Search

Objective: To establish the life expectancy burden of esophago‐gastric cancer by analyzing years of life lost (YLL) for a Western patient population after treatment of early esophageal (EAC) or early gastric (GAC) adenocarcinoma. Background: For patients with early EAC or GAC, the short‐term prognosis after surgical resection is very good. Little data is available regarding long‐term prognosis when compared to the general population. Methods: Two hundred and fourteen patients with pT1 EAC (n = 112) or GAC (n = 102) were included in the study. Patients with EAC underwent transthoracic en‐bloc esophagectomy; those with GAC had total or subtotal gastrectomy with D2‐lymphadenectomy. Surviving patients had a median follow‐up of approximately 14 years. YLL was calculated using average life expectancy data from Germany. Results: Patients with EAC were younger (median age 61 years) than those with GAC (66 years) (p = 0.031). The male:female ratio was 10:1 for EAC and 3:2 for GAC (p < 0.001). Multivariate survival analysis showed the age of the patients ≥60 years and the existence of lymph node metastasis was associated with poor prognosis. The median YLL for all patients who died over follow‐up was 8.0 years. For patients under 60 years, it was approximately 20 years, and for older patients, approximately 5 years (p < 0.001) without difference in tumor stage between these age cohorts. YLL did not differ for GAC vs. EAC. Conclusion: After surgical resection, the prognostic burden as measured by YLL is relevant for all patients with early esophageal and gastric adenocarcinomas and especially for younger patients. Reasons for YLL need further studies. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the predictive value of a single or combination of biomarker(s) for histopathologic non-response to neoadjuvant chemoradiation in esophageal cancer. Summary of Background Data: Patients without response to neoadjuvant chemoradiation for esophageal cancer have no prognostic benefits, but experience time delays and risk side effects. Methods: Inclusion criteria for this prospective diagnostic study were patients with cT3,Nx,M0, esophageal squamous cell or adenocarcinoma and planned neoadjuvant chemoradiation (5- fluorouracil, cisplatin, 40Gy) followed by 2-field transthoracic esophagectomy. Frompretherapeutic endoscopic tumor biopsies, ERCC1 rs11615 single-nucleotide polymorphism (ERCC1-SNP) and a combination of gene expression marker mRNA (ERCC1, DPYD, ERBB2) were analyzed. ERCC1-SNP was subdifferentiated into homozygous C-allele (CC) and T-allele (TT), and heterozygous C/T carriers. The primary endpoint was the prediction of histopathological minor response (≥10%vital tumor cells in the primary tumor) relative to marker levels. Results: From 2009 until 2013, 320 patients were screened, and 85 patients (SCC n=29, AC n=56) were included in the study. Forty-one patients (48%) had major response with 3-year survival rate (3-YSR) of 57% compared with 44 patients with minor response and 3-YSR of 25% (P = 0.001). Patients with ERCC1-SNP CC (n = 8) and TT (n = 37) had similar rates of minor response of 70% and 75%, and a positive predictive value (PPV) of 71% [95% confidence interval (CI 56%-84%)]. PPV increased to 89% (95% CI 73%-96%) when ERCC1-SNP was combined with mRNA markers. Conclusion: ERCC1-SNP in combination with mRNA ERCC1, DPYD, and ERBB2 from pretherapeutic endoscopic biopsies can predict minor response to chemoradiation, as a basis for individualized therapy of advanced esophageal cancer. [ABSTRACT FROM AUTHOR]

Prognostic factors after preoperative chemoradiation for patients with advanced esophageal cancer are under discussion. Treatment response measured in the primary tumor is a well-defined prognostic marker. The prognostic relevance of tumor regression in lymph nodes (LNs), eg, histomorphologic characteristics must be evaluated in a larger series of patients. From 1997-2010, 403 patients with cT3N×M0 esophageal cancer underwent preoperative chemoradiation followed by transthoracic esophagectomy. Histopathologic response of the primary tumor was graded in resected specimens as "minor" (≥10% vital residual tumor cells) or "major." The LNs of all patients without LN metastases (ypN0 n = 222, adenocarcinoma n = 129, squamous cell carcinoma n = 93) were reevaluated for central fibrosis. Univariate and multivariate analyses were performed on histomorphologic criteria of examined LNs and used to correlate these with tumor response and prognosis. The 5-year survival rate (5YSR) for all patients was 30%. Overall, 5480 LNs were reevaluated for the existence of central fibrosis in ypN0 cases. The prognostic relevance of the LN regression (LNR) grading system was confirmed for all patients with univariate (P < 0.001) and multivariate (P = 0.02) analyses. In results, the 5YSR for ypN0 patients overall was 37%, for patients with major response by the primary tumor was 42%, and for minor responders was 19% (P < 0.001). Analyzing LNR in major responders, the group with less than 3 LNs with central fibrosis (n = 52) showed significantly better prognosis (5YSR = 63%) compared to those with more (5YSR = 34%), (P = 0.016). Conclusion includes morphologic signs of metastatic LNR after chemoradiation, such as central fibrosis, are of prognostic relevance for patients with advanced esophageal cancer, especially for those with major response of the primary tumor. [ABSTRACT FROM AUTHOR]

Esophageal cancer is often diagnosed at an advanced stage. Diagnostic markers are needed for achieving a cure in esophageal cancer detecting and treating tumor cells earlier. In patients with locally advanced squamous cell carcinoma of the esophagus (ESCC), we profiled the gene expression of ESCC compared to corresponding normal biopsies for diagnostic markers by genome microarrays. Profiling of gene expression identified 4844 genes differentially expressed, 2122 upregulated and 2722 downregulated in ESCC. Twenty-three overexpressed candidates with best scores from significance analysis have been selected for further analysis by TaqMan low-density array-technique using a validation cohort of 40 patients. The verification rate was 100 % for ESCC. Twenty-two markers were additionally overexpressed in adenocarcinoma of the esophagus (EAC). The markers significantly overexpressed already in earlier tumor stages (pT1-2) of both histological subtypes ( n = 19) have been clustered in a 'diagnostic signature': PLA2G7, PRAME, MMP1, MMP3, MMP12, LIlRB2, TREM2, CHST2, IGFBP2, IGFBP7, KCNJ8, EMILIN2, CTHRC1, EMR2, WDR72, LPCAT1, COL4A2, CCL4, and SNX10. The marker signature will be translated to clinical practice to prove its diagnostic impact. This diagnostic signature may contribute to the earlier detection of tumor cells, with the aim to complement clinical techniques resulting in the development of better detection of concepts of esophageal cancer for earlier therapy and more favorite prognosis. [ABSTRACT FROM AUTHOR]

Background: Presence of nodal skip metastasis is an established prognostic factor for patients with non–small cell lung cancer. Little is known about this form of lymphatic spread in esophageal cancer. The aim of this study was to assess nodal skip metastasis and its clinical importance for patients with cancer of the esophagus. Methods: Resected lymph nodes of 128 patients with esophageal cancer and pN1 status (adenocarcinoma, n = 67; squamous cell cancer, n = 61) were mapped according to the Japanese lymph-node classification for esophageal cancer. Skip metastases were defined as tumor-free N1 lymph nodes, whereas N2 through N4 lymph nodes harbor metastases. Results: Skip metastases were present in 26 of 128 (20%) patients. There was a higher rate of skip metastasis in early tumors (39% versus 23% versus 14% for T1, T2, and T3 tumors; p = 0.032) and tumors in the middle and upper third of the esophagus (37% versus 15% for upper- and middle-third and lower-third tumors; p = 0.022). Patients with skip metastasis had a significantly better 5-year survival rate than patients with continuous metastasis (53% versus 15%; p < 0.0001). Multivariate analysis revealed skip metastasis as an independent prognostic factor. Conclusions: Skip metastasis is a common form of lymphatic spread in esophageal cancer, which is associated with a favorable prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Neoadjuvant treatment strategies have been developed to improve survival of patients with locally advanced esophageal cancer. Since only patients with major histopathological response benefit from this therapy, predictive markers are needed. We examined a panel of selected gene polymorphisms to predict response to neoadjuvant radiochemotherapy (cisplatin, 5-fluorouracil, 36 Gy) in esophageal cancer patients.Materials and Method: Genomic DNA was extracted from paraffin-embedded tissues of 52 patients. Allelic genotyping was performed by real-time polymerase chain reaction using allele-specific TaqMan probes and correlated with therapy response.Results: Single-nucleotide polymorphism ERCC1 C118T was predictive for therapy response (p < 0.003). Within the TT genotype group of 25 patients, 20 (80%) did not respond to chemoradiation. Of 20 patients with heterogeneous C/T genotype, 14 (70%) were major responders. The CC genotype (seven patients) was not of predictive importance. ERCC1 polymorphism was significantly (p < 0.02) associated with formation of lymph node metastases. Predominant GG genotype of XRCC1 A194G was not predictive; however, the rarely occurring AA genotype was response-associated and the A/G variant was associated with nonresponse. Fifteen additionally analyzed polymorphisms did not show any correlation.Conclusion: Our data support the role of ERCC1 as a predictive marker for therapy response. Single-nucleotide polymorphisms of ERCC1 and XRCC1 could be applied to further individualize treatment strategies. [ABSTRACT FROM AUTHOR]

Introduction: Neoadjuvant multimodality treatment is frequently applied to improve the poor prognosis associated with locally advanced esophageal cancer. However, only patients with a major histopathologic response to neoadjuvant therapy will have a significant survival benefit. Predictive markers to allow individualization of multimodality treatment could be very helpful. We aimed to examine the association of survivin protein expression, an inhibitor of apoptosis, with histopathologic response to neoadjuvant chemoradiation and prognosis in patients with esophageal cancer. Patients & methods: A total of 59 patients with esophageal cancer (clinical tumor stage 2-4, Nx, M0) received neoadjuvant chemoradiation followed by transthoracic en bloc esophagectomy. Histomorphologic regression was defined as major response when resected specimens contained less than 10% vital tumor cells. Intratumoral survivin expression was determined by immunohistochemistry in pretherapeutic biopsies and post-therapeutic resection specimens and correlated with clinicopathologic parameters. Results: The pretherapeutic intratumoral survivin protein expression was not associated with any clinicopathologic factor. Survivin protein expression decreased significantly during neoadjuvant therapy, showing lower levels in post-therapeutic tumor samples (p < 0.01). Elevated postoperative survivin levels were significantly associated with a higher pathologic tumor stage after neoadjuvant therapy (ypT) category (p < 0.01), a poorer histopathologic response (p < 0.01) and a shorter overall survival (p < 0.028). Conclusion: Intratumoral survivin protein expression was significantly downregulated during neoadjuvant therapy of esophageal cancers. Elevated survivin levels after preoperative therapy were significantly associated with a minor histopathologic response and prognosis. Therefore, failure in downregulation of intratumoral survivin expression following neoadjuvant chemoradiation in esophageal cancer needs therapeutic strategies to reduce survivin expression or block survivin-mediated pathways to increase the histopathologic response rate and prognosis. [ABSTRACT FROM AUTHOR]

Tumor-infiltrating lymphocytes (TILs) are correlated to prognosis of several kinds of cancer. Most studies focused on T cells, while the role of tumor-associated B cells (TABs) has only recently gained more attention. TABs contain subpopulations with distinct functions, potentially promoting or inhibiting immune responses. This study provides a detailed analysis of TABs in gastro-esophageal adenocarcinoma (EAC). Flow cytometric analyses of single cell suspensions of tumor samples, mucosa, lymph nodes and peripheral blood mononuclear cells (PBMC) of EAC patients and healthy controls revealed a distinct B cell compartment in cancer patients. B cells were increased in tumor samples and subset-analyses of TILs showed increased proportions of differentiated and activated B cells and an enrichment for follicular T helper cells. Confocal microscopy demonstrated that TABs were mainly organized in tertiary lymphoid structures (TLS), which resemble lymphoid follicles in secondary lymphoid organs. A panel of 34 tumor-associated antigens (TAAs) expressed in EAC was identified based on public databases and TCGA data to analyze tumor-specific B cell responses using a LUMINEXTM bead assay and flow cytometry. Structural analyses of TLS and the detection of tumor-specific antibodies against one or more TAAs in 48.1% of analyzed serum samples underline presence of anti-tumor B cell responses in EAC. Interestingly, B cells were decreased in tumors with expression of Programmed Death Ligand 1 or impaired HLA-I expression. These data demonstrate that anti-tumor B cell responses are an additional and underestimated aspect of EAC. Our results are of immediate translational relevance to emerging immunotherapies. [ABSTRACT FROM AUTHOR]