Hon-Ki Hsu

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.

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 his213 allele is important in the development of esophageal cancer in men.

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.

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.

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.

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. (Cancer Sci 2005; 96: 758–765)

Surgical Treatment of Metastatic Pulmonary Tumors

Background: Metastasectomy has been proved to be an opportunity for long-term survival for patients with various neoplasms with pulmonary metastases. A retrospective study was performed to analyze the results and identify the prognostic factors of surgical treatment for pulmonary metastases. Methods: From 1991 to 2003, a total of 73 patients who underwent surgical treatment for pulmonary metastases at the Kaohsiung Veterans General Hospital were enrolled for analysis. Results: The overall 5-year survival rate was 25.1%. The operation-related mortality rate was 2.74%. Gender, origins of the primary cancers, number of pulmonary metastases, and surgical procedures had no significant effect for those patients who underwent pulmonary metastasectomies. However, patients who had a disease-free interval longer than 36 months had a better 5-year survival rate than those who had a shorter disease-free interval (29.6% vs. 10.5%). Conclusion: Pulmonary metastasectomy is a safe and potentially curative procedure. The disease-free interval is an important prognostic factor for patients with pulmonary metastases.

Neoadjuvant Therapy and Surgery for Clinical Unresectable Esophageal Cancer

Objectives. We applied neoadjuvant therapy to our advanced esophageal carcinoma patients who were clinically unresecatable. The primary goal of this study was to increase the resection rate and the secondary goal was to increase the survival time. Methods. From January 1990 to December 2002, 617 patients with squamous cell carcinoma of the esophagus were treated in our hospital. Resection with reconstruction was done in 272patients (44.1%). From January 1999 to December 2002, 31 patients with advanced esophageal carcinoma were enrolled for CCRT study. The tumors were diagnosed as unresectable by clinical experience and examinations including esophagography, esophageal endoscopy and thoracic CT scan. In this study, all of the 31 patients received CCRT (5-FU 800 mg/m2day 1 to 4, 29 to 32,cisplatin 60 mg/m2day 1 and 29, and radiation 36 Gy). Results. Among the 24 patients who completed CCRT and underwent surgical intervention, 5 patients had unresectable tumors and 19 patients received esophagectomy and reconstruction. Hospital mortality in the surgically respectable group was 15.8% (3/19). The pathological complete response rate (CR) in the resected esophageal specimens was 15.8% (3/19). Grade III to IV leukopenia was noted in 25.8% (8/31) of all patients. Among the surgical group, complications included radiation pneumonitis in 7 patients which resulted in prolonged ventilator usage; anastomotic leakage in 2 patients; pericardial effusion in 2 patients; pleural effusion in 1 patient and sepsis in 1 patient. The median survival time in the resection group was 10.60+1.52 months and 7.87+1.97 months in the non-resection group. There was no significant difference between the two groups (p = 0.3716). Conclusions. CCRT and surgery in selected patients with advanced esophageal carcinoma downgraded the tumor and increased the opportunity for surgical resection. However, it also carried high surgical morbidity and mortality rates and provided no survival benefit.

Ectopic Pleura-based Thymoma Mimicking Mesothelioma: Report of a Case

Ectopic thymoma is rare, especially when it arises in the pleural cavity. We report a 32-year-old female patient with diffuse pleural thickening. Computed tomography(CT)-guided needle biopsy was done before operation and mesothelioma was impressed. Left pleuropneumonectomy was performed. After operation pathologic diagnosis of ectopic pleural thymoma was made.