Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. There is an urgent need to identify prognostic markers for patients undergoing curative resection of CRC. The detection of circulating tumor cells in peripheral blood is a promising approach to identify high-risk patients with disseminated disease in colorectal cancer. This study aims to evaluate the prognostic relevance of preoperative CTCs using the Cellsearch® system (CS) in patients, who underwent resection with curative intent of different stages (UICC I-IV) of colorectal cancer. Out of 91 Patients who underwent colorectal resection, 68 patients were included in this study. CTC analysis was performed in patients with CRC UICC stages I-IV immediately before surgery. Data were correlated with clinicopathological parameters and patient outcomes. One or more CTCs/7.5 mL were detected in 45.6% (31/68) of patients. CTCs were detected in all stages of the Union of International Cancer Control (UICC), in stage I (1/4, 25%), in stage II (4/12, 33.3%), in stage III (5/19, 26.3%) and in stage IV (21/33, 63.6%). The detection of ≥ 1 CTCs/ 7.5ml correlated to the presence of distant overt metastases (p = 0.014) as well as with shorter progression-free (p = 0.008) and overall survival (p = 0.008). Multivariate analyses showed that the detection of ≥ 1 CTCs/ 7.5ml is an independent prognostic indicator for overall survival (HR, 3.14; 95% CI, 1.18–8.32; p = 0.021). The detection of CTCs is an independent and strong prognostic factor in CRC, which might improve the identification of high-risk patients in future clinical trials.
Background: The prognostic impact of circumferential resection margin (CRM) involvement in resected esophageal cancer (EC) is controversial discussed. The College of American Pathologists (CAP) and the Royal College of Pathologists (RCP) provide 2 different definitions of CRM involvement. The aim of this systematic review was to evaluate the clinical significance of CRM involvement on patients' survival following esophagectomy due to EC. Methods: PubMed, Science Direct, and Google scholar were searched for studies analyzing the clinical impact of CRM in EC. Summary: A total of 28 studies analyzed the prognostic effect of a positive CRM in EC. A wide range of CRM involvement (8.6-83.1%) was reported. Both available meta-analyses found a significant association between a positive CRM and patients' survival irrespective of RCP (OR 2.52 [95% CI 1.96-3.25; p < 0.001]) or CAP (OR 4.02 [95% CI 2.25-7.20; p < 0.001]) criteria. The influence of neoadjuvant therapy on the CRM remains unclear. Key Messages: CRM involvement is a useful parameter for EC patients' prognosis. The application of CAP criteria should be preferred since patients with a poor prognosis can be identified more sufficiently. Neoadjuvant therapy and en bloc transthoracic esophagectomy show favorable results for achievement of negative CRM.
Objective Reflux promotes esophageal adenocarcinomas (EACs) creating a chronic inflammatory environment. Survival rates are low due to early local recurrences and distant metastasis. Hence, there is a need for new potential treatment options like immunotherapies. However, the inflammatory microenvironment in EACs and its impact on patient outcome remain to be fully understood. Methods mRNA expression levels of pro-and anti-inflammatory markers in 39 EAC patients without neoadjuvant radiochemotherapy were measured. Data were confirmed using flow cytometric analysis of freshly resected surgical specimens. Inflammatory alterations in premalignant lesions of Barrett's esophagus were analyzed by immunohistochemistry. Results Expression levels of IL22 were reduced in EAC, while expression levels of FOXP3, IL10 and CTLA4 were increased. Flow cytometry demonstrated a strong infiltration of CD4 + T cells with a reduction in CD4 + T cells producing IL-22 or IL-17A. We also observed an increase in CD4 + CD127 low FOXP3 + cells producing IL-10. Accumulation of FOXP3 + T cells occurred prior to malignant changes. High expression of IL10 and low expression of IL22 in EAC were associated with reduced overall survival. Moreover, increased expression of IL10, CTLA4 and PD1 in the unaltered esophageal mucosa distant to the EAC was also linked with an unfavorable prognosis. Conclusion EAC shows an anti-inflammatory environment, which strongly affects patient survival. The microscopically unaltered peritumoral tissue shows a similar anti-inflammatory pattern indicating an immunological field effect, which might contribute to early local recurrences despite radical resection. These data suggest that using checkpoint inhibitors targeting anti-inflammatory T cells would be a promising therapeutic strategy in EAC.
Purpose: Esophageal perforations are associated with high morbidity and mortality. Different nonoperative and operative treatment options have been proposed. This study focuses on the impact of different surgical treatments in nonmalignant esophageal perforations and tries to identify predictors of mortality in a single tertiary center over a 15-year period. Methods: From 2002 to 2017, patients with surgically managed esophageal perforation were identified from our database. Patients with esophageal malignancies were excluded. Etiology, clinical data, treatment, and outcome were analyzed. A multivariate logistic regression analysis was performed to investigate the impact on mortality. Results: A total of 72 patients were identified. The majority of perforations were iatrogenic (54.2%) followed by Boerhaave’s syndrome (23.6%). Most ruptures were found in the distal third of the esophagus (59.7%) measuring <3 cm (61.1%). Patients were treated with exploration and drainage (8.3%), primary suture and patch reinforcement (36.1%), resection and restoration of continuity (25.0%), or resection without restoration of continuity (30.6%). Delayed therapy significantly correlated with sepsis (p < 0.0001) and mortality (p = 0.032). A correlation between an increasing perforation length with sepsis (p = 0.012) was observed. A higher Perforation Severity Score (PSS; OR 4.430; 95% CI 1.143–17.174; p = 0.031) and a higher American Society of Anesthesiologists (ASA) score (OR 2.923; 95% CI 1.011–8.448; p = 0.048) were associated with mortality in multivariate analysis. Conclusion: Esophageal perforations are associated with high mortality, and larger ruptures are associated with worse outcome. Rapid diagnosis and treatment are crucial for patient survival. Hence, PSS and ASA score help to identify high-risk patients. The advantage of surgical management lies in the rapid control of the septic focus in an already critically ill patient. Though, the kind of surgical technique needs to be adjusted to the individual situation.
Introduction. Current modalities to predict tumor recurrence and survival in esophageal cancer are insufficient. Even in lymph node-negative patients, a locoregional and distant relapse is common. Hence, more precise staging methods are needed. So far, only the CellSearch system was used to detect circulating tumor cells (CTC) with clinical relevance in esophageal cancer patients. Studies analyzing different CTC detection assays using advanced enrichment techniques to potentially increase the sensitivity are missing. Methods. In this single-center, prospective study, peripheral blood samples from 90 esophageal cancer patients were obtained preoperatively and analyzed for the presence of CTCs by Magnetic Cell Separation (MACS) enrichment (combined anti-cytokeratin and anti-epithelial cell adhesion molecules (EpCAM)), with subsequent immunocytochemical staining. Data were correlated with clinicopathological parameters and patient outcomes. Results. CTCs were detected in 25.6% (23/90) of the patients by combined cytokeratin/EpCAM enrichment (0-150 CTCs/7.5 mL). No significant correlation between histopathological parameters and CTC detection was found. Survival analysis revealed that the presence of more than two CTCs correlated with significantly shorter overall survival (OS) and progression-free survival (PFS). Conclusion. With the use of cytokeratin as an additional enrichment target, the CTC detection rate in esophageal cancer patients can be elevated and displays the heterogeneity of cytokeratin (CK) and EpCAM expression. The presence of >2CTCs correlated with a shorter relapse-free and overall survival in a univariate analysis, but not in a multivariate setting. Moreover, our results suggest that the CK7/8 + /EpCAM + or CK7/8 + /EpCAM − CTC subtype does not lead to an advanced tumor staging tool in non-metastatic esophageal cancer (EC) patients.
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