Esophageal cancer is one of the most aggressive and lethal gastrointestinal tract malignancies, with a poor overall five-year survival rate. Cordycepin, a major compound of Cordyceps sinensis, has been shown to have anticancer potential. This study focuses on the anticancer properties of cordycepin that target esophageal cancer and reveals molecular aspects underlying these effects. In our CCK-8 assays and colony formation assays, cordycepin significantly suppressed esophageal cancer cell proliferation. Moreover, cordycepin induced chromatin condensation in esophageal cancer cells and significantly increased the number of apoptotic cells through activation of caspase cascades, apoptotic signaling, and the regulation of Bcl-2 family members. Cell cycle assays showed that cordycepin altered cyclin-dependent kinase1 and cyclinB1 expression, which resulted in a G2/M phase blockade. Mechanistically, ERK pathway inactivation was involved in the anti-tumor functions of cordycepin. The same results were also observed. Taken together, these findings reveal that cordycepin induces pro-apoptosis and anti-proliferation mechanisms in cancer cells, and may represent a novel therapeutic agent.

Endoscopic cryotherapy is a relatively new thermal ablative modality used for the treatment of neoplastic lesions of the esophagus. It relies on cycles of rapid cooling and thawing to induce tissue destruction with a cryogen (liquid nitrogen or carbon dioxide) leading to intra and extra-cellular damage. Surgical treatment was once considered the standard therapeutic intervention for neoplastic diseases of the esophagus and is associated with considerable rates of morbidity and mortality. Several trials that evaluated cryotherapy in Barrett's esophagus (BE) associated neoplasia showed reasonable efficacy rates and safety profile. Cryotherapy has also found applications in the treatment of esophageal cancer, both for curative and palliative intent. Cryotherapy has also shown promising results as salvage therapy in cases refractory to radiofrequency ablation treatment. Cryoballoon focal ablation using liquid nitrogen is a novel mode of cryogen delivery which has been used for the treatment of BE with dysplasia and squamous cell carcinoma. Most common side effects of cryotherapy reported in the literature include mild chest discomfort, esophageal strictures and bleeding. In conclusion, cryotherapy is an effective and safe method for the treatment of esophageal neoplastic processes, ranging from early stages of low grade dysplasia to esophageal cancer.

The incidence of esophageal adenocarcinoma (EA) and its precursor condition, Barrett's esophagus, has risen rapidly in the United States for reasons that are not fully understood. Therefore, we evaluated the association between use of supplemental vitamins and minerals and risk of neoplastic progression of Barrett's esophagus and EA. The Seattle Barrett's Esophagus Program is a prospective study based on 339 men and women with histologically confirmed Barrett's esophagus. Participants underwent baseline and periodic follow-up exams, which included endoscopy and self-administered questionnaires on diet, supplement use, and lifestyle characteristics. Use of multivitamins and 4 individual supplements was calculated using time-weighted averages of reported use over the observational period. Cox proportional-hazards models were used to calculate hazard ratios (HR) for each endpoint: EA, tetraploidy, and aneuploidy. During a mean follow-up of 5 yr, there were 37 cases of EA, 42 cases of tetraploidy, and 34 cases of aneuploidy. After controlling for multiple covariates including diet, nonsteroidal anti-inflammatory drug use, obesity, and smoking, participants who took 1 or more multivitamin pills/day had a significantly decreased risk of tetraploidy [HR = 0.19; 95% confidence interval (CI) = 0.08-0.47) and EA (HR = 0.38; 95% CI = 0.15-0.99] compared to those not taking multivitamins. Significant inverse associations were also observed between risk of EA and supplemental vitamin C (>or = 250 mg vs. none: HR = 0.25; 95% CI = 0.11-0.58) and vitamin E (>or = 180 mg vs. none: HR = 0.25; 95% CI = 0.10-0.60). In this cohort study, use of multivitamins and single antioxidant supplements was associated with a significantly reduced risk of EA and markers of neoplastic progression among individuals with Barrett's esophagus.

To explore the relation between esophageal cancer and dietary trace elements in humans, we estimated the average daily intake of zinc, copper, iron, selenium, molybdenum, silicon, cadmium, and nickel in 21 Chinese communes, where the annual mortality rate from esophageal cancer among the population 30 years of age and over ranged from 0 to 495/100,000 person-years. We also estimated the relative level of calcium consumption. Zinc and copper intake were inversely related to esophageal cancer mortality, and calcium intake levels was positively related to esophageal cancer mortality. The predicted esophageal cancer mortality among a vegetarian population with a high level of dietary calcium and a low level of dietary zinc was 5.3 times as high as that in a vegetarian population with a low level of dietary calcium and a high level of dietary zinc. The influence of a high level of dietary calcium in a vegetarian population may be explained by a reduction in the absorption of dietary zinc.

UNLABELLED:Background/Aim: This paper reviews ecological studies of the ultraviolet-B (UVB)-vitamin D-cancer hypothesis based on geographical variation of cancer incidence and/or mortality rates.

MATERIALS AND METHODS:The review is based largely on three ecological studies of cancer rates from the United States; one each from Australia, China, France, Japan, and Spain; and eight multicountry, multifactorial studies of cancer incidence rates from more than 100 countries.

RESULTS:This review consistently found strong inverse correlations with solar UVB for 15 types of cancer: bladder, breast, cervical, colon, endometrial, esophageal, gastric, lung, ovarian, pancreatic, rectal, renal, and vulvar cancer; and Hodgkin's and non-Hodgkin's lymphoma. Weaker evidence exists for nine other types of cancer: brain, gallbladder, laryngeal, oral/pharyngeal, prostate, and thyroid cancer; leukemia; melanoma; and multiple myeloma.

CONCLUSION:The evidence for the UVB-vitamin D-cancer hypothesis is very strong in general and for many types of cancer in particular.

OBJECTIVE: To explore the effect and possible mechanism of traditional Chinese medicine (TCM) on survival and quality of life (QOL) in patients with esophageal carcinoma after esophagectomy. METHODS: Adopting prospective controlled method of study, the authors had 128 post-esophagectomy patients, hospitalized from February 2001 to February 2002, randomly divided into 3 groups: the TCM group, treated with TCM drugs alone; the chemotherapy group, with chemotherapy alone applied; and the synthetic group, treated with chemotherapy combined with Chinese medicine. Their survival rate and QOL were compared. RESULTS: In the TCM group, the chemotherapy group and the synthetic group, the respective 3-year relapse and remote metastasis rate were 71.4%, 76.7%, 53.4%, respectively (chi(2) = 6.53, P<0.05); the 1-year survival rate 42.9%, 46.5%, 72.1%; 2-year survival rate 28.6%, 27.9%, 55.8%, and 3-year survival rate 26.2%, 23.1%, 37.2%, respectively. And the QOL improving rate was 69.0%, 37.2%, 58.1%, respectively, all showing significant difference among them (chi(2) = 6.10, all P<0.05). Moreover, immune function was increased in the TCM and the synthetic groups. CONCLUSION: Integrative Chinese and Western medicinal treatment was the beneficial choice for post-operational patients with esophageal carcinoma. However, long time use of simple Chinese medicine was also advisable, especially for those in poverty.

The relation between 5 classes of flavonoids (flavanones, flavan-3-ols, flavonols, flavones and anthocyanidines) and esophageal cancer was investigated using data from a case-control study conducted between 1992 and 1997 in 3 areas of northern Italy. The study included 304 cases (275 men, 29 women) with a first diagnosis of squamous-cell carcinoma of the esophagus and 743 controls (593 men, 150 women) with no history of cancer, admitted for acute illnesses, unrelated to tobacco and alcohol consumption, to major hospitals of the areas under surveillance. Dietary habits were investigated using a validated food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CI) were computed after allowance for age, sex, study centre, years of education, alcohol drinking, tobacco smoking, body mass index and energy intake. An inverse association emerged between flavanone intake and esophageal cancer risk (OR=0.38 for the highest vs. the lowest quintile, 95% CI=0.23-0.66). The inverse relation between flavanones and esophageal cancer tended to be stronger in those who drank>or=6 drinks/day. In conclusion, this study suggests that flavanone intake is inversely associated with esophageal cancer risk and may account, with vitamin C, for the protective effect of fruit, especially citrus fruit, on esophageal cancer.

BACKGROUND/AIMS: Photodynamic therapy (PDT) has been adapted to the endoscopic treatment of digestive cancer, but its indications and efficacy remain uncertain. The aim of this study was to assess its feasibility in the curative treatment of small esophageal tumors. METHODS: From 1983 to 1991, PDT was used to treat 123 patients with esophageal cancer who were recommended for nonsurgical treatment of squamous cell carcinoma (n = 104) and adenocarcinoma (n = 19). Endoscopic ultrasonography (EUS) was performed in 88 patients; 61 were staged uT1 and 27 were staged uT2. A hematoporphyrin derivative was injected 72 hours before laser irradiation with a 630-nm dye laser. PDT was applied alone in 56 patients and as part of a multimodal protocol in the 67 others. RESULTS: The complete response rate at 6 months was 87%. The 5-year survival rate was 25% +/- 6%, and the 5-year disease-specific survival rate was 74% +/- 5%. The complete response rate and survival rate were not different (1) between the PDT alone and the PDT multimodal treatment groups, (2) between the adenocarcinoma and squamous cell carcinoma groups, and (3) between the uT1 and uT2 EUS groups. PDT-related complications were esophageal stenosis (n = 43) and cutaneous photosensitization (n = 16). CONCLUSIONS: In patients with small esophageal tumors who pose high surgical risk, photodynamic therapy is an effective treatment.

BACKGROUND:Chemotherapy, including preoperative chemotherapy, plays an important role in the treatment of esophageal cancer. However, although docetaxel, cisplatin, and fluorouracil (DCF) therapy has a powerful antitumor effect, the associated adverse events make it difficult to maintain the patient's general condition. Oral mucositis is an important adverse effect of chemotherapy, and its severity, frequency, and impact on patient quality of life should not be underestimated. This study evaluated the role of oral cryotherapy for prophylaxis of oral mucositis caused by DCF therapy.

METHODS:We retrospectively examined the incidence and severity of adverse events, including mucositis, in 72 patients with esophageal cancer treated with DCF. Fifty-eight patients received cryotherapy during docetaxel administration and 14 received no cryotherapy.

RESULTS:The incidence of mucositis of all grades and grade 3 was significantly lower in the cryotherapy group compared with the no-cryotherapy group (24.1% vs. 71.4%, P < 0.001 and 0% vs. 28.6%, P = 0.001, respectively). The incidence of anorexia of all grades and grade 3 was also significantly lower in the cryotherapy group (22.4% vs. 57.1%, P = 0.037 and 0% vs. 28.6%, P = 0.010, respectively).

CONCLUSION:Adjunctive oral cryotherapy is effective for the prophylaxis and relief of oral mucositis and anorexia caused by chemotherapy.