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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 tumor tissues of 64 CRC subjects were determined by Western blot. Results The protein levels and their T/N (tumor/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.

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.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.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).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.

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 1.08%. 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 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.

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.

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 (&gt, 90%) and good drug compliance.

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 &gt, 0.05). Among female patients, area of oral leukoplakia was the risk factor related to recurrence (p &lt, 0.05). Clinical morphology and postoperative recurrence were the risk factors related to malignant transformation (p &lt, 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.

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.

Background Among the risks of malignant transformation of oral leukoplakia, tongue has been identified as a high-risk site. Only little information exists on the clinicopathological characteristics and treatment outcomes specific to leukoplakia of the dorsum of the tongue. The comparison of clinicopathological characteristics of the dorsal tongue and ventrolateral tongue leukoplakia is not available in the literature. The purpose of this study is to investigate the clinicopathological characteristics and treatment outcomes between dorsal and ventrolateral tongue leukoplakia. Methods The demographic data and pathological results of the patients who received carbon dioxide laser surgery for tongue leukoplakia from 2002 to 2019 were retrospectively reviewed and analyzed statistically. Results Of 144 enrolled, there were 108 males and 36 females with a mean age 52.17 ± 11.72. The follow-up time was 4.58 ± 4.53 years. Thirty patients had postoperative recurrence (20.83%). Twelve patients developed malignant transformation (8.33%). Annual transformation rate was 2.28%. In comparison of dorsal and ventrolateral tongue leukoplakia, there were no differences in the time to the development of carcinoma (2.62 ± 1.69 VS 3.98 ± 2.77 years), overall cumulative malignant transformation rates (7.50% VS 7.69%), and annual transformation rates (2.86% VS 1.93%). The prevalence of ventrolateral tongue leukoplakia is higher than the dorsal tongue leukoplakia (P

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.

Ching-Chih Hu,1,2 Cheng-Hao Weng,2,3 Liang-Che Chang,4 Chih-Lang Lin,1,2 Yen-Ting Chen,1 Ching-Fang Hu,5 Man-Chin Hua,2,6 Li-Wei Chen,1 Rong-Nan Chien2,7 1Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Keelung, Taiwan; 2College of Medicine, Chang Gung University, Linkou, Taiwan; 3Department of Nephrology and Poison Center, Chang Gung Memorial Hospital, Linkou, Taiwan; 4Department of Pathology, Chang Gung Memorial Hospital, Keelung, Taiwan; 5Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Keelung, Taiwan; 6Department of Pediatrics, Chang Gung Memorial Hospital, Keelung, Taiwan; 7Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Linkou, Taiwan 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

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.

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.

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.

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.

Supplemental Digital Content is available in the text, 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

Immunohistochemical expression of ERα, encoded by the ESR1 (estrogen receptor 1) gene located at 6q25.1, is the most important determinant of responsiveness to endocrine therapy in breast cancer. The prevalence and significance of ESR1 amplification in breast cancer remain controversial. We set out to assess ESR1 status and its relevance in breast cancer in Taiwan. We tested tissue samples from 311 invasive carcinomas in a tissue microarray for ESR1 status by fluorescent in situ hybridization (FISH) and chromogenic in situ hybridization (CISH). In order to examine its association with ERα and ESR1 status, HER2 status was determined by FISH. Of the carcinomas, 58.8 % (183/311) was ERα positive. None of the carcinomas showed amplification of ESR1 by either method, whereas 24.1 % (75/311) of the carcinomas harbored HER2 amplification. Of the carcinomas, 9.6 % (26/301) showed ESR1 gain (1.3 ≤ ratio ESR1/chromosome 6 < 2) by FISH and 10 % (24/299) by CISH. FISH and CISH results showed a good correlation (κ-coefficient = 0.786). ESR1 gain by FISH and CISH was significantly associated with high-grade (P = 0.0294 and 0.0417, respectively) but not with ERα expression, HER2 status, or overall survival. ERα positivity was significantly associated with better overall survival (P = 0.039). HER2 amplification was significantly related with poor overall survival (P = 0.002). Our data confirm that in breast cancer, HER2 amplification is a frequent genetic aberration and a negative prognostic factor, and show that ESR1 amplification is not a key genetic abnormality in the tumorigenesis of breast cancer in Taiwan.

Oxidative stress is a contributing factor in the carcinogenesis of colorectal cancer. The Nrf2 [nuclear factor (erythroid-derived 2)-like 2; NFE2L2] pathway is one of the major cellular defense mechanisms against oxidative stress. This study investigated the expression of the Nrf2 pathway in colorectal cancer. Formalin-fixed paraffin-embedded tissue arrays consisting of the tumor, adjacent normal, and distant normal tissues from the resected specimens of 83 colorectal cancer patients were subjected to immunohistochemical (IHC) staining with antibodies against Nrf2, kelch-like ECH-associated protein 1 (Keap1), p21, P62, Parkinson protein 7 (Park7), prohibitin, BTB and CNC homology 1 (Bach1), CD34 and 8-hydroxy-2'-deoxyguanosine (8-OHdG). The mean IHC density of each IHC staining was digitally analyzed. The results showed that molecules of the Nrf2 pathway were actively expressed, with different expression profiles among the tumor and normal tissues. The oxidative stress, represented by the mean IHC staining density of 8-OHdG, did not differ but was correlated with the expressions of different Nrf2 pathway molecules to a varied extent in tumor and normal tissues of colorectal cancer. Keap1 [estimate, 0.49; 95% confidence interval (CI), 0.19-0.79] and Bach1 (estimate, 0.24; 95% CI, 0.11-0.38) were significant predictors for the expression of 8-OHdG and had the closest proximity to Nrf2 in the cluster dendrogram of the tumor and distant normal tissues, respectively. Advanced stage (estimate, 14.9; 95% CI, 2.99-26.8) and current smoker (estimate, 15.6; 95% CI, 1.92-29.3) were significant predictors with high estimates for Bach1 in the adjacent and distant normal tissues, respectively. In colorectal cancer, the molecules of the Nrf2 pathway have different expression profiles and a difference in their importance, especially Keap1 and Bach1, related to Nrf2 and oxidative stress among tumor and normal tissues.

This study seeks to analyze the factors associated with the occurrence of squamous cell carcinoma in oral non-healing ulcers for more than 3 weeks and investigate the role of endoscopy with narrow-band imaging system (NBI) in detecting carcinoma in these lesions.The demographic and clinicopathological data of patients receiving surgical interventions for chronic oral non-healing ulcers, and the intraepithelial papillary capillary loop patterns shown by NBI were retrospectively reviewed and analyzed.A total of 63 patients (41 males and 22 females) with mean age of 57.9 ± 16.7 years were enrolled. In univariate analysis, ulcers with induration, history of oral cancer, and intraepithelial microvasculature of NBI were factors associated with the occurrence of squamous cell carcinoma in oral non-healing ulcers. Multivariate analysis showed that the intraepithelial microvasculature of NBI was the only independent factor predicting the occurrence of carcinoma in oral chronic non-healing ulcers with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 93.75 %, 91.49 %, 78.95 %, 97.73 %, and 92.06 %, respectively.Morphology of intraepithelial microvasculature of NBI, or twisted, elongated, and destructive pattern of intraepithelial papillary capillary loop, is the only independent factor associated with the occurrence of squamous cell carcinoma in oral chronic non-healing ulcers. Endoscope with NBI is a rapid, safe, and promising tool in detecting squamous cell carcinoma in oral chronic non-healing ulcers.

This study aimed to investigate the clinical efficacy of using broadband white light (BWL) to observe morphologic appearance, narrow-band imaging (NBI) to observe intraepithelial microvasculature, and both BWL and NBI for the detection of high-grade dysplasia and carcinoma in oral leukoplakia. Among 317 patients (274 males and 43 females; aged 52.4±10.7 years), the odds ratio (95% confidence interval) for detecting high-grade dysplasia and carcinomatous lesions based on morphologic appearances of BWL, and microvasculature patterns of NBI, were 39.12 (9.33–64.10), and 97.16 (38.19–247.21), respectively, which were significantly better than BWL ( p −15 ). The sensitivity, specificity, positive and negative predictive values, and accuracy of use of traditional BWL classification, NBI classification, and combined BWL and NBI classification for detecting high-grade dysplasia and carcinomatous lesions were 96.30, 60.08, 33.12, 98.75, 66.25, 39.92, and 3.70%; 87.04, 93.54, 73.44, 97.23, and 92.43%; and 100.00, 60.08, 33.96, 100.00, and 66.88%, respectively. In conclusion, the diagnostic accuracy by NBI classification of oral leukoplakia based on the intraepithelial microvasculature patterns is significantly better than BWL indicating that NBI is a promising non-invasive tool in detecting high-grade dysplasia and carcinomatous lesions in oral leukoplakia.

To investigate the intraepithelial microvascular morphology of oral squamous cell carcinoma (OSCC) by using narrow-band imaging (NBI) and analyze whether the intraepithelial papillary capillary loop (IPCL) patterns correlate with infiltration depth and disease severity in OSCC.The clinicopathologic data, morphology of vascular architecture as observed by NBI, and histopathology of patients with OSCC were retrospectively reviewed and analyzed.A total of 80 patients, including 73 males and 7 females with an average age of 54.18±12.23 years, were enrolled. Three patterns of intraepithelial microvasculature were revealed by NBI and differences in these three patterns were significant with regard to pathologic T-classification (p0.0001), N-classification (p=0.00022), TNM stage (p0.0001), lymphovascular invasion (p0.0001), perineural invasion (p=0.000299), depth of tumor infiltration (p0.0001), and tumor differentiation (p0.0001). A cut-off point of tumor infiltration of 10.012 mm was best predicted for the destructive pattern of IPCL (sensitivity=100%, specificity=90.0%).Three different patterns of IPCL, showing step-wise increased severity according to pathologic parameters, were observed by NBI in cases of OSCC. The pattern indicating IPCL destruction with angiogenesis was associated with more advanced disease stage.

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.

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

Objectives/Hypothesis: To investigate the diagnostic accuracy of the established patterns of intraepithelial microvasculature of narrow-band imaging (NBI) in diagnosing upper aerodigestive tract neoplasm of the squamous epithelium for detecting high-grade dysplasia, carcinoma in situ, and carcinoma in oral leukoplakia. Study Design: Retrospective case-control study. Methods: Using histopathological findings as the standard, clinical diagnosis of oral leukoplakia and 3 different but established NBI criteria were compared and evaluated statistically. Results: A total of 414 patients, including 365 males and 49 females, with mean age of 52.15 ± 10.75 years, were enrolled. The odds ratio of detecting high-grade dysplasia and carcinomatous lesions by twisted elongation of intraepithelial papillary capillary loop (IPCL) and IPCL pattern destruction was 95.53 (confidence interval 95%: 42.19–216.29), and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 84.62%, 94.56%, 74.32%, 97.06%, and 93.0%, respectively, which were significantly better than the other two established NBI criteria (p < 0.001). Conclusions: The NBI images of twisted elongation of IPCL and IPCL pattern destruction are indicators of high-grade dysplasia or carcinomatous lesions in oral leukoplakia.

A 54-year-old male was admitted because of having suffered from progressive watery diarrhea for 12 days. He had no history of diabetes mellitus, hypertension, heart disease, organ transplantation, or malignancy. After admission, he still complained of diarrhea despite medical treatment. The laboratory examination showed leukocytosis with eosinophilia and a stool examination by the concentration method was negative four times. When a sigmoidoscopy was performed as a part of an explorative survey, a single protruding mass consisting if a moving adult hookworm was found. The fifth stool examination by the concentration method identified hookworm ova. The patient was treated with oral mebendazole 100 mg twice a day for 3 days. The diarrhea and eosinophilia subsided after this treatment.

Hwang C-C, Pintye M, Chang L-C, Chen H-Y, Yeh K-Y, Chein H-P, Lee N & Chen J-R (2011) Histopathology59, 984–992 Dual-colour chromogenic in-situ hybridization is a potential alternative to fluorescence in-situ hybridization in HER2 testing Aim: Dual-colour chromogenic in-situ hybridization (dc-CISH) is an emerging methodology for characterizing genomic alterations. This study was aimed at evaluating the performance of a dc-CISH kit (ZytoVision) in determining human epidermal growth factor receptor 2 (HER2) status in breast cancer. Methods and results: Two hundred and twenty-eight invasive breast carcinomas arranged in tissue microarrays were analysed in parallel with dc-CISH, fluorescence in-situ hybridization (FISH), and immunohistochemistry. Of 227 tumours with available FISH and dc-CISH results, HER2 amplification and non-amplification were detected in 49 (21.6%) and 178 (78.4%) tumours, respectively, by both assays. The concordance between dc-CISH and FISH results showed 100% agreement (κ-coefficient = 1.00). Immunohistochemically, 162 (71%), 25 (11.0%) and 41 (18%) tumours were scored 0/1+, 2+, and 3+, respectively. The corresponding results with both FISH and dc-CISH demonstrated HER2 amplification in two (3.2%), nine (36%) and 38 (93%) tumours, respectively. Complete consensus among these three methods was observed in 197 cases, representing 98% of all 3+ and 0/1+ tumours (κ-coefficient = 0.92). Confirmatory testing of 25 2+ tumours showed complete consensus between FISH and dc-CISH. Conclusions: dc-CISH is a promising alternative to FISH in HER2 testing, and the single-institute incidence of HER2 amplification in breast cancer in Taiwan is 21.2%.

Summary Background/Aims: Simple compound of Helicobacter pylori eradication therapy may improve drug compliance of patients. The aims of this study were to compare the efficacy and tolerability of a simple combination containing levofloxacin 7-day once-daily with standard twice-daily triple therapy. Patients and Methods: This was a prospective, randomised, open-label trial. A total of 189 consecutive patients diagnosed with peptic ulcer and H. pylori infection were enrolled. Patients were randomly divided into two groups: LEC group – levofloxacin 500 mg, esomeprazole 40 mg and clarithromycin 500 mg once daily for 7 days; AEC group – amoxicillin 1 g, esomeprazole 40mg and clarithromycin 500 mg twice daily for 7 days. Results: There were 90 patients in the LEC group and 99 patients in the AEC group. By intention-to-treat and per-protocol analysis, the H. pylori eradication rate was 78.9% [71/90; 95% confidence interval (CI), 70.3–87.5%] and 83.5% (71/85; 95% CI, 75.5–91.6%) respectively, in the LEC group; and 74.8% (74/99; 95% CI, 66.0–83.5%) and 86.0% (74/86; 95% CI, 78.6–93.5%) respectively, in the AEC group. The incidence and tolerability of side effects were similar between these two groups. Conclusion: The efficacy and tolerability of once-daily levofloxacin-containing triple therapy are equal to those of the standard twice-daily triple therapy in this study. However, none of the treatment regimens evaluated achieved enough eradication efficacies to be considered as a recommendable first-line treatment.

Endometriosis is a common disease, but ureteral involvement is rare. The symptoms and signs of ureteral endometriosis mimic those of ureteral malignancy. This case report describes a woman who presented with chronic back pain for 5 years. Imaging studies showed a right small contracted kidney with hydronephrosis and a bladder tumor. Endometriosis of the right lower ureter was ultimately diagnosed. The patient was healthy without recurrence during follow-up. It is difficult to differentiate between ureteral endometriosis and malignancy; in fact, renal loss may occur before diagnosis. Ureteral endometriosis should be considered for women with ureteral obstruction manifesting as chronic backache.

Background and objective: Binding of Toll-like receptors (TLRs) to microbial or endogenous ligands activates and triggers the associated signalling pathway, which leads to the production of inflammatory cytokines and type I interferons. The extent of TLR pathway activation may vary with the ligands present in different pleural diseases. Methods: The relative mRNA expression levels of TLRs and their adaptors in pleural fluid were determined by PCR and gel electrophoresis in 36 transudative, 25 infectious and 39 malignant pleural effusions. Results: The relative mRNA expression levels of TLR8 and myeloid differentiation factor 88 were low in infectious effusions and that of ras-related C3 botulinum toxin substrate 1 was low in malignant pleural effusions. Different cellular components correlated significantly with the relative mRNA expression of TLRs or their adaptors in pleural effusions with different aetiologies. Conclusions: The relative mRNA expression profiles of TLRs and their adaptors in pleural fluid differ among transudative, infectious and malignant pleural effusions.

Background and objective: Cancer cells are larger in size and more rigid than blood cells. As the size and rigidity of cells contribute to blood viscosity, an association may exist between high pleural fluid viscosity and cancer cells in pleural effusions. The aim of this study was to determine the correlation between pleural fluid viscosity and cell constituents or laboratory data in pleural diseases with different aetiologies. Methods: Fluid viscosities were determined in pleural effusions obtained via thoracocentesis. Pleural fluid viscosities were correlated with the laboratory data and with the percentages of different cellular constituents as assessed by cytological examination. Results: Pleural fluid viscosity was highest in malignant pleural effusions with positive results on cytological examination, and was correlated with the percentages of tumour cells (Spearman's rho = 0.24, P = 0.037) and mitotic figures (rho = 0.23, P = 0.041) in the exudates. Multivariate logistic regression analysis showed that pleural fluid viscosity was a significant determinant of positive results on cytological examination (odds ratio (OR) 6.26, 95% confidence interval (CI) 1.32–29.8), as were the levels of protein (OR 1.48, 95% CI 1.01–2.16) and LDH (OR 1.001, 95% CI 1–1.002). Conclusion: High pleural fluid viscosity may suggest a potential diagnosis of malignant pleural effusion.

Hepatitis C virus (HCV) and hepatitis B virus (HBV) share similar transmission routes, but concurrent acute HCV and HBV infection was rarely reported. Little is known about viral interaction and hepatic biochemical features of acute HBV and HCV coinfection. We report an intravenous drug abuser with simultaneous acute HBV and HCV infections presenting as biphasic elevation of both alanine aminotransferase (ALT) and total bilirubin levels. HCV infection is the major cause of continuing hepatitis after termination of HBsAg antigenemia.

Background The role of single nucleotide polymorphisms (SNPs) of interleukin (IL)-28B in predicting therapeutic response of pegylated interferon (peg-IFN) plus ribavirin (PR) for genotype 1 infected chronic hepatitis C patients with advanced fibrosis (AF) is limited. The aim of this study is to assess its role in predicting sustained virologic responses (SVR) to treatment. Methods Forty-two patients with biopsy proven hepatitis C virus (HCV) related AF (group A; Ishak fibrosis score, ≥4) and 126 sex- and HCV genotype-matched patients without AF (group B; Ishak fibrosis score, ≤3) were recruited into study. All patients received PR therapy for 24 weeks. Baseline and on-treatment clinical, virological and host factors were evaluated for treatment efficacy. Results The SVR rate was significantly lower in group A than group B patients with genotype 1 infection (24% vs. 53.3%; p = 0.011). However, it was similar in those with genotype non-1 infection (76.5% vs. 76.5%; p = 1.0). IL-28B rs8099917 genotype TT is the strongest predictor for SVR in genotype 1 infection. Patients who had TT genotype and achieved RVR in group A had similar SVR rates with those in group B (44.4% vs. 53.3%; p = 0.614). One third of patients in group A developed hematological adverse effects and had required modified doses during antiviral therapy. Conclusions In HCV genotype 1 infected AF receiving 24 weeks of PR treatment, patients with IL28B rs8099917 genotype TT, achieving RVR had similar SVR rate with those without AF. In contrast, patients with IL-28B rs8099917 non-TT genotype without achieving RVR are suggested to stop therapy.

The authors assessed the gene polymorphisms of missense C/T polymorphism in exon 6 of the urokinase-plasminogen activator (PLAU) gene (PLAU P141L), Alu-repeat in intron 8 of the tissue-type plasminogen activator (PLAT) gene (PLAT TPA25 Alu insertion), and 4G/5G in the promoter region of the serine proteinase inhibitor, clade E (SERPINE) or plasminogen activator inhibitor type 1 gene (SERPINE1 -675 4G/5G) in 153 healthy volunteers and 154 retired coal miners with coal miners' pneumoconiosis (CWP). The CWP subjects included 94 individuals with simple pneumoconiosis and 60 individuals with progressive massive fibrosis presenting with worse pulmonary function. The distributions of genotypes of these three genes did not differ between the control and CWP subjects or between subjects with simple pneumoconiosis and those with progressive massive fibrosis. However, by assessing duration of work and its interaction with genotypes by means of logistic regression, the authors found the missense C/T polymorphism in exon 6 of the PLAU gene to be an effect modifier of the association between work duration and the development of progressive massive fibrosis.

Hepatic actinomycotic abscesses are rare and secondary to other intra-abdominal infections. History of intra-abdominal surgery is a principal contributing factor for the abscess formation. Patients with hepatic actinomycotic abscess may suffer from fever, malaise, abdominal pain and bodyweight loss. The clinical progress of actinomycotic abscess is more indolent than the usual course of other pyogenic abscess. It is sometimes diagnosed as malignancy. This report consists of two cases of hepatic actinomycotic abscess mimicking tumours. Laboratory data revealed elevated alkaline phosphatase and leucocytosis. The abdominal computed tomography scan showed multiloculated lesions with peripheral contrast enhancement appearance. Diagnosis confirmation was based on the typical histologic feature of sulfur granules with inflammatory process by echo-guided fine needle biopsy or surgical specimen. These two cases were resolved with extended courses of intravenous and oral penicillin treatment.

Oral erythroplakia is a precancerous lesion with high malignant potential, and resection is the recommended treatment. We designed a retrospective study to analyse the outcome of treatment in patients who had operations for oral erythroplakia. A total of 84 patients (74 men and 10 women, mean (SD) age 54 (12) years, range 29-83) were enrolled. Histopathologically the diagnoses were invasive carcinoma (n=3), dysplasia/carcinoma in situ (n=61), and squamous hyperplasia (n=20), and all patients were treated by carbon dioxide laser excision. There was no postoperative malignant transformation, but invasive carcinoma found after initial excision (n=3) was treated by further radical excision. The mean (SD) follow-up period was 46 (29) months (range 1-124), The postoperative recurrent rate was 14/84 (16.7%). The area of oral erythroplakia was the only factor associated with postoperative recurrence on univariate analysis, and was also the only independent factor that predicted postoperative recurrence in multivariate logistic regression analysis. An area exceeding 80 mm2 had the best predictive value (sensitivity=0.71, specificity=0.67) with a 5.1 times increased risk (odds ratio=5.1, CI 95% 1.45 to 18.05, p=0.01) of recurrence. Laser excision is effective for oral erythroplakia that is still confined to dysplasia of any degree, with low morbidity. The area of oral erythroplakia is a predictive factor for postoperative recurrence.

Introduction The aim of the present report was to draw the attention of oncologists to the importance of prompt diagnosis of primary clear cell adenocarcinoma of the lung, which allows early initiation of treatment to maintain quality of life. Case presentation A 63-year-old Chinese woman initially presented to our facility with multifocal bilateral choroid metastatic lesions that were found to originate from a primary clear cell adenocarcinoma of the lung (T2bN2M1b, stage IV). A thorough ophthalmologic evaluation, study of our patient’s history, imaging studies and comprehensive immunohistochemical staining tests led to the diagnosis of this rare lung tumor. Conclusions Although this uncommon cancer is unfortunately already at a late stage when choroid metastases develop, systemic chemotherapy alone is sufficient to preserve vision and gain control over the disease.

Objectives: To measure tumor necrosis factor-a (TNF-a) and interleukin-1b (IL-1b) in pleural effusions caused by tuberculosis (TB) and malignancy and their relationship with plasminogen activator inhibitor type I (PAI-1) and tissue type plasminogen activator (tPA), and to compare the differences between tuberculous and malignant pleural effusions. In addition, the relationship between the effusion levels of these parameters and the development of residual pleural thickening was evaluated in the patients with tuberculous pleurisy. Design: Prospective study. Materials and methods: TNF-a, IL-1b, PAI-1, and tPA were measured simultaneously in blood and pleural fluid using an enzyme-linked immunosorbent assay in 33 patients with tuberculous and in 30 patients with malignant pleural effusions. Residual pleural thickening was measured and defined as a pleural thickness of > 10 mm found on chest radiographs at the completion of anti-TB chemotherapy in tuberculous pleurisy patients. Results: In both groups, the levels of proinflammatory cytokines and fibrinolytic enzymes were significantly higher in pleural fluid than in blood. The levels of TNF-a and PAI-1 were significantly higher in tuberculous than in malignant effusions. In contrast, malignant pleural fluid had significantly higher values of tPA than did tuberculous pleural fluid. In tuberculous effusions, the values of PAI-1 and the PAI-1/tPA ratio correlated positively and the levels of tPA correlated negatively with those of TNF-a and IL-1b. In malignant pleural fluid, positive correlations were found between the values of proinflammatory cytokines (TNF-a and IL-1b) and PAI-1. Residual pleural thickening was found in 9 of 33 patients (27.3%) with tuberculous pleurisy. The pleural fluid values of TNF-a, IL-1b, and PAI-1 were significantly higher and the concentrations of tPA were significantly lower in tuberculous pleurisy patients with residual pleural thickening. Conclusions: Compared to malignant pleural effusion, fibrinolytic activity in pleural fluid was reduced in tuberculous effusion. Pleural inflammation caused by TB may enhance the release of proinflammatory cytokines, particularly TNF-a, which subsequently may increase PAI-1 and decrease tPA in pleural fluid. The imbalance of PAI-1 and tPA in pleural space may lead to fibrin deposition and pleural thickening. (CHEST 1999; 116:1292‐1296)

Microvesicles (MV) in the blood stream are associated with distant metastasis in cancer. Platelet or endothelial cell-related MV actively participate in thrombogenesis, which is an important step in cancer metastasis. This study investigated the correlations between MV levels of platelet-poor plasma and distant metastasis in lung cancer.Platelet-poor plasma from 44 treatment-naive lung cancer (23 with distant metastasis) and 19 normal subjects was used to determine the levels of glycoprotein Iβ (CD42) + platelet MV (PMV), P-selectin (CD62P) + PMV, VE-cadherin (CD144) + endothelial MV (EMV), tissue factor (CD142) + MV, thrombin-antithrombin complex and vascular endothelial growth factor (VEGF).The level of CD142 + MV was significant (odds ratio 5.86, 95 % confidence interval 1.31-38.3) in predicting distant metastasis in lung cancer, and a cutoff value of 2.668 (after logarithm transformation) in the ROC curve had a specificity of 90 % and a sensitivity of 59 %. The presence of distant metastasis showed a significant correlation between CD144 + EMV and VEGF, but not between CD144 + EMV and CD42 + PMV or CD62P + PMV in lung cancer subjects.The finding of CD142 + MV in platelet-poor plasma may be useful for suggesting distant metastasis in lung cancer. In addition to thrombogenesis, interaction between VE-cadherin and VEGF may be needed for successful metastasis in lung cancer.

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 ± 13.0 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 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.

To investigate the diagnostic accuracy of the established patterns of intraepithelial microvasculature of narrow-band imaging (NBI) in diagnosing upper aerodigestive tract neoplasm of the squamous epithelium for detecting high-grade dysplasia, carcinoma in situ, and carcinoma in oral leukoplakia.Retrospective case-control study.Using histopathological findings as the standard, clinical diagnosis of oral leukoplakia and 3 different but established NBI criteria were compared and evaluated statistically.A total of 414 patients, including 365 males and 49 females, with mean age of 52.15 ± 10.75 years, were enrolled. The odds ratio of detecting high-grade dysplasia and carcinomatous lesions by twisted elongation of intraepithelial papillary capillary loop (IPCL) and IPCL pattern destruction was 95.53 (confidence interval 95%: 42.19-216.29), and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 84.62%, 94.56%, 74.32%, 97.06%, and 93.0%, respectively, which were significantly better than the other two established NBI criteria (p0.001).The NBI images of twisted elongation of IPCL and IPCL pattern destruction are indicators of high-grade dysplasia or carcinomatous lesions in oral leukoplakia.

Ovarian granulosa cell tumor (GCT) is a malignant tumor with slow progression. The recurrence of granulosa cell tumor often happens after 5 years, leading to a ‘forgotten tumor’ by the patient. We present the case of a 64-year-old woman with a presentation of left flank pain. An initial computed tomography scan revealed a single tumor with multiple adjacent organ invasions. Surgical intervention was prescribed and the pathological results revealed a metastatic granulosa cell tumor. We also review the literature for the follow-up and further management of this tumor.