Transthoracic, thoracoabdominal, and transabdominal surgical approaches for gastric cardia adenocarcinomas: a survival evaluation based on a cohort of 7103 patients.

BACKGROUND: This study compared the survival outcomes of different surgical approaches to determine the optimal approach for gastric cardia adenocarcinoma (GCA) and aimed to standardize the surgical treatment guidelines for GCA. METHODS: A total of 7103 patients with GCA were enrolled from our previously established gastric cardia and esophageal carcinoma databases. In our database, when the epicenter of the tumor was at or within 2 cm distally from the esophagogastric junction, the adenocarcinoma was considered to originate from the cardia and was considered a Siewert type 2 cancer. The main criteria for the enrolled patients included treatment with radical surgery, no radio- or chemotherapy before the operation, and detailed clinicopathological information. Follow-up was mainly performed by telephone or through home interviews. According to the medical records, the surgical approaches included transthoracic, thoracoabdominal, and transabdominal approaches. Kaplan-Meier and Cox proportional hazards regression models were applied to correlate the surgical approach with survival in patients with GCA. RESULTS: There were marked differences in age and tumor stage among the patients who underwent the three surgical approaches (P < 0.001). Univariate analysis showed that survival was related to sex, age, tumor stage, and N stage (P < 0.001 for all). Cox regression model analysis revealed that thoracoabdominal approach (P < 0.001) and transabdominal approach (P < 0.001) were significant risk factors for poor survival. GCA patients treated with the transthoracic approach had the best survival (5-year survival rate of 53.7%), and survival varied among the different surgical approaches for different tumor stages. CONCLUSION: Thoracoabdominal approach and transabdominal approach were shown to be poor prognostic factors. Patients with (locally advanced) GCA may benefit from the transthoracic approach. Further prospective randomized clinical trials are necessary.

Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: a meta-analysis of genome-wide association studies.

Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P< 5 × 10(-8), and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19-1.40) and P= 7.63 × 10(-10). An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants.

[Prediction of temporal trends in gastric cancer mortality in Linzhou city from 1988 to 2010].

OBJECTIVE: To describe the temporal trends in the mortality rate of gastric cancer during the period of 1988 and 2010, and to predict the gastric cancer mortality between 2016 - 2020. METHODS: The data of gastric cancer mortality in Linzhou city between 1988 and 2010 was extracted from the cancer registry, including a total of 11 714 cases, covering 22 447 073 person-years. The mortality rate of gastric cancer of each 5-year period was calculated by sub-site and gender. Age-standardized rate (ASR) was calculated using the Chinese standard population in 1982. Intrinsic estimator (IE) model was used to fit the mortality trend by sub-site and gender, and to predict the mortality of gastric cancer in Linzhou city between 2016 and 2020. RESULTS: From 1988 to 2010, the gastric cancer mortality in Linzhou city was 52.18/100 000 (11 714/22 447 073) with the ASR at 49.23/100 000; the mortality in male was 67.02/100 000 (7678/11 455 512) with ASR at 68.68/100 000 while the mortality in female was 36.72/100 000 (4036/10 991 561) with ASR at 32.12/100 000. The mortality of cardia carcinoma was 27.87/100 000 (6257/22 447 073) with the ASR at 26.37/100 000; while the mortality of non-cardia carcinoma was 24.31/100 000 (5457/22 447 073) with the ASR at 22.86/100 000. The ASR of gastric cancer during 1988 - 1990 was 63.37/100 000 (1653 cases) and decreased by 28.34%, to 45.41/100 000 (2622 cases) during 2006 - 2010. The IE model showed that the birth cohort effect decreased greatly. The mortality risk of cardia carcinoma in population born after 1950s, decreased significantly; and the mortality risk of non-cardia carcinoma in population born in 20 century continually decreased. The death of gastric cancer among the population over 30 years old was predicted to be 3626 cases, increasing by 40.60% compared with the number between 2006 and 2010 (2579 cases). Among them, the mortality of cardia carcinoma increased by 51.89% (predicted number between 2016 and 2020 was 2456 cases, and 1617 cases between 2006 and 2010), and the mortality of non-cardia carcinoma increased by 21.62% (predicted number between 2016 and 2020 was 1170 cases, and 962 cases between 2006 and 2010). CONCLUSION: The mortality rate of gastric cancer in Linzhou city showed a decreasing trend during the period of 1988-2010, being mainly attributed to the cohort effect. However, the mortality will still increase in the future, between 2016 and 2020.

[Time trends in esophageal cancer mortality in Linzhou city in 1986 - 2010 and future prediction].

OBJECTIVE: To analyze the trends in mortality of esophageal cancer and explore the effects of age, period and cohort on esophageal cancer mortality rate in Linzhou city in 1986 - 2010, and predict the mortality of esophageal cancer in 2016 - 2020. METHODS: All of the esophageal cancer-attributed deaths in 1986 - 2010 were drawn from the database in Center of Cancer and Vita Statistics in Henan Province. The numbers of the death cases and population were tabulated into 5-year age groups and 5-year period groups for each sex and linked each other. The age-adjusted mortality rates were calculated by direct standardization to the Chinese population structure in 1982. Intrinsic estimator model (IE model)was used to perform the age-period-cohort analysis and estimate the corresponding parameters. Age effect, period effect and cohort effect on esophageal cancer mortality rate was plotted separately. The mortality of esophageal cancer during 2016 - 2020 was predicted according to the parameters by that model. RESULTS: A total of 15432 cases died from esophageal cancer in Linzhou city in1986 - 2010. The overall crude mortality rate was 63.89 per 100, 000. Among men, the age-adjusted mortality rate was 109.66 per 100, 000 during 1986-1990 and decreased to 60.59 per 100, 000 during 2006 - 2010. For women, the age-adjusted mortality rate decreased from 74.72 per 100, 000 to 39.05 per 100, 000 at the same two calendar periods. The IE model showed that age effect was remarkable, the period effect was stable and the cohort effect decreased greatly. The predicted mortality of over 30-years old population during 2016 - 2020 is 1501 for men and 1083 for women. Compared with 2006 - 2010 period the mortality will be decreased by 6.71% and 11.08%, respectively. CONCLUSIONS: The mortality rate of esophageal cancer in Linzhou city shows a decreasing trend during the period of 1986 - 2010. This trend is mainly attributed to the cohort effect. The predicted mortality in the future will decrease continually.

[Period survival analysis of esophageal cancer in Linzhou city of Henan province].

OBJECTIVE: To analyze the survival level and variation of esophageal cancer in Linzhou city of Henan province from 1988 to 2004, and evaluate the effects of diagnosis and treatments on esophageal cancer in this area. METHODS: All incidence and death records for esophageal cancer during 1988 to 2004 were collected from Linzhou Tumor Registry. Cases with duplicate information or death certificate only were excluded. A total of 12,160 cases of esophageal cancer were collected, of which, 6914 cases were male, and 5246 cases were female. The sex-specific and age-specific probabilities of survival in 1992, 1997 and 2002 were calculated and linked to the data of incidence and death on esophageal cancer in this area. Five-year observed survival rate and five-year relative survival rate during 1990 to 1994, 1995 to 1999, 2000 to 2004 were calculated respectively using period survival analysis and cohort survival analysis and Z test. RESULTS: The 5-year relative survival rates among the three-episode were 28.24%, 35.24% and 40.76% respectively during 1988 to 2004. This showed an increasing trend by periods (Z values were 3.94 and 3.07, P < 0.05). The 5-year observed survival rates in men among the three-episode were 13.67%, 18.08% and 22.46% respectively, the 5-year relative survival rates were 29.94%, 36.96% and 38.40%. The 5-year observed survival rates in women among the three-episode were 15.56%, 19.29% and 28.01% respectively, the 5-year relative survival rates were 26.78%, 33.12% and 43.70%. During the two former periods, there was no significant difference in the 5-year observed survival rate and relative survival rate between men and women (Z values of observed survival rate were 1.48 and 0.88, P > 0.05. Z values of relative survival rate were 1.27 and 1.50, P > 0.05). In the third period, the 5-year observed survival rate and relative survival rate in women was higher than that in men (observed survival rate Z = 3.56, P < 0.05; relative survival rate Z = 2.09, P < 0.05). The relative survival rate that calculated using period method (respectively 35.24% and 40.76%) was higher than that using cohort method (respectively 28.77% and 33.35%) from 1995 to 1999, and from 2000 to 2004. CONCLUSION: The survival rate on esophageal cancer in Linzhou city was increasing in the three different periods. This indicated a rising status in the secondary prevention and clinical diagnosis and treatments on esophageal cancer.

[Descriptive analysis of incidence and time trends of esophageal and gastric cancers in Linzhou city].

OBJECTIVE: To analyze the incidence and time trends of esophageal and gastric cancers in Linzhou city bassed on the data of Linxian Tumor Registry, and to provide valid reference data for research and effective estimation of cancer control in this area. METHODS: All incidence records for the both cancers during 1988-2003 were drawn from Linzhou Tumor Registry and grouped by sex, age, year and then linked to corresponding population data. The incidence rates of those two topographic site cancers were calculated and the age-adjusted rates were calculated by direct standardization to the world population. A joinpoint model was used to get the annual percentage change (APC) of the age-adjusted rates, and to estimate the epidemiological trends of both cancers in population of Linzhou city. RESULTS: In the year 2003 the age-adjusted incidence rates of esophageal and gastric cancers were 81.78 per 100 000 and 77.08 per 100 000, respectively, in the population of Linzhou city. The incidence rate of both cancers showed a decreasing trend from 1988 to 2003. The APC of the incidence rates of esophageal cancer was - 2.6% and that of gastric cancer was - 1.8%, and both indexes were statistically significant (P < 0.05). CONCLUSION: The incidence rates of esophageal and gastric cancers have presented a decreasing trends in the population of Linzhou city. This trend will continue along with the development of social economy, elevation of living standard and improvement in living habit and environment.

[The trends on the mortality for esophagus and stomach cancers in Linzhou city from 1988 to 2003].

OBJECTIVE: Using the data on death for esophagus and stomach cancers in Linzhou cancer registration system, the mortality was described as well as the changing trend was analyzed. METHODS: 18 240 death recorders for the both cancers during 1988 to 2003 were drawn from Linzhou cancer registration system. Of which, 10138 cases were esophageal cancer and 8102 cases were gastric cancer. Then data were stratified by sex, age, year and then linked to demographic classifications. The mortalities of two topographic site cancers were calculated and the age-adjusted rates were calculated by direct standardization to the world population. The Joinpoint model was used to get the estimated annual percent change (EAPC) of the age-adjusted rates, so to estimate the death rate change trends of both cancers in population of Linzhou city. RESULTS: In 2003, the age-adjusted mortalities of esophageal cancer and gastric cancer were 68.47 per 100,000 and 57.01 per 100,000 respectively of Linzhou city. From 1988 to 2003 the death rates for both of cancers had showed the decline trends. The EAPC of the mortality for esophageal cancer was -3.82 (-4.81 - -2.82, P < 0.001) and that for gastric cancer was -2.95 (-4.16 - -1.73, P < 0.001) respectively. CONCLUSION: The declining trend in was observed the mortality of esophageal and gastric cancer in Linzhou by this study.

Esophageal/gastric cancer screening in high-risk populations in Henan Province, China.

OBJECTIVE: To summarize the endoscopic screening findings in high-risk population of esophageal and gastric carcinoma and analyze influential factors related to screening. METHODS: In seven selected cities and counties with high incidences of esophageal carcinoma, people at age of 40-69 were set as the target population. Those with gastroscopy contradictions were excluded, and all who were voluntary and willing to comply with the medical requirements were subjected to endoscopic screening and histological examination for esophageal, gastric cardia and gastric carcinoma in accordance with national technical manual for early detection and treatment of cancer. RESULTS: In three years, 36,154 people were screened, and 16,847 (46.60%) cases were found to have precancerous lesions. A total of 875 cases were found to have cancers (2.42%), and among them 739 cases had early stage with an early diagnosis rate is 84.5%. Some 715 patients underwent prompt treatment and the success rate was 81.8%. CONCLUSIONS: In a high-risk population of esophageal and gastric carcinoma, it is feasible to implement early detection and treatment by endoscopic screening. Screening can identify potential invasive carcinoma, early stage carcinoma and precancerous lesions, improving efficacy through early detection and treatment. The exploratory analysis of related influential factors will help broad implementation of early detection and treatment for esophageal and gastric carcinoma.

Time trends of esophageal cancer mortality in Linzhou city during the period 1988-2010 and a Bayesian approach projection for 2020.

In recent decades, decreasing trends in esophageal cancer mortality have been observed across China. We here describe esophageal cancer mortality trends in Linzhou city, a high-incidence region of esophageal cancer in China, during 1988-2010 and make a esophageal cancer mortality projection in the period 2011-2020 using a Bayesian approach. Age standardized mortality rates were estimated by direct standardization to the World population structure in 1985. A Bayesian age-period-cohort (BAPC) analysis was carried out in order to investigate the effect of the age, period and birth cohort on esophageal cancer mortality in Linzhou during 1988-2010 and to estimate future trends for the period 2011-2020. Age-adjusted rates for men and women decreased from 1988 to 2005 and changed little thereafter. Risk increased from 30 years of age until the very elderly. Period effects showed little variation in risk throughout 1988-2010. In contrast, a cohort effect showed risk decreased greatly in later cohorts. Forecasting, based on BAPC modeling, resulted in a increasing burden of mortality and a decreasing age standardized mortality rate of esophageal cancer in Linzhou city. The decrease of esophageal cancer mortality risk since the 1930 cohort could be attributable to the improvements of social- economic environment and lifestyle. The standardized mortality rates of esophageal cancer should decrease continually. The effect of aging on the population could explain the increase in esophageal mortality projected for 2020.

Cost-benefit analysis of esophageal cancer endoscopic screening in high-risk areas of China.

AIM: To estimate the cost-benefit of endoscopic screening strategies of esophageal cancer (EC) in high-risk areas of China. METHODS: Markov model-based analyses were conducted to compare the net present values (NPVs) and the benefit-cost ratios (BCRs) of 12 EC endoscopic screening strategies. Strategies varied according to the targeted screening age, screening frequencies, and follow-up intervals. Model parameters were collected from population-based studies in China, published literatures, and surveillance data. RESULTS: Compared with non-screening outcomes, all strategies with hypothetical 100,000 subjects saved life years. Among five dominant strategies determined by the incremental cost-effectiveness analysis, screening once at age 50 years incurred the lowest NPV (international dollar-I$55 million) and BCR (2.52). Screening six times between 40-70 years at a 5-year interval [i.e., six times(40)f-strategy] yielded the highest NPV (I$99 million) and BCR (3.06). Compared with six times(40)f-strategy, screening thrice between 40-70 years at a 10-year interval resulted in relatively lower NPV, but the same BCR. CONCLUSION: EC endoscopic screening is cost-beneficial in high-risk areas of China. Policy-makers should consider the cost-benefit, population acceptance, and local economic status when choosing suitable screening strategies.

Estimating the costs of esophageal cancer screening, early diagnosis and treatment in three high risk areas in China.

BACKGROUND: The incidence and mortality of esophageal cancer (EC) in some rural areas with poor health resources in China are the highest around the world. In these areas, screening programs for EC are conducted for prevention and control. However, costs associated with esophageal cancer screening have not been characterized in detail. This study is aimed to estimate the screening, early diagnosis and treatment costs of EC using micro-costing methods, which could provide basic cost inputs for further systematic health economic evaluation. MATERIALS AND METHODS: Micro-costing methods were adopted to collect data on quantity and unit cost of used resources. Data was obtained from face-to-face interview with medical staff, local hospitals' database, and experts' input. We used 80% capacity utilization and 3% discount rate to annualize capital investments, and all costs were adjusted to year 2008 using the gross domestic production deflator, and then converted from Chinese currency unit to international dollars (I$) using purchasing power parity. RESULTS: Screening costs per case were around I$60. For severe dysplasia, carcinoma in situ and intramucosal carcinoma, the costs per capita of endoscopic mucosal resection were I$1292~I$1620, and around I$450 for argon plasma coagulation. For submucosal carcinoma (T1N0M0), and invasive carcinoma treated by esophagectomy, the treatment costs ranged from I$1485 to I$2171. The costs of treatment of invasive carcinoma were: I$497~I$685.2 for radiotherapy; I$4652~I$7966.15 for chemotherapy; I$1928~I$2805 for combination of esophagectomy and radiotherapy; I$6632~I$8082 for esophagectomy, radiotherapy and chemotherapy in combination. CONCLUSION: The cost analysis found screening, early diagnosis and treatment for EC could provide great cost savings. The results provide important information for further health economic evaluation, and to help the local policy makers on updating such screening program in high risk areas in China.

Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54.

We performed a genome-wide association study of esophageal squamous cell carcinoma (ESCC) by genotyping 1,077 individuals with ESCC and 1,733 control subjects of Chinese Han descent. We selected 18 promising SNPs for replication in an additional 7,673 cases of ESCC and 11,013 control subjects of Chinese Han descent and 303 cases of ESCC and 537 control subjects of Chinese Uygur-Kazakh descent. We identified two previously unknown susceptibility loci for ESCC: PLCE1 at 10q23 (P(Han combined for ESCC) = 7.46 x 10(-56), odds ratio (OR) = 1.43; P(Uygur-Kazakh for ESCC) = 5.70 x 10(-4), OR = 1.53) and C20orf54 at 20p13 (P(Han combined for ESCC) = 1.21 x 10(-11), OR = 0.86; P(Uygur-Kazakh for ESCC) = 7.88 x 10(-3), OR = 0.66). We also confirmed association in 2,766 cases of gastric cardia adenocarcinoma cases and the same 11,013 control subjects (PLCE1, P(Han for GCA) = 1.74 x 10(-39), OR = 1.55 and C20orf54, P(Han for GCA) = 3.02 x 10(-3), OR = 0.91). PLCE1 and C20orf54 have important biological implications for both ESCC and GCA. PLCE1 might regulate cell growth, differentiation, apoptosis and angiogenesis. C20orf54 is responsible for transporting riboflavin, and deficiency of riboflavin has been documented as a risk factor for ESCC and GCA.

[Genetic diversity of Hippophae rhamnoides L. sub-populations on loess plateau under effects of varying meteorologic conditions].

The genetic diversity and genetic differentiation of eight Hippophae rhamnoides L. populations in eastern Gansu Province, as well as the effects of varying meteorologic conditions on them were assessed by using inter-simple sequence repeat (ISSR) molecular marker method. A total of 240 individuals in the populations were sampled. Using eleven primers, 165 bands were generated, ranging in size from 300 to 1500 bp, and 157 (95.76%) were found to be polymorphic. The analysis of molecular variance (AMOVA) demonstrated that there was a relatively high level (76.5%) of genetic variation within the populations, with the gene differentiation coefficient (Gst) and gene flow being 0.2418 and 1.5675, respectively. Therefore, to protect the gene resources of H. rhamnoides, the individuals within the populations should be first considered. Mantel test showed that genetic distance was significantly positively correlated with geographical distance (r = 0.65, p = 0.002), and regression modeling between genetic diversity and meteorologic factors suggested that there was a significant positive correlation between wind speed during blooming and genetic diversity of H. rhamnoides, illustrating that wind speed in blooming period and geographic distance were the vital factors affecting the genetic diversity of H. rhamnoides population.

[Relationship between carcinoma cell embolus of esophageal or cardiac cancer and its clinical pathology].

BACKGROUND & OBJECTIVE: Carcinoma cell embolus is a common pathological phenomenon in malignant tumors. However, there was few reports about the factors that affect the formation of carcinoma cell embolus. This study was designed to investigate the relationship between carcinoma cell embolus of esophageal or cardiac cancer and its clinical pathology. METHOD: To analyze the relations among carcinoma cell embolus, tumor invasion depth lymph node metastasis number, and cell differentiation in 59 patients with esophageal cancer and cardiac cancer. RESULTS: The relationship between carcinoma cell embolus and its formation factors were reflected as follow, there was no obvious difference among T1, T2, T3 (P > 0.05), and, quite obvious difference between T4 and T1, T2, T3 (P < 0.01). Carcinoma cell embolus is related to lymph node metastasis numbers in direct proportion and has relations with degree of carcinoma cell differentiation (P < 0.01). CONCLUSION: There was obvious relationship among tumor invasion depth, numbers of lymph node metastasis, and low-undifferentiation of carcinoma cell for carcinoma cell embolus.