Management of primary gastric small cell carcinoma in China.

BACKGROUND: Primary gastric small cell carcinomas (GSCCs) are increasingly identified by endoscopy, and account for 15-20% of all gastric neuroendocrine tumors (NETs). GSCCs have the worst prognosis with the highest rate of metastases. PURPOSE: To provide useful information for clinicians and researchers to better manage patients with GSCC, we studied the clinical features of GSCC and explored the corresponding therapies and prognosis. METHODS: A literature search was conducted through PUBMED, EMBASE, CNKI and WanFang Databases using search terms "stomach" or "gastric" and "small cell carcinoma" or "poorly differentiated neuroendocrine carcinoma", for the period 1999 to 2012. And the cases reported were all from China. Relevant articles were identified through manual review. The reference lists of these articles were reviewed to include further appropriate articles. RESULTS: Two hundred and five eligible cases were analyzed. The median age of patients was 62 years, with a male-to-female ratio of 5.4:1. Of the tumors, 53.17% were located in the upper stomach, 25.37% in the mid, 18.54% in the distal stomach, the remaining 2.93% were found in the total stomach. The mean size was 68mm in maximum diameter, with a range of 15-150 mm. Of the one hundred and thirty-five patients, fifty appeared to be pure GSCCs, eighty-five were mixed. The median overall survival time of 195 patients was 18.50 months. The 1-, 2-, and 5-year average survival rates of 142 patients were 66.75%, 37.13%, and 20.15%, respectively. CONCLUSIONS: GSCC is a rare tumor and it is notoriously aggressive with a strong propensity for both regional and distant spread. Therapies including surgical resection, chemotherapy, and local radiotherapy, by itself or in combination with other treatment, have been used to treat GSCCs in China. To identify the most effective treatment modalities for GSCCs, we still need prospective, multicenter, randomized clinical researches.

Endoscopic survey of esophageal cancer in a high-risk area of China.

AIM: To characterize the histological types of esophageal and cardiac mucosa by endoscopic survey of a population in a high-risk area of esophageal cancer of China. METHODS: A selected cohort of residents in Cixian County during December 2001 and May 2002 was surveyed by using Lugol's staining, followed by computer-based statistical analysis of the data with SPSS 10.0 software. RESULTS: Histologically, the detection rates of squamous epithelial acanthosis, squamous epithelial atrophy, and basal cell hyperplasia in the esophagus were 1.9% (38/2,013), 0.1% (3/2,013) and 0.9% (18/2,013) respectively, and those of mild, moderate, and severe esophagitis were 34.9% (703/2,013), 1.6% (33/2,013) and 0.2% (2/2,013) respectively. Mild, moderate, and severe esophageal dysplasia were detected in 8.6% (172/2,013), 7.8% (157/2,013) and 2.6% (53/2,013) respectively in the selected population, whereas in situ carcinoma, intramucosal carcinoma, invasive squamous carcinoma of the esophagus in 2.5% (50/2,013), 0.2% (4/2,013) and 0.7% (14/2,013) respectively. The detection rates of non-atrophic gastritis and atrophic gastritis of the cardia were 36.3% (730/2,013) and 11.5% (232/2,013) respectively, with mild and severe dysplasia of the cardia detected in 2.5% (51/2,013) and 0.8% (17/2,013), respectively, in this population; the rates of intramucosal adenocarcinoma and invasive adenocarcinoma of the cardia were 0.1% (3/2,013) and 0.8% (17/2,013) respectively. The detection rate of esophageal cancer at early stage was 79.4% (54/68). The survey rate (ratio of examined population to expected population) was 73.8% (2,013/2,725). CONCLUSION: Histologic types of the esophageal and cardiac mucosa were characterized by endoscopic survey in a high-risk population of esophageal cancer, which may help the early detection and treatment of esophageal and cardiac cancers and dysplasia, and reduce the mortality of such malignancies.

Management of small cell carcinoma of esophagus in China.

PURPOSE: Small cell carcinoma of esophagus (SCEC) is characterized by high malignancy and early metastasis. Although the morbidity of SCEC is very low, few studies of patients with SCEC have been conducted in China, there are no sufficient studies of SCEC conducted and reported in the existing published works, and the choices of treatment remain controversial. In this work, we aim to study the clinical characteristics of SCEC, and explore the corresponding treatment and prognosis through retrospective analysis. MATERIAL AND METHODS: The original articles were identified through the leading digital libraries in China in which the terms "esophagus or esophageal" and "small cell esophageal carcinoma" appeared from 2005 to 2009, 1,176 eligible cases were reviewed for clinical data. Analysis of survival was conducted using the Kaplan-Meier method, and differences were compared using the log-rank test. RESULTS: One thousand one hundred seventy-six eligible cases were analyzed; the median age of patients was 57 years, with a male-to-female ratio of 2.4:1. The number of SCEC accounted for 1.26 % of esophageal cancer treated in the same period. Of the tumors, 89.7 % were located in mid- and lower thoracic esophagus. The average tumor length was 5.4 cm (0.5-17 cm). The median overall survival was 11.1 months for all patients. The 1-, 2-, 3-, and 5-year average overall survival rates of 469 patients was 51.1, 25.5, 13.2, 7.9 %, respectively. The median survival time for LD patients who received systemic treatment was 16.8 m, whereas for those who received local treatment (surgery), the median survival time was 10.1 m; the median survival time for ED patients who received systemic treatment was 7.4 m, compared with 5.8 m for those who received sole treatment (chemotherapy or radiotherapy). CONCLUSIONS: SCEC is a tumor characterized by high malignancy and early metastasis. Although our retrospective analysis cannot provide definitive conclusions on the optimal treatment modality for SCEC, however, our results suggest that systemic treatment combined with surgical resection plays a major role in the therapy of SCEC, systemic therapy may be an effective approach for the treatment of SCEC, and randomized, prospective, multicenter studies are needed to identify optimal treatment modalities for SCEC.

A randomized controlled trial of conventional fraction and late course accelerated hyperfraction three-dimensional conformal radiotherapy for esophageal cancer.

We compared the curative and side-effects in esophageal carcinoma treated by conventional fraction (CF) and late course accelerated hyperfraction (LCAF) three-dimensional conformal radiotherapy. Ninety-eight patients were randomly assigned to two different radiotherapy model groups. Fifty patients were treated using CF three-dimensional conformal radiotherapy at a total dose of 60-68 Gy; 2 Gy/F; 5 fractions/week (median 64 Gy), 48 patients were treated with LCAF (First CF-treated at the dose 40 Gy. Later, LCAF-treated 1.5 Gy/F; 2 fractions/day; 21-27 Gy; a total dose of 61-67 Gy; median 64 Gy). The data showed that the 1-, 2- and 3-year-survival rates in LCAF group were 79.2, 56.3, and 43.8%, compared to 74, 54, and 36% in CF group (P = 0.476). The 1-, 2- and 3-year-local control rates in LCAF group were 81.3, 62.5, and 50%, compared to 78, 58, and 42% in CF group (P = 0.454). In CF group, the incidence of radiation-induced esophagitis was lower than that in LCAF group (72 vs. 93.8%; P = 0.008) and there was no significant difference between rates of radiation-induced pneumonitis in CF and LCAF groups (10 vs. 6.25%; P = 0.498). It was concluded that the 1-, 2- and 3-year-local control and survival rates of esophageal carcinoma patients treated with LCAF were slightly better than CF radiotherapy; however, the radiation side-effects in LCAF group were greater than those in CF group.

[Mechanisms of preventive effect of tetrandrine on acquired multidrug resistance in K562 cells].

This study was purposed to explore the mechanisms of preventive effect of tetrandrine (TTD) on doxorubicin (ADM)-induced multidrug resistance (MDR) in human leukemia cell line K562 from two aspects of the transcription control of MDR1 gene and cell apoptosis. The experiment was divided into 3 groups: group I-blank control; group II-ADM-induced drug-resistance; group III-ADM-induced drug-resistance after pretreatment with TTD. Reverse transcription-PCR (RT-PCR) was used to detect the mRNA expression levels of c-Jun, YB-1 and Survivin genes. Western blot was used to determine the nuclear protein expression levels of c-Jun and YB-1. Flow cytometry was used to assay the apoptosis of cells. The results showed that as compared with group I, the expression levels of c-Jun mRNA and nuclear protein decreased (p < 0.05), as well as the expression levels of YB-1 mRNA and nuclear protein increased in group II (p < 0.05). However, the expression of Survivin mRNA had no change (p > 0.05); the apoptosis rate of cells was 8.31%. As compared with group II, the expression levels of c-Jun mRNA and nuclear protein increased (p < 0.05), expression levels of YB-1 mRNA and nuclear protein as well as Survivin mRNA decreased in group III (p < 0.05). The apoptosis of cells was 97.2%. It is concluded that TTD can inhibit the expression of YB-1 and up-regulate the expression of c-Jun, thus inhibit the expression of MDR1 gene. TTD can also inhibit the expression of Survivin and increase the apoptosis of cells induced by ADM.

[Effect of tetrandrine on the doxorubicin-induced expression of mdr1 gene in K562 cells].

OBJECTIVE: To investigate the effect of tetrandrine (TTD) on doxorubicin-induced mdr1 gene expression and its mechanism. METHODS: MTT assay was used to detect the cytotoxicity of TTD to K562 cells. K562 cells were treated with doxorubicin alone or 0.6 microg/ml doxorubicin combined with various concentrations of TTD. RT-PCR was used to detect the mRNA expression of mdr1 and NF-kappa B. Flow cytometry was used to assay the expression of P-glycoprotein (P-gp). Intracellular rhodamine 123 (Rho123) retention assay was applied to test the P-gp function. RESULTS: After treatment with 0.6 microg/ml doxorubicin for 24 hours, the expressions of mdr1 mRNA, NF-kappa B mRNA and P-gp in K562 cells were increased from 0.171 +/- 0.012, 0.783 +/- 0.090, 7.85 +/- 0.15 to 0.428 +/- 0.012, 1.075 +/- 0.047 and 73.68 +/- 1.84, respectively. The intracellular Rho123 retention was decreased from 711.9 +/- 63.6 to 347.8 +/- 60.6, indicating up-regulation of P-gp function (P<0.05). Pretreatment of K562 cells with 2.0 microg/ml TTD for 24 hours and then incubated for another 24 h with doxorubicin, the expressions of mdr1 mRNA, NF-kappa B mRNA, P-gp and up-regulation of P-gp function induced by doxorubicin were prevented in K562 cells (0.148 +/- 0.006, 0.627 +/- 0.098, 7.18 +/- 0.38 and 799.7 +/- 45.8, respectively P<0.05). But 0.5 microg/ml and 1.0 microg/ml TTD had little effect. CONCLUSIONS: TTD inhibits the expression of mdr1 mRNA, P-gp and up-regulated P-gp function induced by doxorubicin in a dose dependent manner. The mechanism of this effect may be down-regulation of NF-kappa B by TTD.