Jui-Ying Lee

Substance use (alcohol, areca nut and cigarette) is associated with poor prognosis of esophageal squamous cell carcinoma.

Background Few studies have reported the association between lifestyle factors and prognosis of esophageal squamous cell carcinoma (ESCC) and among these, the effects of habitual areca nut chewing have never been examined. Methodology/Principal Findings Data from 718 pathology-proven ESCC patients recruited in a multicenter hospital-based case-control study between 2000 and 2008 in Taiwan were analyzed. Clinical and lifestyle information were obtained by chart review and questionnaire survey. Death was confirmed using the National Death Index. The mean age at diagnosis was 59.8 years and 506 (70.5%) patients presented with stage III or IV diseases. The overall 1- and 5-year survival rates were 41.8% and 9.75% respectively. In addition to clinical stage, habitual alcohol drinking was found to be the strongest predictor for ESCC survival, followed by areca chewing and smoking. Compared with non-users, patients who regularly used all three substances (alcohol, areca nut, and cigarette) had 1.52 times the risk of early death (adjusted hazard ratiou200a=u200a1.52, 95% CIu200a=u200a1.02–2.27, pu200a=u200a0.04). In addition, the more the number of substances used, the worse the prognosis of ESCC (adjusted p for trendu200a=u200a0.01). Conclusions/Significance Our study found that indulgence in more substances is a significant predictor of ESCC survival. Further mechanistic studies are necessary to elucidate how these substances lead to an adverse outcome.

Effect of hormone replacement therapy on uterine fibroids in postmenopausal women—a 3-year study

OBJECTIVEnThe aim of this prospective 3-year clinical study was to examine the effect of hormone replacement therapy (HRT) on uterine fibroid growth among postmenopausal women.nnnMETHODSnThirty-seven postmenopausal women with uterine solitary fibroids were recruited randomly for HRT in a 3-year program. All participants received 0.625 mg conjugated equine estrogen (CEE) and 5 mg medroxyprogesterone (MPA) daily. Fibroid volume was measured by transvaginal ultrasonography at baseline and then at 12-month intervals for 3 times. Clinically, significant fibroid growth was defined as an increase in volume of more than 25% compared with baseline. Also, 35 postmenopausal women with uterine fibroid were studied as control who did not receive HRT during the study period.nnnRESULTSnFibroid volume had increased significantly after 1 year both in HRT users and non-users. These increases continued to the second year significantly in HRT users but not in non-users. However, the volumes declined significantly at the third year to similar levels as those measured at baseline in control. In HRT users, fibroid volume though significantly increased at the third year (vs. baseline) but declined insignificantly in comparison with the second year. Clinically, at end of the third year study, one of 34 and three of 34 women increased fibroid volume over 25% compared with baseline in HRT non-users and users, respectively.nnnCONCLUSIONSnHRT does increase uterine fibroid volume statistically. However, its effect appears in the first 2 years of use. The increased fibroid volume begins to decline at the third year both in HRT users and non-users. Clinically, the increased effect of HRT on uterine fibroid of postmenopausal women should be not over-emphasized at least for 3 years of usage.

Liver metastasis predicts poorer prognosis in stage IV lung adenocarcinoma patients receiving first-line gefitinib

OBJECTIVESnGefitinib is currently used as a first-line therapy in patients of advanced non-small cell lung cancer (NSCLC) with susceptible epidermal growth factor receptor (EGFR) mutations. However, treatment outcomes of these patients vary. This study was conducted to evaluate the impact of specific metastatic sites on treatment outcomes of patients with stage IV lung adenocarcinoma with susceptible EGFR mutations receiving first-line gefitinib, focusing on the impact of liver metastasis.nnnMATERIALS AND METHODSnBetween October 2009 and April 2014, patients of stage IV lung adenocarcinoma harboring EGFR mutation in exon 19 or 21, who received first-line gefitinib treatment, were enrolled in two hospitals and followed until December 22, 2014. The impacts of various clinical features, including sex, age, smoking history, performance status, EGFR mutation site, metastatic sites, etc., on progression-free survival (PFS) and overall survival (OS) were analyzed.nnnRESULTSnA total of 148 patients were eligible for analysis. Patients with liver metastasis on initial diagnosis (n=19) had shorter PFS and OS than those without liver metastasis did (median of PFS, 6.7 vs. 11.2 months, p<0.0001; median of OS, 9.2 vs. 17.5 months, p<0.0001). Multivariable Cox regression analysis showed liver metastasis was an independent poor prognostic factor for PFS (HR=2.939 [95% CI: 1.729-4.997], p<0.0001) and OS (HR=3.300 [95% CI: 1.708-6.373], p=0.0004).nnnCONCLUSIONnLiver metastasis predicts poorer PFS and OS in stage IV lung adenocarcinoma patients with susceptible gene mutations receiving first-line gefitinib. Further study is warranted to elucidate the underlying mechanisms and find treatment modalities to improve prognosis of these patients.

Poorer prognosis in Taiwanese female ever smokers with stage IV lung adenocarcinoma who were readministered a tyrosine kinase inhibitor.

Background Readministering a second epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in patients with lung adenocarcinoma with acquired resistance to an initial EGFR TKI is a common treatment strategy. However, the prognostic factors for the second EGFR TKI are still uncertain. Patients and methods In this retrospective study, we enrolled patients with stage IV lung adenocarcinoma diagnosed between June 2009 and October 2013 at two university-affiliated hospitals in Taiwan. Basic characteristics including age, sex, smoking status, performance status, EGFR mutation status, tumor response, and progression-free survival (PFS) of the second EGFR TKI (PFS2) were recorded. Results A total of 72 patients with stage IV adenocarcinoma with susceptible EGFR gene mutations who had been treated with a second EGFR TKI were enrolled. Survival analysis using the Kaplan–Meier method and log-rank test showed a significant difference in PFS2 when classifying the patients according to smoking history and sex (P=0.0179). When stratifying the patients by sex, a significant difference was found in PFS2 between ever smokers and never smokers in the female (1.87 vs 4.87 months, P=0.0081) but not in the male (2.83 vs 2.9 months, P=0.9605) patients. A reduced multivariate model developed using the backward variable selection method showed that only ever smoking remained an independent poor prognostic factor for PFS2, and that sex and ever smoking remained independent poor prognostic factors for PFS2 in the female patients (hazard ratio [HR] =3.386, 95% confidence interval [CI]: 1.015–11.298, P=0.0473). Conclusion This study is the first to demonstrate that female ever smokers have a poorer PFS if they have acquired resistance to an initial EGFR TKI and receive a second EGFR TKI. Further large-scale studies are urgently needed to elucidate the mechanism.

An Unusual Pulmonary Mass With Mediastinal Invasion and Multiple Intrapulmonary Nodules in a 52-Year-Old Man

A 52-year-old previously healthy smoker was examined. He had a fever of up to 38°C accompanied by cough with yellowish sputum for about 1 month. He visited our chest clinic for assistance in November 2010. His physical examination revealed clear breathing sounds but a palpable, fi xed lymph node approximately 2 cm 3 1.5 cm in size over the right supraclavicular area. Laboratory data showed leukocytosis (WBC count, 14,600/ m L) with neutrophilia (segment form 78%). His carcinoembryonic antigen level was 0.54 ng/mL (normal , 5 ng/mL); lactate dehydrogenase level, 142 IU/L (normal 91-180 IU/L); prostate-specifi c antigen level, An Unusual Pulmonary Mass With Mediastinal Invasion and Multiple Intrapulmonary Nodules in a 52-Year-Old Man

Pemetrexed had significantly better clinical efficacy in patients with stage IV lung adenocarcinoma with susceptible EGFR mutations receiving platinum-based chemotherapy after developing resistance to the first-line gefitinib treatment

Background Increased evidences show that epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors such as gefitinib could prolong progression-free survival (PFS) compared with cytotoxic chemotherapy for metastatic lung nonsquamous cell carcinoma harboring susceptible EGFR mutation, and gefitinib was served as the first-line therapy. However, acquired resistance is inevitable, but the salvage therapies are still unclear. Patients and methods We designed a retrospective study of the salvage therapy and enrolled patients with stage IV lung adenocarcinoma who had mutated EGFR and developed an acquired resistance to the first-line gefitinib in two university-affiliated hospitals in Taiwan during June 2011 to December 2014. Age, sex, smoking history, EGFR gene mutation, performance statuses, response rate, PFS2 (the PFS in salvage therapy), and overall survival (OS2, the OS in salvage therapy) were recorded. Results Two hundred and nine patients with mutated EGFR and who took gefitinib as first-line therapy were identified in the period, and a total of 98 patients who had been treated with salvage therapy with cytotoxic chemotherapy or erlotinib were eligible for this study. The overall response rate of second salvage therapy is 13%, and none of them received erlotinib. Patients who received chemotherapy had a trend for better PFS2 than those who received erlotinib (4.3 months vs 3.0 months, P=0.1417) but not in OS. Furthermore, patients who received platinum-based doublet had a trend for better PFS2 and a significantly better OS2 than those who received chemotherapy without platinum (PFS2: 4.9 months vs 2.6 months, P=0.0584; OS2: 16.1 months vs 6.7 months, P=0.0007). Analyses of the patients receiving platinum-based doublet showed that patients receiving pemetrexed had a significantly better PFS2 (6.4 months vs 4.1 months, P=0.0083) and a trend for better OS2 than those without pemetrexed treatment. Conclusion Pemetrexed-based platinum chemotherapy may be the most optimal therapy in acquired resistance to gefitinib. Further prospective randomized controlled study is needed urgently.

Methylation status of retinoic acid receptor beta2 promoter and global DNA in esophageal squamous cell carcinoma

Focal hypermethylation in promoter regions of tumor suppressor genes against the background of global hypomethylation is a landmark of carcinogenesis. This study aimed to investigate the methylation status of retinoic acid receptor beta2 (RARβ2) and long interspersed nuclear elements (LINE‐1) in different stages of esophageal squamous cell carcinoma (ESCC).

Plasma matrix metalloproteinase 1 improves the detection and survival prediction of esophageal squamous cell carcinoma.

This study aimed to identify noninvasive protein markers capable of detecting the presence and prognosis of esophageal squamous-cell carcinoma (ESCC). Analyzing microarray expression data collected from 17-pair ESCC specimens, we identified one protein, matrix metalloproteinase-1 (MMP1), as a possibly useful marker. Plasma MMP1 was then measured by enzyme-linked immunosorbent assay (ELISA) in 210 ESCC patients and 197 healthy controls. ESCC patients had higher mean levels of MMP1 than controls (8.7u2009±u20097.5u2009vs. 6.7u2009±u20094.9u2009ng/mL, pu2009<u20090.0001). Using the highest quartile level (9.67u2009ng/mL) as cut-off, we found a 9.0-fold risk of ESCC in those with higher plasma MMP1 after adjusting for covariates (95% confidence intervalu2009=u20092.2, 36.0). Heavy smokers and heavy drinkers with higher plasma MMP1 had 61.4- and 31.0 times the risk, respectively, than non-users with lower MMP1. In the survival analysis, compared to those with MMP1u2009≤u20099.67u2009ng/mL, ESCC patients with MMP1u2009>u20099.67u2009ng/mL had a 48% increase in the risk of ESCC death (adjusted hazard ratiou2009=u20091.48; 95% CIu2009=u20091.04–2.10). In conclusion, plasma MMP1 may serve as a noninvasive marker of detecting the presence and predicting the survival of ESCC.

The salvage therapy in lung adenocarcinoma initially harbored susceptible EGFR mutation and acquired resistance occurred to the first-line gefitinib and second-line cytotoxic chemotherapy

BackgroundEpidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib can provide better efficacy and prolonged progression free survival (PFS) than cytotoxic chemotherapy for metastatic lung non-squamous cell carcinoma harboring susceptible EGFR mutations when used as first-line therapy. Cytotoxic chemotherapy is regarded as being the standard therapy to overcome acquired resistance to an initial EGFR TKI. However, there is currently no consensus on how best to treat patients who develop resistance to both an initial EGFR TKI and chemotherapy.MethodsWe enrolled stage IV lung adenocarcinoma patients with an EGFR mutation and who had developed acquired resistance to gefitinib and cytotoxic chemotherapy from two university-affiliated hospitals in Taiwan from June 2011 to December 2014. Basic demographic data, included Eastern Cooperative Oncology Group (ECOG) performance status were collected, and the response rate, progression-free survival (PFS) and overall survival (OS) were analyzed.ResultTwo hundred and nine patients with mutated EGFR and who took gefitinib as the first-line therapy were identified in the study period, of whom 86 received second-line cytotoxic chemotherapy, and 60 who received third-line therapy were eligible for this study. The patients who received cytotoxic chemotherapy had a significantly higher disease control rate than those who received erlotinib (73% vs. 46%, pu2009=u20090.0363), however there were no significant differences in PFS (2.9xa0months vs. 3.1xa0months, pu2009=u20090.9049) and OS (8.9xa0months vs. 7.9xa0months, pu2009=u20090.4956). Platinum- or pemetrexed-based chemotherapy provided similar PFS and OS as others did. The only significant poor prognostic factors for OS were old age (≥65xa0years) (HRu2009=u20095.97 [2.65–13.44], pu2009<u20090.0001) and poor performance status (ECOG ≥2) (HRu2009=u20095.84 [2.61–13.09], pu2009<u20090.0001).ConclusionRetreatment with an EGFR TKI is not inferior to cytotoxic chemotherapy when used as salvage therapy for patients with adenocarcinoma with an EGFR mutation, especially if a third-generation EGFR TKI is not available, or if the reason for resistance is unknown or is not related to the T790M mutation. Old age and poor ECOG score were both poor prognostic factors in the salvage therapy.

Right Ptosis, Anhidrosis, and Miosis Developed in a 49-Year-Old Man With Chronic Dry Cough for 2 Months

Laboratory data showed a carcinoembryonic anti gen level of 0.7 ng/mL (normal, , 5 ng/mL), WBC count of 8,600/ m L, hemoglobin level of 12.0 mg/dL, and platelet count of 342,000/ m L. Hepatic and renal functions were all within normal range. A bronchoscopic biopsy showed total obstruction of the right upper bronchus, and the pathology report showed necrotic tissue and bronchial submucosal fi brosis with atypical spindle cell proliferation. The spindle cells were negative for cytokeratin (CK), smooth muscle actin, thyroid transcription factor-1 (TTF-1), and anaplastic lymphoma kinase. The diagnosis was, therefore,