adenocarcinoma and have been reported in small cell lung cancer (SCLC) for decades. This retrospective single-center study aimed to determine the frequency and types of EGFR mutations in SCLC in Taiwan. METHODS: This study comprises a consecutive cohort of 161 patients histologically diagnosed with SCLC between January 1992 and August 2014 at the Department of Pathology in Keelung Chang Gung Memorial Hospital, Taiwan. Archived formalin-fixed paraffin-embedded sections from 71 patients were eligible for molecular analysis. EGFR mutation analysis was performed using a fully-automated IdyllaTM EGFR Mutation Test and confirmed a comparable result through Qiagen Therascreen® EGFR RGQ PCR. In addition, EGFR gene copy number was assessed in EGFR-mutated tumors by fluorescence in situ hybridization (FISH). RESULTS: Mutational status of the EGFR gene was successfully analyzed in 63 specimens by both IdyllaTM and Qiagen platforms. Both methods detected L858R point mutation in exon 21 in an 81-year-old female and a 47-year-old male non-smoker. Both tumors show no concurrent EGFR gene amplification. The overall agreement between results obtained with the Idylla™ EGFR Mutation Test and Qiagen Therascreen® EGFR RGQ PCR was 100% Conclusions. Our results showed that EGFR mutation is a rare mutation type in a consecutive series of de novo SCLC. Furthermore, the performance of Idylla™ EGFR Mutation Test and Qiagen Therascreen® EGFR RGQ PCR on archived paraffin sections of limited quantities is available with the high agreement of results.

Comparing the Expressions of Vitamin D Receptor, Cell Proliferation, and Apoptosis in Gastric Mucosa With Gastritis, Intestinal Metaplasia, or Adenocarcinoma Change.

Background: This study aimed to compare the expression of vitamin D receptor (VDR), cell proliferation, and apoptosis in the gastric mucosa of patients with gastritis, intestinal metaplasia (IM), and adenocarcinoma using artificial intelligence. Material and Methods: This study retrospectively enrolled patients at the Keelung Chang Gung Memorial Hospital from November of 2016 to June, 2017, who were diagnosed with gastric adenocarcinoma. The inclusion criteria were patients' pathologic reports that revealed all compartments of Helicobacter pylori infection, gastritis, IM, and adenocarcinoma simultaneously in the same gastric sample. Tissue slides after immunohistochemical (IHC) staining were transformed into digital images using a scanner and counted using computer software (QuPath and ImageJ). IHC staining included PA1-711 antibody for VDR, Ki67 antigen for proliferation, and M30 antibody CK18 for apoptosis. Results: Twenty-nine patients were included in the IHC staining quantitative analysis. The mean age was 69.1 ± 11.3 y/o. Most (25/29, 86.2%) patients had poorly differentiated adenocarcinoma. The mean expression of Ki67 and CK18 increased progressively from gastritis and IM to adenocarcinoma, with statistical significance (P < 0.05). VDR expression did not correlate with Ki67 or CK18 expression. Survival time was only correlated with tumor stage (correlation coefficient = -0.423, P value < 0.05), but was not correlated with the expression of VDR, Ki67, and CK18. Conclusion: Ki67 expression and CK18 expression progressively increased in the areas of gastritis, IM, and adenocarcinoma. No correlation between VDR expression and Ki67 or CK18 expression was found in this study.

The Application of High-Dose Proton Pump Inhibitor Induction Treatment before Dual Therapy for Helicobacter pylori Eradication: An Open-Label Random Trial.

This was a prospective, randomized, open-label trial. Patients without previous Helicobacter pylori eradication therapy were randomly assigned to either a high-dose dual therapy (HDDT) group or a traditional clarithromycin/amoxicillin triple therapy (CATT) group. In the HDDT group, patients took rabeprazole, 20 mg, four times per day for three days and then dual therapy with rabeprazole, 20 mg, and amoxicillin, 500 mg, four times per day during the patient's breakfast, lunch, dinner, and bedtime for 14 days. In the CATT group, patients received conventional triple therapy for 14 days (rabeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg twice per day). In the HDDT group, the success rates of H. pylori eradication were 91.7% (95% confidence interval (CI): 0.78-0.97) by intention-to-treat (ITT) and 94.3% (95% CI: 0.79-0.99) by per-protocol (PP) analysis. In the CATT group, the eradication rates were 77.1% (95% CI: 0.61-0.87) by ITT and 84.3% (95% CI: 0.66-0.94) by PP analysis. The study completion rates were 97.2% (35/36) in the HDDT group. Three-day high-dose rabeprazole induction treatment before dual therapy and a schedule of taking the drug at meal and bed times could achieve an acceptable H. pylori eradication rate (>90%) and good drug compliance.

The level of S-glutathionylated protein is a predictor for metastasis in colorectal cancer and correlated with those of Nrf2/Keap1 pathway.

INTRODUCTION: The Nrf2 (nuclear factor erythroid 2-like 2; NFE2L2)/Keap1 (Kelch-like ECH-associated protein 1) pathway and the TXN (thioredoxin)/GSH (glutathione) system interact mutually and regulate cellular redox with impacts on cancer metastasis and S-glutathionylation of protein, which is an indicator of cell distress. This study investigates the levels of proteins in the Nrf2/Keap1 pathway and the TXN/GSH system and SGP (S-glutathionylated protein) in CRC (colorectal cancer) with or without metastasis. MATERIALS AND METHODS: The protein levels of Nrf2, Keap1, Bach1 (BTB domain and CNC homolog 1), TXN, TXNRD1 (thioredoxin reductase 1), GSR (glutathione reductase) and SGP with molecular weight 31-172 kDa in the normal and tumour tissues of 64 CRC subjects were determined by Western blot. RESULTS: The protein levels and their T/N (tumour/normal tissue) ratios of the Nrf2/Keap1 pathway, the TXN/GSH system and SGP were correlated to different extents in the tissues of CRC subjects with or without lymph node/distant metastasis. The T/N ratios of SGP (odd ratio: 0.19; 95% CI: 0.04-0.74) and lympho-vascular invasion (4.2; 1.39-13.73) were significant predictors for metastasis. CONCLUSIONS: SGPs have protein levels correlated with those of the Nrf2/Keap1 pathway and their T/N ratios are a negative predictor for metastasis in CRC.

A Retrospective Cohort Study of Oral Leukoplakia in Female Patients-Analysis of Risk Factors Related to Treatment Outcomes.

BACKGROUND: The aim of this study was to make a comparison of clinicopathological characteristics of oral leukoplakia between male and female patients following carbon dioxide laser excision for oral leukoplakia and analyze the factors associated with the treatment outcomes in female patients. METHODS: Medical records of patients with oral leukoplakia receiving laser surgery from 2002 to 2020 were retrospectively reviewed and analyzed statistically. RESULTS: A total of 485 patients were enrolled, including 412 male (84.95%) and 73 female (15.05%). Regarding the locations, the predilection site of oral leukoplakia in male patients was buccal mucosa (p = 0.0001) and that for women patients was tongue (p = 0.033). The differences of recurrence and malignant transformation between both sexes were not significant (p > 0.05). Among female patients, area of oral leukoplakia was the risk factor related to recurrence (p < 0.05). Clinical morphology and postoperative recurrence were the risk factors related to malignant transformation (p < 0.05). CONCLUSIONS: In comparison with male patients, there was no significant difference of the postoperative recurrence and malignant transformation of oral leukoplakia in female patients. Among the female patients, clinicians should pay more attention to large-sized and non-homogeneous leukoplakia, and postoperative recurrent lesions.

An anatomical perspective on clinicopathological characteristics and treatment outcomes of dorsal and ventrolateral tongue leukoplakia after carbon dioxide laser surgery.

BACKGROUND: The tongue has been identified as a high-risk site for malignant transformation of oral leukoplakia. The purpose of this study was to investigate the clinicopathological characteristics and treatment outcomes of the dorsal and ventrolateral tongue leukoplakia. METHODS: Demographic data and pathological results of patients who underwent carbon dioxide laser surgery for tongue leukoplakia from 2002 to 2019 were retrospectively reviewed and analyzed statistically. RESULTS: Of the 111 patients enrolled, 80 were males and 31 females, with a mean age of 51.86 ± 11.84 years. The follow-up time was 3.74 ± 4.19 years. Fifteen patients had a postoperative recurrence (13.51%). Four (3.6%) patients developed malignant transformation. Annual transformation rate was 4.03%. There were no differences in the time to develop carcinoma (3.19 ± 1.94 vs. 3.51 ± 2.12 years, P = 0.83), overall cumulative malignant transformation rates (7.41% vs. 2.25%, P = 0.12), and annual transformation rates (2.32% vs. 0.64%, P = 0.099). The prevalence of the ventrolateral tongue leukoplakia was higher than that of the dorsal tongue leukoplakia (P < 0.001). The results of multivariate logistic regression analysis showed that the degree of pathology was the only independent prognostic factor related to postoperative malignant transformation (P = 0.045). CONCLUSIONS: Dorsal tongue leukoplakia is not as frequently encountered clinically as ventrolateral tongue leukoplakia. The response of the dorsal tongue and ventrolateral tongue leukoplakia to laser therapy of are comparable in postoperative recurrence and postoperative malignant transformation. Clinicians should take a more aggressive attitude toward oral tongue leukoplakia with higher grade of dysplasia.

Oral tongue leukoplakia: analysis of clinicopathological characteristics, treatment outcomes, and factors related to recurrence and malignant transformation.

OBJECTIVES: The tongue is identified as a high-risk site for oral leukoplakia and malignant transformation. The purpose of this study is to investigate the clinicopathological characteristics and treatment outcomes of tongue leukoplakia and assess the factors related to recurrence and malignant transformation. MATERIALS AND METHODS: One hundred and forty-four patients who received carbon dioxide laser surgery for tongue leukoplakia from 2002 to 2019 were analyzed statistically. RESULTS: The follow-up period was 54.90 ± 54.41 months. Thirty patients showed postoperative recurrence (20.83%), and 12 patients developed malignant transformation (8.33%). The annual transformation rate was 2.28%. Univariate analysis showed that a history of head and neck cancer, size of lesion area, clinical appearance, and pathology were significant factors for both recurrence and malignant transformation. In the multivariate logistic regression, a history of head and neck cancer and size of lesion area were independent prognostic factors for recurrence, and a history of head and neck cancer was the only independent factor for postoperative malignant change. CONCLUSIONS: Clinicians should adopt more aggressive strategies for tongue leukoplakia patients with a history of head and neck cancer. CLINICAL RELEVANCE: These results may help clinicians gain a better understanding of oral tongue leukoplakia.

Clincopathological characteristics and treatment outcomes of oral leukoplakia by carbon dioxide laser excision in the elderly patients.

BACKGROUND: Older age is one of the factors associated with malignant transformation of oral leukoplakia (OL). The purpose of this study is to analyze the clincopathological features and treatment outcomes of OL in the elderly patients. METHODS: The demographic data and histopathological results of the patients (age ≥ 65) who received carbon dioxide laser surgery for OL from 2002 to 2017 were analyzed statistically. RESULTS: There were 53 males and 16 females, with a mean age 71.2 ± 4.9. The follow-up time was 42.5 ± 35.2 months. In the univariate analysis, morphology, pathology, and area were found to be factors associated with postoperative recurrence. Among these factors, pathology and area were the independent predictive factors for recurrence in the multivariate logistic regression model. Malignant transformation occurred in 8 of 69 patients (11.6%). CONCLUSIONS: The pathological high-risk dysplasia and area of OL were the two prognostic factors for postoperative recurrence.

Associations between the Nrf2/Keap1 pathway and mitochondrial functions in colorectal cancer are affected by metastasis.

BACKGROUND: Both mitochondria and the Nrf2/Keap1 pathway are targets of cancer therapy. Reactive oxygen species released from mitochondria can activate Nrf2, and the Nrf2/Keap1 pathway affects glycolysis, oxidative phosphorylation, mitochondrial biogenesis and mitophagy. OBJECTIVE: This study investigates the associations between the expressions of proteins in the Nrf2/Keap1 pathway and those related to mitochondrial function and glycolysis in colorectal cancer (CRC) with or without metastasis. METHODS: The protein levels of HO1, Nrf2, Keap1, Bach1, p21, p62, NRF1, LC3, ATP5B, HSP60 and GAPDH in the normal and tumor tissues of 60 CRC subjects were determined by Western blot. RESULTS: The Keap1 protein levels, the ATP5B/HSP60 ratio and the BEC index were higher in the tumor than in the normal tissues of CRC with or without metastasis. The following clusters were found in the dendrogram: Nrf2 and p21 with ATP5B and GADPH in all the tissues and with NRF1 in all except the tumor tissues with metastasis; Bach1 with ATP5B and GAPDH in the tumor tissues; Keap1 with p62 in all the tissues, with LC3 in the tumor tissues and with NRF1 and HO1 in the tumor tissues with metastasis. CONCLUSIONS: Nrf2, Keap1, Bach1 and p21 have the association with the proteins related to mitochondrial functions different among the tissues of CRC with or without metastasis.

N-acetylgalactosamine-6-sulfatase (GALNS), Similar to Glycodelin, Is a Potential General Biomarker for Multiple Malignancies.

BACKGROUND/AIM: The aim of this study was to evaluate N-acetylgalactosamine-6-sulfatase (GALNS) as a new biomarker candidate for detecting lung cancer. Glycodelin or PAEP, the serum levels of which are known to be elevated in lung and other cancers, served as a benchmark for comparison. PATIENTS AND METHODS: A total of 170 serum samples from healthy controls and patients with pneumonia, lung cancer, breast cancer, colon cancer, liver cancer, and head and neck cancer were analyzed for the levels of GALNS and PAEP by ELISA. RESULTS: The median serum levels of GALNS and PAEP in all cancer types as well as pneumonia patients were significantly higher than those of the healthy controls. CONCLUSION: In addition to previously known cancers, the median serum levels of PAEP were also found to be higher in liver and head and neck cancer patients. GALNS and PAEP are promising general biomarkers for multiple cancers and deserve further evaluation.

The Protein Expression of PDL1 Is Highly Correlated with Those of eIF2α and ATF4 in Lung Cancer.

INTRODUCTION: The expression of programmed death 1 (PD1) and programmed death ligand 1 (PDL1) can be induced by the interferon (IFN)/signal transducer and activator of transcription (STAT) pathway. The PD1/PDL1 reverse signaling can activate the eukaryotic translation initiation factor 2 (eIF2α)/activating transcription factor 4 (ATF4) pathway which in turn regulates the expression of IFN regulatory factor (IRF) 7 and IFNα. The eIF2α/ATF4 pathway is responsible for the integrated stress response (ISR) of unfolded protein response (UPR) which can affect immune cell function in tumor microenvironment. MATERIALS AND METHODS: The protein levels of PDL1, IRF1, IRF7, STAT1, STAT2, IFNAR1, eIF2α, and ATF4 in the normal and tumor tissues of 27 subjects with lung cancer were determined by Western blot. RESULTS: The protein level of PDL1 was significantly correlated with those of IRF1, eIF2α, and ATF4 in the tissues of all subjects and the subgroup of squamous cell carcinoma but not in the normal tissue of adenocarcinoma. The protein levels of IRF1, eIF2α, and ATF4 were consistently correlated in the tumor tissues but to various extents in the normal ones. The protein level of PDL1 was not correlated with those of STAT1 and STAT2 in all the tissues. CONCLUSION: The PDL1 expression in lung cancer may be independent of STAT1 and STAT2. The PD1/PDL1 axis and UPR/ISR may be closely associated in the tumor tissues of lung cancer.

Simple score to predict risk of hepatocellular carcinoma in chronic hepatitis C patients with advanced fibrosis after pegylated interferon and ribavirin therapy.

PURPOSE: Eradication of chronic hepatitis C virus (HCV) after interferon-based therapy and its association with the reduction of risk of hepatocellular carcinoma (HCC) in HCV-infected patients with advanced fibrosis is controversial. The study is aimed to develop a simple scoring model for HCC prediction among advanced fibrotic chronic hepatitis C (CHC) patients after pegylated interferon (pegIFN) and ribavirin (RBV) therapy. PATIENTS AND METHODS: We enrolled 271 biopsy-proven CHC patients with advanced fibrosis between 2003 and 2016, and divided them into non-HCC (n=211) and HCC (n=60) groups. The median observation duration was 6.0 years (range: 0.9-12.6 years). RESULTS: The HCC prevalence after pegIFN and RBV therapy in CHC patients with sustained virologic response (SVR) and without SVR was 14.7% and 32.2%, respectively. Multivariate Cox regression showed age ≥59.5 years old at initiation of therapy (HR: 2.542, 95% CI: 1.390-4.650, P=0.002), pretreatment total bilirubin ≥1.1 mg/dL (HR: 2.630, 95% CI: 1.420-4.871, P=0.002), pretreatment platelet counts <146.5 × 103/µL (HR: 2.751, 95% CI: 1.373-5.511, P=0.004), no achievement of SVR (HR: 2.331, 95% CI: 1.277-4.253, P=0.006), and no diabetes at treatment initiation (HR: 3.085, 95% CI: 1.283-7.418, P=0.012) were significant predictors of HCC development. The scoring model consisted of the five categorical predictors and had an optimal cutoff point of 2.5. The area under receiver operating characteristic (AUROC) of the scoring model was 0.774±0.035 (P<0.001). The sensitivity and specificity of the cutoff value to detect HCC were 81.3% and 57.5%. The 5-year and 10-year cumulative incidence of HCC was 4.9% and 10.0% in patients with simple score ≤2; and 25.9% and 44.6% in patients with simple score ≥3 (P<0.001). CONCLUSION: The simple clinical-guided score has high discriminatory power for HCC prediction in advanced fibrotic CHC patients after pegIFN and RBV therapy.

The ratio of thioredoxin/Keap1 protein level is a predictor of distant metastasis in colorectal cancer.

AIM: Thioredoxin can reduce the cysteine group of Keap1 which could induce proteasome degradation of Nrf2, PGAM5 and Bcl-xL. Nrf2 regulates redox balance and Bcl-xL is anti-apoptotic and both are important in tumor progression. METHODS: The protein levels of Keap1, thioredoxin, PGAM5 and Bcl-xL in the normal and tumor tissues of 64 subjects with colorectal cancer (CRC) were determined by western blot. RESULTS: The tumor had higher Keap1 but lower PGAM5s and Bcl-xL protein expression than the normal tissue. The ratio of thioredoxin/Keap1 protein level in the normal (OR: 0.12; 95% CI: 0.02-0.83) or tumor tissue (OR: 0.17; 95% CI: 0.03-0.89) was a negative predictor for distant metastasis in CRC. CONCLUSION: Keap1-mediated degradation of PGAM5 and Bcl-xL may be active in CRC. The ratio of thioredoxin/Keap1 protein level may be useful for suggesting distant metastasis in CRC.

Amplification of HER2 and TOP2A and deletion of TOP2A genes in a series of Taiwanese breast cancer.

BACKGROUND: The prognostic relevance of topoisomerase II alpha (TOP2A) copy number change remains not well established. This study is aimed to investigate the frequency and pattern of TOP2A aberrations; to correlate TOP2A alterations with human epidermal growth factor receptor 2 (HER2) status and clinicopathological parameters, and further to explore prognostic value of TOP2A and HER2 status in breast cancer in Taiwan. METHODS: We analyzed tissue samples from 311 invasive carcinomas in tissue microarrays for TOP2A and HER2 status by fluorescent in situ hybridization. RESULTS: TOP2A copy number change is an infrequent genetic event (9.8% amplification and 2.7% deletion) and is present in both HER2-amplified and nonamplified tumors. TOP2A amplification is statistically associated with age >50 at diagnosis (P = 0.016) and HER2 amplification (P < 0.001). HER2 amplification, but not TOP2A amplification, is a predictor of unfavorable prognosis (P = 0.002). Univariate and multivariate analysis showed that higher histologic grading, positive nodal involvement, and HER2 positivity were associated with poorer overall survival. Cytogenetically, double minutes-type amplification is the predominant pattern for both genes (HER2: 64% and TOP2A: 93.1%). Homogeneous staining region-type signals of both genes are resistant to RNase digestion, supporting that these were not nuclear accumulation of mRNA transcripts. CONCLUSION: Our results demonstrate the prognostic value of tumor grading, nodal involvement, and HER2 status in Taiwanese breast cancer. TOP2A aberrations are an infrequent event independent of HER2 status, and TOP2A amplification carries no prognostic value. The predictive value of TOP2A aberrations in patients of breast cancer taking athracycline-containing treatment in Taiwan remains to be determined in prospectively well-designed clinical trials.

Analyzing the influence of gastric intestinal metaplasia on gastric ulcer healing in Helicobacter pylori-infected patients without atrophic gastritis.

BACKGROUND: Gastric epithelial hyper-proliferation was reported in patients with Helicobacter pylori (H. pylori)-infected gastric mucosa with intestinal metaplasia (IM) changes. In patients with gastric ulcer (GU) and IM, the GU may have a different healing rate in comparison to patients without IM. This study aimed to compare the difference in GU healing between H. pylori-infected patients with IM and those without IM. METHODS: We retrospectively analyzed patients at the Keelung Chung Gung Memorial Hospital during the period from March 2005 to January 2011. The inclusion criteria were: 1) endoscopic findings of GU and biopsy histological examination plus rapid urease test indicating H. pylori infection; 2) gastric IM adjacent to a GU but with no atrophic gastritis changes; 3) patients receiving H. pylori eradication triple therapy and 8 weeks of maintenance therapy with a proton pump inhibitor; and 4) patients receiving follow-up endoscopy within the 3rd and the 4th months after treatment. RESULTS: In total, 327 patients with GU and H. pylori infection (136 with IM and 191 without IM) were included. Patients with IM had a higher GU healing rate than those without IM (91.9% vs. 84.3%, P = 0.040). Multivariate logistical regression analysis revealed that failure of H. pylori eradication (Odds = 4.013, 95% CI: 1.840-8.951, P < 0.001) and gastric IM (Odds = 0.369, 95% CI: 0.168-0.812, P = 0.013) were the predictors of non-healing GU following treatment. CONCLUSIONS: Patient with gastric IM change may have a higher GU healing rate than those without gastric IM. However, successful H. pylori eradication is a more important factor for GU healing than gastric IM.

Treatment outcome of vocal cord leukoplakia by transoral laser microsurgery.

The aim of this study is to evaluate the treatment outcome and analyze the associated factors of postoperative recurrence in patients who received transoral laser microsurgery for vocal cord leukoplakia. The demographic, histopathological data were retrospectively reviewed and the factors associated with recurrence of vocal leukoplakia after surgery were analyzed statistically. A total of 44 patients, including 36 males and 8 females, with a mean age of 50.4 ± 13.4 years, were enrolled. All the patients received excision of the vocal leukoplakia by carbon dioxide laser (2-4 Watt, ultrapulse mode) under general anesthesia. No patients had malignant transformation after surgery. Postoperative recurrence occurred in 10 patients (22.7 %). Univariate analysis showed that patients who had the habit of cigarette smoking, alcohol drinking, and presence of gastroesophageal reflux disease tended to recur. Among these risk factors, presence of gastroesophageal reflux disease (odds ratio 8.43) was the independent prognostic factor for recurrence using multivariate logistic regression analysis. Carbon dioxide laser excision is effective for treating vocal leukoplakia that is still confined to dysplasia of any degree, with acceptable morbidity. This study suggests that the presence of gastroesophageal reflux disease is the prognostic indicator for postoperative recurrence of vocal leukoplakia. Aggressive treatment of reflux disease for those who have received surgical excision for vocal leukoplakia is indicated.

The Ratio of Hmox1/Nrf2 mRNA Level in the Tumor Tissue Is a Predictor of Distant Metastasis in Colorectal Cancer.

Heme oxygenase 1 (Hmox1) plays an important role in the growth and spread of tumor, and its expression is regulated positively by Nrf2 [nuclear factor (erythroid-derived 2)-like 2; NFE2L2] and negatively by kelch-like ECH-associated protein 1 (Keap1) and by BTB and CNC homology 1 (Bach1). Both Hmox1 and Nrf2 contribute to distant metastasis of cancer. The mRNA levels of Hmox1, Nrf2, Keap1, and Bach1 in the tumor and normal tissues of 84 subjects with colorectal cancer (CRC) were determined by real-time polymerase chain reaction. The tumor had lower Hmox1 but higher Bach1 mRNA levels than the normal tissue. The correlations of Hmox1 with components of the Nrf2 pathway were not significant in the tumor tissue of CRC subjects with distant metastasis. The ratio of Hmox1/Nrf2 mRNA level (by percentage) in the tumor tissue was lower in the subjects with distant metastasis (97.4% (84.4-111.1%)) than in those without (101.0% (92.7-136.5%)) and was a predictor for distant metastasis in CRC (odds ratio: 0.83; 95% confidence interval: 0.68-0.97) along with serum carcinoembryonic antigen (1.0027, 1.006-1.064). The mRNA level of Hmox1 in the tumor tissue of CRC is not correlated with that of the Nrf2 pathway molecules, and its ratio to the Nrf2 level may be useful for suggesting distant metastasis in CRC.

The Associations Between Helicobacter pylori Infection, Serum Vitamin D, and Metabolic Syndrome: A Community-Based Study.

The associations between Helicobacter pylori infection, serum vitamin D level, and metabolic syndrome (MS) are controversial. The present community-based study aimed to investigate the effect of H pylori infection and serum vitamin D deficiency on MS development.Individuals from the northeastern region of Taiwan were enrolled in a community-based study from March, 2014 to August, 2015. All participants completed a demographic survey and underwent the urea breath test (UBT) to detect H pylori infection as well as blood tests to determine levels of vitamin D, adiponectin, leptin, and high-sensitivity C-reactive protein. The ATP III criteria for MS were used in this study.A total of 792 men and 1321 women were enrolled. The mean age was 56.4 ±â€Š13.0 years. After adjusting for age and sex, the estimated odds of MS development for a UBT-positive subject were 1.503 (95% confidence interval [CI]: 1.206-1.872, P < 0.001) when compared to a UBT-negative subject. For participants with vitamin D deficiency (<20 ng/mL), the odds of MS development were 1.423 (95% CI: 1.029-1.967, P = 0.033) when compared to those with sufficient vitamin D level (>30 ng/mL). For participants with both H pylori infection and vitamin D deficiency, the odds of MS development were 2.140 (95% CI: 1.348-3.398, P = 0.001) when compared to subjects without H pylori infection and with sufficient vitamin D levels.H pylori infection and vitamin D deficiency could be predictors of MS. For individuals with both H pylori infection and vitamin D deficiency, the odds of MS development were 2.140 when compared to individuals without H pylori infection and with sufficient vitamin D levels.