Patient attitudes towards chemotherapy and survival: a prospective observational study in advanced non-small cell lung cancer.

This multicenter, non-interventional, prospective, observational study aimed to determine whether patients' attitude to chemotherapy is an independent prognostic factor for survival in patients with advanced non-small cell lung cancer (NSCLC) who are treated with gemcitabine-platinum. Chemonaive patients (n=1895) with stage IIIB or IV NSCLC not amenable to curative surgery or radiotherapy were treated with a combination of gemcitabine plus cisplatin/carboplatin and followed for a maximum of 18 months. Patients' attitude to treatment was measured on a 5-point scale and responses were used to assign patients to one of the three need categories: A, maximum extension of survival with the acceptance of high toxicity (60.0% of patients); B, maximum extension of survival only if coupled with normal lifestyle (26.1%); C, relief of symptoms (13.8%). Median survival varied significantly among the need categories (A=13.00 months, B=15.70 months, C=15.33 months; log-rank test P=0.0415). Patient attitude to treatment (need categories) was not a significant prognostic factor for survival after adjusting for known prognostic factors (P=0.0503). After adjusting for baseline differences, patients in this study had a significantly lower risk of death than patients in three randomized trials (hazard ratio 0.879; 95% confidence interval: 0.775, 0.998; P=0.0458). In conclusion, in this observational study, patient attitude to chemotherapy was not an independent prognostic factor of survival.

Intake of vitamin A-rich foods and lung cancer risk in Taiwan: with special reference to garland chrysanthemum and sweet potato leaf consumption.

A case-control study was conducted to investigate the association between the consumption of local common foods that are rich in vitamin A and the risk of lung cancer in Taiwan. A total of 301 incident lung cancer cases, 602 hospital controls, and 602 neighborhood controls were recruited. The consumption of 13 food items and vitamin supplements was estimated by use of a food frequency questionnaire. The conditional logistic regression models were used to estimate the adjusted odds ratios (AOR) and 95% confidence intervals (CI) for lung cancer risk with each control group as reference by adjustment of covariates. A reduced risk for lung cancer was found to be associated with increased intakes of vitamin A, alpha-carotene, and beta-carotene from 13 food items. More servings of vegetables (AOR for the highest versus the lowest quartile = 0.67-0.70, 95% CI = 0.42-1.08, (plinear trend )= 0.04), garland chrysanthemum (AOR for the highest versus the lowest tertile = 0.58-0.74, 95% CI = 0.37-1.14, (plinear trend )<= 0.04) and sweet potato leaves (AOR for the highest versus the lowest tertile = 0.43-0.65, 95% CI = 0.28-0.96, (plinear trend )<= 0.03) were associated with the reduced risk for lung cancer. In conclusion, higher consumption of vitamin A-rich vegetables, especially garland chrysanthemum and sweet potato leaves might provide potential protection from lung cancer.

An audit of surgical outcomes of esophageal squamous cell carcinoma.

OBJECTIVE: Esophageal squamous cell carcinoma and adenocarcinoma were increasingly recognized as two entities with different biologic behaviors and prognosis. Surgical risks and oncologic benefits of transthoracic and transhiatal esophagectomy for esophageal squamous cell carcinoma patients are not confessed. METHODS: Between 1994 and 2005, 216 esophageal squamous cell carcinoma patients underwent esophagectomy were enrolled and analyzed retrospectively. RESULTS: One hundred sixty-six patients underwent transthoracic esophagectomy and 50 patients underwent transhiatal esophagectomy. The overall hospital mortality and postoperative complication rates were 9.7 and 49%, respectively. The amount of intra-operative blood loss or transfusion, postoperative complication rate, lengths of hospital stay and hospital mortality rate were not significantly different between both groups. However, shorter operative time was noticed in transhiatal group (p<0.001). The overall 5-year survival rate was 16.8%. ESCC patients underwent either transthoracic or transhiatal esophagectomy had comparable long-term survival. The pTNM stage was independent prognostic factor for patients underwent transthoracic esophagectomy. However, location of tumor (p=0.009) and pathologic tumor length (p=0.012) were predictors of prognosis for patients underwent transhiatal esophagectomy. CONCLUSIONS: For esophageal squamous cell carcinoma patients, no significant differences in postoperative mortality or morbidity rates were observed between transthoracic and transhiatal esophagectomy. However, traditional pTNM staging system might underestimate the severity of esophageal squamous cell carcinoma patients who underwent transhiatal esophagectomy. The information of dissimilar prognostic factors for transhiatal or transthoracic esophagectomies will be helpful in tailoring more individualized adjuvant therapy to optimize esophageal squamous cell carcinoma patient's outcome.

The association between microsomal epoxide hydrolase genotypes and esophageal squamous-cell-carcinoma in Taiwan: interaction between areca chewing and smoking.

One hundred and forty-five ESCC patients and 352 controls were recruited from three hospitals in Taiwan to determine the association between esophageal squamous-cell-carcinoma (ESCC) and microsomal epoxide hydrolase (mEH) genotypes at Thy113His and His139Arg. Stratified by their exposures, the His113His genotype was a significant protective factor for ESCC in areca chewers and tobacco smokers. Stratified by His113 polymorphisms, the risk of contracting ESCC for participants with His113His who chewed areca and smoked was >50% less than for those with Thy113Thy. We suggest that the mEH His113His genotype can differentiate the association between smoking, areca chewing, and ESCC.

Risk of p53 gene mutation in esophageal squamous cell carcinoma and habit of betel quid chewing in Taiwanese.

A recent report suggested that BQ (BQ) chewing significantly correlated with the occurrence of esophageal squamous cell carcinoma (ESCC) in Taiwanese. BQ chewing was shown to be associated with p53 mutation in oral cancers. However, the relationship between BQ chewing and p53 mutation in ESCC is unclear. Seventy-five primary ESCC patients were enrolled for mutational analysis of the p53 gene using polymerase chain amplification and direct sequencing of amplified product. Thirty-seven mutations of the p53 gene were detected in 45.5% (34/75) of tumor specimens. These mutations significantly clustered in exon 5 (21/37) of the p53 gene. The incidence of p53 mutations did not associate with clinicopathological characteristics or the habits of cigarette smoking or alcohol consumption. However, BQ chewers exhibited significantly higher incidence of p53 gene mutations than non-chewers (67.6% vs 32.4%, P = 0.007). After controlling the confounding factors of cigarette smoking and alcohol intake, BQ chewing still showed significant association with the incidence of p53 mutation in ESCCs (RR = 4.23; 95% CI, 1.317-13.60). The A:T to G:C transition (8/37, 21.6%) and G:C to T:A transversion (5/23, 13.5%) were the prevalent spectrum of p53 gene mutations. All A:T to G:C transitional mutations occurred in patients with the habits of BQ chewing and cigarette smoking. Noticeably, alcohol consumption could enhance this peculiar spectrum of p53 mutation in ESCC. Accordingly, p53 might be an important molecular target of BQ carcinogens in the development of ESCC in Taiwanese.

Deregulated p21(WAF1) overexpression impacts survival of surgically resected esophageal squamous cell carcinoma patients.

BACKGROUND: Prognostic effects of cell cycle regulation associated tumor suppressor genes for esophageal squamous cell carcinoma patients are controversial. Clarifying the effects of these genes is beneficial for optimizing patient's outcome. METHODS: Forty esophageal squamous cell carcinoma patients were included in the study. Tissue samples were analyzed for cell proliferation, DNA content, mutation of p53 gene, and expression of p21 and p53 proteins. Prognostic effects of these parameters were assessed by multivariate analysis. RESULTS: Seventy-five percent of tumors exhibited aneuploid DNA content. Significantly higher S-phase fractions were detected in tumor samples (p < 0.001). The p53 gene mutated in 52.5% (21 of 40) of tumor samples, p53 immunostaining was detected in 62.5% (25 of 40) of tumor tissues and 50% of tumors over expressed p21. Overexpression of p21 protein did not correlate with p53 gene status, but significantly correlated with abnormal DNA content (p = 0.028). Advanced pTNM stage, lymph node metastasis and p21 overexpression conferred survival disadvantages in univariate analysis (p = 0.013, 0.045 and 0.017, respectively). A Cox multivariable analysis revealed pTNM stage (IIB/III/IV vs. I/IIA; p = 0.024) associated with p21 overexpression (positive vs. negative; p = 0.035) as independent prognostic factors in esophageal squamous cell carcinomas. Surprisingly, p21 overexpression significantly compromised the survival of patients with mutated p53 gene (p = 0.035). However, no significant dismal effect of p21 overexpression can be seen in patients with wild-type p53 gene (p = 0.175). CONCLUSIONS: Overexpression of p21 correlates with chromosomal instability and serves as an adverse prognostic predictor for patients with esophageal squamous cell carcinoma. Its adverse effect is more prominent when the p53 gene is mutated.

Relationship between genetic polymorphisms of alcohol and aldehyde dehydrogenases and esophageal squamous cell carcinoma risk in males.

AIM: To investigate the association between the genetic polymorphisms of ADH2 and ALDH2, lifetime alcohol consumption and esophageal cancer risk in the Taiwanese men. METHODS: Between August 2000 and June 2003, 134 pathologically-proven esophageal squamous cell carcinoma male patients and 237 male controls were recruited from Kaohsiung Medical University Hospital and Kaohsiung Veterans General Hospital in southern Taiwan. ADH2 and ALDH2 polymorphisms were genotyped using PCR-RFLP. RESULTS: Compared to those with ADH2*2/*2, individuals with ADH2*1/*2 and ADH2*1/*1 had 2.28- and 7.14-fold, respectively, increased risk of developing esophageal cancer (95%CI = 1.11-4.68 and 2.76-18.46) after adjusting for alcohol consumption and other covariates. The significant increased risk was also noted among subjects with ALDH2*1/*2 (adjusted OR (AOR) = 5.25, 95%CI = 2.47-11.19), when compared to those with ALDH2*1/*1. The increased risk of esophageal cancer was made greater, when subjects carried both ADH2*1/*1 and ALDH2*1/*2, compared to those with ADH2*1/*2 or ADH2*2/*2 and ALDH2*1/*1 (AOR = 36.79, 95%CI = 9.36-144.65). Furthermore, we found a multiplicative effect of lifetime alcoholic consumption and genotypes (ADH2 and ALDH2) on esophageal cancer risk. CONCLUSION: Our findings suggest that polymorphisms of ADH2 and ALDH2 can modify the influence of alcoholic consumption on esophageal cancer risk.

Helicobacter pylori infection: a protective factor for esophageal squamous cell carcinoma in a Taiwanese population.

AIM: Many researchers have reported the inverse relationship between Helicobacter pylori (H. pylori) infection and esophageal adenocarcinoma risk, but very few studies have examined the association between H. pylori infection and the development of esophageal squamous-cell carcinoma (ESCC). Therefore, the aim of this study is to evaluate the relationship between H. pylori infection and ESCC risk. METHOD: Subjects were cancer cases, pathologically proven to have ESCC, in two large medical centers in Kaohsiung metropolitan of southern Taiwan between August 2000 and May 2003. Controls were from the healthy subjects who lived in Kaohsiung metropolitan and voluntarily participated in one large multiyear of gene-environmental study. In total, 127 cases (116 males and 11 females) and 171 controls (161 males and 10 females) were recruited in the same period of time for interviews. H. pylori seropositivity was determined by an enzyme-linked immunosorbant assay measuring IgG. RESULTS: A total of 28 (22.1%) and 74 (43.3%) out of 127 cases and 171 controls, respectively, had positive H. pylori infection. After adjusting for other covariates, subjects with positive H. pylori infections had a significantly reduced risk (adjusted odds ratio (AOR) = 0.51; 95% CI = 0.27-0.96; p= 0.037) of developing ESCC than those without. This result was even more pronounced in the groups of younger subjects, nonsmokers, or nondrinkers. In addition, among the 117 cancer patients who provided information about site of cancer lesion, the present study found that subjects with cancer lesions in the lower third of the esophagus had significantly fewer positive H. pylori infections (AOR = 0.34; 95% CI = 0.14-0.80; p= 0.013) than controls. CONCLUSION: Our findings suggest that H. pylori infection may protect against the development of ESCC. Additional studies are needed to confirm these findings.

Independent and combined effects of alcohol intake, tobacco smoking and betel quid chewing on the risk of esophageal cancer in Taiwan.

A multicenter case-control study was conducted in northern and southern Taiwan to clarify the independent and combined effects of alcohol intake, tobacco smoking and betel quid chewing on the risk of esophageal cancer. A total of 513 patients with newly diagnosed and histopathologically confirmed squamous cell carcinoma of the esophagus and 818 gender, age and study hospital-matched controls were included. We found a significant dose-response relationship between the duration and intensity of consumption of the 3 substances and the development of this neoplasm in this site. Although the amount of alcohol consumed had a stronger effect on the risk of esophageal cancer than the number of years it was consumed, however, the number of years one smoked had a stronger effect on the risk than the amount of cigarettes consumed. The strongest risk factor of esophageal cancer was alcohol intake, with highest risk (OR = 13.9) being for those who consumed more than 900 g/day-year. Combined exposure to any 2 of 3 substances brought the risks up to 8.8-19.7 fold and, to all 3 substances, to 41.2-fold. A multiplicative interaction effect for alcohol drinkers who smoked on cancer risk was detected, whereas an additive interaction effect was found among drinkers who chewed. The combined effect of all 3 substances accounted for 83.7% of the attributable fraction of contracting esophageal cancer in this population. In conclusion, these results suggest that the intensity and the length of time alcohol and tobacco are used play different roles in the etiology of esophageal cancer. Alcohol separately interacts with tobacco and betel quid in a differently synergistic way in determining the development of this site of cancer.

Bilateral severe bronchial obstruction after metallic tracheal stent insertion for tracheal stenosis--a case report.

Metallic wire expandable stents are increasingly used to alleviate tracheal obstruction due to malignancies. Patients usually tolerate these stents well and benefit from good to excellent palliation of their symptoms. Nevertheless, some miserable complications have also come to our notice. We report here an unfortunate case in whom severe bilateral main bronchial obstruction occurred immediately after the insertion of a Wall-stent over the tracheal stenosis.

Association between diet and esophageal cancer in Taiwan.

BACKGROUND: Several studies have reported the importance of dietary factors in the development of esophageal cancer. The purpose of the present study was to evaluate the effects of several common dietary factors on the risk of squamous cell carcinoma of the esophagus in a Taiwanese population. METHODS: The association between diet and esophageal cancer was examined in 284 male patients and 480 male controls, who were recruited during 6 year period. RESULTS: Consumption of preserved and overheated foods was found to be associated with increased risk of esophageal cancer, whereas intake of fresh fruits, vegetables, and tea was inversely associated with this risk. Men who consumed fermented bean products, salted food and preserved/pickled vegetables more than once a week after age 40 years had a 3.4-fold risk (95% confidence interval (CI): 1.9-6.2), 2.3-fold risk (95%CI: 1.2-4.2), and 2.5-fold risk (95%CI: 1.3-4.5), respectively, compared to men eating these items less than once a week. It was further found that these preserved foods were more strongly associated with esophageal cancer among men who consumed fruit less than once per day than those who consumed fruits one or more times per day. CONCLUSIONS: These results suggest that a high intake of preserved foods and overheated drinks might increase the risk of esophageal cancer, and intake of fruit, vegetables, and tea might be negatively associated with risk of esophageal cancer. The results also suggest that diet is an important factor in the development of esophageal cancer in Taiwan.

Association between p21 codon 31 polymorphism and esophageal cancer risk in a Taiwanese population.

P21, which regulates the cell growth cycle, is crucial for normal growth and differentiation. One polymorphism in the p21 codon 31 produces variant proteins with an amino acid change (serine (ser) or arginine (arg)). Although several epidemiologic studies have examined the effect of this polymorphism on cancer risk, the findings remain inconclusive, which has motivated us to evaluate the relationship between p21 codon 31 polymorphism and esophageal cancer risk. In this study, 128 cases of esophageal squamous cell carcinoma and 178 control cases from two hospitals in southern Taiwan were genotyped. Frequencies of arg/arg, arg/ser and ser/ser were 23 (18.0%), 62 (48.4%) and 43 (33.6%) in carcinoma cases and 51 (28.6%), 84 (47.2%) and 43 (24.2%) in control cases, respectively. After factoring out other potential contributing factors, patients with ser/ser or arg/ser were 2.17 times more at risk (95% CI=1.03-4.56) for developing esophageal cancer than those with arg/arg. Males (n=274) were found to have a slightly stronger association (adjusted OR=2.45; 95% CI=1.03-5.80). Although the sample size is relatively small, these findings suggest that a codon 31 polymorphism in p21 may be associated with the development of esophageal cancer.

SULT1A1 polymorphism and esophageal cancer in males.

Sulfotransferase (SULT) 1A1 detoxifies and bioactivates a broad spectrum of substrates including xenobiotics. It has been suggested that the SULT1A1 his (histidine) allele, which is caused by a his for arg (arginine) substitution due to a G-->A transition at codon 213, carries a significantly higher risk for women to develop breast cancer. We investigated the association between the SULT1A1 arg/his genotype and esophageal cancer in men, 187 cases of esophageal squamous cell carcinoma and 308 controls from 3 medical centers in Taiwan. Cigarette smoking, areca chewing and alcohol consumption were the major risks for developing esophageal cancer. The frequencies of arg/his in cases and controls were 27.8% (52/187) and 11.0% (34/308), respectively (p < 0.0001). No subjects carried his/his. After adjusting for substance use and other covariates, individuals with arg/his had a 3.53-fold higher risk (95% CI = 2.12-5.87) of developing esophageal cancer than those with arg/arg. Unexpectedly, this positive association was found to be even stronger (adjusted OR = 4.04-4.80) among non-smokers, non-drinkers or non-chewers. Our findings suggest that the SULT1A1 his(213) allele is important in the development of esophageal cancer in men.

Prognostic evaluation of the expression of p53 and bcl-2 oncoproteins in patients with surgically resected non-small cell lung cancer.

BACKGROUND: Tumor staging remains the most important prognostic predictor in patients with non-small cell lung cancer (NSCLC). However, the prognostic significance of expression of oncoproteins involved in regulation of cellular uncontrolled proliferation remains controversial. METHODS: In this retrospective study, we investigated the expression of bcl-2 and p53 oncoproteins in 114 surgically resected NSCLC patients (46 stage I, 39 stage II and 29 stage IIIa) using immunohistochemical analysis and correlated the molecular markers with survival. RESULTS: Positive bcl-2 immunoreactivity was detected in 26 of 114 (22.8%) NSCLC, including 15 of 43 (34.9%) squamous cell carcinoma and 11 of 71 (15.5%) adenocarcinoma cases. Nuclear staining for p53 was observed in 59 of 114 (51.8%) NSCLC, including 26 of 43 (60.5%) squamous cell carcinoma and 33 of 71 (46.5%) adenocarcinoma patients. There was no correlation between pathological staging and expression of bcl-2 and p53. However, the expression frequency of bcl-2 was significantly higher in squamous cell carcinoma than in adenocarcinoma (P < 0.02). The presence of bcl-2 expression did not provide a favorable prognosis (P = 0.23) and the overexpression of p53 oncoprotein was also not significantly associated with adverse prognosis (P = 0.09). No inverse relationship was found between bcl-2 and p53 expression (P = 0.83). CONCLUSION: Expressions of bcl-2 and p53 using immunohistochemical staining are not independent prognostic predictors in patients undergoing surgery for NSCLC.

Prediction of postoperative lung function in patients with lung cancer: comparison of quantitative CT with perfusion scintigraphy.

OBJECTIVE: Prediction of postoperative lung function is important in preoperative evaluation of patients with lung cancer. Perfusion scintigraphy is the current method to assess the fractional contribution of lung function of the remaining lung. We developed a quantitative CT method and compared it with perfusion scintigraphy for predictions of postoperative forced expiratory volume in 1 sec (FEV1) in patients with lung cancer. SUBJECTS AND METHODS: Forty-four patients with lung cancer undergoing lung resection with preoperative CT and perfusion scintigraphy were enrolled. Quantitative CT used a dual threshold (-500 and -910 H) on standard preoperative CT to semiautomatically extract lung volume without emphysema or tumor and atelectasis, which we defined as "functional lung volume." Prediction was calculated from preoperative FEV1 multiplied by the fractional contribution of functional lung volume of the remaining lung by quantitative CT. Perfusion scintigraphy was the standard method. Predictions were correlated with postoperatively measured FEV1. RESULTS: Both quantitative CT and perfusion scintigraphy predicted postoperative FEV1 well in patients who underwent pneumonectomy (n = 28, r = 0.88 vs r = 0.86) and in lobectomy (n = 16, r = 0.90 vs r = 0.80) (both, p < 0.001). There was good agreement between the two methods by the Bland-Altman method. In the four patients with low measured postoperative FEV1 (<40% predicted normal), quantitative CT had true-positive prediction in four and perfusion scintigraphy, in only two. CONCLUSION: Given its simplicity, we proposed that quantitative CT be widely used in predicting postoperative FEV1.