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BackgroundThe impact of hospital volume on the long-term survival of esophageal squamous cell carcinoma (ESCC) has not been well assessed in China, especially for stage I–III stage ESCC. We performed a large sample size study to assess the relationships between hospital volume and the effectiveness of ESCC treatment and the hospital volume value at the lowest risk of all-cause mortality after esophagectomy in China.AimTo investigate the prognostic value of hospital volume for assessing postoperative long-term survival of ESCC patients in China.MethodsThe date of 158,618 patients with ESCC were collected from a database (1973–2020) established by the State Key Laboratory for Esophageal Cancer Prevention and Treatment, the database includes 500,000 patients with detailed clinical information of pathological diagnosis and staging, treatment approaches and survival follow-up for esophageal and gastric cardia cancers. Intergroup comparisons of patient and treatment characteristics were conducted with the X2 test and analysis of variance. The Kaplan-Meier method with the log-rank test was used to draw the survival curves for the variables tested. A Multivariate Cox proportional hazards regression model was used to analyze the independent prognostic factors for overall survival. The relationship between hospital volume and all-cause mortality was assessed using restricted cubic splines from Cox proportional hazards models. The primary outcome was all-cause mortality.ResultsIn both 1973-1996 and 1997-2020, patients with stage I-III stage ESCC who underwent surgery in high volume hospitals had better survival than those who underwent surgery in low volume hospitals (both PConclusionHospital volume can be used as an indicator to predict the postoperative survival of ESCC patients. Our results suggest that the centralized management of esophageal cancer surgery is meaningful to improve the survival of ESCC patients in China, but the hospital volume should preferably not be higher than 1027 cases/year.Core tipHospital volume is considered to be a prognostic factor for many complex diseases. However, the impact of hospital volume on long-term survival after esophagectomy has not been well evaluated in China. Based on a large sample size of 158,618 ESCC patients in China spanning 47 years (1973-2020), We found that hospital volume can be used as a predictor of postoperative survival in patients with ESCC, and identified hospital volume thresholds with the lowest risk of death from all causes. This may provide an important basis for patients to choose hospitals and have a significant impact on the centralized management of hospital surgery.

BackgroundThis 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.MethodsA 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.ResultsThere were marked differences in age and tumor stage among the patients who underwent the three surgical approaches (P P P P ConclusionThoracoabdominal 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.

BACKGROUND Gastric cardia adenocarcinoma (GCA), which has been classified as type II adenocarcinoma of the esophagogastric junction in western countries, is of similar geographic distribution with esophageal squamous cell carcinoma in China, and even referred as "sister cancer" by Chinese oncologists. The molecular mechanism for GCA is largely unknown. Recent studies have shown that decreased expression of E-cadherin is associated with the invasion and metastasis of multiple cancers. However, the E-cadherin expression has not been well characterized in gastric cardia carcinogenesis and its effect on GCA prognosis. AIM To characterize E-cadherin expression in normal gastric cardia mucosa, dysplasia and GCA tissues, and its influence on prognosis for GCA. METHODS A total of 4561 patients with GCA were enrolled from our previously established GCA and esophageal cancer databases. The enrollment criteria included radical surgery for GCA, but without any radio- or chemo-therapy before operation. The GCA tissue from 4561 patients and matched adjacent normal epithelial tissue (n = 208) and dysplasia lesions (n = 156) were collected, and processed as tissue microarray for immunohistochemistry. The clinicopathological characteristics were retrieved from the medical records in hospital and follow-up was carried out through letter, telephone or home interview. E-cadherin protein expression was determined by two step immunohistochemistry. Kaplan–Meier and Cox regression analyses were used to correlate E-cadherin protein expression with survival of GCA patients. RESULTS Of the 4561 GCA patients, there were 3607 males with a mean age of 61.6 ± 8.8 and 954 females with a mean age of 61.9 ± 8.6 years, respectively. With the lesions progressed from normal gastric cardia mucosa to dysplasia and GCA, the positive immunostaining rates for E-cadherin decreased significantly from 100% to 93.0% and 84.1%, respectively (R2 = 0.9948). Furthermore, E-cadherin positive immunostaining rate was significantly higher in patients at early stage (0 and I) than in those at late stage (II and III) (92.7% vs 83.7%, P = 0.001). E-cadherin positive expression rate was significantly associated with degree of differentiation (P = 0.001) and invasion depth (P < 0.001). Multivariate analysis showed that the GCA patients with positive E-cadherin immunostaining had better survival than those with negative (P = 0.026). It was noteworthy that E-cadherin positive expression rate was similar in patients with positive and negative lymph node metastasis. However, in patients with negative lymph node metastasis, those with positive expression of E-cadherin had better survival than those with negative expression (P = 0.036). Similarly, in patients with late stage GCA, those with positive expression of E-cadherin had better survival than those with negative expression (P = 0.011). CONCLUSION E-cadherin expression may be involved in gastric cardia carcinogenesis and low expression of E-cadherin may be a promising early biomarker and overall survival predictor for GCA.

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 P5 × 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.

Esophageal squamous cell carcinoma (ESCC) remains one of the leading cause of cancer-related death in China. Moreover, more than 90% of the ESCC patients have been in the advanced stage when diagnosed, the 5-year survival is very poor even though the medical techniques have been improved in the past decades. Although the accumulated evidences have suggested the crucial role of genetic changes in esophageal carcinogenesis, the target therapy based on these genetic changes is largely in the very beginning, and radical esophagectomy and radiochemotherapy remain the chief choice for ESCC treatment at present. The present study was thus designed to evaluate the efficacy of the present treatment methods in China to provide more information for optimal choice in advanced ESCC treatment. The enrolled 20,712 ESCC patients in this study were from the ESCC database in Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University. Of the patients, there were 12,818 males with a mean age of 59.59±8.2 and 7,894 females with a mean age of 60.34±8.3. All the 20,712 patients were confirmed by histopathology as ESCC at II to IV stage (advanced stage) and classified into three groups based on the treatment methods: radical esophagectomy (R0) alone (17,577, 84.8%), R0 plus radiochemotherapy (2,510, 12.1%) and radiochemotherapy alone (625, 3.1%). The followed-up was undertaken until 2016. The SPSS21.0 software and Kaplan-Meier survival analysis and Log Rank test were used to evaluate the efficiency of different treatments. The results demonstrated that the overall median survival time for the three groups was 5.81 years, 4.82 years and 2.85 years, respectively (P Note: This abstract was not presented at the meeting. Citation Format: Rang Cheng, Fu You Zhou, Neng Chao Wang, Ran Wang, Wei Peng Wang, Xian Zeng Wang, Wen Bin Yue, Jian Wei Zhou, Zhan Hui Miao, Guang Cheng Ding, De Chao Bu, Li Dong Wang. Impact of the different treatments on the survival of advanced esophageal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3276. doi:10.1158/1538-7445.AM2017-3276

Lymph node (LN) metastasis has been recognized as one of the most important factors for poor prognosis of esophageal cancer (EC). However, the influence of dissected LN number on metastatic detection rate and survival in EC has not been well documented. The present study was undertaken to correlate the total number of dissected LN, metastatic detection rate and survival on 10,382 EC patients. All the patients had been performed surgical treatment and confirmed as esophageal squamous cell carcinoma (ESCC) by histopathological examination. The patients were from Henan, Hebei and Shanxi provinces, the high incidence areas for EC in northern China, including 6,375 males with a mean age of 58±9 and 4,007 females with a mean age of 59±9. Of the patients, 2,714 cases have been followed up by interview at home until July, 2010. Eight EC groups had been classified based on the total number of dissected LN (1-3, 4-5, 6-7, 8-9, 10-11, 12-13, 14-16 and ≥17). The results showed that the positive metastatic detection rate apparently increased with the total extended dissected LN number (P< 0.05) until reaching the level with a total of 17 or more dissected LN. 5-year survival analysis showed that the patients without LN metastasis had a higher survival rate than those with LN metastasis in all seven groups (P0.05). We concluded that the total dissected LN number could affect the survival rate for EC and that a total of 10 to 16 dissected LN should be recommended for EC surgical treatment. (supported by Innovation Scientists and Technicians Troop Construction Projects of Henan Province). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5525. doi:1538-7445.AM2012-5525